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

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

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	1464-1469
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	12
Issue number	9
DOIs	https://doi.org/10.1021/acsmedchemlett.1c00310
Publication status	Published - 2021 Sept 9

Keywords

Total synthesis
absolute structure determination
indole alkaloid
monoamine oxidase (MAO) inhibitory activity
structurally simplified derivatives

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.1c00310

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

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.",

keywords = "Total synthesis, absolute structure determination, indole alkaloid, monoamine oxidase (MAO) inhibitory activity, structurally simplified derivatives",

author = "Yuta Sato and Naoko Oyobe and Takao Ogawa and Sayo Suzuki and Hiroshi Aoyama and Tomonori Nakamura and Hiromichi Fujioka and Satoshi Shuto and Mitsuhiro Arisawa",

note = "Funding Information: This study was partially supported by a Grant-in-Aid from JSPS KAKENHI (Grant No. JP 15KT0063), by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP20am0101084, and by the Cooperative Research Program of “Network Joint Research Center for Materials and Devices” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT). Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = sep,

day = "9",

doi = "10.1021/acsmedchemlett.1c00310",

language = "English",

volume = "12",

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journal = "ACS Medicinal Chemistry Letters",

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T1 - Design, Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives

AU - Sato, Yuta

AU - Oyobe, Naoko

AU - Ogawa, Takao

AU - Suzuki, Sayo

AU - Aoyama, Hiroshi

AU - Nakamura, Tomonori

AU - Fujioka, Hiromichi

AU - Shuto, Satoshi

AU - Arisawa, Mitsuhiro

N1 - Funding Information: This study was partially supported by a Grant-in-Aid from JSPS KAKENHI (Grant No. JP 15KT0063), by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP20am0101084, and by the Cooperative Research Program of “Network Joint Research Center for Materials and Devices” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT). Publisher Copyright: © 2021 American Chemical Society.

PY - 2021/9/9

Y1 - 2021/9/9

N2 - 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.

AB - 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.

KW - Total synthesis

KW - absolute structure determination

KW - indole alkaloid

KW - monoamine oxidase (MAO) inhibitory activity

KW - structurally simplified derivatives

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DO - 10.1021/acsmedchemlett.1c00310

M3 - Article

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SN - 1948-5875

VL - 12

SP - 1464

EP - 1469

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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