β-Mannosidase and β-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxy-valienamine from D-mannose
2009 (English)In: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 20, no 6-8, 795-807 p.Article in journal (Refereed) Published
A partially protected C-5C-5a unsaturated carbasugar with α-lyxo configuration is synthesised in five steps and 26% overall yield from a known mannose-derived hemiacetal, using ring-closing metathesis as a key step. This carbasugar is converted into valienamine derivatives with β-lyxo (i.e., corresponding to β-manno at C-1–C-4), α-lyxo (i.e., corresponding to α-manno at C-1–C-4) and β-2-acetamido-2-deoxy-xylo (i.e., corresponding to β-GlcNAc at C-1–C-4) configurations. This is the first report of the synthesis of the β-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi β-mannosidase (CfMan2A) with Ki 140 μM. We report the crystal structures of three protected C-5C-5a unsaturated carbasugars with lyxo configuration.
Place, publisher, year, edition, pages
Elsevier Ltd. , 2009. Vol. 20, no 6-8, 795-807 p.
IdentifiersURN: urn:nbn:se:su:diva-28978DOI: 10.1016/j.tetasy.2009.02.016ISI: 000266735500018OAI: oai:DiVA.org:su-28978DiVA: diva2:228356