Lead Diversification through a Prins-Driven Macrocyclization Strategy: Application to C13-Diversified Bryostatin Analogues

To a friend and scholar in recognition of his towering contributions to education and to mechanistic and synthetic chemistry

Abstract

The design, synthesis, and biological evaluation of a novel class of C13-diversified bryostatin analogues are described. An innovative and general strategy based on a Prins macrocyclization-nucleophilic trapping cascade was used to achieve late-stage diversification. In vitro analysis of selected library members revealed that modification at the C13 position of the bryostatin scaffold can be used as a diversification handle to regulate biological activity.

Key words

macrocycles - cyclizations - drugs - polyketides

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