Dr. Iwao Ojima

8/14/2019 Dr. Iwao Ojima

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Iwao Ojima was born in Yokohama, Japan in 1945. He received his B.S. (1968), M.S. (1970), and Ph(1973) degrees from the University of Tokyo, Japan. He joined the Sagami Institute of Chemical Researand held a position as Senior Research Fellow until 1983. He joined the faculty at the Department Chemistry, State University of New York at Stony Brook first as Associate Professor (1983), was promotto Professor (1984), Leading Professor (1991), and then to Distinguished Professor (1995). He served as tDepartment Chairman from May 1997 through October 2003. Since early 2003 he has been the foundiDirector of the Institute of Chemical Biology and Drug Discovery at Stony Brook.He has a wide range of research interests in synthetic organic, organometallic and medicinal chemistincluding asymmetric synthesis, organic synthesis based on homogeneous catalysis, peptide and pepti

mimetics, -lactam chemistry, enzyme inhibitors, anticancer agents, antithrombotic agents, and medicinarelevant organofluorine compounds.He is a recipient of the E. B. Hershberg Award (for Important Discovery of Medicinally Active Substanc(2001) and the Arthur C. Cope Scholar Award (1994) from the American Chemical Society; the ChemiSociety of Japan Award (for distinguished achievements) (1999) and National Young Investigators Awafrom the Chemical Society of Japan (1976). He is a Fellow of the J. S. Guggenheim Memorial Foundat(1995), the American Association for the Advancement of Science (1997), and The New York AcademySciences (2000). He also received the Outstanding Inventor Award from The Research Foundation of State University of New York in 2002, and a NYSTAR Faculty Development Award in 2003 from tGovernor of the State of New York.He has served as an advisory committee member for the National Institutes of Health, National Scien

Foundation and the U.S. Department of Energy. He has served or currently serves as Editorial AdvisoBoard member ofJournal of Organic Chemistry, Organometallics,Journal of Molecular Catalysis, CurrTopics in Medicinal Chemistry (current) , Medicinal Chemistry (current), and Letters in Drug DesignDiscovery (current).He has published more than 340 papers and reviews in leading journals as well as edited 5 books. Hcurrently holds or has applications pending for more than l40 patents. SciFinder lists more than 6publications to his credits. Since he started his career in the U.S. at Stony Brook unversty in 1983, he hgiven more than 400 invited lectures at universities, research institutes, and industries. Also, he has givmore than 70 Plenary and Invited Lectures at international conferences and symposia.

Dr. Iwao OjimaDistinguished Professor of Chemistry

Director, the Institute of Chemical Biology & Drug Discovery

State University of New York at Stony Brook


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Stony Brook Symposium on

New Horizons in Organic Chemistry

September 29-30, 2005

The Charles B. Wang Center

Thursday, September 29

8:00 AM 1:00 PM Registration

9:00 AM 11:40 AM SBU Alumni Symposium

11:45 AM- 1:00 PM Buffet Lunch for Registered Participants and Poster Setup

Opening Lecture (1:00-2:00 PM)

Greetings: Dr. Robert L. McGrath, Provost

Moderator: ProfessorMichael G. White, Chair, Department of Chemistry

ProfessorRyoji Noyori(Nobel Laureate in Chemistry, 2001; President, RIKEN, Japan)

Asymmetric Hydrogenation: Science and Opportunities

Session I: Medicinal Chemistry and Drug Discovery (2:00-5:30 PM)

Moderator: ProfessorFrank W. Fowler

2:00 2:30 ProfessorGunda I. Georg (University of Kansas)Taxol: Brain Delivery

2:30 3:00 Dr. Alain Commeron (Sanofi-Aventis, France)

New Generation Taxoids: Discovery and Development of RPR109881

3:00 3:30 Dr. John Piwinski (Schering-Plough Research Institute, NJ))

Utilizing SAR and SBDD to Discover Novel Antiviral Agents

3:30 4:00 Coffee break, Poster Session

Moderator: ProfessorJoseph W. Lauher

4:00 4:30 Dr. Ezio Bombardelli (Indena, SpA, Italy)

Colchicine and its analogues as potential anticancer drugs

4:30 5:00 Dr. Ralph J. Bernacki (Roswell Park Cancer Institute)

IDN 5390, a novel seco-taxane with anti-angiogenic activity, inhibits

endothelial cell motility at sub-cytotoxic concentrations


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5:00 5:30 ProfessorDavid G. I. Kingston (Virginia Tech.)The shape of things to come: Structural and synthetic studies of Taxol and

related compounds

5:30 6:15 Short talks by poster presenters

6:15 7:00 Reception, Student Activity Center Ballroom B(Registered Participants Only)

7:00 9:30 Symposium Banquet, Student Activity Center Ballroom A

(Registered Participants Only)

Friday, September 30

8:00 8:40 Continental Breakfast, Charles B. Wang Center

8:40 Greetings: Dr. James V. Staros, Dean, College of Arts and Sciences,

Session II: Synthetic Methodology and Organic Synthesis (8:45-12:30)

Moderator: ProfessorKathlyn A. Parker

8:45 9:15 ProfessorEiichi Negishi (Purdue University)

ZACA Reaction: Zr-Catalyzed Asymmetric Carboalumination of Alkenes

9:15 9:45 ProfessorMasahiro Murakami (Kyoto University, Japan)

Torque Control by Metal-Orbital Interactions

9:45 10:15 ProfessorHisashi Yamamoto (University of Chicago)Designer Acid Catalysis for Selective Organic Transformation

10:15-10:30 Short Coffee Break

Moderator: ProfessorNancy S. Goroff

10:30 11:00 ProfessorMichael P. Doyle (University of Maryland)New Advances in Catalysis with Dirhodium(II) Compounds

11:00 11:30 ProfessorGary A. Molander (University of Pennsylvania)Expanding Organoboron Chemistry with Organotrifluoroborates

11:30 12:00 ProfessorThomas W. Bell (University of Nevada, Reno)Synthesis and Photochemistry in Pursuit of a Light-Driven Molecular Motor

12:00 12:30 ProfessorEiichi Nakamura (University of Tokyo)

Organic Synthesis: The Key Science for the Future

12:30 1:30 Lunch, Poster Session


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Session III: Bioorganic Chemistry and Chemical Biology (1:30-5:30 PM)

Moderator: ProfessorDale G. Drueckhammer

1:30 2:00 ProfessorKoji Nakanishi (Columbia University)

Bioorganic studies on gingkolides

2:00 2:30 ProfessorPeter J. Tonge (Stony Brook University)Mycolic Acid, Menaquinone and Mycobactin Biosynthesis: Mining the Magic

Mountain for Novel Tuberculosis Chemotherapeutics

2:30 3:00 ProfessorScott M. Sieburth (Temple University)

Silicon as a Central Drug Design Component

3:00 3:30 Coffee Break, Poster Session

Moderator: ProfessorDaniel P. Raleigh

3:30 4:00 ProfessorNicole S. Sampson (Stony Brook University)

Multivalent and Stereoregular Polymers to Probe Fertilin Function inFertilization

4:00 4:30 ProfessorSteven Rokita (University of Maryland)

Selective Alkylation of DNA through a Recognition-Dependent Process

4:30 5:00 ProfessorCynthia J. Burrows (University of Utah)Heterocyclic Chemistry leading to Mutagenesis via Oxidation of DNA Bases

5:00 5:30 ProfessorGlenn D. Prestwich (University of Utah)

Injectable synthetic extracellular matrix for tissue engineering and repair

5:30 Closing Remarks:Robert C. Kerber, Associate Chair, Department of Chemistry


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SBU Alumni Symposium

September 29 (9:00 11:40 AM), 2005

8:30 9:00 Coffee and Danish, Charles B. Wang Center

Greetings: Dr. Donna M. Iula, Chair of Organizing Committee, Pfizer

Moderator: Dr. Seung-Yub Lee, ICB & DD

9:00 9:20 Dr. Scott D. Kuduk (Merck Research Laboratories, PA)2,3-Diaminopyridine Bradykinin B1 Receptor Antagonists

9:20 9:40 Dr. An T. Vu (Wyeth Research, PA)2-Phenylquinolines as Potent and Selective Estrogen Receptor beta (ER)Ligands

9:40 10:00 ProfessorThierry Brigaud (Universit de Cergy-Pontoise, France)Chiral fluorinated imines and oxazolidines: synthons for organofluorine

chemistry and asymmetric synthesis

10:00 10:20 Dr. Joseph Zhu (Amgen, Inc., CA)Design and Synthesis of Conformationally Constrained TRPV1 Antagonists

10:20 10:40 Dr. Matthew M. Zhao (Merck Research Laboratories, NJ)Development of the Manufacturing Process to Emend

(Aprepitant), Winner

of 2005 Presidential Green Chemistry Challenge Award

10:40 11:00 Dr. Ivan Habu (Ruer Bokovi Institute, Croatia)

Diels-Alder reactions on imines derived from 3-amino--lactams11:00 11:20 Dr. Masakatsu Eguchi (Institute for Chemical Genomics, WA)

Design, Synthesis, and Application of Peptide Secondary Structure Mimetics

11:20 11:40 Professor Elke Schoffers (Western Michigan University)Looking for a Ligand with a New Twist? Chiral Phenanthrolines for Organic

Chemistry

11:40 Greeting and Remarks: Professor Iwao Ojima


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Ryoji Noyori was born in 1938 in Japan, was educated at Kyoto University and became an Instructor in

Hitosi Nozaki's group at the same university in 1963. He was appointed Associate Professor at Nagoya

University in 1968, spent a postdoctoral year at Harvard with E.J. Corey in 19691970 and, shortlyafter returning to Nagoya, was promoted to Professor in 1972. In 2003, he was appointed President o

RIKEN and also University Professor at Nagoya. Noyori is a Member of the Japan Academy and the

Pontifical Academy of Sciences, and a Foreign Member of the National Academy of Sciences, USA

the Russian Academy of Sciences, and the Royal Society, UK. His research has long focused on the

fundamentals and applications of molecular catalysis based on organometallic chemistry, particularly

asymmetric catalysis and what is now known as "green chemistry. In 2001, he received the Wol

Prize in Chemistry and the Roger Adams Award, and also shared the Nobel Prize in Chemistry with W

S. Knowles and K. B. Sharpless.

Asymmetric Hydrogenation: Science and Opportunities

Asymmetric catalysis is four-dimensional chemistry. High efficiency can be achieved only by using a

combination of both an ideal three-dimensional structure (x, y, z) and suitable kinetics (t). Although H

H bonds are readily cleaved by transition metal complexes, truly useful asymmetric hydrogenations are

limited. BINAP-transition metal complexes are shaped in a manner that is beneficial for chira

recognition, and these complexes can act as hydrogenation catalysts. However, their efficiency highly

depends on the metal and the auxiliary anionic or neutral ligands, and the reaction conditions. No

universal catalysts exist because of the diversity of unsaturated organic compounds. The means o

developing efficient asymmetric hydrogenations is discussed from a mechanistic point of view.

