3709-21-5Relevant articles and documents
Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions
Kokkala, Paraskevi,Voreakos, Kostas,Lelis, Angelos,Patiniotis, Konstantinos,Skoulikas, Nikolaos,Devel, Laurent,Ziotopoulou, Angeliki,Kaloumenou, Eleni,Georgiadis, Dimitris
, (2022/02/21)
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.
Discovery of Oxygen α-Nucleophilic Addition to α,β-Unsaturated Amides Catalyzed by Redox-Neutral Organic Photoreductant
Luan, Zi-Hong,Qu, Jian-Ping,Kang, Yan-Biao
, p. 20942 - 20947 (2020/12/22)
The conjugate additions of oxygen-centered nucleophiles to conjugate acceptors are among the most powerful C-O bond formation reactions. The conjugate addition normally takes place at the β-position carbon to the electron-withdrawing group, resulting in the formation of a stabilized carbanion intermediate that can be quenched by proton or electrophiles to form the β-addition (i.e., hetero-Michael addition) products. On the contrary, the formation of α-hydroxyl or alkoxyl amides through conjugate addition needs an α,β-inverse addition. Nevertheless, a regio-inversed nucleophilic α-addition of oxygen-centered nucleophiles to α,β-unsaturated carbonyl compounds still remains less explored because of the electronic mismatch. In this research, we discovered the first α-specific nucleophilic addition of α,β-unsaturated amides with oxygen and fluoride nucleophiles. This region-inversed nucleophilic addition is enabled by the catalysis of a novel redox-neutral nondonor-acceptor organic photoreductant (CBZ6). As low as 0.5 mol % of visible light photoreductant was employed. The mechanistic insights were also explored. The oxidative potential of the excited state of CBZ6 is obtained in -1.92 V (vs SCE), presenting a stronger reductive potential than representative metal-cored or organic photoredox catalysts. This feature enabled the umpolung of α,β-unsaturated amides to take place α-nucleophilic addition other than the normal β-addition.
α-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases
Orrling, Kristina M.,Marzahn, Melissa R.,Gutierrez-de-Teran, Hugo,Aqvist, Johan,Dunn, Ben M.,Larhed, Mats
experimental part, p. 5933 - 5949 (2009/12/24)
The impact of moving the P1 side-chain from the β-position to the α-position in norstatine-containing plasmepsin inhibitors was investigated, generating two new classes of tertiary alcohol-comprising α-benzylnorstatines and α-phenylnorstatines. Twelve α-s
