An attempted synthesis of biotin

Abstract

Renewed interest in the total synthesis of hiotin (1)1 has been spurred by recent findings2 that emphasize the importance of this substance in the areas of nutrition and growth promotion. Despite efforts to develop new and efficient approaches to 1, the cofactor is still prepared commercially by the original Sternbach synthesis.3 We have been attempting to effect a short, high yield, stereoselective total synthesis of biotin via the novel strategy outlined in Scheme I. It was our intention to prepare tetrahydrothiophene derivative 3, where X is an appropriate leaving group, and couple it with a synthetic equivalent for carbanion 2 to produce 1. We hoped that 3 could be synthesized from olefinic sulfide 4, which should be available via our recently reported4,5 methodology for stereoselective synthesis of unsaturated vicinal diamines. Clearly, in order for this route to be successful, the key cyclization of 4 to 3 must be achieved with the proper regiochemistry and stereochemistry at C-2. © 1988, American Chemical Society. All rights reserved.