Abstract: AIM: To investigate feasible method for total synthesis of d- biotin on a large scale. METHODS AND RESULTS: cis-1,3-Dibenzyl-5-(1S,2S)-(+)-threo-1-hydroxymethyl-2-(p-nitrophenyl)-2-hydroxyethyl tetrahydro 4H pyrro3,4-dimidazole-2,4,6-trione (3) prepared from (1S,2S)-(+)-threo-(p-nitro-phenyl)-2-amino-1,3-propanediol and cis-1,3-dibenzyl-tetrahydro-4H-furo3,4-dimidazole-2,4,6-trione. (2) by melting condensation was converted to (3aS,6aS)-1,3-dibenzyl-tetrahydro-4H-furo3,4-dimidazole-2,4(1H)-dione(6) via highly stereoselective reduction, hydrolytic lactonization. Compound 6 was subjected to sulfurization, Grignard reaction, reduction to give (3aS,6aS)-1,3-dibenzyl-4-hydroxy-4-(3-ethoxypropyl)-tetrahydro-4H-thieno3,4-dimidazole-2(3H)-one(9). Compound 9 underwent dehydration, reduction, cleavage cyclization, debenzylation in four steps procedure to lead to the formation of (3aS,8aS,8bS)-2-oxo-decahydro imidazo4,5-cthieno1,2-athiolium bromide(12), which was transformed into d-biotin by condensation/ring openning, hydrolysis and decarboxylation in an overall yield of 25.7% from compound 2.CONCLUSION: A practical and cost effective process for the manufacture of d-biotin was developed.