Chemoenzymic synthesis of potentially caged glycosphingolipids [correction of glycoshingolipids] (GSLs): potentially caged lyso-G(M3) and its analogue.

In a previous work, a number of potentially caged sphingolipids and glycosphingolipids were chemically synthesized (Zehavi, 1997. Chem. Phys. Lipids 90, 55-61). The effects of GM3 and to a lesser extent, of lyso-GM3, are being studied. Considering that biologically inert, caged lyso-GM3 could be photolysed in the cell to release lyso-GM3, thus creating an attractive opportunity to study the subsequent sequence of events in the cell, the chemoenzymic synthesis of the potentially caged lyso-GM3, (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylo nic acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyloxy (1-1)- (2S,3R,4E)-2-(4-carboxymethyl-2-nitrobenzyloxycarbonyl-amino)-3-hy droxy-4- octadecene and of a potentially caged GM3 analogue, (5-acetamido-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylonic acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyloxy -(1-3)- (2S, 3R, 4E)-2-(4-carboxymethyl-2-nitro-benzyloxycarbonylamino)-1- hydroxy-4-octadecene was undertaken. Both compounds, being 2-nitrobenzyloxycarbonyl derivatives, are light-sensitive and could be efficiently photolysed to the biologically active, corresponding lyso-GSLs.

Enzymic glycosphingolipid synthesis on polymer supports. III. Synthesis of GM3, its analog [NeuNAcalpha(2-3)Galbeta(1-4)Glcbeta(1-3)Cer] and their lyso-derivatives.

Two water-soluble polymers, carrying 0.24 meq g(-1) of lactosyl-beta(1-1)-sphingosine (7) and 0.13 meq g(-1) of lactosyl-beta(1-3)-sphingosine (8) were prepared. The polymers served as acceptors in the alpha-(2-3)-sialyltransferase reaction (up to 55.3 and 38.5% transfer yields, respectively). Subsequent photolysis, released compounds 11 (lyso-GM3) and 12 (lyso-GM3 analog), respectively; acylation and chromatography afforded (5-acetamido-3,5-dideoxy-D-glycero-alpha-galacto-2-nonulopyranosyloni c acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-1)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (13, GM3) and (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylo nic acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-3)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (14, GM3 analogue), respectively, thus presenting a route to glycosphingolipids possessing the unusual glycosyl-beta(1-3)-spingosine linkage.