Professor Ryoji Noyori (President, RIKEN, Japan)

Nobel Laureate in Chemistry, 2001


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Gunda I. Georg is a University Distinguished Professor in the Departm

nt of Medicinal Chemistry at the University of Kansas. She also is th

Director of the Center for Drug Discovery and the Director of the Exp

imental Therapeutics Program of the Kansas Masonic Cancer Institut

She is the PI of a statewide NIH COBRE Center for Cancer Experime

al Therapeutics. She received the Dr. rer. nat. degree in Medicinal Chmistry from the University of Marburg in Germany in 1980 and was a

ostdoc in the Department of Chemistry at the University of Ottawa, C

ada. She has over 130 publications in the area of organic medicinal c

mistry with a focus on the synthesis and structure-activity studies of an

cancer natural products and male contraceptive agents. She is the co-in

entor of Aquavan, a water-soluble anesthetic, which is in phase III c

nical trails. She has served on various scientific advisory boards, for

ample for the NIH, the American Cancer Society, and the Institute for

he Study of Aging. She is an AAAS Fellow and has received the Sa

Memorial International Award of the Pharmaceutical Society of Japan

mong other honors.

Taxol: Brain Delivery

Taxol, commonly used for the treatment of breast, ovarian, and lung cancer, is not significantlyabsorbed across the gastrointestinal epithelium after oral administration and does not cross the blood-

brain-barrier. A primary mechanism limiting taxol distribution into the brain is active efflux by thmulti-drug resistant gene product 1 (MDR1) or P-glycoprotein (Pgp) localized on the blood side of the

microcerebrovascular endothelium comprising the BBB. We hypothesized that specific modifications

of the taxol molecule could reduce binding or recognition by Pgp, resulting in improved BBBpermeability. Our approach is based on Seeligs suggestion that clusters of hydrogen bond acceptor

(electron donating groups), arranged in fixed spatial distances from each other, are required for

recognition by Pgp binding sites. The recognition elements are formed either by two or by threeelectron donating groups. It was also hypothesized that the number and strength of the hydrogen bonds

present in a molecule determine Pgp affinity. This implies that one could remove recognition element

from the molecule that are not necessary for biological activity and improve BBB penetration. It was

further observed that certain functional groups with a negative charge do not interact with Pgp. Weinvestigated a number of taxol analogues that were modified at the 3-amide group, at C9, C10, and C7to test this hypothesis. The analogues were analyzed for cytotoxicity against the MCF7 breast cance

cell line and the drug resistant breast cancer cell line NCI/ADR-RES. They were also investigated fortheir influence on rhodamine 123 uptake into brain microvessel endothelial cells to assess interaction

with Pgp. One of the derivatives, the C10 hemisuccinate analogue of Taxol (Tx-67), was also examined

in an in situ rat brain perfusion experiment (J. Med. Chem. 2005, 48, 832). Several of the taxoanalogues, including Tx-67 showed reduced interaction with Pgp in the BBB.

Professor Gunda I. Georg

(University of Kansas)


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2005-present : Currently head of Natural Products Chemistry at

Sanofi-Aventis

2004-2005 : Senior Director at Aventis. Head of HTMC (High Throu

put Medicinal Chemistry) and Coordinator of NPCT (Nat

ural Product Chemistry Team)

Member of the National Commissions of ARC French Association fo

Cancer Research (2000-2004).

Member of the board of SFC (Socit Franaise de Chimie)

Member of the board of SCT (Socit de Chimie Thrapeutique)

Member of the Scientific Board of Ariana Pharmaceuticals

Sanofi-aventis New Generation Taxoids:

Discovery and Development of RPR109881

Cancer is still the leading cause of death throughout the world. Although chemotherapy plays the key

role for treating advanced cancer, results of currently available chemotherapy regimens are still

disappointing. Recently, several new compounds, such as taxanes and camptothecines, havedemonstrated promising activities. Among these compounds, the taxanes, paclitaxel and docetaxel, have

the same mechanism of action and have broad antitumor activity on solid tumors (e.g. breast, ovarianlung, prostate) . These compounds interact with polymerized tubulin to promote the formation o

microtubules, to prevent their disassemble, and, thus, to block cell division at the G2-M phase.

At present taxanes are key compounds in chemotherapy treatment. However recurrences are commonand new agents active after taxanes failure are necessary. As part of our research program on new

generation taxoids, a main objective has been the targeting of resistant / refractory tumor cells. Ourefforts led to the discovery of new generation compounds. Within this set of promising molecules was

RPR109881, a new modified taxane generated by a serendipitous chemical rearrangement. The initia

approach leading to RPR109881 will be disclosed along with preclinical data. This compound iscurrently undergoing clinical trials. Phase I data led to 90 mg/m2 as the recommended dose with 1h

infusion duration. Recent data from Phase II against MBC (metastatic breast cancer) showed tha

patients tolerability was acceptable in taxotere non-resistant and taxoid resistant strata, and was similato that reported in Phase I studies. Neutropenia was the main hematological toxicity and diarrhea the

most frequent non-hematological toxicity. Efficacy data showed nearly 20% response rate for theresistant stratum.

These results support the on-going evaluation of RPR109881 versus standard therapy in a randomizedPhase III study of patients with MBC.

Dr. Alain Commeron

(Sanofi-Aventis, France)


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1960 B.A.(Chemistry) Cambridge University, England1964 Ph.D. (Organic Chemistry) Cambridge University, England

(Advisors: Lord Todd and D.W. Cameron)1963-1964 Research Associate, M.I.T. Cambridge, Massachusetts1964-1966 NATO Fellow, Cambridge University

1966-1971 Assistant Professor of Chemistry, SUNY Albany1971-present Associate Professor - University Distinguished ProfessorVirginia Polytechnic Institute and State University, Blacksburg,Virginia.

1999 Research Achievement Award, American Society ofPharmacognosy

2002 Virginia Scientist of the Year, April 2002.1983-1998 Associate Editor of theJournal of Natural Products2000-2004 Member of NIH Bioorganic and Natural Products Chemistr

Study Section.

The shape of things to come: Structural and synthetic studies

of Taxol and related compounds.

Paclitaxel (TaxolTM, 1) and its semisynthetic analog docetaxel (2) are two of the most importananticancer agents developed over the last 30 years, and Professor Ojima has made major contribution

to their chemistry and biology. The compounds continue to excite interest as new activities arediscovered for them and their analogs. Their primary mechanism of action is by interaction with the

cellular protein tubulin, causing irreversible polymerization to microtubules. A detailed knowledge of

this crucial interaction is thus of paramount importance in the design and development of highly potentanalogs and also for the development of non-taxane tubulin polymerization agents. The lecture wil

review our work on discovering the tubulin-binding conformation of paclitaxel by a combination o

REDOR NMR and fluorescence spectroscopic studies, and by molecular modeling combined with theresults of electron crystallographic studies. This work has resulted in the design and synthesis o

bridged paclitaxel analogs such as 3 that have tubulin-assembly and cytotoxic activities equal to o

better than those of paclitaxel. The implications of this work for the future development of paclitaxel

like compounds will be discussed, and the synthesis of the simplified analog 4 will be described.

Professor David G. I. Kingston

(Virginia Tech.)

OCOPhHO

O

OAc

OR2O

O

OH

Ph

NH

OH

OR1

O

1 R1 = Ph, R2 = Ac

2 R1 = Me3CO, R2 = H

PhCOOHO

O

O

OAcO

O

OH

O

3

O

HO

PhCONH

4

O

X

HO

NH

Ph

O

BzO

O

O

O


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Dr. Bombardelli is President of the Scientific Board for Research and

Development of Natural Products, Indena SpA, Milan Italy. He

received his B.Sc. in Biology from the University of Pavia in 1962,

and completed a 5 year postdoctoral role of Assistant Professor at the

Biochemistry Institute at the University of Milan, 1962-1966. In

1962 he went on to join Inverni Della Beffa SpA, Milan, Italy, asDeputy Director of Research and Development, 1962-1985. Main

duties were conducting chemical research on natural products of

natural semi-synthetic origin, isolation, structure elucidation,

synthesis and medicinal chemistry. From 1986 he became Scientific

Director of Indena SpA before becoming President. Special research

interests have been Botanical Derivatives, Anti-tumour, Anti-

inflammatory, Anti-microbial, Anti-viral and CNS compounds. Over

390 research papers have been published and about 120 patents. He

has been an active participant to many conferences and symposia,

where he has presented numerous scientific papers.

