Chem. Pharm. Bull., 53(7),743-746, July 2005

Regular Articles

Synthetic Studies on d-Biotin, Part 9.¹⁾ An Improved Asymmetric Synthetic Route to d-Biotin via Hoffmann-Roche Lactone-Thiolactone Approach

Fen-Er CHEN,^*,a Hui-Qing JIA,^a Xu-Xiang CHEN,^b Hui-Fang DAI,^a Bin XIE,^a Yun-Yan KUANG,^a and Jian-Feng ZHAO^a

^a Department of Chemistry, Fudan University; Shanghai, 200433, People's Republic of China: and ^b School of Pharmaceutical Engineering, Shenyang Pharmaceutical University; 110016, People's Republic of China. * To whom correspondence should be addressed. e-mail: rfchen@fudan.edu.cn

An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine-catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.

Key words d-biotin; vitamin H; polymer-supported oxazaborolidine; asymmetric reduction; Wittig reaction; desymmetrization