Synthesis of non-glycosidic 4,6′-thioether-linked disaccharides as hydrolytically stable glycomimetics

María Laura Uhrig, László Szilágyi, Katalin E. Kövér, Oscar Varela

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Michael addition of 1,2:3,4-di-O-isopropylidene-6-thio-α-d-galactose (2) to 2-propyl 6-O-acetyl-3,4-dideoxy-α-d-glycero-hex-3-enopyranosid-2-ulose (1) afforded, as the major diastereoisomer, 2-propyl 6-O-acetyl-3-deoxy-4-S-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-ga lactopyranos-6-yl)-4-thio-α-d-threo-hexopyranosid-2-ulose (3, 91% yield). Reduction of the carbonyl group of 3, followed by O-deacetylation gave the two epimers 7 (α-d-lyxo) and 8 (α-d-xylo) in a 1:2 ratio. On removal of the protecting groups of 8 by acid hydrolysis, formation of an 1,6-anhydro bridge was observed in the 3-deoxy-4-thiohexopyranose unit (10). The free non-glycosidic thioether-linked disaccharide 3-deoxy-4-S-(6-deoxy-α,β-d-galactopyranos-6-yl)-4-thio- α,β-d-xylo-hexopyranose (11) was obtained by acetolysis of 10 followed by O-deacetylation. A similar sequence starting from the enone 1 and methyl 2,3,4-tri-O-benzoyl-6-thio-α-d-glucopyranoside (12) led successfully to 2-propyl 3-deoxy-4-S-(methyl 6-deoxy-α-d-glucopyranos-6-yl)-4-thio-α-d-lyxo-hexopyranosid e (17) and its α-d-xylo analog (19, major product). In this synthetic route, orthogonal sets of protecting groups were employed to preserve the configuration of both reducing ends and to avoid the formation of the 1,6-anhydro ring.

Original languageEnglish
Pages (from-to)1841-1849
Number of pages9
JournalCarbohydrate Research
Volume342
Issue number12-13
DOIs
Publication statusPublished - Sep 3 2007

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Keywords

  • 4,6′-Thioether-linked sugars
  • Michael addition
  • Sugar enones
  • Thioether-linked disaccharide analogues

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

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