SYNTHESIS OF THIO-LINKED ANALOGS OF LEWIS-X AND SIALYL-LEWIS-X

The synthesis of thio-linked Lewis X and sialyl Lewis X-derived epitop es 3-5 has been achieved using a small number of building blocks. The key building-block was 1-O-silyl-protected a-L-fucopyranosyl)-3,4-dith io-beta-D-glucopyranose (15), which was obtained from the fucosyl dono r 6 together with 3-thiogalactose 7 as the acceptor. Their acid-cataly zed S-glycosylation afforded the thio-linked disaccharide 8 which was subsequently converted to the 4a-O-unprotected derivative 12. Conversi on to the 4a-triflate followed by treatment with KSAc in tetrahydrofur an led, under inversion of configuration, to 15 in good overall yield. Selective removal of the S-acetyl group followed by base-promoted S-g lycosylation with acetobromogalactose gave the acyl-protected Lewis X analogue 25. Acetobromogalactose gave the acyl-protected Lewis X analo gue 25. Transformation into trichloroacetimidate 27, followed by acid- catalyzed S-glycosylation of heptylthiol and complete deacylation affo rded target molecule 3. Similarly, acid-catalyzed reaction of donor 27 and the 3b,4b-O-unprotected lactose derivative 31 as acceptor led to pentasaccharide 32, complete deacylation of which afforded target mole cule 4. Transformation of 15 into the donor trichloroacetimidate 34, f olio-eyed by acid-catalyzed S-glycosylation of heptylthiol afforded th ioglycoside 35. Selective removal of the S-acetyl group and subsequent base-promoted S-glycosylation with the known donor 37 furnished the t hio-linked tetrasaccharide 38. Cleavage of all the O-acyl groups and h ydrolysis of the methyl ester moiety afforded the sialyl Lewis X analo gue 5.