Dolabriferol and dolabriferol B are secondary metabolites isolated from the Cuban and Puerto Rican anaspidean mollusk Dolabrifera dolabrifera, respectively. An unusual non-contiguous polypropionate skeleton characterized both. These structures consist of two stereochemically related polypropionate subunits joined by an ester linkage. The difference between dolabriferol and dolabriferol B is the substituent at C18; the isopropyl group and ethyl groups, respectively. A polypropionate chain consists of an array of alternating methyl and hydroxy groups on an aliphatic chain with a particular configuration. As part of our ongoing efforts to develop a general non-aldol methodology for the elaboration of termini-differentiated polypropionate modules, we have developed a general enantioselective epoxide-based methodology for the construction of polypropionates that consists of a regioselective epoxide cleavage with an alkynyl aluminum reagent, reduction of the alkyne, and the stereoselective epoxidation of the resulting alkene. This sequence could be modified to include other organometallics and epoxides structures. Employing this, we have engaged in a divergent/convergent synthesis of the polypropionate acid and alcohol moieties of (-)-dolabriferol and (-)-dolabriferol B from a common epoxide precursor. Our approach lends itself to the synthesis of these compounds requiring only minor variations in the synthetic steps. Using our approach, we have successfully synthesized the enantioselective key precursor. This precursor has the required framework to produce both, the anti,anti C3-C9 and anti,anti,anti C12-C18 polypropionate fragments with the correct absolute configuration. From this precursor, we have been able to synthesize the polypropionate acid and alcohol moieties of (-)-dolabriferol and (-)-dolabriferol B using our non-aldol methodology. The details and recent advances will be presented. Work supported by the NIH SCORE (2S06GM-08102-29) and NIH RISE (2R25GM061151-14) programs.

Divergent/convergent approach towards the synthesis of the polypropionate acid and alcohol moieties of (-)-dolabriferol and (-)-dolabriferol B from a common precursor

251st National Meeting (2016)

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