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A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

ABSTRACT: Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy for dimer formation that obviates these difficulties, one which rapidly constructs the coccinellid dimers psylloborine A and isopsylloborine A through a terminating sequence of two reaction cascades that generate five bonds, five rings, and four stereocenters. In addition, a common synthetic intermediate is identified which allows for the rapid, asymmetric formal or complete total syntheses of eight monomeric members of the class.

SUBMITTER: Sherwood TC

PROVIDER: S-EPMC4105056 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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A strategy for complex dimer formation when biomimicry fails: total synthesis of ten coccinellid alkaloids.

Sherwood Trevor C TC Trotta Adam H AH Snyder Scott A SA

Journal of the American Chemical Society 20140624 27

Although dimeric natural products can often be synthesized in the laboratory by directly merging advanced monomers, these approaches sometimes fail, leading instead to non-natural architectures via incorrect unions. Such a situation arose during our studies of the coccinellid alkaloids, when attempts to directly dimerize Nature's presumed monomeric precursors in a putative biomimetic sequence afforded only a non-natural analogue through improper regiocontrol. Herein, we outline a unique strategy ...[more]

PMID: 24959981

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