Synthesis of carbon‐bridged N ‐acetyl‐c‐lactosamine and derivatives

1995; Wiley; Volume: 1995; Issue: 12 Linguagem: Inglês

10.1002/jlac.1995199512297

ISSN

0947-3440

Autores

Thomas Eisele, Hideharu Ishida, Gerd Hummel, Richard R. Schmidt,

Tópico(s)

Click Chemistry and Applications

Resumo

Abstract 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 ′.

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