New antitumour agents with α,β-unsaturated δ-lactone scaffold: Synthesis and antiproliferative activity of (-)-cleistenolide and analogues

被引：20

作者：

Benedekovic, Goran ^{[1
]}

Kovacevic, Ivana ^{[1
]}

Popsavin, Mirjana ^{[1
]}

Francuz, Jovana ^{[1
]}

Kojic, Vesna ^{[2
]}

Bogdanovic, Gordana ^{[2
]}

Popsavin, Velimir ^{[1
]}

机构：

[1] Univ Novi Sad, Dept Chem Biochem & Environm Protect, Fac Sci, Trg Dositeja Obradovica 3, Novi Sad 21000, Serbia

[2] Oncol Inst Vojvodina, Put Dr Goldmana 4, Sremska Kamenica 21204, Serbia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 14期

关键词：

Cleistenolide; Cleistenolide mimics; Antitumour delta-lactones; SAR; Analogue synthesis; STEREOSELECTIVE TOTAL-SYNTHESIS; CLEISTOCHLAMYS-KIRKII; MONOACETONE-GLUCOSE; EMMONS OLEFINATION; UNSATURATED ESTERS; STYRYL-LACTONES; DERIVATIVES; CONSTITUENTS; ETHERS;

D O I：

10.1016/j.bmcl.2016.05.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A stereoselective total synthesis of (-)-cleistenolide (1) from D-glucose has been achieved. This new approach for the synthesis of (-)-cleistenolide and analogues involves a one-C-atom degradation of the chiral precursor, (Z)-selective Wittig olefination, followed by the final delta-lactonisation. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially 2,4,6-trichlorobenzoyl derivative 12, which in the culture of MDA-MB 231 cells displayed the highest activity (IC50 0.02 mu M) of all compounds under evaluation. A preliminary SAR study reveals the structural features that are beneficial for antiproliferative activity of synthesized delta-lactones, such as presence of either electron-withdrawing or electron-donating substituents in the aromatic ring, as well as the presence of cinnamoyl functionality instead of benzoyl group at the O-7 position. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：3318 / 3321

页数：4

共 34 条

[1] Total Synthesis of (-)-Cleistenolide [J].