Convergent Total Synthesis of (–)-Cyclopamine

23 August 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 15-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans-6,5 hetero-bicycle 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.


total synthesis
convergent disconnection

Supplementary materials

Supporting information
Procedures, spectra, background information


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