Synthesis of the Leishmania LPG Core Heptasaccharyl myo-Inositol

• Published in: Journal of the American Chemical Society 2000-11, Vol.122 (45), p.11067-11072
• Main Authors: Ruda, Katinka, Lindberg, Jan, Garegg, Per J, Oscarson, Stefan, Konradsson, Peter
• Format: Article
• Language: English
• Subjects: NATURAL SCIENCES; NATURVETENSKAP
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja001515t

Total synthesis of the core heptasaccharyl myo-inositol, Galp(α1−6)Galp(α1−3)Galf(β1−3)[Glcp(α1-PO4-6)Manp](α1−3)Manp(α1−4)GlcNp(α1−6)Ins-1-PO4, and the corresponding hexasaccharyl myo-inositol, Galp(α1−6)Galp(α1−3)Galf(β1−3)Manp(α1−3)Manp(α1−4)GlcNp(α1−6)Ins-1-PO4, found in the lipophosphoglycans of Leishmania parasites are described. The target molecules contain synthetic challenges such as an unusual internal galactofuranosyl residue and an anomeric phosphodiester. The synthesis was accomplished using a convergent block synthetic strategy. Four building blocks, a trigalactoside, a dimannoside, a glucosyl inositolphosphate, and a glucosyl-α-1-H-phosphonate, all appropriately protected, were used. The trigalactoside was linked to the dimannoside followed by glycosylation with the glucosyl inositolphosphate to produce the fully protected hexasaccharyl myo-inositol. Subsequent oxidative coupling of the glucosyl-H-phosphonate formed the anomeric phosphodiester linkage to produce the protected heptasaccharyl myo-inositol. Both the assembly order of the subunits and sequence of deprotection were essential for the successful synthesis of these complex molecules. The deprotection was accomplished by deacetylation and clevage of benzyl ethers with sodium in liquid ammonia, followed by acidic deacetalization/desilylation to produce the target molecules.