beta-Mannosidase and beta-hexosaminidase inhibitors: synthesis of 1,2-bis-epi-valienamine and 1-epi-2-acetamido-2-deoxy-valienamine from D-mannose
Publikation/Tidskrift/Serie: Tetrahedron: Asymmetry
Förlag: Elsevier Science Ltd
A partially protected C-5=C-5a unsaturated carbasugar with alpha-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 beta-lyxo (i.e., corresponding to beta-manno at C-1-C-4), alpha-lyxo (i.e., corresponding to alpha-manno at C-1-C-4) and beta-2-acetamido-2-deoxy-xylo (i.e., corresponding to beta-GlcNAc at C-1-C-4) configurations. This is the first report of the synthesis of the beta-lyxo compound, 1,2-bis-epi-valienamine, which was found to inhibit Cellulomonas fimi beta-mannosidase (CfMan2A) with K-i 140 mu M. We report the crystal structures of three protected C-5=C-5a unsaturated carbasugars with lyxo configuration. (C) 2009 Elsevier Ltd. All rights reserved.
- ISSN: 0957-4166