US EPA

7487073 

Journal Article 

Photoredox Alkenylation of Carboxylic Acids and Peptides: Synthesis of Covalent Enzyme Inhibitors 

Kammer, LM; Lipp, B; Opatz, T 

2019 

Yes 

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 

American Chemical Society 

84 

5 

2379-2392 

English 

30571115 

10.1021/acs.joc.8b02759 

The synthesis of vinyl sulfones and (α,β-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777. Copyright © 2018 American Chemical Society. 

Carboxylation; Scaffolds; Covalent enzyme; Different class; Natural products; Oxidative decarboxylation; Protease inhibitor; Rapid construction; Three-step synthesis; Vinyl sulfones; Carboxylic acids; 2 [2 [[[(9h fluoren 9 yl)methoxy]carbonyl]amino] 3 phenylpropanamido] 4 phenylbutanoic acid; 4 methyl n [5 methyl 1 (phenylsulfonyl)hex 1 en 3 yl]benzenesulfonamide; 4 [2 (phenylsulfonyl)ethenyl]tetrahydro 2h pyran; 9,10 dicyanoanthracene; 9h fluoren 9 ylmethyl [1 (4 bromphenyl) 4 (phenylsulfonyl)but 3 en 2 yl]carbamate; 9h fluoren 9 ylmethyl [1 [[4 methyl 1 (phenylsulfonyl)pent 1 en 3 yl]amino] 1 oxopropan 2 yl]carbamate; 9h fluoren 9 ylmethyl [4 hydroxy 1 (phenylsulfonyl)but 1 en 3 yl]carbamate; 9h fluoren 9 ylmethyl [4 hydroxy 1 (phenylsulfonyl)pent 1 en 3 yl]carbamate; 9h fluoren 9 ylmethyl [4 methyl 1 (phenylsulfonyl)pent 1 en 3yl]carbamate; 9h fluoren 9 ylmethyl [5 methyl 1 (phenylsulfonyl)hex 1 en 3 yl]carbamate; acrylonitrile; anthracene derivative; benzyl (4 cyano 1 phenylbut 3 en 2 yl)carbamate; benzyl 2 [(tert butoxycarbonyl)amino] 5 (phenylsulfonyl)pent 4 enoate; benzyl [1 oxo 3 phenyl 1 [[5 phenyl 1 (phenylsulfonyl) pent 1 en 3 yl]amino]propan 2 yl]carbamate; benzyl [4 phenyl 1 (phenylsulfonyl)but 3 en 2 yl]carbamate; benzyl [4 phenyl 1 (phenylsulfonyl)prop 1 en 2 yl]carbamate; biphenyl; carboxylic acid derivative; cysteine proteinase inhibitor; hex 1 en 1 yl phenylsulfone; k 11777; sulfone derivative; tert butyl 3[(tert butoxycarbonyl)amino] 5 (phenylsulfonyl)pent 4 enoate; tert butyl 4 hydroxy 2[2 (phenylsulfonyl)ethenyl]pyrrolidine 1 carboxylate; tert butyl 4 [2 (phenylsulfonyl)ethenyl]piperidine 1 carboxylate; tert butyl [1 phenyl 4 (phenylsulfonyl)but 3 en 2 yl]carbamate; tert butyl [2 [(tert butoxycarbonyl)amino] 4 (phenylsulfonyl)but 3 en 1 yl] 1h imidazole 1 carboxylate; tert butyl [4 dimethyl 1(phenylslfonyl)pent 1 en 3 yl]carbamate; unclassified drug; unindexed drug; vinyl derivative; Article; catalyst; controlled study; covalent bond; decarboxylation; drug synthesis; electron transport; electrophilicity; enzyme inhibition; hydrogenation; Michael addition; oxidation reduction potential; protonation; reaction analysis