Synthesis, conformational analysis and SAR research of OSW-1 analogues

A series of novel OSW-1 analogues were synthesized by coupling disaccharides (2-O-4-methoxylbenzoyl-beta-D-xylopyranosyl-(1 -> 3)-2-O-acetyl-alpha-L-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-beta-D-xylopyranosyl-(1 -> 3)-2-O-acetyl-alpha-L-arabinopyranosyl) and their 1 -> 4 linked analogues [(2-O-4-methoxylbenzoyl-beta-D-xylopyranosyl-(1 -> 4)-2-O-acetyl-alpha-L-arabinopyranosyl) or (2-O-4-(E)-cinnamoyl-beta-D-xylopyranosyl-(1 -> 4)-2-O-acetyl-alpha-L-arabinopyranosyl)] with three different steroidal sapogenins at 16 beta-hydroxy. Their conformation was analyzed with NMR spectroscopy and molecule simulation. The arabinose moiety of 1-3 linked analogues was in chair conformation and 1-4 linked analogues was in boat conformation. 1-3 linked analogues exhibited potent anti-proliferation activity against a panel of human tumor cells at nanomolar concentration level, while 1-4 linked analogues did not show antitumor activity. This work should provide an evidence that the conformation plays an important role in the antitumor activity. (C) 2016 Elsevier Ltd. All rights reserved.