EFFICIENT SYNTHESIS OF THE LEWIS ANTIGEN-X (LE(X)) FAMILY

tert-Butyldimethylsilyl 2-azido-4,6-O-benzylideneglucopyranoside 5 pro ved to be a versatile starting material for the synthesis of the Le(x) antigen family. 3-O-Fucosylation of 5, ensuing reductive benzylidene ring cleavage, and then 4-O-galactosylation afforded Le(x) trisacchari de building block 12 which was readily converted into trisaccharide do nor 14alpha,beta and into trisaccharide 3c-O-acceptor 16. Their reacti on in acetonitrile as solvent at low temperatures (nitrile effect) aff orded exclusively the beta-connected hexasaccharide 17, which was tran sformed via the same steps into hexasaccharide donor 20alpha,beta and acceptor 22. The use of these building blocks and known lactose deriva tive 23b, and 3-O-benzoyl-protected azidosphingosine 32 as acceptors l ed to ready formation of the target molecules. Thus, from 20alpha,beta and 23b octasaccharide 24b was obtained which was converted via 25b a nd 26b into O-unprotected octasaccharide 27; the derived O-acyl-protec ted donor 29balpha was linked to 32, thus providing by application of the ''azidosphingosine glycosylation procedure'' dimeric Le(x) 1B. Fro m 20alpha,beta and 16 nonasaccharide 35a was obtained; its transformat ion via 36a and 37a into donor 38aalpha,beta gave by reaction with 23b undecasaccharide 39a; the derived donor 43aalpha furnished by treatme nt with 32 trimeric Lex 1C. Similarly, from 20alpha,beta and 22 dodeca saccharide 35b was generated which gave via 36b, 37b, and donor 38balp ha,beta by reaction with 23b as acceptor tetradecasaccharide 39b; 39b, after transformation into the corresponding donor 43balpha,beta gave by treatment with 32 as acceptor tetrameric Le(x) 1D. Additionally, oc tasaccharide donor 29balpha,beta was attached to spacer 30, thus yield ing spacer-connected dimeric Le(x) antigen 2.