A Direct Synthesis of 2-(ω-Carboxyalkyl)isoflavones from ortho-Hydroxylated Deoxybenzoins

Galyna P. Mrug; Bohdan A. Demydchuk; Svitlana P. Bondarenko; Vitaliy M. Sviripa; Przemyslaw Wyrebek; James L. Mohler; Michael V. Fiandalo; Chunming Liu; Mykhaylo S. Frasinyuk; David S. Watt

doi:10.1002/ejoc.201801171

A Direct Synthesis of 2-(ω-Carboxyalkyl)isoflavones from ortho-Hydroxylated Deoxybenzoins

Galyna P. Mrug, Bohdan A. Demydchuk, Svitlana P. Bondarenko, Vitaliy M. Sviripa, Przemyslaw Wyrebek, James L. Mohler, Michael V. Fiandalo, Chunming Liu, Mykhaylo S. Frasinyuk, David S. Watt

Molecular and Cellular Biochemistry

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

5 Scopus citations

Abstract

As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin-modified isoflavones to identify potential biological targets, and we selected the C-2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base-catalyzed condensation of 2,4-dihydroxy-substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene led to an efficient synthesis of the desired 2-(ω-carboxyalkyl)isoflavones with functional groups at C-5, 6 and 7 and with various substituents in the C-3 phenyl group.

Original language	English
Pages (from-to)	5460-5463
Number of pages	4
Journal	European Journal of Organic Chemistry
Volume	2018
Issue number	39
DOIs	https://doi.org/10.1002/ejoc.201801171
State	Published - Oct 24 2018

Bibliographical note

Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funding

C. L. and D. S. W. were supported from the NIH by CA172379. D. S. W. was also supported by the Office of the Dean of the College of Medicine, by the Center for Pharmaceutical Research and Innovation in the College of Pharmacy, and from the National Institute of General Medical Sciences by NIH grant Number P30 GM110787 to L. Hersh, PI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. D. S. W. was also supported by a subcontract under NIH grant CA205108 to J. Mohler, PI. D. S. W. was also supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program under Department of Defence Award No. W81XWH-16-1-0635. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

Funders	Funder number
Center for Pharmaceutical Research and Innovation in the College of Pharmacy
US Department of Defence/Department of Army	W81XWH-16-1-0635
National Institutes of Health (NIH)	CA172379
U.S. Department of Defense
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	CA205108, P30 GM110787
Office of the Assistant Secretary for Health

Keywords

Cyclic anhydride
Isoflavone
Natural products
Ring-closure

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

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title = "A Direct Synthesis of 2-(ω-Carboxyalkyl)isoflavones from ortho-Hydroxylated Deoxybenzoins",

abstract = "As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin-modified isoflavones to identify potential biological targets, and we selected the C-2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base-catalyzed condensation of 2,4-dihydroxy-substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene led to an efficient synthesis of the desired 2-(ω-carboxyalkyl)isoflavones with functional groups at C-5, 6 and 7 and with various substituents in the C-3 phenyl group.",

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note = "Publisher Copyright: {\textcopyright} 2018 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim",

year = "2018",

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doi = "10.1002/ejoc.201801171",

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AU - Demydchuk, Bohdan A.

AU - Bondarenko, Svitlana P.

AU - Sviripa, Vitaliy M.

AU - Wyrebek, Przemyslaw

AU - Mohler, James L.

AU - Fiandalo, Michael V.

AU - Liu, Chunming

AU - Frasinyuk, Mykhaylo S.

AU - Watt, David S.

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N2 - As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin-modified isoflavones to identify potential biological targets, and we selected the C-2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base-catalyzed condensation of 2,4-dihydroxy-substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene led to an efficient synthesis of the desired 2-(ω-carboxyalkyl)isoflavones with functional groups at C-5, 6 and 7 and with various substituents in the C-3 phenyl group.

AB - As part of a program focused on the development of new antineoplastic agents based on scaffolds found in natural products, we explored the isoflavone family as potential enzyme inhibitors. We required biotin-modified isoflavones to identify potential biological targets, and we selected the C-2 position in isoflavones as an attachment site for an alkyl group bearing a terminal carboxylic acid to which we could attach a biotin derivative. The base-catalyzed condensation of 2,4-dihydroxy-substituted deoxybenzoins with cyclic anhydrides mediated by a combination of triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene led to an efficient synthesis of the desired 2-(ω-carboxyalkyl)isoflavones with functional groups at C-5, 6 and 7 and with various substituents in the C-3 phenyl group.

KW - Cyclic anhydride

KW - Isoflavone

KW - Natural products

KW - Ring-closure

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ER -

A Direct Synthesis of 2-(ω-Carboxyalkyl)isoflavones from ortho-Hydroxylated Deoxybenzoins

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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