Total Synthesis of Alpha-galactosyl Cerebroside

A highly convergent synthetic approach was developed to obtain alpha-galactosyl cerebroside O-(alpha-D-galactopyranosyl)-2-hexacosylamino-D-ribo-1,3,4-octa decantriol, which has previously been demonstrated to have immunostimulatory activity. Known 4,6-O-benzylidene galactose was the starting material for both the required alpha-galactosyl and the phytosphingosine building blocks O-(2,3-di-O-benzyl-4,6-O-benzylidene-D-galactopyranosyl) trichloroacetimidate (4) and 2-O-methanesulfonyl-D-arabino-1,2,3,4-octadecantetrol (5). The key step of the synthetic strategy is the highly regio- and stereoselective O-galactosylation of 1,3,4-O-unprotected phytosphingosine acceptor 5 using known 4 as donor. The total synthesis required only 11 synthetic steps starting from galactose.