Colchicine and its analogues as potential anticancer drugs

Colchicine is an alkaloid extracted from the seeds of Colchicum autumnale, a plant native of theCaucasian area and reported since the Greek Antiquity for the treatment of joints-pain.Curiously neglected in Europe for centuries, the plant was introduced in the States by BenjaminFranklin after a trip to United Kingdom where he got relief from gout by application an extract oColchicum.The demand of colchicine in the world is today appreciably high not only because of its use in thetreatment of the gout, but also because of its importance as starting material for the manufacturing its 3-O-glucosyl thio-analogue, thiocolchicoside, widely used in Europe for the treatment of spasticity andmuscular contractures.Colchicine is also known as an antimitotic agent and its citotoxic properties were discovered in 1889when the Italian scientist Pernice described the influence of such an alkaloid on tissues proliferation Nevertheless the compound is probably the oldest citotoxic drug known still lacking of any clinicaapplication. A colchicine analogue, known with the trademark of Colcemid, has been in use for afairly limited period for the treatment of Hodgkins lymphoma.The major limiting factors of the class of colchinoids were the appreciable toxicity and the developmen

of resistance.Believing in the potentiality of this class we kept on re-examining many natural and semisyntheticderivatives, together their thio-analogues, focusing our attention particularly on the activity against platinum resistant, taxane resistant and MDR tumours. After an extensive SAR study we found thaappreciable result in vitro were obtained by modification of ring B and derivatization of nitrogen. In particular we found that dimeric derivatives of thiocolchicine, whose IDN 5404 is the lead, werextremely active against colon tumor platinum-resistant cell lines. Furthermore it has been found thatthose dimers, besides their classical ability to inhibit the polymerization of tubulin, are able to interactwith topoisomerase I with a mechanism different from that peculiar to camptothecin.Recently, dosage formulations of IDN 5404 with human serum albumin demonstrated a consistentreduction in toxicological effects, enhancing therefore the therapeutic index of the class and openingnew possibilities in the treatment of colon cancer.

Dr. Ezio Bombardelli

(Indena SpA)


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Pharmacology & Therapeutics Dept.Grace Cancer Drug Center,Roswell Park InstituteBuffalo, NY 14263

1972-1974 Cancer Research Scientist I1974-1976 Cancer Research Scientist II1976-1977 Senior Cancer Research Scientist1977-1980 Cancer Research Scientist IV1981-1993 Cancer Research Scientist V1993-2000 Cancer Research Scientist VI2000-present Member

IDN 5390, a novel seco-taxane with anti-angiogenic activity,

inhibits endothelial cell motility at sub-cytotoxic concentrations

The protracted low-dose administration of conventional chemotherapeutic agents, including the taxanespaclitaxel and docetaxel, has been shown to inhibit tumor growth by an anti-angiogenic mechanism. Howeverthe feasibility of these two clinical agents for protracted scheduling is limited by host toxicity and poor oral

bioavailibility. IDN 5390, a novel seco-taxane derivative with demonstrated anti-tumor activity, has improvedoral bioavailability and a toxicity profile suitable for daily administration, rendering it an excellent candidate forprotracted dosing in vivo to achieve an anti-angiogenic effect. The aims of these studies were to evaluate the invitro activity of IDN 5390 on endothelial cell functions relevant to angiogenesis, namely endothelial celproliferation, motility and microcapillary formation, and to compare the efficacy of IDN 5390 to paclitaxel anddocetaxel. In a modified Boyden chamber migration assay, a monolayer wound closure assay and a capillarytube formation assay, IDN 5390 inhibited human umbilical vein endothelial cell (HUVEC) migration andcapillary formation in a dose-dependent manner at concentrations that did not compromise cell viability. Incontrast, paclitaxel and docetaxel, although more potent inhibitors of endothelial cell proliferation, did notexhibit selectivity for inhibition of cell migration or capillary tube formation. Further evaluation of these agentsrevealed that while paclitaxel, docetaxel and IDN 5390 all potently polymerized purified tubulin in vitro, IDN5390 did not stabilize microtubules against depolymerization as potently as paclitaxel or docetaxel, suggesting

that the dynamic instability of microtubules of these agents may be differentially regulated in a cellular contextIndeed, treatment of HUVEC with IDN 5390, even at high concentrations, resulted in only a transient G2/Marrest, while paclitaxel and docetaxel induced sustained G2/M arrest to an overall greater extent than IDN 5390The in vivo anti-angiogenic activities of IDN 5390 and docetaxel were compared in a subcutaneous Matrigeplug assay of neovascularization. Docetaxel administered intravenously to mice Q3D x 3 doses at 20, 10 and 5mg/kg/dose was compared to IDN 5390 adminstered orally, QD at 120, 60 and 30 mg/kg/dose. The antiangiogenic effect of docetaxel even at the highest dose of 20mg/kg/dose was only equal to that of IDN 5390 athe lowest dose, as determined by microvessel density in the CD31 immunnostained plug. Additionally, greatertoxicity, as determined by animal weight loss, was observed among docetaxel-treated animals compared to IDN5390-treated animals. Thus, the selective anti-motility activity on endothelial cells and the differentialregulation of microtubule dynamics by IDN 5390 represent a novel mechanism of taxane drug action and a new paradigm in anti-angiogenic taxane drug development. (Supported in part by funds from Indena SpA, MilanItaly.)

Dr. Ralph J. Bernacki

(Roswell Park Cancer Institute)


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John J. Piwinski received his B.S. degree in Chemistry and Biochemi

from the State University of New York at Stony Brook in 1976. As

undergraduate, he received his first exposure to research by work

under the direction of Professor Frank W. Fowler. In 1980 he recei

his Ph.D. in Organic Chemistry from Yale University working w

Professor Frederick E. Ziegler. He joined Revlon Health Care (ULaboratories) in 1980 as a Senior Scientist working in the cardiovascu

diseases area. In 1983 he moved to Schering-Plough where he worke

the respiratory diseases group. He was promoted to Director of Chemi

for Allergy and Immunology in 1992, to Vice President of Chem

Research in 1999 and most recently Group Vice President of Chem

Research in 2004. He also has approximately 120 published resea

papers, abstracts and approved U.S. patents. He is a member of

Scientific Advisory Board for the New Jersey Academy of Sciences si

1996, a member of the American Chemical Society since 1975 and m

recently serves as a member for the Institute of Chemical Biology & D

Discovery Advisory Board at SUNY at Stony Brook.

Utilizing SAR and SBDD to Discover Novel Antiviral Agents

Over the past century medicinal chemistry has played a pivotal role in the discovery of new therapeutic

agents for the treatment of disease. The fundamental role of organic synthesis for investigating

structure-activity relationships (SAR) to attain a desired pharmacological profile for a therapeutic agenhas not changed much during this time. However, as we gained a better understanding of how

therapeutic agents work at the molecular level, a new direction in the drug discovery process emerged

towards the latter half of the century. Simultaneously, new methods and technologies emerged tha

improved the drug discovery process, such as tools to aid in structure-based drug design (SBDD).

These new technologies enabled the medicinal chemist to design more potent and selective agents with

improved pharmacokinetic and in vivo profiles. As a result, new medicines are being approved today

that are very safe and treat diseases that previously had no cures. This presentation will illustrate how

scientists have been integrating many of these new technologies to discover modern medicines. Efforts

at Schering-Plough have resulted in a series of CCR5 antagonists and HCV protease inhibitors, which

have resulted in compounds that are currently in clinical development for the treatment of HIV andHepatitis C.

Dr. John Piwinski

(Schering-Plough Research Institute, NJ)


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H. C. Brown Distinguished Professor of Chemistry, Purdue Universgrew up in Japan and received his Bachelors degree from the Univerof Tokyo (1958). He then joined a chemical company, Teijin. In 1960came to the University of Pennsylvania on a Fulbright Scholarship obtained his Ph.D. degree in 1963. He returned to Teijin but joiProfessor H. C. Browns Laboratories at Purdue as a Postdocto

Associate in 1966. He was appointed Assistant to Professor Brown1968. It was during the following few years that he began to see the nfor some catalytic ways of promoting organoborane reactions. Negwent to Syracuse University as Assistant Professor in 1972 and wpromoted to Associate Professor in 1976. In 1979 he was invited bacPurdue University as Full Professor. In 1999 he was appointed inaugural H. C. Brown Distinguished Professor of Chemistry. Variawards he has received include the Guggenheim Fellowship (1987),1996 A. R. Day Award, a 1997 Chemical Society of Japan Award, 1998 ACS Organometallic Chemistry Award, a Humboldt SenResearcher Award, Germany (1998 2001), and the 2000 RSC SirFrankland Prize Lectureship. At Purdue University, he was the recip

of the 1998 McCoy Award and the 2003 Sigma Xi Award.

ZACA Reaction:

Zr-Catalyzed Asymmetric Carboalumination of Alkenes

The Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction) was discovered a decadeago.

The ZACA reaction represents a prototypical example of enantioselective carbon-carbon bond-formingreactions of alkenes of one-point binding. It is catalytic in both Zr and a chiral auxiliary, e.g., NMI. Theenantioface selectivity of methylalumination has only been 70-80% ee, although that of ethyl- andhigher alkylmetalation has been 90-95% ee. Despite the less than satisfactory enantioselectivity formethylalumination, a highly efficient asymmetric method for the synthesis of a wide range ofstereochemically pure chiral organic compounds including (i) deoxypolypropionates, and (ii) reducedterpenoids, such as vitamins E and K, has been developed. The current status of the ZACA-basedasymmetric method will be discussed with emphasis on several methodological breakthroughs. Some ofthe noteworthy transformations are shown below. In cases where the products cannot be readily purified by simple means, such as chromatography and recrystallization, the lipase-catalyzed selectiv

acetylation may be used to produce stereoisomerically pure compounds in 60-80% recovery.

