Design, Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives

Yuta Sato; Naoko Oyobe; Takao Ogawa; Sayo Suzuki; Hiroshi Aoyama; Tomonori Nakamura; Hiromichi Fujioka; Satoshi Shuto; Mitsuhiro Arisawa

doi:10.1021/acsmedchemlett.1c00310

Design, Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives

ACS Med Chem Lett. 2021 Aug 24;12(9):1464-1469. doi: 10.1021/acsmedchemlett.1c00310. eCollection 2021 Sep 9.

Authors

Yuta Sato¹, Naoko Oyobe¹, Takao Ogawa², Sayo Suzuki³, Hiroshi Aoyama¹, Tomonori Nakamura³, Hiromichi Fujioka¹, Satoshi Shuto², Mitsuhiro Arisawa^{1

2}

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
² Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0808, Japan.
³ Graduate School of Pharmaceutical Sciences, Keio University, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, Japan.

Abstract

The absolute structure of an indole alkaloid (+)-cinchonaminone by total synthesis of both (+)-cinchonaminone and its enantiomer was determined. The main focus of the study was the enantioselective synthesis of both enantiomers of a chiral cis-3,4-disubstituted piperidine. We also evaluated monoamine oxidase (MAO) inhibitory activities of these enantiomers. Furthermore, its structurally simplified derivatives were synthesized that did not have any chiral center. Two of these derivatives showed stronger MAO inhibitory activities than that of (+)-cinchonaminone.