Dolabriferol and dolabriferol B are secondary metabolites isolated from the Cuban and Puerto Rican anaspidean mollusk <i>Dolabrifera dolabrifera, </i>respectively. An unusual non-contiguous polypropionate skeleton characterized both. These structures consist of two stereochemically related polypropionate subunits linked by an ester function. This structural feature consists of an array of alternating methyl and hydroxy groups on an aliphatic chain with a particular configuration<b>. </b>Both molecules have similar structure, except for a substituent at C-18. Dolabriferol has an isopropyl group while dolabriferol B has en ethyl group. We have developed a reiterative enantioselective epoxide-based methodology for polypropionate construction. Our approach consists of three steps: 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 sequence, we have engaged in a divergent/convergent synthesis of (-)-dolabriferol and (-)-dolabriferol B in which the same precursor is used for the elaboration of the two-polypropionate fragments. 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. Our approach allows the introduction of the ethyl group at C-18 required for dolabriferol B making minor variations in the synthetic steps. The details of this study in the context of the synthesis of (-)-dolabriferol and (-)-dolabriferol B will be presented.

Epoxide approach towards the synthesis of (-)-dolabriferol and (-)-dolabriferol B

253rd National Meeting (2017)

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