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Asymmetric synthesis of all the known phlegmarine alkaloids.

ABSTRACT: The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late intermediate. These syntheses confirmed the absolute stereochemistry of all of the known phlegmarines.

SUBMITTER: Wolfe BH

PROVIDER: S-EPMC3006060 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Asymmetric synthesis of all the known phlegmarine alkaloids.

Wolfe Bradley H BH Libby Adam H AH Al-Awar Rima S RS Foti Christopher J CJ Comins Daniel L DL

The Journal of organic chemistry 20101115 24

The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun c ...[more]

PMID: 21077636

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