Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin‐like Molecules

Abstract

AbstractWe report a new synthetic strategy for the flexible preparation of forskolin‐like molecules. The approach is different from the previously published works and employs a convergent assembly of the tricyclic labdane‐type core from pre‐functionalized cyclic building blocks. Stereoselective Michael addition enabled the fragment coupling with excellent control over three newly created contiguous stereocenters, all‐carbon quaternary centers included. Silyl enol ether‐promoted ring‐opening metathesis paired with ring closure were the other key steps enabling concise assembly of the tricyclic core. Late‐stage functionalization sequences transformed the tricyclic intermediates into a set of different forskolin‐like molecules. The modular nature of the synthetic scheme described herein has the potential to become a general platform for the preparation of analogs of forskolin and other complex tricyclic labdanes.