Facile Synthesis and Antitumor Activities of Timosaponin AIII and Its Analogs

Abstract

An efficient synthesis of timosaponin AIII (TAIII) and five structurally modified analogs via a one-pot sequential glycosylation strategy is described. A partially protected D-galactopyranosyl thioglycoside was employed for regioselective glycosylation to facilitate the target synthesis. The antitumor activities of the synthetic saponins against human epithelial cervical cancer cell (HeLa) were preliminarily evaluated by means of CCK-8 assay. An L-rhamnosyl analog was discovered to display stronger inhibitory activity (IC₅₀ 3.3 μM) than TAIII (IC₅₀ 10.7 μM) to HeLa cell. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file.

Keywords:

• Timosaponin AIII
• Thioglycoside
• One-pot sequential glycosylation strategy
• Saponin
• Antitumor activity

ACKNOWLEDGMENTS

This work was supported by grants from the Research Fund for Promotion of Excellent Young and Middle-aged Scientists of Shandong Province (No. BS2009YY006), NNSF of China (Project 31000368), and Independent Innovation Foundation of Shandong University (No. 2009TS088 and 2009DX002).

Supplementary data available: Supplementary data contain the ¹H NMR, ¹³C NMR, and ESI-MS spectra for compounds 5a–f and 1a–f.

Min Fang and Li Gu contributed equally to this work.