Professor Eiichi Negishi

(Purdue University)

R1

(i) R3Al, cat. (-)-(NMI)2ZrCl2(ii) O2

R1

R

OH

R = Me, 70-80% ee

R = Et or higher alkyl, 90-95% ee

OH

(ii) cat. (-)-(NMI)2ZrCl2

(i) Et3Al, IBAO

OH92%90% ee

R1cat. (-)-(NMI)2ZrCl2

R1AlMe2

(i) Zn(OTf)2, DMF

(ii) vinyl bromide, cat. PdLn

71% overallR1

75% ee

cat. (+)-(NMI)2ZrCl2

HO (ii) I2, (iii) TBSCl, baseITBSO

(i) tBuLi then ZnBr2(ii) vinyl bromide, cat. PdLn

TBSO

"One-pot"(-)-ZACA-Pd-cat. vinyl.

"One-pot"(+)-ZACA-Pd-cat. vinyl.

etc.

Me3Al

(i) Me3Al

H3O+


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1984 Doctor of Science The University of Tokyo

(Prof. Mukaiyama)

1984 1987 Assistant, The University of Tokyo1987 1993 Assistant, Kyoto University

1991 1992 Postdoctoral Fellow, ETH Zrich, Switzerland

(Prof. Eschenmoser)1993 2001 Associate Professor, Kyoto University

2002 Present Professor, Kyoto University

Contrasteric Torque Control by Metal-Orbital Interactions

The electrocyclic ring-opening of cyclobutenes is a classical textbook example of concerted pericyclicreactions that proceed under the control of the WoodwardHoffmann rules. Substituents located at the

3- and 4-positions can move either inward or outward during the thermal ring opening reaction. Rondanand Houk proved that the selectivity of the rotational direction, termed torquoselectivity, is subject toelectronic control. We discovered the interesting preference of silyl groups to rotate inwardcontradicting intuitive expectation for outward rotation based on steric grounds. The antibonding *orbital of a siliconcarbon linkage is energetically low-lying and able to accept electron density fromthe HOMO of the opening cyclobutene skeleton, stabilizing the inward transition state.

The following reaction of trans-3,4-bis(trimethylsilyl)cyclobutene presents a striking example ofcontrasteric behaviors.1 In addition, exclusive inward rotation was experimentally identified with 3-borylcyclo-butene.2

Professor Masahiro Murakami

(Kyoto University, Japan)

H

H

H

PhMe2Si

HHH

PhMe2Si110 C

H

HPhMe2Si

H +

77 : 23

CCCC

Si

SiMe3

H

H

Me3Si

110 CH

SiMe3Me3Si

H +

78 : 22

H

H

H

(pin)B

92 CH

H(pin)B

H

exclusive

E,E-isomer

(pin)B = pinacolatoboryl

1. Murakami M., Hasegawa, M. Angew. Chem. Int. Ed.

2004, 43, 4874.

2. Murakami M., Usui I., Hasegawa M., Matsuda T. J. Am

Chem. Soc. 2005, 127, 1366.


16/37

Hisashi Yamamoto received his Bachelor from Kyoto University and

D. from Harvard under the mentorship of Professor E. J. Corey. His f

academic position was as Assistant Professor and lecturer at Ky

University, and in 1977 he was appointed Associate Professor

Chemistry at the University of Hawaii. In 1980 he moved to Nag

University where he became Professor in 1983. In 2002, he movedUnited States as Professor at the University of Chicago. He has b

honored to receive the Prelog Medal in 1993, the Chemical Society

Japan Award in 1995, the Max-Tishler Prize in 1998, Le Grand Prix d

Fondation Maison de la Chimie in 2002, National Prize of Purple Me

(Japan) in 2002, and Yamada Prize in 2004.

His current interests are mainly development of new synthetic reacti

in the filed of acid catalysis including designer Lewis acids, desig

Brnsted acids, and combination of these two acid systems. Recently

is also interested in a new field on Niroso aldol reactions.

Designer Acid Catalysis for Selective Organic Transformation

Professor Hisashi Yamamoto

(University of Chicago)

Lewis and Brnsted acids can be utilized as more effective tools for chemical reactions by sophisticatengineering as designer acids. Needless to say, the ultimate goal of such designer acids is to achiehigh reactivity, selectivity, and versatility as a useful tool o f organic synthesis. The full potential of ac

catalysts has not yet been realized. One possible way to take advantage of such abilities may be to applycombined acids system to the catalyst design. The concept of combined acids, which can be classifiinto Brnsted acid assisted Lewis acid (BLA), Lewis acid assisted Lewis acid (LLA), Lewis acid assistBrnsted acid (LBA), and Brnsted acid assisted Brnsted acid (BBA), can be a particularly useful tool fthe design of asymmetric catalysis,

because combining such acids will bring outtheir inherent reactivity by associativeinteraction, and also provide moreorganized structure, which will allow aneffective asymmetric environment to besecured.(1) Table 1 summarizes therepresentative examples for each acid

catalysts. The other way to generate highlyreactive acid catalysis is designing superLewis acid catalysis based on superBrnsted acid systems. Several newBrnsted acids are introduced and used forselective organic transformations. Thelecture will include these new trends of acidcatalysis in organic synthesis.

1. H. Yamamoto and K. Futatsugi, Angew. Chem. Int.Ed. Engl., 2005, 44, 1924-1942; See also the followinggeneral introduction of acid catalysis: a) Lewis Acids inOrganic Synthesis, Vols. 1 and 2 (Ed. H. Yamamoto),Wiley-VCH, Weinhelm, 2000; b) Lewis Acid Reagents:

A Practical Approach (Ed. H. Yamamoto), OxfordUniversity Press, Oxford, 1999.


17/37

Michael P. Doyle received his B.S. degree from the College of Thomas in St. Paul, MN, and his Ph.D. degree from Iowa State UniverFollowing a postdoctoral engagement , he joined the faculty at HCollege in 1968. In 1984, he moved to Trinity University in San AntoTX, as the Dr. D. R. Semmes Distinguished Professor of Chemistry, in 1997 he came to Tucson, AZ, as Vice President, then President,Research Corporation and Professor of Chemistry at the UniversityArizona. In 2003 he moved to the University of Maryland, College Pwhere he is Professor and Chair of the Department of Chemistry Biochemistry. Among the awards that he has received are a Camille Henry Dreyfus Teacher-Scholar Award (1973), a ChemManufacturers Association Catalyst Award (1982), the AmeriChemical Society Award for Research at Undergraduate Instituti(1988), Doctor Honoris Causa from the Russian Academy of Scien(1994), Alexander von Humboldt Senior Scientist Award (1995), James Flack Norris Award for Excellence in Undergraduate Educat(1995), the George C. Pimentel Award for Chemical Education (200

and the Arthur C. Cope Scholar Award (2006). He has writtencoauthored ten books, including Basic Organic Stereochemistry, 20 bchapters, and he is the co-author of more than 250 journal publications

New Advances in Catalysis with Dirhodium(II) Compounds

The challenge of development of catalysts that are effective for a broad range of transformations has

been met with dirhodium carboxamidates. With high turnover numbers and selectivities, they arhighly effective for catalytic reactions with diazo esters, as Lewis acids in catalytic processes, and as

oxidation catalysts. Chiral catalysts for metal carbene transformations have been developed

Dirhodium(II) carboxamidate catalysts that possess four chiral pyrrolidone, oxazolidinone, azetidinone

or imidazolidinone ligands with pendent ester substituents are highly effective. Optical yields of greate

than 95% have been achieved in intramolecular cyclopropanation reactions in alkyne cyclopropenation

reactions, in gamma-lactone production from carbon-hydrogen insertion reactions of diazoacetate esters

New applications of these catalysts as Lewis acids (hetero-Diels-Alder and ketene cycloadditio

reactions) and for chemical oxidations will be presented.

Professor Michael P. Doyle

(University of Maryland)


18/37

Consultant, Hauser Chemical Research, 1991-1999. NIH MedicChemistry Study Section, 1993-1997. Associate Chair, DepartmentChemistry and Biochemistry, University of Colorado, 1992-1995. ElecMember-at-Large, ACS Division of Organic Chemistry ExecutCommittee, 1999. Executive Director, 37th National Organic Sympos1999-2001. Editorial Advisory Board, Organometallics, 2000-20Chair-Elect, Philadelphia Organic Chemists Club, 2000. ChPhiladelphia Organic Chemists Club, 2001. Alternate CounciPhiladelphia Section of the American Chemical Society, 2001-20Associate Editor, Organic Letters, 2002-.Editorial Advisory Board, Current Topics in Medicinal Chemistry, 200Associate Editor, Comprehensive Organic Functional GrTransformations II, Pergamon Press, 2003-2004. Board of ConsultEditors, Tetrahedron and Tetrahedron Letters, 2003-2008. DirecPhiladelphia Section of the American Chemical Society, 2004-20Volume Editor, Science of Synthesis, Thieme Publishers, 2004-20Editor, Encyclopedia of Reagents for Organic Synthesis, Wiley, 20

present. Secretary/Treasurer, ACS Division of Organic Chemistry, 20 present. Vice Chair, Department of Chemistry, UniversityPennsylvania, 2005- presnet.

