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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
+
4
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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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
Recommended