A general and stereoselective route to alpha- or beta-galactosphingolipids via a common four-carbon building block.
A general synthetic strategy toward alpha- or beta-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 alpha-GalCer-related compounds have been synthesized and evaluated for their ability to activate CD1d-restricted T-cells.
Matto
Pamela
P
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133-Milano, Italy.
Modica
Emilia
E
Franchini
Laura
L
Facciotti
Federica
F
Mori
Lucia
L
de Libero
Gennaro
G
Lombardi
Grazia
G
Fallarini
Silvia
S
Panza
Luigi
L
Compostella
Federica
F
Ronchetti
Fiamma
F
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology