Synthesis of 3,4-Di-O-benzyl-1-O-methyl-L-galactitol, a key precursor of the C33-C37 fragment of calyculins

3,4-di-o-benzyl-1-o-methyl-l-galactitol (3) has been synthesized in a seven step sequence starting from 1,2:3,4-di-o-isopropylidene-a-d-galactopyranose (4). the synthesis involves the methyllation of ho-6 of 4, followed by methanolysis to the mixture of the corresponding methyl 6-o-methyl-a-d-galactopyranoside (6, major product) and the b-furanoside analog (8). compound 6 was converted into the 3,4-o-isopropylidene derivative 9, and the free ho-group was protected as the methoxyethoxymethyl (mem) ether. chemoselective removal of the acetonide by hydrolysis, followed by benzylation gave the methyl 3,4-di-o-benzyl-2-o-methoxyethoxymethyl-6- o-methyl-a-d-galactopyranoside (12). simultaneous acid hydrolysis of the methyl glycoside and mem group of 12 led to 13, which was then reduced with sodium borohydride to the target molecule 3.