Synthesis, conformational analysis and SAR research of OSW-1 analogues. Issue 27 (7th July 2016)

• Record Type: Journal Article
• Authors: Liu, Chao; Wang, A-peng; Jin, Longlong; Guo, Yanshen; Li, Yan; Zhao, Zhehui; Lei, Pingsheng
• Is Part Of: Tetrahedron. Volume 72:Issue 27/28(2016)
• Page Start: 4091
• Page End: 4102
• Publication Date: 2016-07-07
• Subjects: OSW-1 analogues -- Synthesis -- Conformation analysis -- Molecule simulation -- Antitumor activity; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.05.049
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A series of novel OSW-1 analogues were synthesized by coupling disaccharides (2- O -4-methoxylbenzoyl-β-d -xylopyranosyl-(1→3)-2- O -acetyl-α-l -arabinopyranosyl) or (2- O -4-( E )-cinnamoyl-β-d -xylopyranosyl-(1→3)-2- O -acetyl-α-l -arabinopyranosyl) and their 1→4 linked analogues [(2- O -4-methoxylbenzoyl-β-d -xylopyranosyl-(1→4)-2- O -acetyl-α-l -arabinopyranosyl) or (2- O -4-( E )-cinnamoyl-β-d -xylopyranosyl-(1→4)-2- O -acetyl-α-l -arabinopyranosyl)] with three different steroidal sapogenins at 16β-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. Graphical abstract: The highest antiproliferative activity was displayed by compounds containing 1–3 linked disaccharide which had convergent structures at nanomolar concentrations level. 1–4 linked analogues which had divergent structures showed a lower activity. The key role of triangular molecular shape of 1–3 linked OSW-1 analogues for the high activity was confirmed.