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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Convergent Total Synthesis of (-)-Cyclopamine
Manolis Sofiadis1, Dongmin Xu1, Anthony J Rodriguez1
1Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Abstract:
A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans-6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji-Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.
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