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.
Nicolaou
K C
KC
Department of Chemistry Research Institute of Scripps Clinic, La Jolla, California 92037.
Caulfield
T J
TJ
Katoaka
H
H
D000117:Acetylglucosamine / Q000031:analogs & derivatives; D002240:Carbohydrate Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D006017:Glycolipids / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013107:Sphingolipids / Q000138:chemical synthesis*; D014281:Trihexosylceramides / Q000138:chemical synthesis*
D006017:Glycolipids; D013107:Sphingolipids; D014281:Trihexosylceramides; C063288:globotriaosyl lysosphingolipid; C066012:1,3,4,6-tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-glucopyranose; C018549:globotriaosylceramide; D000117:Acetylglucosamine