SYNTHESIS OF THE 2-DEOXYISOMALTOSE ANALOG OF ACARBOSE BY AN IMPROVED ROUTE TO CHIRAL VALIENEAMINES

A 2-deoxyisomaltose analogue of acarbose was stereoselectively synthes ised 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 lac tol, converted to the methyl glycoside (7) and hydrogenated to the met hyl 6-bromo-2,6-dideoxyglycoside (8). Benzylation of the hydroxy group s, elimination of bromine to a 5-ene and Ferrier carbocyclisation gave (2S,3R)-2,3-bisbenzyloxycyclohex-5-enone (12). 1,2-addition of benzyl oxymethyl lithium at -110 degrees C gave a 6:1 mixture of tertiary alc ohols 13; the (1S) isomer was the major one. Reaction with trichloroac etyl isocyanate gave a carbamate 19, which, when dehydrated to the cya nate, spontaneously underwent [1,3] sigmatropic rearrangement to an is ocyanate, which on addition of methanol gave the methylcarbamate 20. B asic hydrolysis of this compound gave (2R, 3R, 1-benzyloxymethyl-2,3-b is(benzyloxy)cyclohex-6-ene (22), which could be deprotected to 2-deox yvalieneamine (5). Reaction with 2-azidoethyl 3,4-tri-O-benzyl-6-O-tri flyl-alpha-glucopyranoside (34) gave the secondary amine 35, which was completely de-O-protected with sodium in ammonia to give oxy-5-hydrox ymethylcyclohex-5-enylamino)-D-glucose (4), the 2-deoxyisomaltose anal ogue of acarbose.