Natural-Like Spirocyclic Δα,β-Butenolides Obtained from Diazo Homophthalimides

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Natural-Like Spirocyclic Δ^α,β-Butenolides Obtained from Diazo Homophthalimides. / Dar'in, Dmitry; Kantin, Grigory; Chupakhin, Evgeny ; Sharoyko, Vladimir ; Krasavin, Mikhail.

In: Chemistry - A European Journal, Vol. 27, No. 31, 01.06.2021, p. 8221-8227.

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

BibTeX

@article{76e2c9e7acb9480b833fd3b03e54fca9,

title = "Natural-Like Spirocyclic Δα,β-Butenolides Obtained from Diazo Homophthalimides",

abstract = "α-Diazo homophotalimides were reacted with various propiolic acids on Rh2(esp)2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δα,β-spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δα,β-spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δα,β-spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC50 1.49±0.08 μM), by using MALDI-TOF mass-spectrometry it was shown that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.",

keywords = "5-endo-dig cyclization, Michael acceptors, spirobutenolides, synthetic methods, thioredoxin reductase, ASSAY, THIOREDOXIN, IDENTIFICATION, CYCLIZATION",

author = "Dmitry Dar'in and Grigory Kantin and Evgeny Chupakhin and Vladimir Sharoyko and Mikhail Krasavin",

year = "2021",

month = jun,

day = "1",

doi = "10.1002/chem.202100880",

language = "English",

volume = "27",

pages = "8221--8227",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley-Blackwell",

number = "31",

}

RIS

TY - JOUR

T1 - Natural-Like Spirocyclic Δα,β-Butenolides Obtained from Diazo Homophthalimides

AU - Dar'in, Dmitry

AU - Kantin, Grigory

AU - Chupakhin, Evgeny

AU - Sharoyko, Vladimir

AU - Krasavin, Mikhail

PY - 2021/6/1

Y1 - 2021/6/1

N2 - α-Diazo homophotalimides were reacted with various propiolic acids on Rh2(esp)2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δα,β-spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δα,β-spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δα,β-spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC50 1.49±0.08 μM), by using MALDI-TOF mass-spectrometry it was shown that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.

AB - α-Diazo homophotalimides were reacted with various propiolic acids on Rh2(esp)2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δα,β-spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δα,β-spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δα,β-spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC50 1.49±0.08 μM), by using MALDI-TOF mass-spectrometry it was shown that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.

KW - 5-endo-dig cyclization

KW - Michael acceptors

KW - spirobutenolides

KW - synthetic methods

KW - thioredoxin reductase

KW - ASSAY

KW - THIOREDOXIN

KW - IDENTIFICATION

KW - CYCLIZATION

UR - http://www.scopus.com/inward/record.url?scp=85105168360&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c9a53b46-c276-336b-a735-8d1c299baa1a/

U2 - 10.1002/chem.202100880

DO - 10.1002/chem.202100880

M3 - Article

AN - SCOPUS:85105168360

VL - 27

SP - 8221

EP - 8227

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 31

ER -

ID: 76894142