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Total synthesis of (±)-phomactin A. Lessons learned from respecting a challenging structural topology.

ABSTRACT: Our struggles and ultimate success in achieving a total synthesis of phomactin A are described. Our strategy features an intramolecular oxa-[3 + 3] annulation to construct its unique ABD-tricyclic manifold. Although the synthesis would constitute a distinctly new approach with the 12-membered D-ring of phomactin A being assembled simultaneously with the 1-oxadecalin at an early stage, the ABD-tricycle represents a unique structural topology that would pose a number of unprecedented challenges. One challenge concerned elaborating this tricycle to have oxygenation at the proper carbon atoms. To overcome this, we would utilize a Kornblum-DeLaMare ring-opening of a peroxide bridge as well as a challenging late-stage 1,3-allylic alcohol transposition. Further, the structural intricacies of the ABD-tricycle were uncovered by a conformational analysis that would be critical for the C5a-homologation.

SUBMITTER: Buchanan GS

PROVIDER: S-EPMC3163054 | biostudies-other | 2011 Sep

REPOSITORIES: biostudies-other

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Total synthesis of (±)-phomactin A. Lessons learned from respecting a challenging structural topology.

Buchanan Grant S GS Cole Kevin P KP Tang Yu Y Hsung Richard P RP

The Journal of organic chemistry 20110805 17

Our struggles and ultimate success in achieving a total synthesis of phomactin A are described. Our strategy features an intramolecular oxa-[3 + 3] annulation to construct its unique ABD-tricyclic manifold. Although the synthesis would constitute a distinctly new approach with the 12-membered D-ring of phomactin A being assembled simultaneously with the 1-oxadecalin at an early stage, the ABD-tricycle represents a unique structural topology that would pose a number of unprecedented challenges. O ...[more]

PMID: 21819039

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