Stereoselective synthesis of novel N-(α-L-arabinofuranos-1-yl)-L-amino acids

In lead detoxification, the of.-anomer of N-glycocyl-L-amino acid is more potent than its beta-anomer. Here a six-step-reaction route for stereoselectively preparing N-(alpha-L-arabinose-1-yl)-L-amino acids is reported. Treating L-arabinose with acetic anhydride and sodium acetate provided 1,2,3,5-tetra-O-acetyl-L-arabinofuranose in 90% yield. After removing the 1-acetyl group, the thus formed 2,3,5-tri-O-acetyl-L-arabinofuranose and N-(2-nitrophenylsulfonyl)-L-amino acid t-butylesters were treated With triphenylphosphine to perform Mitsunobu dehydration and form 2,3,5-tri-O-acetyl-L-arabinofuranosyl-L-[N-(2-nitrophenylsulfonyl)]amino acid t-butylesters 2a-f, and the ratios of their alpha- to beta-anomer ranged from 8/1 to 9/1. Chromatographic separation provided epimerically pure 2a-f-alpha and 2a-f-beta. In the presence of CF3CO2H, 2a-f-alpha and 2a-f-beta were converted to alpha- and beta-anomers of N-(2,3,5-tri-O-acetyl-L-arabinofuranosyl)-N(2-nitrobenzenesulfonyl)-L-amino acids, 3a-f-alpha and 3a-f-beta, in 87-92% yields. While in the presence of NaOCH3, 3a-f-alpha and 3a-f-beta were converted to alpha- and beta-anomers of N-(L-arabinofuranosyl)-N-(2-nitrobenzenesulfonyl)-L-amino acids, 4a-f-alpha and 4a-f-beta, in 90-96% yields. Treating 4a-f-alpha and 4a-f-beta with N-ethyldiisopropylamine (DIPEA) and thiophenol, their 2-nitrophenylsulfonyl groups were removed, and the alpha- and beta-anomers of N-(L-arabinose-1-yl)-L-amino acids were formed in 70-79% yields. The bio-assay confirmed that the lead detoxification activity of the alpha-anomer was significantly higher than that of the beta-anomer. (C) 2009 Elsevier Ltd. All rights reserved.