Chiral 1,5-polyol moieties are present in a variety of biologically active natural products, and the isolated stereogenic centers pose problems in synthesis and stereochemical assignment. The stereochemical features of the fibrinogen receptor antagonist tetrafibricin include both a 1,5,9-triol and an anti,syn-1,5,7-triol which appears in the C15-C25 fragment. We previously introduced a general synthetic strategy toward 1,5,9-triols with unambiguous stereocontrol by exploiting iterative Julia-Kocienski couplings, using building blocks with alcohol configurations previously encoded in O-silylcyanohydrin functionality. Now, we present an application of this approach to the synthesis of an anti,syn-1,5,7-triol. We address this challenge by merging our configuration-encoded 1,5-polyol strategy with the tactic of intramolecular benzylidene acetal construction via conjugate addition. The C15-C25 fragment of tetrafibricin is thereby accessed from a 1,5,9-triol with excellent control of its anti,syn-1,5,7-triol stereochemistry.

Configuration-encoded 1,5-polyol synthesis: Access to the anti,syn-1,5,7-triol within the C15-C25 fragment of tetrafibricin

249th National Meeting (2015)

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