Expanding Organoboron Chemistry with Organotrifluoroborate

Organotrifluoroborates have emerged as complementary boron reagents for Suzuki-Miyaura type cross

coupling reactions. For many years, boronic acids, boronate esters or organoboranes have been

employed as the principle organoboron partners in these transformations. However, these reagent

possess many limitations. Boronic acids are notorious for the difficulty involved in their purification a

well as their uncertain stoichiometry. Even though the use of boronate esters is more attractive from

this point of view, these reagents lack atom economy and are more expensive to employ

Organoboranes are limited by the inherent characteristics of the in situ hydroboration reaction used to

create them. These latter reagents also suffer from high sensitivity to air and poor functional group

compatibility in some cases. In contrast, organotrifluoroborates are unique compounds that have been

shown to overcome these limitations. These reagents can be easily prepared from inexpensive materials

They are stable to air and moisture, allowing storage for long periods of time without noticeable

degradation. In fact, their high versatility and stability has made them excellent partners in Suzuki

Miyaura type coupling reactions.

The presentation will outline the utility and versatility of organotrifluoroborates in cross-coupling

reactions. Additionally, the ability of these reagents to resist chemical oxidation will be highlighted

This feature of organotrifluoroborates offers the unique opportunity to preserve the carbon-boron bond

in the oxidation of remote functionality within the same molecule.

Professor Gary A. Molander

(University of Pennsylvania)


19/37

Thomas Bell, born in 1951, received his PhD from University Colle

London in 1980, having conducted his thesis research with F. Sondheim

and D.J. Cram (UCLA). He worked with J. Meinwald as an N

Postdoctoral Fellow at Cornell University, then joined the S

University of New York at Stony Brook as an Assistant Professor in 19

There, he reached the rank of Professor in 1991, then moved to current position as Professor of Chemistry at the University of Neva

Reno, in 1995. He has been a Fellow of the American Association of

Advancement of Science since 1994; in 1990 and 1996 he was appoin

Visiting Professor at Universit Louis Pasteur in Strasbourg, France.

current interests include advanced materials, antiviral

immunomodulatory drugs, nanoscale molecular assemblies and devi

and supramolecular chemistry, as well as hiking, mountain biking, sk

and snowboarding.

Synthesis and Photochemistry

in Pursuit of a Light-Driven Molecular Motor

A multidisciplinary team at UNR has planned the synthesis of a light-driven molecular motor of

potential use in nanotechnology. Design and modeling of a molecular motor based on stericall

geared 9-(2,2,2-triphenylethylidene)fluorene (1)[1] are discussed. Several substituted analogs of 1such as the 2-tert-butyl derivative (2), have been synthesized to investigate photoisomerization

efficiency. This first photoisomerization study of a dibenzofulvene reveals significant quantum yields (4

9%), despite theoretical prediction of inefficient or negligible isomerization of the parent hydrocarbon

fulvene. Polar substituents increase absorption wavelengths and can greatly enhance

photoisomerization quantum yields. The current status of our efforts to synthesize the target molecula

motor is also described.

Professor Thomas W. Bell

(University of Nevada, Rino)

[1] T.W. Bell, V. J. Catalano, M.G.B. Drew, D. J. Phillips, Chem. Eur. J., 2002, 8, 2219.

1

Ph3C

(E)-6

CPh3

(Z)-6


20/37

Eiichi Nakamura received his first degree in chemistry with Prof.

Mukaiyama and his Ph.D. degree in 1978 with Prof. I. Kuwajima bot

Tokyo Institute of Technology. After two postdoctoral years with Pro

Stork at Columbia University, he started his academic career at To

Institute of Technology in 1980, and in 1995, he moved to the Univer

of Tokyo as a Professor of Physical Organic Chemistry. He is currenthe Project Leader of "Nakamura Functional Carbon Cluster" ERA

Project (Japan Agency for Science and Technology) and a Senior Scie

Officer at the Japan Society for Promotion of Science. He is a recipien

The Japan IBM Science Prize (1993), Nagoya Medal in Orga

Chemistry, Silver Meal (2001) and The Chemical Society of Japan Aw

(2003). He is a Fellow of the American Association for Advancemen

Science and a Fellow of the Royal Society of Chemistry.

Organic Synthesis: The Key Science for the Future

Carbon clusters remain to be the subject of 2000 papers every year. While a majority of these reports

are concerned with the materials per se, it is our belief that the future science of carbon clusters depend

on chemically modified carbon cluster complexes and control of their nano architectures-a new

challenge for synthetic chemists.

Some time ago, we discovered that addition of an organocopper reagent to [60]fullerene takes place

regioselectiviely to give penta-addition product.[1] The reaction is completely regioselective, often

quantitative and can be carried out on a multi-gram scale with minimum synthetic skill. The adduct can

be converted to a variety of metal complexes, where the fullerene cyclopentadienide (FCp) serves as

5-ligand to the metal, an intriguing example being "bucky ferrocene".[2] We also found that meta

atoms can be introduced also in a "ship-in-bottle" way into carbon nanotubes to make endohedra

metallonanotubes.[3] Such engineered carbon clusters can then be transformed into one- or two

dimensional nano-architectures.[4]

Professor Eiichi Nakamura

(University of Tokyo)

[1] M. Sawamura, H. Iikura, and E. Nakamura, J. Am. Chem. Soc., 118 (1996) 12850-12851.

[2] A. Hashimoto, H. Yorimitsu, K. Ajima, K. Suenaga, H. Isobe, J. Miyawaki, M. Yudasaka, S. Iijima, E. Nakamura, Proc

Natl. Acad. Sci., 101 (2004) 8527-8530.

[3] M. Sawamura, Y. Kuninobu, M. Toganoh, Y. Matsuo, M. Yamanaka and E. Nakamura, J. Am. Chem. Soc., 124 (2002)

9354-9355.

[4] S. Zhou, C. Burger, B. Chu, M. Sawamura, N. Nagahama, M. Toganoh, U. E. Hackler, H. Isobe, and E. Nakamura,

Science, 291, (2001) 1944-1947; M. Sawamura, K. Kawai, Y. Matsuo, K. Kanie, T. Kato and E. Nakamura, Nature, 419

(2002) 702-705; E. Nakamura and H. Isobe Acc. Chem. Res. 36, (2003) 807-815.


21/37

Born in Hong Kong, and brought up in Lyon, London, and Alexandria

graduated from Nagoya University, 1947 with Fujio Egami. After 2 y

of post-graduate work with Louis Fieser, Harvard University, he retur

to Nagoya University where he completed his Ph.D. in 1954 w

Yoshimasa Hirata He was Assistant Professor at Nagoya until 1958

then Professor of Chemistry at Tokyo Kyoiku University. In 1963moved to Tohoku Univeersity, Sendai, and in 1969 joined Colum

University, becoming Centennial Professor in 1980.

He was a founding member and research director of the Internatio

Centre of Insect Physiology and Ecology (ICIPE) in Kenya, 1969-19

and 1978-1991, Director of Suntory Institute for Bioorganic Resea

and was a director at Biosphere 2, Arizona, Columbia University, fr

April 2001, until its termination in December 2003.

His research covers isolation and structural studies of natural produ

vision and chiroptical spectroscopy. He discovered NMR NOE

structure determinations, determined structures of 200 natural produ

published 800 papers. He has received awards from 12 countries

Nakanishi Prize of the Am. Chem. Society and the Chem. Soc. Ja

started in 1996 and is awarded in alternate years in Japan and the U.S.

Bioorganic studies on gingkolides

The tree Ginkgo biloba was mentioned in the Chinese Material Medica 5000 years. Fossil records show

that the Ginbkgo genus was present 180 millionsa years ago with many widespread species. However

today only one species , G. biloba , has survived. The morphology of the Ginkgo tree appears to have

changed very little for over 100 milion years and hence the name the fossil tree. The standardized

extract, containing 21% flavonoids and 7% terpene trilactones (TTL), is the best selling herb selling 1

billion dollars in 1997, the main reputed activity being prevention of dementia and memor

enhancement. The TTL consist of the diterpenoid ginkgolides and the sesquiterpenoid bilobalide,(1) al

having tight cage structures.

Professor Koji Nakanishi

(Columbia University)

The TTL has attracted immense interest when it

was found to be antagonists of PAFR (patelet

activating factor receptor) in 1986; it has since

been found that they are also ligands for several

other receptors.

(2,3)

Despite the intense interests, their mode of action on a molecular structure level is hardly known.

With such clarifications in mind, we have been performing studies on chemical conversions,

preparation of photoaffinity probes and bioactivities.(4) These aspects including the finding that TTL

inhibit progress of Alzheimers disease(5) will be presented.

(1). a) M. Maruyama, A. Terahara, Y. Nakadaira, M.C. Woods, Y. Takagi, K. Nakanishi, Tetrahedron Lett., 315(1967). b) M.C. Woods, I. Miura, Y. Nakadaira, A. Terahara, M. Maruyama, K. Nakanishi, Tetrahedron Lett., 321(1967). (discovery of NOE).

(2). K. Stromgaard and K. Nakanishi.Angew. Chem. Int. Ed. 43, 1640 (2004)(3). S. Jaracz, K. Nakanishi,A.A.Jensen, K.Stromgaard. Chem. Eur. J, 10,150 (2004).(4). K. Nakanishi,Bioorg. Med. Chem., 13, 4987 (2005).

(5). O. Vitolo, B.Gomg. Z. Cao, H. Ishii, S. Jaracz, K. Nakanishi, O. Arancio, S. Dzyuba, M. Shelanski, submitted.


22/37

1988-1993 Research Associate, Institute for Biological Sciences, NOttawa, Canada.

1993-1994 Research Officer, Institute for Biological Sciences, NROttawa, Canada.

