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

Abstract

In lead detoxification, the α-anomer of N-glycocyl- l-amino acid is more potent than its β-anomer. Here a six-step-reaction route for stereoselectively preparing N-(α- 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 α- to β-anomer ranged from 8/1 to 9/1. Chromatographic separation provided epimerically pure 2a–f-α and 2a–f-β. In the presence of CF 3CO 2H, 2a–f-α and 2a–f-β were converted to α- and β-anomers of N-(2,3,5-tri- O-acetyl- l-arabinofuranosyl)- N-(2-nitrobenzenesulfonyl)- l-amino acids, 3a–f-α and 3a–f-β, in 87–92% yields. While in the presence of NaOCH 3, 3a–f-α and 3a–f-β were converted to α- and β-anomers of N-( l-arabinofuranosyl)- N-(2-nitrobenzenesulfonyl)- l-amino acids, 4a–f-α and 4a–f-β, in 90–96% yields. Treating 4a–f-α and 4a–f-β with N-ethyldiisopropylamine (DIPEA) and thiophenol, their 2-nitrophenylsulfonyl groups were removed, and the α- and β-anomers of N-( l-arabinose-1-yl)- l-amino acids were formed in 70–79% yields. The bioassay confirmed that the lead detoxification activity of the α-anomer was significantly higher than that of the β-anomer.