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Synthesis of carbon‐bridged N ‐acetyl‐c‐lactosamine and derivatives
Author(s) -
Eisele Thomas,
Ishida Hideharu,
Hummel Gerd,
Schmidt Richard R.
Publication year - 1995
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.1995199512297
Subject(s) - chemistry , nucleophile , regioselectivity , silylation , methylene , diastereomer , electrophile , stereochemistry , wittig reaction , disaccharide , isomerization , derivative (finance) , medicinal chemistry , trimethylsilyl chloride , trifluoromethanesulfonate , catalysis , organic chemistry , financial economics , economics
4‐ C ‐Formyl‐2‐azidoglucopyranoside 12a , required for N ‐acetyl‐C‐lactosamine synthesis as electrophile, was obtained from thexyldimethylsilyl 2‐azido‐2‐deoxy‐glucopyranoside 3 via readily available 4‐ O ‐unprotected 6a and then 4‐C‐methylene derivative 8a in overall seven steps. Alternatively, regioselective silylation of 3 with tert ‐butyldimethylsilyl chloride gave 4‐ O ‐unprotected 6b which was transformed by a similar reaction sequence into 12a . In order to circumvent a Wittig reaction, 6a was transformed into triflate 13 the reaction of which with 4‐ C ‐cyano derivative 14 followed by reduction with DIBAH and base‐catalyzed isomerization also afforded 12a . Reaction of 12a with 1‐ C ‐lithiated 2‐phenylsul‐finyl‐ D ‐galactal 15 as nucleophile furnished C‐disaccharide intermediates 16a and 16b as diastereoisomers. Ensuing removal of the phenylsulfinyl group with Raney nickel and diastereospecific 2b‐hydrogen and 3b‐hydroxy transfer afforded β(1→4)‐connected N ‐acetyl‐C‐lactosamines 19a and 19b ; their structures were deduced from derivatives 20a, b and 21a, b on the basis of 1 H‐NMR data. Hydrogenolytic O ‐debenzylation of 19b afforded hydroxymethylene‐bridged N ‐acetyl‐C‐lactosamine 2b ′.