ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Facile preparation and preliminary cytotoxicity evaluation of dehydroepiandrosterone C-16 spiro-pyrrolidine derivatives

Hong-Wen Tao, Wen-Yu Peng, Jiang-Chun Yuan, Qiang Li, Lu-Yao Zeng, Xian-Yong Yu, and Ping-Gui Yi

Key Laboratory of Theoretical Organic Chemistry and Functional Molecules, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, People’s Republic of China

E-mail: hongwtao@hnust.edu.cn

Received: 7 January 2020  Accepted: 9 September 2020

Abstract:

A facile synthesis of dehydroepiandrosterones derived by C-16 spiro-pyrrolidine and their cytotoxic evaluation are reported. Seven derivatives, 3a–3g, were prepared by the [3 + 2] cycloaddition reaction of the 16-arylidene dehydroepiandrosterone and the azomethine ylide, where the azomethine ylide was generated in situ from 11H-indeno[1,2-b]quinoxalin-11-one and sarcosine. Their cytotoxicity was evaluated on brine shrimp assay and the bioactivities represented by LC₅₀ values were found in the range of 6.19–27.2 µg/mL. Among them, the activities of 3d and 3g are the best, as manifested by LC₅₀ values less than 10 µg/mL. All products were confirmed by NMR, HR MS and X-ray analysis.

Graphic abstract

Keywords: [3 + 2] cycloaddition; Dehydroepiandrosterone; Steroidal spiro-pyrrolidine; Azomethine ylide

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01346-4

Chemical Papers 75 (2) 823–829 (2021)