A General and Stereoselective Route to α- or β-Galactosphingolipids via a Common Four-Carbon Building Block

• Published in: Journal of organic chemistry 2007-09, Vol.72 (20), p.7757-7760
• Main Authors: Matto, Pamela, Modica, Emilia, Franchini, Laura, Facciotti, Federica, Mori, Lucia, De Libero, Gennaro, Lombardi, Grazia, Fallarini, Silvia, Panza, Luigi, Compostella, Federica, Ronchetti, Fiamma
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - chemical synthesis; Adjuvants, Immunologic - pharmacology; Animals; Chemistry; Exact sciences and technology; Galactose - analogs & derivatives; Galactose - chemical synthesis; Galactosylceramides - chemical synthesis; Galactosylceramides - pharmacology; Lipids; Lymphocyte Activation - drug effects; Mice; Organic chemistry; Preparations and properties; Stereoisomerism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo070849z

A general synthetic strategy toward α- or β-galactosylceramides and their analogues from 3-azido-2-O-benzyl-1-O-(4-methoxybenzyl)butane-1,2,4-triol is described. The key steps for the installation of the main lipid chain are either a diasteroselective alkynylation reaction yielding the 4R stereocenter of phytosphingosine or a Wittig olefination generating the trans double bond of sphingosine. The methodology allows the preparation of different glycolipids with variations in the structure of the sphingoid base. In particular, three α-GalCer-related compounds have been synthesized and evaluated for their ability to activate CD1d-restricted T-cells.