Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Concise Total Synthesis of (+)-Zeylenone with Antitumor Activity and Structure-Activity Relationship of Its Derivatives

Zhonghao Sun
* ,
Shuxian Yang
ORCID logo ,
Chengfang Xu
,
Guoxu Ma
,
Li Cao
,
Yu Tian
,
Jiahao Lin
* ORCID logo ,
Xudong Xu
*
Version 1 : Received: 19 April 2019 / Approved: 24 April 2019 / Online: 24 April 2019 (05:29:48 CEST)

A peer-reviewed article of this Preprint also exists.

Sun, Z.; Yang, S.; Xu, C.; Yi, F.; Cao, L.; Tian, Y.; Lin, J.; Xu, X. Concise Total Synthesis of (+)-Zeylenone with Antitumor Activity and the Structure–Activity Relationship of Its Derivatives. Bioorganic Chemistry 2021, 116, 105333, doi:10.1016/j.bioorg.2021.105333. Sun, Z.; Yang, S.; Xu, C.; Yi, F.; Cao, L.; Tian, Y.; Lin, J.; Xu, X. Concise Total Synthesis of (+)-Zeylenone with Antitumor Activity and the Structure–Activity Relationship of Its Derivatives. Bioorganic Chemistry 2021, 116, 105333, doi:10.1016/j.bioorg.2021.105333.

Abstract

(-)-Zeylenone is a promising cytotoxic agent，which is a natural product isolated from Uvaria grandiflora Roxb. Though substantial antitumor mechanism has been researched , little has focused on its enantiomer (+)-Zeylenone.This article will try to find a gram scale synthesis method of (+)-Zeylenone and explain the structure-activity relationship of this kind of compound. Total synthesis of (+)-zeylenone was completed in 13 steps with quinic acid as starting material in 8.8% overall yield. The highlight of the route was the control of the three carbon’s chirality by clever use of single step dihydroxylation under the direction of the key C-3 chirality. In addition, zeylenone derivatives were designed and synthesized and their antitumor activity were evaluated against three human cancer cell lines using the CCK8 assay. Structure-activity relationship suggested compounds with both two absolute configurations exhibited good activity. Besides, hydroxyls at C-1/2 position were crucial for the activity and esterification of C-1 hydroxyl with large groups made the activity disappeared. Hydroxyl at C-3 position was also important as proper ester substituent could increase the potency.

Keywords

total synthesis; antitumor activity; structure-activity relationship

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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