Studies on the asymmetry total synthesis of d-biotin(II)

An efficient and practical total synthesis of d-biotin is described. (4S,5R)-cis-1,3-dibenzyl-5-methoxycarbonyl-2-oxo-imidazoline-4-carboxylic acid, prepared from 1, 3-dibenzylimidazolidone-2-cis-4, 5-dicarboxylic acid via dehydration, monoesterification, optical resolution was subjected to reduction-cyclization, sulfuration to produce (3aS,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazol-2, 4(1H)-dione(7). Compound 7 via Grignard reaction, dehydration, reduction, cleavage-cyclization in one-pot procedure led to (3aR, 8aS, 8bS)-1, 3-dibenzyl-2-oxo-decahydromidazo[4, 5-c]-thieno[1, 2-a]thiolium bromide(ii), which was converted to d-biotin via condensation, ring-opening, hydrolysis, decarboxylation, debenzylation in an overall yield of 14.5%.