1995-1995 Staff Investigator, The Picower Institute for MedResearch, Manhasset, NY

1996-2000 Assistant Professor, Department of Chemistry, SUNYStony Brook.

2000-2004 Associate Professor, Department of Chemistry, SUNYStony Brook.

1996-present Member, Biophysics Graduate Program, Stony Brook.1997-present Member, Molecular and Cellular Biology Gradu

Program, Stony Brook.1999-present Member, Biochemistry and Structural Biology Gradu

Program, Stony Brook.1999-present Member, Center for Infectious Diseases, Stony Brook.1999-present Member, Molecular Genetics and Microbiology Gradu

Program, Stony Brook.1999-present Member, Molecular and Cellular Pharmacology GraduProgram, Stony Brook.

2004-present Member, Institute for Chemical Biology & Drug Discov

Mycolic Acid, Menaquinone and Mycobactin Biosynthesis:Mining the Magic Mountain for Novel Tuberculosis

Chemotherapeutics

Novel chemotherapeutics for treating multi-drug resistant (MDR) strains of Mycobacterium

tuberculosis (MTB) are required to combat the spread of tuberculosis, a disease that kills more than two

million people annually. Using structure-based drug design we have developed a series of alkyl-

substituted diphenyl ethers that are uncompetitive inhibitors of InhA, the MTB fatty acid enoy

reductase. The most potent compound has a Ki value of 1 nM for InhA and MIC99 values of 1-3 M

for both drug sensitive and drug resistant strains of MTB.

In addition to fatty acid biosynthesis, we are using structural and mechanistic approaches to characterize

enzyme targets involved in the biosynthesis of the electron carrier menaquinone and the siderophore

mycobactin, compounds that are essential for MTB viability. Current studies are focused on MenB, the

dihydroxynapthoyl-CoA synthase in menaquinone biosynthesis, as well as MenF the first enzyme in

this pathway which converts chorismate into isochorismate. The mechanism of MenF is being

compared with that of MbtI, the first enzyme in the mycobactin pathway which converts chorismate

into salicylate. Finally we are also studying the tubulin homolog FtsZ, which plays an essential role in

mycobacterial cell division.

Professor Peter J. Tonge

(Stony Brook University)


23/37

Scott Sieburth grew up in Rhode Island and graduated from Worce

Polytechnic Institute in 1977. He was awarded his Ph.D. from Harv

University after studying with Paul Wender there and at Stanf

University. In 1982 he joined the Agricultural Chemicals Group of F

Corporation in New Jersey. After seven years with FMC he moved to

State University of New York at Stony Brook where he was promotedAssociate Professor in 1996. In 2001 he moved to Temple Universit

Philadelphia where he continues to study organosilicon chemistry

biological activity, synthetic photochemical methods, and total synthes

Silicon as a Central Drug Design Component

Organosilanes can be incorporated into peptides and peptide-like molecules as a substituent (e.g., 1) or

in a central position such as silanediol 2. Alpha-silyl amino acid derivatives 1 are relatively new and

can suffer from hydrolytic instability in which the bond between silicon and the peptide chain is broken

Silanediols such as 2 are potentially unstable toward polymerization reactions (silicone formation). In

both cases, stability is readily achieved by appropriate choice of the silicon environment. Recen

advances in the preparation of 1 and 2, as well as applications of this chemistry toward biologically

active molecules, will be described.

Professor Scott M. Sieburth

(Temple University)

N

H

OHN

SiO

SiHN

O O

HN

OHHO

1 2


24/37

Nicole S. Sampson was born in Indianapolis, Indiana in 1965

acquired her B.S. degree in chemistry at Harvey Mudd College in 19

She obtained her Ph.D. in the laboratory of Paul A. Bartlett at

Berkeley in 1990 and then carried out postdoctoral research in

laboratory of Jeremy R. Knowles at Harvard University. Nicole joi

the faculty at Stony Brook University in 1993 and is currently a Profesof Chemistry, as well as a member of the graduate programs

Pharmacology, Biochemistry & Structural Biology, and Biophysics.

research interests are in the areas of mechanistic enzymology

chemical biology. Her work presently focuses on catalysis

cholesterolmodifying enzymes, how they modify the lipid bilayer

their role in bacterial pathogenesis, investigating the role of prot

segmental dynamics in catalysis, and probing proteinprotein interacti

in mammalian fertilization using synthetic molecules.

Multivalent and Stereoregular Polymers

to Probe Fertilin Function in FertilizationIn the post-genomic era, understanding protein function is a critical focus of chemical biology research

The sperm protein fertilin, a member of the ADAM family of proteins is implicated in sperm-egg

binding in all mammals studied to date. The three-amino acid sequence ECD is the essential egg

binding element of fertilin. We present the synthesis and mechanistic investigation of polymers tha

display the ECD motif in multivalent fashion to probe fertilin-egg interactions.

Professor Nicole S. Sampson

(Stony Brook University)


25/37

Steven E. Rokita (b.1957), Professor, Department of Chemistry Biochemistry, University of Maryland, College Park, MD. B.S., 19University of California at Berkeley; Ph.D., 1983, Massachusetts Instiof Technology (mentor: Christopher T. Walsh); NIH PostdoctFellowship, 1984-1986, Rockefeller University (mentor: E. ThomKaiser). Catacosinos Young Investigator for Cancer Research, 19Molecular Biochemistry Advisory Panel, NSF 1993-1996; Bioorgaand Natural Products Study Section, NIH, 1997-2001. Advisory BoardBioconjugate Chemistry, 1997-1999. Vice-Chair (1998) and Chair (19Bioorganic Chemistry Gordon Conference. Nominating CommitBiological Chemistry Division, American Chemical Society, 20Alternative Councilor, Biological Chemistry Division, AmeriChemical Society, 2002- 2004. Awards (Univ. of Maryland) inclOutstanding Invention (2001) and Faculty Excellence in Research (200Area of Research. Bioorganic/biochemistry. Nucleic acid structure reactivity; target promoted alkylation of DNA, excess electron transfeDNA; biological and biomimetic reactions of nickel and copper; enzy

mechanisms of dehalogenation.

Selective Alkylation of DNA

through a Recognition-Dependent Process

Professor Steven Rokita

(University of Maryland)

O

HO

HO

O

OH

reversible self-adduct formation

quinone methide regenerationand full target recognition

target promted alkylation of achosen nucleobase sequence

Highly electrophilic quinone methides are generated during metabolism of numerous compoundsranging from food preservatives to anti-cancer drugs. These species readily alkylate the most

nucleophilic sites of DNA. Reaction is reversible, however, and the major adducts act as a reservoir forcontinually regenerating quinone methides over an extended period. The consequence of thisreversibility is evident in the evolution of DNA products generated by a simple model quinone methideas well as quinone methides that have been conjugated to DNA binding ligands. In particularoligodeoxynucleotide-quinone methide conjugates appear to form instrastrand adducts with alnucleotides except for T. Intrastrand reaction remains reversible and yet is not sensitive to trapping byexternal agents such as non-complementary DNA, thiols or water. The alternative interstrand reactionis only observed after association with complementary DNA. Once the self-adduct spontaneouslyregenerates the quinone methide, further base pairing with the target strand is allowed. This additionarecognition in turn inhibits reformation of the intrastrand self-adduct and promotes interstrandalkylation of the chosen target. This overall process represents

type of safety catch mechanism fodelivering a highly reactivintermediate to a precise target anmay ultimately provide a generaapproach to gene specific reactions ivivo.


26/37

Cindy Burrows studied physical organic chemistry at the UniversityColorado (B. A. 1975) and Cornell University (Ph. D. with B. Carpenter, 1982) before becoming an NSF-CNRS postdoctoral fellwith Nobelist J.-M. Lehn in Strasbourg, France. From 1983-1995, held the positions of Assistant through Full Professor of ChemistryStony Brook and was the western neighbor of the Ojima group. In 19she returned to the West, along with her husband (Prof. Scott Andersand triplets (now age 13), as Professor of Chemistry at the UniversityUtah. Research in the Burrows lab ranges from the identification of nheterocyclic compounds and the mechanisms by which they are formduring DNA oxidation to the investigation of the biological effectsthese lesions on DNA replication and repair. Prof. Burrows has beemember of numerous editorial boards and review panels; she also seras Associate Editor of Organic Letters from its inception until 2002 ancurrently Senior Editor of the Journal of Organic Chemistry. She Fellow of the AAAS and the recipient of the Robert Parry TeachAward at the University of Utah; her research was recently recogni

with the ACS Utah Award and the U of Us Distinguished Creative Scholarly Research Award.

Heterocyclic Chemistry leading to Mutagenesis

via Oxidation of DNA Bases

DNA in under constant assault by reactive oxygen species generated endogenously as a byproduct orespiration and exogenously under conditions of oxidative stress or radiation. Prolonged oxidative

stress forms part of the etiology of cancer, atherosclerosis, neurological diseases and aging. The

guanosine heterocycle is a principal target of oxidation leading to 8-oxoguanosine as well as newly

characterized spirocyclic and guanidinium-derived products. The latter products have been the subjec

of some controversy concerning structural characterization and mechanism of formation, and the use of

13C, 15N, and 18O labeling has helped resolve some of these issues. Clues to the mechanism o

formation have suggested parallel pathways for elucidation of adducts formed in oxidative polyamine

and protein cross-linking to DNA. Synthetic methods for generation of new DNA lesions permi

biochemical studies of DNA polymerases and DNA repair enzymes. These studies, in conjunction with

in vivo mutagenesis analysis, suggest that these unusual oxidation products of guanosine may be highly

detrimental to the integrity of the genome due to the formation of unusual base pairs that proliferate and

escape repair.

