Approach to the Homoerythrina Alkaloids Using a Tandem N

15 Pages·2007·0.48 MB·English

by  Peter Wipf

Approach to the Homoerythrina Alkaloids
Using a Tandem N-Alkylation/Azomethine Ylide Cycloaddition
Pearson, W. H.; Kropf, J. E.; Choy, A. L.; Lee, I. Y.; Kampf, J. W.
J. Org. Chem.; 2007; 72(11); 4135-4148.
Wipf group Current lit 08-18-07
Akira Nakamura
Akira Nakamura @ Wipf Group 1 10/29/2007
Background
Activities
Curarelike
Hypnotic
Sedative
Hypotensive
Neuromuscular blocking
CNS
Akira Nakamura @ Wipf Group 2 10/29/2007
Target Alkaloids
-Isolated from D. lenticellare Gillespie grown in the Fiji Islands in 1983.
-There are no reports on pharmacological effect either 1 or 2.
-Isolated alkaloids from D. lentivellare which include 3 are shown to
have both cardiac effects in rats and molluscicidal activity.
J. Nat. Prod. 1987, 50, 1041., Phytochemistry 1988, 27,
3789.
Akira Nakamura @ Wipf Group 3 10/29/2007
Construction of the erythrinan ring system
OMe OMe OMe
NaN3 TFA, DCM
O
TMSO OMe O OMe 81% N OMe
N
MsO 3
J.d’Angelo, J. J. Org. Chem. 1993, 58, 2933
78%
Padwa, A. Org. Lett. 2006, 8, 601.
Akira Nakamura @ Wipf Group 4 10/29/2007
Retrosynthetic sequence
Akira Nakamura @ Wipf Group 5 10/29/2007
Starting material synthesis
a
a
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Synthesis
b
b
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Key cycloaddition test
Akira Nakamura @ Wipf Group 8 10/29/2007
2nd Retrosynthetic sequence
Akira Nakamura @ Wipf Group 9 10/29/2007
2nd Key cycloaddition test
c
1.
c
Akira Nakamura @ Wipf Group 10 10/29/2007