Total synthesis of globotriaosylceramide (Gb3) and lysoglobotriaosylceramide (lysoGb3).

We have recently reported a highly efficient and stereocontrolled synthesis of globotriaosylceramide (Gb3, 1) in optically pure form. Key to our synthetic strategy was the implementation of the two-stage activation of thioglycosides for formation of the glycosidic bonds and the utilization of (2S, 3S, 4E)-2-azido-3-O-(tert-butyldimethylsilyl)-4-octadecen-1,3-di ol (9) as a sphingosine equivalent. The syntheses of Gb3 (1) and lysoGb3 (2) were achieved by stereocontrolled coupling of 2,3,4,6-tetra-O-benzyl-alpha-D-galactosyl fluoride (15) with phenyl O-(6-O-benzoyl-2,3-di-O-pivaloyl-beta-D-galactopyranosyl)- (1----4)-2,3,6-tri-O-pivaloyl-1-thio-beta-D-glucopyranoside (14) to form the P kappa antigen trisaccharide masked as a phenyl 1-thioglycoside at the reducing end. Thioglycoside 16 was converted into glycosyl fluoride 19, which was coupled to 9 in high yield. The coupled product 20 was converted into the title compounds 1 and 2 in four and three steps, respectively. This article presents the total synthesis of 1 and 2 in full experimental detail.