A Strategy for Complex Dimer Formation When Biomimicry Fails: Total Synthesis of Ten Coccinellid Alkaloids

作者：Sherwood Trevor C; Trotta Adam H; Snyder Scott A^*

来源：Journal of the American Chemical Society, 2014, 136(27): 9743-9753.

DOI：10.1021/ja5045852

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.

• 出版日期2014-7-9