104239-20-5

Upstream product

• 104239-15-8 4-Oxo-3-(3-phenyl-propyl)-tetrahydro-thiophene-3-carbonitrile 
• 1823-14-9 5-phenyl-1-pentyne 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 16563-14-7 4-oxotetrahydrothiophene-3-carbonitrile 
• 637-59-2 1-Bromo-3-phenylpropane 

Relevant academic research and scientific papers

Metallo-β-lactamase inhibitors by bioisosteric replacement: Preparation, activity and binding

Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent scaffolds reported as MBL inhibitors. In this study, the carboxylate group of mercaptocarboxylic acids was replaced with bioisosteric groups like phosphonate esters, phosphonic acids and NH-tetrazoles. The influence of the replacement on the bioactivity and inhibitor binding was evaluated. A series of bioisosteres of previously reported inhibitors was synthesized and evaluated against the MBLs VIM-2, NDM-1 and GIM-1. The most active inhibitors combined a mercapto group and a phosphonate ester or acid, with two/three carbon chains connecting a phenyl group. Surprisingly, also compounds containing thioacetate groups instead of thiols showed low IC50 values. High-resolution crystal structures of three inhibitors in complex with VIM-2 revealed hydrophobic interactions for the diethyl groups in the phosphonate ester (inhibitor 2b), the mercapto bridging the two active site zinc ions, and tight stacking of the benzene ring to the inhibitor between Phe62, Tyr67, Arg228 and His263. The inhibitors show reduced enzyme activity in Escherichia coli cells harboring MBL. The obtained results will be useful for further structural guided design of MBL inhibitors.

PROCESS FOR HYDROCYANATION OF TERMINAL ALKYNES

The present invention refers to a process for a Rh-catalyzed Anti-Markovnikov hydrocyanation of terminal alkynes which process discloses, for the first time, the highly stereo- and regio-selective hydrocyanation of terminal alkynes to furnish E- configured alkenyl nitriles and the catalyst used in the present process.

Rh-Catalyzed Anti-Markovnikov Hydrocyanation of Terminal Alkynes

We report the first highly stereo- and regioselective hydrocyanation of terminal alkynes to furnish E-configured alkenyl nitriles. Acrylonitriles can be accessed on gram scale with broad substrate scope and functional group tolerance. The hydrocyanation reaction employs acetone cyanohydrin as a practical alternative to HCN gas.

A New Simple Synthesis of α-Substituted Acrylonitriles

An efficient preparation of α-substituted acrylonitriles 6 based on the utilization of 4-cyano-3-ketothiolane enolate anion (3) as a synthetic equivalent to α-acrylonitrile anion (1) is described.