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

A concise total synthesis of cribrostatin 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 1 in 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.