Tandem Electrocyclic Ring Opening/Radical Cyclization: Application to the Total Synthesis of Cribrostatin 6

摘要

A concise total synthesis ofcribrostatin 6 (>1), an antimicrobial and antineoplastic agent,was accomplished using a tandem electrocyclic ring opening/radical cyclization sequence. Specifically, intermediate>4 underwent a 4π-electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence followed by an oxidation to afford the natural product>1in one pot. Owing to the rapid buildup of complexity in the key step, >1 could be synthesized from commercially available starting materials in only four linear steps. Application of this chemistry to the concise syntheses of analogs of cribrostatin 6 (>1) is also reported.