Total synthesis of (+)-biotin via a quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride strategy

A concise asymmetric total synthesis of (+)-biotin 1 has been accomplished in which the absolute stereochemistry of C3a, C6a of 1 was established by utilizing an efficient and practical quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride 2 in a single step, the C4 stereochemistry was installed by a direct stereoselective ionic hydrogenation of the thiolactol 7.

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(4S,5R)-1,3-Dibenzyl-5-(propargyloxycarbonyl)-2-oxo-imidazolidine-4-carboxylic acidC22H20N2O5Ee = 97%[α]D25=+15.6 (c 1.0, CHCl3)Absolute configuration: (4S,5R)

Benzyl(3aS,4S,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-5-yl)pentanoateC31H34N2O3S[α]D25=-20.7 (c 1.0, MeOH)Absolute configuration: (3aS,4S,6aR)

Benzyl(3aS,4Z,6aR)-5-(1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-5-ylidene)pentanoateC31H32N2O3S[α]D25=+154.4 (c 1.0, MeOH)Absolute configuration: (3aS,4Z,6aR)