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Efficient green synthesis of the targeted proteolysis system component

Maria A. Zakharova 1
Maria A. Zakharova
, 
Mikhail Vasil'evich Chudinov 1
Mikhail Vasil'evich Chudinov
, 
Maxim E. Zhuravlev 1
Maxim E. Zhuravlev
, 
Alexei Yur'evich Lukin 1
Alexei Yur'evich Lukin
10.71267/mencom.7928
Published 2026-03-24
Communication , Volume 36, Issue 3, 295-297
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Zakharova M. A. et al. Efficient green synthesis of the targeted proteolysis system component // Mendeleev Communications. 2026. Vol. 36. No. 3. pp. 295-297.
GOST all authors (up to 50) Copy
Zakharova M. A., Chudinov M. V., Zhuravlev M. E., Lukin A. Y. Efficient green synthesis of the targeted proteolysis system component // Mendeleev Communications. 2026. Vol. 36. No. 3. pp. 295-297.
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TY - JOUR
DO - 10.71267/mencom.7928
UR - https://mendcomm.colab.ws/publications/10.71267/mencom.7928
TI - Efficient green synthesis of the targeted proteolysis system component
T2 - Mendeleev Communications
AU - Zakharova, Maria A.
AU - Chudinov, Mikhail Vasil'evich
AU - Zhuravlev, Maxim E.
AU - Lukin, Alexei Yur'evich
PY - 2026
DA - 2026/03/24
PB - Mendeleev Communications
SP - 295-297
IS - 3
VL - 36
ER -
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@article{2026_Zakharova,
author = {Maria A. Zakharova and Mikhail Vasil'evich Chudinov and Maxim E. Zhuravlev and Alexei Yur'evich Lukin},
title = {Efficient green synthesis of the targeted proteolysis system component},
journal = {Mendeleev Communications},
year = {2026},
volume = {36},
publisher = {Mendeleev Communications},
month = {Mar},
url = {https://mendcomm.colab.ws/publications/10.71267/mencom.7928},
number = {3},
pages = {295--297},
doi = {10.71267/mencom.7928}
}
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Zakharova, Maria A., et al. “Efficient green synthesis of the targeted proteolysis system component.” Mendeleev Communications, vol. 36, no. 3, Mar. 2026, pp. 295-297. https://mendcomm.colab.ws/publications/10.71267/mencom.7928.
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Keywords

Cereblon
diazonium salt
Green chemistry
Heck--Matsuda reaction
proteolysis-targeting chimera

Abstract

This study presents an efficient, scalable, and green synthetic route for cereblon ligase modulator used in proteolysis-targeting chimera (PROTAC) technology. The one-pot Heck–Matsuda reaction of the special diazonium salt with tert-butyl acrylate is accompanied by the elimination of the tert-butyl ester group and affords (2E)-3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]acrylic acid in high yield and high stereoselectivity. The resulting alkyl-linked ligand demonstrates applicability in PROTAC design, offering a safe, cost-effective, and industrially adaptable pathway for producing key PROTAC component.

Funders

Russian Science Foundation
075-15-2025-548
Ministry of Education and Science of the Russian Federation
FSFZ-2026-0007

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