Professor Cynthia J. Burrows

(University of Utah)


27/37

Dr. Prestwich graduated with a B.Sc. (Honors) in Chemistry from tCalifornia Institute of Technology in 1970, he earned a Ph.D. Chemistry from Stanford University in 1974, followed by three years an NIH postdoctoral fellow, first at Cornell University and then at tInternational Centre for Insect Physiology and Ecology in NairobKenya. From 1977 to 1996, he was at The University at Stony Brook New York, as Professor of Chemistry, Professor of Biochemistry & CBiology, and Director of the New York State Center for AdvancTechnology in Medical Biotechnology. He co founded Clear SolutioBiotechnology, Inc. (Stony Brook, New York) to commercialihyaluronan biomaterials. He is a recipient of Alfred P. Sloan Researand Dreyfus Teacher-Scholar Awards, and was honored with the 19Paul Dawson Biotechnology Award of the American Association Colleges of Pharmacy. He was elected as a Fellow of the AmericInstitute for Medical and Biological Engineering in 2005 and wselected as a V100 Top 100 Venture Entrepreneurs in Utah in 2005.

Injectable synthetic extracellular matrix

for tissue engineering and repair

We recently developed a novel approach to the creation of a fully synthetic, covalently crosslinked

extracellular matrix (sECM). This material may be crosslinked in situ in the presence of cells to

provide an injectable cell-seeded hydrogel for tissue repair, or with drugs in a controlled-release formatChemical modification of hyaluronan (HA), other glycosaminoglycans (GAGs), proteins, or othe

carboxylate-containing polymers with thiol residues creates macromonomers that can be crosslinked

with biocompatibile polyvalent electrophiles. In the first section of this overview, we present the vision

and strategy for creating sECMs. In the second section, we highlight selected in vitro and in vivo

applications of this technology. Among the applications, we first show in vitro and in vivo growth o

healthy cellularized tissues using films, sponges, and hydrogels based on the sECM technology. We

then extend the use of the in situ crosslinkable sECM to the growth for the in vivo repair of cartilage

defects and healing of tympanic membrane perforations. Next, we describe the use of biointeractive

crosslinked heparin-containing GAG dressings for controlled release of bFGF and re-epithelialization o

full-thickness wounds in a diabetic mouse model of chronic wound healing. Finally, we illustrate theuse of in situ crosslinkable HA hydrogels, with and without covalently linked antiproliferatives, fo

prevention of abdominal surgical adhesions and maintenance of sinus ostia in vivo.

Professor Glenn D. Prestwich

University of Utah


28/37


29/37

Scott Kuduk was born in Long Island, NY. He obtained his B.S. a

Ph.D. degrees at the State University of New York Stony Brook und

the guidance of Professor Iwao Ojima. He joined the Merck Resear

Laboratories in 1999 after completing postdoctoral studies wi

Professor Samuel Danishefsky at the Sloan-Kettering Institute fCancer Research. He is currently a Research Fellow at Merck where h

research has dealt with organofluorine chemistry and with the design

novel therapeutic agents for the treatment of pain.

2,3-Diaminopyridine Bradykinin B1 Receptor Antagonists

The quest for improved treatments of chronic pain and inflammation continues to be an area of intense

research. Human bradykinin B1 receptor antagonists embody a novel approach for the treatment of

these disease states. A series of 2,3-diaminopyridine based BK B1 receptor antagonists was optimized

to have sub-nanomolar affinity for the human B1 receptor and good pharmacokinetic properties. The

optimization was achieved by blocking a number of potential metabolic pathways, particularly through

the use of various ester isosteres. Lead compounds were shown to exhibit good efficacy in rabbit in

vivo models of pain and inflammation.

Dr. Scott D. Kuduk

(Merck Research Laboratories, PA)

NHN

HN

R3

O

R2

NHN

HN

CO2Me

O

R1

R4


30/37

An Vu was born and raised in Saigon, Vietnam. During his youth,

emigrated along with his parents to the United States and settled in

small town in Georgia where he continued his secondary education.

1992 he obtained his B.S. in Chemistry from Mercer University

Macon, GA. He received his Ph.D. in Organic Chemistry in 1997 fro

Emory University in Atlanta, GA, where he studied the transition metmediated reductive cyclization reactions under the direction of Profess

William E. Crowe. He then worked with Professor Iwao Ojima as

NIH Postdoctoral Research Fellow at the State University of New Yo

at Stony Brook, where he developed useful catalytic synthetic process

involving rhodium-catalyzed silylcarbocyclization (SiCaC

heterosilylcarbocyclization and silylcarbotricyclization (SiCa

reactions. In 1999 he joined Wyeth Research in Collegeville, PA whe

he is currently a Senior Research Scientist and working in the areas

womens health, cardiovascular and metabolic diseases. He is the authof a number of scientific articles, book chapter, abstracts, presentation

and patent publications.

2-Phenylquinolines as Potent and Selective

Estrogen Receptor beta (ER) Ligands.The discovery in 1996 of a second subtype of estrogen receptor, estrogen receptor beta (ER), with its

unique tissue distribution patterns and transcriptional properties from those of ER, has prompted

intense research to elucidate its physiological functions and identify its potential therapeutic targetsOur approach toward this goal has been to utilize highly selective ER agonists. Recently, we have

designed and developed a series of 2-phenylquinolines as a new class of ER selective ligands. A

number of substituted 2-phenylquinolines displayed low nanomolar affinity and as high as 100 fold

ERselectivity. A select group of compounds were profiled as either full or partial ER agonists in a

cell-based functional assay measuring the transcription of KRT19 mRNA. The uterine weigh

estrogenic bioassay of the most selective compounds showed no significant uterine stimulation, thus

indicating no activation of ER in this sensitive estrogen target organ. The design, synthesis, biologica

evaluation, and potential binding modes within the ligand binding pocket of this class of compounds

will be discussed.

Dr. An T. Vu

(Wyeth Research, PA)

N

OH

HO

R2

R1

R3

R4R5

R6


31/37

Born 16 August 1962 in Paray-le-Monial (France). Ph.D in organ

chemistry in 1990 at the Universit Claude Bernard, Lyon I (Franc

under the direction of Prof. E. Laurent: Nucleophilic fluorination in

position of an aromatic ring or a thioether. Postdoc at the St

University of New York at Stony Brook (USA) in 1990-1991 under t

supervision of Prof. I. Ojima : Asymmetric synthesis of non-proteamino acids. In 1991, appointed matre de confrences of the Universde Reims Champagne-Ardenne (France). From 2002, appoint

professor of the universit de Cergy-Pontoise (France). Main domain interest: Organofluorine chemistry, asymmetric synthesis, Synthesis

fluorinated analogs of natural products (carbohydrates, terpenes, amin

acids).

Chiral fluorinated imines and oxazolidines:

synthons for organofluorine chemistry and asymmetric synthesi

Fluorinated imines, hydrazones and oxazolidines derived from chiral amino alcohols are very usefusynthons for the stereoselective synthesis of -fluoroalkylated amino compounds.1,2The Strecker and the Mannich-type reactions with chiral fluorinated iminium constitute a powerfu

method for the synthesis of enantiopure fluorinated and -amino acids, -amino ketones, aminoalcohols and diamines in a few steps.

Professor Thierry Brigaud

(Universit de Cergy-Pontoise, France)

N O

F3C R1

H

R

F3C R1

NR

R2-M

F3C

NH2

R

O

NH2

F3CR1

CO2H

NH2

F3CR

1

NH2

NH2

F3CR

1

OH

NH2

F3CR

1R

2

F3C

NH2 OH

*

*

orou R

2SiMe3

-amino acids

-amino acid and ketones

Diamines

Amino alcohols

Recent results about the use of fluorinated oxazolidines as chiral auxiliaries will also be presented. Toxazolidines derived from fluoral hemiacetal and (R)-phenylglycinol are very stable to hydrolysTherefore these oxazolidines can be used as highly efficient chiral auxiliaries for amide enolates alkylati

1) Base

2) R'X

N

O

Ph

F3C

R O

N

O

Ph

F3C

R O

R'

High diastereoselectivity

(1) Lebouvier, N.; Laroche C., Huguenot, F.; Brigaud, T. Tetrahedron Lett. 2002, 43, 2827.(2) Fries, S.; Pytkowicz, J.; Brigaud, T. Tetrahedron Lett. 2005, 46, 4761.


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Joseph (Jiawang) Zhu, Ph.D. is currently a Senior Scientist in th

Department of Chemistry Research & Discovery at Amgen, Inc. H

research interests are design and syntheses of biologically an

therapeutically interesting molecules, and studying the

pharmacokinetics, pharmacodynamics, and other properties. He

published more than 10 articles and co-authored more than 10 patenHe holds a B.S. in Chemistry from Nanjing University, China, and

Ph.D. in Chemistry from Colorado State University at Fort Collins und

the supervision of Professor Louis S. Hegedus, and Pursued Post-do

research in Professor Iwao Ojimas laboratories at SUNY-Stony Brook

Design and Synthesis of Conformationally

Constrained TRPV1 Antagonists

The vanilloid receptor-1 (VR1 or TRPV1) belongs to the family of transient receptor potential (TRP)

cation channels and is activated by heat, acid, and plant irritants such as capsaicin. TRPV1 is

predominantly expressed in primary sensory neurons and is involved in the transmission process o

noxious pain stimuli to the brain. Blockade of the cell signaling with a TRPV1 antagonist offers a

potential for the development of novel analgesics.

