Stereoselective Synthesis and Biological Evaluation of ent‐Asperolide C and its Analogues. Issue 4 (24th January 2018)

• Record Type: Journal Article
• Authors: Xin, Zhengyuan; Song, Yunlong Lu, Zhiqiang; He, Yuchen; Li, Jiabin; Lin, Kejiang; Xue, Xiaowen
• Is Part Of: European journal of organic chemistry. Issue 4(2018)
• Page Start: 477
• Page End: 484
• Publication Date: 2018-01-24
• Subjects: Total synthesis -- Chiral pool -- Natural products -- Epoxidation -- Synthesis design -- Biological activity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201701292
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : A stereoselective synthesis of ent ‐asperolide C and its analogues is described. A chiral‐pool approach was used with a linear sequence of 10 steps, starting from readily available and inexpensive andrographolide. The approach features the construction of a five‐membered lactone skeleton with suitable chiral centres from andrographolide through diastereoselective epoxidation of the exocyclic double bond, and tandem oxidative cleavage of the C‐14=C‐15 double bond and subsequent epoxide ring opening. The stereochemistry of8 was established by X‐ray crystallographic analysis. Four analogues of ent ‐asperolide C were synthesized, and their biological activities were evaluated against A539 and HeLa cell lines. Compound12 was found to show a weak to moderate antiproliferation effect against both cell lines. Abstract : The first synthesis of ent ‐asperolide C and its analogues is described, along with an evaluation of their cytotoxicity. ent ‐Asperolide C was synthesized in 10 steps from the naturally occurring diterpenoid andrographolide, with asymmetric epoxidation of the exocyclic double bond, and tandem oxidative cleavage of the C‐14=C‐15 double bond and subsequent epoxide ring opening as the key steps.