An alternative and efficient synthesis of MLN4924, a selective NEDD8 inhibitor

Hong Rae Kim; Young Eum Hyun; Dnyandev B. Jarhad; Jinha Yu; Lak Shin Jeong

doi:10.1039/c9qo00507b

An alternative and efficient synthesis of MLN4924, a selective NEDD8 inhibitor

Hong Rae Kim, Young Eum Hyun, Dnyandev B. Jarhad, Jinha Yu, Lak Shin Jeong

Department of Pharmaceutical Sciences

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

1 Scopus citations

Abstract

An efficient synthesis of MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trial as an anticancer agent, has been accomplished via regioselective α-alkoxy removal by Al(Hg) and stereoselective reduction based on the conformational study as key steps. The present synthesis was achieved through a versatile cyclopentanone intermediate, which is expected to provide an easy access to structural analogues of MLN4924 for further exploration as a biologically privileged template.

Original language	English
Pages (from-to)	2480-2487
Number of pages	8
Journal	Organic Chemistry Frontiers
Volume	6
Issue number	14
DOIs	https://doi.org/10.1039/c9qo00507b
State	Published - 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.

Publisher Copyright:
© the Partner Organisations 2019.

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abstract = "An efficient synthesis of MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trial as an anticancer agent, has been accomplished via regioselective α-alkoxy removal by Al(Hg) and stereoselective reduction based on the conformational study as key steps. The present synthesis was achieved through a versatile cyclopentanone intermediate, which is expected to provide an easy access to structural analogues of MLN4924 for further exploration as a biologically privileged template.",

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language = "English",

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AU - Hyun, Young Eum

AU - Jarhad, Dnyandev B.

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. Publisher Copyright: © the Partner Organisations 2019.

PY - 2019

Y1 - 2019

N2 - An efficient synthesis of MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trial as an anticancer agent, has been accomplished via regioselective α-alkoxy removal by Al(Hg) and stereoselective reduction based on the conformational study as key steps. The present synthesis was achieved through a versatile cyclopentanone intermediate, which is expected to provide an easy access to structural analogues of MLN4924 for further exploration as a biologically privileged template.

AB - An efficient synthesis of MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trial as an anticancer agent, has been accomplished via regioselective α-alkoxy removal by Al(Hg) and stereoselective reduction based on the conformational study as key steps. The present synthesis was achieved through a versatile cyclopentanone intermediate, which is expected to provide an easy access to structural analogues of MLN4924 for further exploration as a biologically privileged template.

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JO - Organic Chemistry Frontiers

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An alternative and efficient synthesis of MLN4924, a selective NEDD8 inhibitor

Abstract

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