Recently, we have discovered and reported a series of N-aryl cinnamides as potent, selective, and

competitive TRPV1 antagonists. Probing the antagonist-binding pocket of TRPV1 via studies of its

ligands of (E)-3-(4-tert-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamides have lead to

the hypothesis of that the bioactive conformations, the receptor-binding modes, of the N-aryl

cinnamides are the co-planar, s-cis conformation with respect to the carbonyl group. The synthesis

conformational analysis, and biological properties of these analogs will be presented.

Furthermore, the synthesis and biological activities of conformationally constrained pharmacophores

will be addressed.

Dr. Joseph Zhu

(Amgen, Inc., )


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Development of the Manufacturing Process to Emend

(Aprepitant), Winner of 2005 Presidential Green Chemistry

Challenge Award

Aprepitant (1), an antagonists of the neurokinin-1 (NK-1) receptor is a new therapeutic agents for the

treatment of chemotherapy-induced emesis. The first generation synthesis allowed us to made multi-

kilogram quantities of the drug substance. Search for better alternatives synthesis of aprepitan

ultimately lead to discovery of a much more efficient manufacturing route with over 80% reduction in

cost, energy and raw material volumes.

Dr. Matthew M. Zhao

(Merck Research Laboratories, NJ)

HN

NH

NO

N

O

F

O

CF3

CF3

1

Born in 1965, Xingtai, Hebei Province, China. He obtained his BS

chemistry from Lanzhou University in 1985. He was awarded CG

scholarship in 1986 to pursue graduate study in the US. He join

professor Ojimas group in 1987 and obtained his PhD degree in 199He then went on to Professor Leo Paquette group for postdoctor

research and was awarded Merck Postdoctoral Fellowship. He joinProcess Research Department in Merck Research Laboratories in 19

focusing on the development of efficient, robust and environmental

benign process for the production of novel Merck drug candidates. H

has worked on numerous projects highlighted by the development

manufacture processes for two successful Merck drugs, SingulairanEmend. He has over 25 publications and hold more then ten patenHe is currently a Senior Research Fellow.


34/37

Ivan Habus, Associate Professor, Rudjer Boskovic Institute (RBZagreb, Croatia), Division of Physical Chemistry, Laboratory fAnalytical ChemistryHead of the Laboratory. He was born in 19and received his Ph.D. in 1988 at RBI. Research project was involved the transformations of monosaccharides into new chiral bidentaligands, bis-diphenyl-phosphinites and phosphines, and development their rhodium(I) complexes as the catalysts for the homogeneocatalytic hydrogenation of various prochiral substrates. From 1988 1990 he was engaged in postdoctoral research with Prof. Iwao OjimaSUNY at Stony Brook, NY, USA. He was involved in asymmetrsynthesis of various non-protein amino acids by applying -LactaSynthon Method. From 1990 to 1992 he spent with Prof. FrancJohnson as postdoctoral fellow at SUNY at Stony Brook. At HybridoInc., Cambridge, MA, USA, he was appointed as research scient(1992-1997) and senior research scientist (1997-1998) in the field oligonucleotide synthesis. From 1998 to 2000 he was employed principal scientist at ArQule, Inc., Woburn, MA, USA, working in t

field of combinatorial chemistry. Currently at RBI, he is supervising tcustom service activities: Organic Elemental Microanalysis (C, H, N, halogens) and FT-IR Spectroscopic Analysis of Urinary/Gall CalcuBased on the analysis of urinary calculi in the Laboratory is followed tpresence of urolitiase in the Republic of Croatia dependent on regiosex, and age of the patients.

Diels-Alder reactions on imines derived from 3-amino--lactamsSynthesis of diversily substituted monocyclic -lactams have been of considerable interest to the

synthetic community in the past few decades [1]. Because of the recent developments using -lactamsas synthons for several biologically active compounds, research on this topic has gained tremendous

attention [2,3]. Hetero Diels Alder reactions involving imino-dienes or imino-dienophiles are widely

used for the construction of nitrogen-containing compounds [4,5]. Our interest in the use of 3-amino--

lactams [6,7] as starting substrates for the preparation of potentially bioactive products prompted us to

evaluate the combination of the aza-Diels Alder reaction of 2-azetidinone-tethered imines I with

siloxydienes as a route to the asymmetric synthesis of 5,6-dihydro--pyridones II using -lactams as

chiral building blocks (Scheme 1) [8,9]. Effects of various dienes and substituents on dienophile, Lewis

acids, and solvents on the product formation and diastereoselectivity of the reactions will be discussed.

Dr. Ivan Habu

(Ruer Bokovi Institute, Croatia)

1. G.S. Singh, Tetrahedron, 59 (2003) 7631.2. H.C. Neu, Science, 257(1992) 1064.3. A.K. Bose, B.K. Banik, C. Mathur, D.R. Wagle, M.S. M

Tetrahedron, 56(2000) 5603.4. P. Buonora, J.-C. Olsen, and T. Oh, Tetrahedron, 57(2006099.5. K.A. Jorgensen, Angew. Chem. Int. Ed., 39 (2000) 35586. I. Ojima and I. Habu, Tetrahedron Lett., 31 (1990) 42897. I. Habu et al., J. Mol. Struct., (2005).8. J.F. Kerwin, Jr. and S. Danishefsky, Tetrahedron Lett., 2(1982) 3739.9. B. Alcaide, P. Almendros, J.M. Alonso, and M.F. Aly,

Eur. J., 9 (2003) 3415.

N

O

R2N

R1

OTMS

OMeN

O

R2N

R1

O

R3

N

O

R2N

R1

O

R3

+ +Lewis acid

CH3CN, -20oC

R1 = H, Aryl

R2 = Fc, Aryl

R3 = Fc, Aryl, Alkyl

R1 = H, Aryl

R2 = Fc, Aryl

R3 = Fc, Aryl, Alkyl

I II


35/37

Masakatsu Eguchi received his B.S. degree in 1981 and M.S. degree

1983 in pharmaceutical science from Tokyo College of Pharmacy (no

Tokyo University of Pharmacy and Life Science). His Ph.D. degree w

granted from Brigham Young University, department of chemistry

1990, where he worked under the late Prof. Bryant Rossit

Subsequently, he did postdoctoral work at State University of New Yoat Stony Brook with Prof. Iwao Ojima ('90-'93) and Sandoz (no

Novartis). In 1994, he joined Molecumetics Ltd. as a senior scientist a

was promoted to senior research fellow in 1999 working on the desi

and combinatorial synthesis of peptidomimetics. He moved to Pacif

Northwest Research Institute as a staff scientist with Prof. Michael Ka

in 2000. In 2004, Prof. Kahn's research group established a new no

profit research organization, Institute for Chemical Genomics. Masa h

been actively involved in drug discovery efforts for 10 years.

Design, Synthesis, and Application of Peptide

Secondary Structure Mimetics

Secondary structure elements in proteins play a key role in molecular recognition events in biological

systems through their characteristic three-dimensional presentation of functional groups on their

surfaces. Cytokine-receptor interaction and many protein-DNA interactions are mediated through -

helical structure, many peptide ligand-receptor interactions and antigenantibody interactions are

mediated through reverse turns, and proteases, kinases, most SH2 domains, and MHC recognize their

substrates through -strand structures. Most of these proteinprotein interactions are initiated or

mediated by a key local secondary structure element in the protein; therefore, small molecules bearing a

similar local structural feature can effectively mimic the ligand binding function of a protein or peptide.

A successful peptidomimetic must be able to present the correct pharmacophoric residues in the proper

three-dimensional space. Conformationally constrained analogs of such peptidomimetics pay a lower

entropy cost upon binding to their receptor or enzymes. The rapid generation of secondary structure-

templated chemical libraries through solid-phase synthesis is a key technology to develop nove

pharmaceutical agents effectively.

We have developed -turn and -strand scaffolds readily accessible through solid phase synthesis from

commercially available diversity components and applied these scaffolds for the preparation of

biologically active compounds such as protease inhibitors, opioid receptor agonists, or transcriptio

factor modulators. Design and synthesis of these chemical libraries and some preliminary biological

data will be presented.

Dr. Masakatsu Eguchi

(Institute for Chemical Genomics, WA)


36/37

Prof. Schoffers started her academic career at the Johannes Gutenbe

University in Mainz, Germany, and continued graduate studies in t

United States under the supervision of Professors I. Ojima (SUNY Sto

Brook, M.S., 1991), C.R. Johnson (WSU, Ph.D., 1996), and A.J. Pears

(CWRU, postdoc, 1996-98). Her expertise is in the area

stereoselective synthesis with background in organometallheterocyclic, and biochemistry. Specific projects address t

development of N-containing ligands for asymmetric catalysis and t

synthesis of metabolites that influence biological signals. This includ

the preparation of inosamines that have been proposed to be nutrition

mediators for nitrogen fixation in legume plants. Over the last 5 year

Professor Schoffers has worked with 7 graduate and 9 undergradua

students (8 female, 2 minorities) on various research projects.

Looking for a Ligand with a New Twist?

Chiral Phenanthrolines for Organic Chemistry

1,10-Phenanthroline has long been known for its complexes with metals and non-metals and has thus

found numerous applications in analytical chemistry since the 1930s. More recently, there has been a

renewed interest in 1,10-phenanthroline and its derivatives for their potential applications in asymmetric

catalysis.

Herein we report our progress towards functionalizing the 1,10-phenanthroline template, and give

details about the preparation and application of novel optically active derivatives (1, 2). Among others

we tested these new ligands in asymmetric alkylation, aminohalogenation, reduction and Aldo

reactions

Professor Elke Schoffers

(Western Michigan University)

NN

(1,10-Phen)

N

O N

O

N

Ph

(1)

N

NH HN

N

PhPh

(2)


37/37

Biomedical innovation

Through Multidisciplinary

and Translational Research

From Bench to Bed Side

Documents

Dr. Iwao Ojima