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-alpha -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-alpha -D-galactopyranoside (6, major product) and the beta -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- alpha -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.