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

A concise total synthesis ofcribrostatin 6 (1), an antimicrobial and antineoplastic agent,was accomplished using a tandem electrocyclic ring opening/radical cyclization sequence. Specifically, intermediate4 underwent a 4π-electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence followed by an oxidation to afford the natural product1in 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.