Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions - Archive ouverte HAL
Article Dans Une Revue Molecules Année : 2022

Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions

Paraskevi Kokkala
  • Fonction : Auteur
Kostas Voreakos
  • Fonction : Auteur
Angelos Lelis
  • Fonction : Auteur
Konstantinos Patiniotis
  • Fonction : Auteur
Nikolaos Skoulikas
Angeliki Ziotopoulou
  • Fonction : Auteur
Eleni Kaloumenou
  • Fonction : Auteur
Dimitris Georgiadis

Résumé

In this report, a synthetic protocol for the preparation of phosphinic dipeptides of type 5 is presented. These compounds serve as valuable building blocks for the development of highly potent phosphinopeptidic inhibitors of medicinally relevant Zn-metalloproteases and aspartyl proteases. The proposed method is based on the tandem esterification of α-aminophosphinic and acrylic acids under silylating conditions in order to subsequently participate in a P-Michael reaction. The scope of the transformation was investigated by using a diverse set of readily available acrylic acids and (R)-α-aminophosphinic acids, and high yields were achieved in all cases. In most examples reported herein, the isolation of biologically relevant (R,S)-diastereoisomers became possible by simple crystallization from the crude products, thus enhancing the operational simplicity of the proposed method. Finally, functional groups corresponding to acidic or basic natural amino acids are also compatible with the reaction conditions. Based on the above, we expect that the practicality of the proposed protocol will facilitate the discovery of pharmacologically useful bioactive phosphinic peptides.

Domaines

Chimie

Dates et versions

hal-03968454 , version 1 (01-02-2023)

Identifiants

Citer

Paraskevi Kokkala, Kostas Voreakos, Angelos Lelis, Konstantinos Patiniotis, Nikolaos Skoulikas, et al.. Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions. Molecules, 2022, 27 (4), pp.1242. ⟨10.3390/molecules27041242⟩. ⟨hal-03968454⟩
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