The methylene isostere of the glycosphingolipid β-D-galactosyl N- palmitoyl C18 ceramide has been synthesized by a linear reaction sequence starting from a β-linked D-galactopyranosyl aldehyde. First, this sugar aldehyde was converted into a methylenephosphorane which in turn was coupled with N-Boc serinal acetonide. The double bond of the resulting olefin was reduced and the oxazolidine ring was cleaved and oxidized to give a C- glycosyl N-Boc α-amino butanal (three-carbon chain elongation). Then, an additional C15 carbon chain was installed by addition of lithium 1- pentadecyne to the above glycosyl amino aidehyde. The syn/anti ratio (70:30) of the resulting mixture of amino alcohols was reversed (5:95) by an oxidation-reduction sequence to achieve the same stereochemistry as in the hydrophilic head of D-erythro-sphingosines. The major product was subjected to the reduction of the triple bond with LiAlH4 to give the olefin with E geometry. Finally the N-amide group was installed by reaction with palmitoyl chloride and the O-benzyl protective groups of the sugar moiety were removed by treatment with lithium in liquid NH3-THF. The final product was characterized as the O-acetyl derivative.
Synthesis of beta-D-galactosyl ceramide methylene isostere
DONDONI, Alessandro;PERRONE, Daniela;
1999
Abstract
The methylene isostere of the glycosphingolipid β-D-galactosyl N- palmitoyl C18 ceramide has been synthesized by a linear reaction sequence starting from a β-linked D-galactopyranosyl aldehyde. First, this sugar aldehyde was converted into a methylenephosphorane which in turn was coupled with N-Boc serinal acetonide. The double bond of the resulting olefin was reduced and the oxazolidine ring was cleaved and oxidized to give a C- glycosyl N-Boc α-amino butanal (three-carbon chain elongation). Then, an additional C15 carbon chain was installed by addition of lithium 1- pentadecyne to the above glycosyl amino aidehyde. The syn/anti ratio (70:30) of the resulting mixture of amino alcohols was reversed (5:95) by an oxidation-reduction sequence to achieve the same stereochemistry as in the hydrophilic head of D-erythro-sphingosines. The major product was subjected to the reduction of the triple bond with LiAlH4 to give the olefin with E geometry. Finally the N-amide group was installed by reaction with palmitoyl chloride and the O-benzyl protective groups of the sugar moiety were removed by treatment with lithium in liquid NH3-THF. The final product was characterized as the O-acetyl derivative.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
