Asymmetric Synthesis of Fluoro-MLN4924 as a Selective NEDD8-Activating Enzyme (NAE) Inhibitor

Hong Rae Kim; Dnyandev B. Jarhad; Pramod K. Sahu; Kisu Sung; Dayoung An; Young Eum Hyun; Jinha Yu; Lak Shin Jeong

doi:10.1002/ajoc.201900350

Asymmetric Synthesis of Fluoro-MLN4924 as a Selective NEDD8-Activating Enzyme (NAE) Inhibitor

Hong Rae Kim, Dnyandev B. Jarhad, Pramod K. Sahu, Kisu Sung, Dayoung An, Young Eum Hyun, Jinha Yu, Lak Shin Jeong

Department of Pharmaceutical Sciences

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

2 Scopus citations

Abstract

Based on bioisosteric rationale, fluorinated analogues of MLN4924, which is a selective NEDD8-activating enzyme inhibitor, were designed and their asymmetric syntheses were accomplished via stereoselective reduction, regioselective isopropylidene cleavage and diethylaminosulfur trifluoride (DAST) fluorination as key steps.

Original language	English
Pages (from-to)	1641-1647
Number of pages	7
Journal	Asian Journal of Organic Chemistry
Volume	8
Issue number	9
DOIs	https://doi.org/10.1002/ajoc.201900350
State	Published - 1 Sep 2019

Bibliographical note

Funding Information:
This work was supported by grants from Mid‐career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea.

Funding Information:
This work was supported by grants from Mid-career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea.

Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

Bioisotere
DAST fluorination
Fluoro-MLN4924
MLN4924
NEDD8 inhibitor

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10.1002/ajoc.201900350

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title = "Asymmetric Synthesis of Fluoro-MLN4924 as a Selective NEDD8-Activating Enzyme (NAE) Inhibitor",

abstract = "Based on bioisosteric rationale, fluorinated analogues of MLN4924, which is a selective NEDD8-activating enzyme inhibitor, were designed and their asymmetric syntheses were accomplished via stereoselective reduction, regioselective isopropylidene cleavage and diethylaminosulfur trifluoride (DAST) fluorination as key steps.",

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author = "Kim, {Hong Rae} and Jarhad, {Dnyandev B.} and Sahu, {Pramod K.} and Kisu Sung and Dayoung An and Hyun, {Young Eum} and Jinha Yu and Jeong, {Lak Shin}",

note = "Funding Information: This work was supported by grants from Mid‐career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea. Funding Information: This work was supported by grants from Mid-career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea. Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = sep,

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doi = "10.1002/ajoc.201900350",

language = "English",

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AU - Kim, Hong Rae

AU - Jarhad, Dnyandev B.

AU - Sahu, Pramod K.

AU - Sung, Kisu

AU - An, Dayoung

AU - Hyun, Young Eum

AU - Yu, Jinha

AU - Jeong, Lak Shin

N1 - Funding Information: This work was supported by grants from Mid‐career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea. Funding Information: This work was supported by grants from Mid-career Research Program (2016R1A2B3010164) and the Ministry of Science, ICT & Future Planning (2017M3A9A8032086) of the National Research Foundation (NRF), Korea. Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Based on bioisosteric rationale, fluorinated analogues of MLN4924, which is a selective NEDD8-activating enzyme inhibitor, were designed and their asymmetric syntheses were accomplished via stereoselective reduction, regioselective isopropylidene cleavage and diethylaminosulfur trifluoride (DAST) fluorination as key steps.

AB - Based on bioisosteric rationale, fluorinated analogues of MLN4924, which is a selective NEDD8-activating enzyme inhibitor, were designed and their asymmetric syntheses were accomplished via stereoselective reduction, regioselective isopropylidene cleavage and diethylaminosulfur trifluoride (DAST) fluorination as key steps.

KW - Bioisotere

KW - DAST fluorination

KW - Fluoro-MLN4924

KW - MLN4924

KW - NEDD8 inhibitor

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JO - Asian Journal of Organic Chemistry

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IS - 9

ER -

Asymmetric Synthesis of Fluoro-MLN4924 as a Selective NEDD8-Activating Enzyme (NAE) Inhibitor

Abstract

Bibliographical note

Keywords

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