A phospine free hydroarylation reaction applied to norbornene derivatives is described for the first time and was exploited for the regioselective gram scale synthesis of AR-148, a known Rac1–Tiam1 PPI inhibitor. Umpolung conversion of the nitro group into free amine allowed the regiocontrol of the key arylation step via a long range effect. The effect of AR-148 in comparison with its enantiomers on Rac1 activation of has been evaluated and (−)AR-148 has been identified as the first enantiomerically pure inhibitor of Rac1–Tiam1 PPI.

Identification of the first enantiopure Rac1–Tiam1 protein–protein interaction inhibitor and its optimized synthesis via phosphine free remote group directed hydroarylation / A. Ruffoni, N. Ferri, A. Pinto, S. Pellegrino, A. Contini, F. Clerici. - In: MEDCHEMCOMM. - ISSN 2040-2503. - 10:2(2019 Feb), pp. 310-314. [10.1039/C8MD00477C]

Identification of the first enantiopure Rac1–Tiam1 protein–protein interaction inhibitor and its optimized synthesis via phosphine free remote group directed hydroarylation

A. Ruffoni
Primo
;
N. Ferri
Secondo
;
A. Pinto;S. Pellegrino;A. Contini
Penultimo
;
F. Clerici
Ultimo
2019-02

Abstract

A phospine free hydroarylation reaction applied to norbornene derivatives is described for the first time and was exploited for the regioselective gram scale synthesis of AR-148, a known Rac1–Tiam1 PPI inhibitor. Umpolung conversion of the nitro group into free amine allowed the regiocontrol of the key arylation step via a long range effect. The effect of AR-148 in comparison with its enantiomers on Rac1 activation of has been evaluated and (−)AR-148 has been identified as the first enantiomerically pure inhibitor of Rac1–Tiam1 PPI.
Settore CHIM/06 - Chimica Organica
26-dic-2018
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/614777
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