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Undergraduate Laboratory Research by Community College Students:

Episode 2

Derek Ross, Arlene Flores, Dennis Mitchell (Los Angeles City College)Donald Deardorff (Occidental College)

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Los Angeles City College

About 15,000 students, located in Hollywood,one of nine colleges in the Los Angeles Community College District

Occidental College

About 1800 students, located in Eagle Rock, a suburb of Los Angeles, a highly selective, four-year, private liberal arts college

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First project (Su’03), by Armen Mardiros, Glendale College. Synthesis of compounds for the study of electron transfer between a gold electrode and a

protein. The general synthetic strategy is shown below:

ROC

O

(CH2)n

Br

NH2

CNH2

S

EtOH

Δ

HO

C

O

(CH2)n

SH

Δ

NaOH HCl

n = 4, 11, R = Hn = 9, R = CH3

+

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Second project (Su ‘04), by Amit Vachher-Gnanathurai, Los Angeles City College.

Synthesis of potential glycosidase inhibitors. This project continues.

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The general synthetic scheme for Amit:

O

HCN

N

H

Ph

OSi(t-Bu)Me2

OH

HCN

OsO4

ClSi(t-Bu)Me2

OSi(t-Bu)Me2

HPh

HN

N

H

Ph

OH

OH

HO

OSi(t-Bu)Me2

HCN

BrOSi(t-Bu)Me2

HPh

H2N

(R)-cyanohydrin

1) PhMgBr, Et2O

2) NaBH4, MeOH

3) H+/H2O, -OH/H2O

Grubb's

catalyst

Glycosidase inhibitor?

Oxynitrilase (courtesy of Trader Joe's almonds)

pyridine

**

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Derek Ross and Arlene Flores accomplished part of the continuing project at Los Angeles City College

Their synthetic goal is shown below:

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OOH

CN

Oxynitrilase (from almonds)

6eq HCNDiisopropyl Ether4oC, 48hrs.Crotonaldehyde

OTBDMS

O

Ph

OH

CN

2 eq. TBDMSCl

Pryidine

O

CN

Si

OTBDMS

CN

1) 2 eq. PhMgBr, Et2O

2) NH4Cl sat. (aq)

Performed at Occidental

Performed at LACC

Value of [ approximately 16o

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Derek now works on two projects at Occidental College:

1) Enantioselective synthesis of Prozac (Fluoxetine)

2) Synthesis of glycosidase inhibitors

He will be a full-time student at Oxy in the fall.

Arlene is transferring as a pre-med student to

Cal State University, Los Angeles,

to major in Biology or Biochemistry.

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Synthetic scheme for Prozac

Ph O Ph

OH

CN

Ph

OH

CO2Et

Ph

OCO2Et

CO2Et

Oxynitrilase

HCN

1) H+, EtOH

2) H2O

Ethylchloroformate

Catalytic Pd0

4-(Trifluoromethyl)phenol

Ph CO2Et

O

F3C

Ph CO2Et

OArAdams catalyst,

H2

Ph CONH2

OAr

NH3

Hofmann rearrangement, EtOH

Ph NHCO2Et

OAr

Ph NHMe

OArLAH

(+)-(S)-Fluoxetine

cinnamaldehyde

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Ph CO2Et

OAr

LiBH4

Ph

OAr

OH(S)-Moshers acid chloride

Ph

OAr

O

O

OMe

CF3

Ph

Ph

OAr

O

O

OMe

CF3

Ph

Via a similar

Racemic path

Determination of enantiomeric excess

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Revised synthesis of glycosidase inhibitors

O

OH

CN

Oxynitrilase

HCNCrotonaldehydeOTBDMS

CN

TBDMSCl

OTBDMS

1) PhMgBr2) H2O

O

Ph

OCO2Et

COPh

Deprotection

Ethylchloroformate

COPh

N3Catalytic Pd0,

N3-

1) SnCl2

2) Boc2O

COPh

NHBoc

SharplessDihydroxylation

COPh

NHBoc

OH

OH

Deprotection

N

OH

HO

Ph

NH

OH

HO

Ph

NaBH4

2,5- Disubstituted dihydroxy pyrrolidine

Annulation

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16

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N

HO

C9H19

Ph

(+)-Preussin

NH

HO

OH

OMe

(-)-Codonopsinine

Future Synthetic Targets

- Naturally occurring antifungal antibiotics

- 2,5-disubstituted hydroxy pyrrolidines

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What is the feasibility of community college research?

What are the benefits for the students?

What are the benefits for the instructor?

Is there a downside?

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Thanks to:

1) The Dreyfus Foundation (summer support for DM)

2) NSF-REU (summer support for DR)

3) Ralph M. Parsons Foundation (LACC, NMR purchase)

4) Petroleum Research Fund (Prozac synthesis)

5) Cal State, Northridge (Paul Shin): Donation of a polarimeter

6) William Kaska, UC Santa Barbara: Donation of glassware and argon/vac line