A CONVENIENT SYNTHESIS OF N-ACETYLLACTOSAMINE DERIVATIVES FROM LACTAL

In a thermal inverse-type hetero-Diels-Alder reaction of O-silyl-protected lactal 1 and bis(2,2,2-trichloroethyl) azodicarboxylate (2), the dihydrooxadiazine derivative 3 was obtained in a very high yield; transesterification with benzyl alcohol furnished the corresponding derivative 4- Treatment of 3 with methanol in the presence of BF3.OEt2 afforded the methyl lactoside derivative 5 which, after, transesterification with benzyl alcohol, then hydrogenolytic debenzylation and concomitant NN-cleavage with Raney nickel, and N-acetylation, furnished methyl O-(2,4,6-tri-O-tert-butyldimethylsilyl-beta-D-galactopyranosyl)-(1 --> 4)-2-acetamido-3,6-di-O-tert-butyldimethylsilyl-2-deoxy-beta-D-glucopyranosid e (7) in high yield. Desilylation of 4, then O-acetylation, methyl glycoside formation with methanol-BF3. OEt2, hydrogenolytic debenzylation, and NN-cleavage with Raney nickel, and N-acylation afforded methyl O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1 --> 4)-2-acetamido-3,6-di-O-acetyl-2-deoxy-beta-D-glucopyranoside (10).