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

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Abstract
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.