Abstract: 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 4-Hthienoimidazol-2, 4(¹H NMR) 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 thienothiolium bromide(11), which was converted to d-biotin via condensation, ring opening, hydrolysis, decarboxylation, debenzylation in an overall yield of 14.5%.

Key words: d-Biotin, Vitamin H, (1 S,2 S)-(+)-threo-1-(p-Nitrophenyl)-2-amino-1,3-propanediol, Catalytic hydrogen transfer, Diastereoisomeric crystallization resolution, Total asymmetry synthesis, Chase transfer catalysis