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Synthesis of Thio‐Linked Analogues of Lewis X and Sialyl Lewis X
Author(s) -
Eisele Thomas,
Schmidt Richard R.
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970705
Subject(s) - chemistry , lewis acids and bases , glycosylation , stereochemistry , disaccharide , glycosyl donor , sialyl lewis x , trifluoromethanesulfonate , catalysis , glycoside , organic chemistry , adhesion , biochemistry , selectin
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 .