Gm. Coppola et al., SYNTHESIS OF A CONFORMATIONALLY RESTRAINED 4-ARYL-THIOPHENE-3-HEPTENOIC ACID AND ITS EVALUATION AS AN HMG COENZYME-A REDUCTASE INHIBITOR, Heterocyclic communications, 4(2), 1998, pp. 105-111
A 4-phenylthiophene tethered to the 5-position of the heterocycle was
synthesized from 1-benzosuberone. The key steps in the synthesis were
the tandem thiolacetate hydrolysis - Michael addition intramolecular W
ittig reaction ((5) under bar --> (7) under bar) and the chelation-con
trolled reduction of the hydroxy beta-ketoester (<(12)under bar> --> <
(13)under bar>). The product <(14)under bar> exhibited nearly identica
l in vivo potency to the non-tethered analogs.