Total Synthesis of the Aglycone of IB-00208.

A total synthesis of the aglycone of IB-00208 was accomplished in 22 steps using a newly developed approach towards polycyclic 1,4-dioxygenated xanthones from benzocyclobutenones. The generality of this entry to xanthones was initially established on several model systems before it was successfully applied to the construction of the hexacyclic core of the natural product. A new and potentially general approach towards angularly-fused benzocyclobutenones using ring-closing metathesis (RCM) was also developed.

Approaches to polycyclic 1,4-dioxygenated xanthones. Application to total synthesis of the aglycone of IB-00208.

Hexacyclic xanthone natural products such as IB-00208 present a formidable challenge in organic synthesis. A new approach to polycyclic 1,4-dioxygenated xanthones from benzocyclobutenones has been developed and applied to the first total synthesis of the aglycone of IB-00208. The 22-step synthesis features an acetylide stitching process that joins an aryl aldehyde with an angularly fused benzocyclobutenone, which was prepared by a ring-closing metathesis reaction. The resulting acetylenic benzocyclobutenone diol underwent a Moore rearrangement to give an intermediate that was further elaborated to the aglycone of IB-00208 as a mixture of hydroquinone-quinone tautomers.

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.

Total synthesis of cribrostatin 6.

Fast and furious: Cribrostatin 6, an antimicrobial and antineoplastic agent, was the target of a total synthesis where the longest linear sequence was only four steps. The key step involves a tandem 4pi electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence to afford the tricyclic core of the natural product.

Concise, stereoselective approach to the spirooxindole ring system of citrinadin A.

The spirooxindole ring system of citrinadin A has been synthesized with excellent control over the absolute stereochemistry at the spirocenter. The key step involves a novel diastereoselective DMDO-mediated oxidative rearrangement employing an 8-phenylmenthol chiral auxiliary on the indole nitrogen.