Biomimetic Syntheses and Antiproliferative Activities of Racemic, Natural (鈭?, and Unnnatural (+) Glyceollin I

详细信息    查看全文

• 作者：Rahul S. Khupse ; Jeffrey G. Sarver ; Jill A. Trendel ; Nicole R. Bearss ; Michael D. Reese ; Thomas E. Wiese ; Stephen M. Boue ; Matthew E. Burow ; Thomas E. Cleveland ; Deepak Bhatnagar ; Paul W. Erhardt
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：May 26, 2011
• 年：2011
• 卷：54
• 期：10
• 页码：3506-3523
• 全文大小：1287K
• 年卷期：v.54,no.10(May 26, 2011)
• ISSN：1520-4804

文摘

A 14-step biomimetic synthetic route to glyceollin I (1.5% overall yield) was developed and deployed to produce the natural enantiomeric form in soy, its unnatural stereoisomer, and a racemic mixture. Enantiomeric excess was assessed by asymmetric NMR shift reagents and chiral HPLC. Antiproliferative effects were measured in human breast, ovarian, and prostate cancer cell lines, with all three chiral forms exhibiting growth inhibition (GI) in the low to mid 渭M range for all cells. The natural enantiomer, and in some cases the racemate, gave significantly greater GI than the unnatural stereoisomer for estrogen receptor positive (ER⁺) versus ER^{鈥?/sup> breast/ovarian cell lines as well as for androgen receptor positive (AR+) versus AR鈥?/sup> prostate cancer cells. Surprisingly, differences between ER+ and ER鈥?/sup> cell lines were not altered by media estrogen conditions. These results suggest the antiproliferative mechanism of glyceollin I stereoisomers may be more complicated than strictly ER interactions.}