Synthesis of Thio‐Linked Analogues of Lewis X and Sialyl Lewis X

The synthesis of thio‐linked Lewis X and sialyl Lewis X‐derived epitopes 3–5 has been achieved using a small number of building blocks. The key building‐block was 1‐ O ‐silyl‐protected 4‐ S ‐acetyl‐2,6‐di‐ O ‐benzoyl‐3‐ S ‐(2,3,4‐tri‐ O ‐acetyl‐α‐ L ‐fucopyranosyl)‐3,4‐dithio‐β‐ D ‐glucopyranose ( 15 ), which was obtained from the fucosyl donor 6 together with 3‐thiogalactose 7 as the acceptor. Their acid‐catalyzed S ‐glycosylation afforded the thio‐linked disaccharide 8 which was subsequently converted to the 4a‐ O ‐unprotected derivative 12 . Conversion to the 4a‐triflate followed by treatment with KSAc in tetrahydrofuran led, under inversion of configuration, to 15 in good overall yield. Selective removal of the S ‐acetyl group followed by base‐promoted S ‐glycosylation with acetobromogalactose gave the acyl‐protected Lewis X analogue 25 . Acetobromogalactose gave the acyl‐protected Lewis X analogue 25 . Transformation into trichloroacetimidate 27 , followed by acid‐catalyzed S ‐glycosylation of heptylthiol and complete deacylation afforded 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 molecule 4 . Transformation of 15 into the donor trichloroacetimidate 34 , followed by acid‐catalyzed S ‐glycosylation of heptylthiol afforded thioglycoside 35 . Selective removal of the S ‐acetyl group and subsequent base‐promoted S ‐glycosylation with the known donor 37 furnished the thio‐linked tetrasaccharide 38 . Cleavage of all the O ‐acyl groups and hydrolysis of the methyl ester moiety afforded the sialyl Lewis X analogue 5 .