Difluoromethyleneketone retroamide, a versatile concept of inactivation of proteolytic enzymes

Synthesis of α,α-difluoro-β-amino carbonyl-containing sulfonamides and related compounds

“…4,137.2,134.8,132.1,132.0,129.6,129.1,128.9,128.7,128.5,128.2,128.1,116.5 (dd,J = 262.0,256.8 Hz), 59.7 (dd, J = 28. 8,22.3 Hz); 19 1712,1337,1185,1169,1085,1046,935,921,853,820,756,744,718,704,667,638,552 134.9, 131.9, 129.6, 129.6, 129.1, 128.9, 128.6, 128.1, 128.0, 123.9, 116.4 (dd, J = 262.0, 257. 8, 137.1, 135.0, 133.3, 131.9, 130.4, 130.2, 130.2, 129.4, 129.2, 129.1, 129.0, 127.3, 126.1, 116.5 8,25.8 Hz),142.7,137.1,134.9,132.3,132.0,131.9,130.5,130.4,129.5,129.1,129.0,127.7,126.1,124.4,116 4, 134.8, 134.5, 132.9, 131.9, 129.7, 129.6, 129.1, 129.0, 128.7, 128.3, 127.7, 126.3, 116.3 (dd, J = 262.3, 256. 8 Hz,…”

“…In the past years, the synthesis of polyfunctional fluorinated derivatives possessing keto/hydroxyl/amino groups attracted many research interests [7]. For example, a,a-difluoro carbonyl compounds are known to form relatively stable hydrates, the feature that renders them inhibitors of wide range of the enzymatic cleavage of peptide bonds [8]. Consequently, synthesis of this type of compounds, in particular, b-amino-a,a-difluoro ketone or acid derivatives has received appropriate attention [9].…”

“…214-215 8C. 1 H NMR (400 MHz, d 6 -DMSO) d 9.23 (dd, J = 10.1, 3.8 Hz, 1H), 8.02 (d, J = 7.7 Hz, 2H), 7.80-7.73 (m, 1H), 7.70-7.54 (m, 6H), 7.36 (dd, J = 7.7, 2.6 Hz, 2H), 7.08-6.99 (m, 2H), 5.46-5.29 (m, 1H), 2.22 (s, 3H); 13 C NMR (101 MHz, d 6 -DMSO) d 188.4 (t, J = 27.5 Hz), 142 8,. 137.7, 137.3, 134.9, 131.8, 130.0, 129.7, 129.1, 126.4, 118.3, 116.3 (dd, J = 262.6, 257.2 Hz), 111.2, 59.1 (dd, J = 29.4, 22.4 Hz), 20.8; 19 F NMR (376 MHz, d 6 -DMSO) d À100.8 (d, J = 262.0 Hz, 1F), À111.7 (d, J = 262.0 Hz, 1F).…”

Asymmetric synthesis of long chain α-methyl-β-thiotrifluoromethyl ketones employing the SAMP-/RAMP-hydrazone alkylation methodology

“…7,8 In this context, fluorinated ketones are particularly attractive from a pharmacological point of view as strong inhibitors of a variety of serine hydrolases, including acetylcholinesterase, 9 chymotrypsin, 10 trypsin, 11 juvenile hormone esterase, 12 human liver microsomal carboxylesterases, 13 cytosolic human phospholipase A 2 14 or HIV-1 proteases. 15 The fluorinated ketones function as transition-state analogues of the enzyme, with the inhibition activity arising from the formation of an adduct of tetrahedral geometry between the serine residue, present at the active site of the enzyme, with the highly electrophilic carbonyl moiety. 16,17 We and others have previously shown that linear saturated or unsaturated trifluoromethyl ketones (TFMKs) are good antagonists of the pheromone activity in insects resulting in potential biorational agents for pest control.…”

A facile synthesis of 4-gem-difluoromethylene β-lactam and its derivatives from BrCF2CF2Br

“…Among them, gem-difluoro compounds have been the subject of an important area of research as the CF 2 /CH 2 transposition has been recognized as a valuable tool in the blockage of metabolic processes. Replacement of various functional groups by a gemdifluoromethylene group has generated potent transition-statetype inhibitors [3]. The preparation of gem-difluoromethylene substituted molecules falls broadly into two classes.…”