Synthesis of the 2-deoxyisomaltose analogue of acarbose by an improved route to chiral valieneamines

A 2-deoxyisomaltose analogue of acarbose was stereoselectively synthesised in 11 steps with a total yield of 7% starting from 2,6-dibromo-2,6-dideoxy-D-mannono-1,4-lactone (6). The latter was reduced to the lactol, converted to the methyl glycoside (7) and hydrogenated to the methyl 6-bromo-2,6-dideoxyglycoside (8). Benzylation of the hydroxy groups, elimination of bromine to a 5-ene and Ferrier carbocyclisation gave (2S,3R)-2,3-bisbenzyloxycyclohex-5-enone (12). 1,2-addition of benzyloxymethyl lithium at -110 degrees C gave a 6:1 mixture of tertiary alcohols 13; the (1S) isomer was the major one. Reaction with trichloroacetyl isocyanate gave a carbamate 19, which, when dehydrated to the cyanate, spontaneously underwent [1,3] sigmatropic rearrangement to an isocyanate, which on addition of methanol gave the methylcarbamate 20. Basic hydrolysis of this compound gave (2R, 3R, 5R)-5-amino-1-benzyloxymethyl-2,3-bis(benzyloxy)cyclohex-6-ene (22), which could be deprotected to 2-deoxyvalieneamine (5). Reaction with 2-azidoethyl 2,3,4-tri-O-benzyl-6-O-triflyl-alpha-glucopyranoside (34) gave the secondary amine 35, which was completely de-O-protected with sodium in ammonia to give 6-deoxy-6-((1R,3R,4R)-3,4-dihydroxy-5-hydroxymethylcyclohex-5-enylamino)-D-glucose (4), the 2-deoxyisomaltose analogue of acarbose.