Total Synthesis of (±)-Phomactin B2 via an Intramolecular Cyclohexadienone Annulation of a Chromium Carbene Complex

摘要

Phomactins are novel platelet activating factor (PAF) antagonists isolated from the culture of marine fungus Phoma sp. Members of the phomactin family share a unique [9.3.1] pentadecane ring system, and their biosynthetic pathway shares a branchpoint with the taxane family of natural products. Substantial synthetic efforts have been described in the literature toward the synthesis of several phomactins, but of the 11 known members of the phomactin family, total syntheses have only been reported for phomactins A, D, and G. The nexus to all of the published retrosynthetic plans, realized or not, is the construction of the six-membered ring prior to the 12-membered ring. We report here a different approach to the phomactins that involves the simultaneous assembly of both the six- and 12-membered rings via an intramolecular cyclohexadienone annulation of a chromium carbene complex and which is rendered to practice in a total synthesis of (±)-phomactin B2.