73053-80-2Relevant academic research and scientific papers
Active-Site-Directed Inhibition of &α-Chymotrypsin by Deaminatively Produced Carbonium Ions: An Example of Suicide or Enzyme-Activated-Substrate Inhibition
White, Emil H.,Jelinski, Lynn W.,Politzer, Ieva R.,Branchini, Bruce R.,Roswell, David F.
, p. 4231 - 4239 (2007/10/02)
N-Nitroso amides derived from phenylalanine and alanine were utilized as inhibitors of α-chymotrypsin.During the enzyme-catalyzed hydrolysis of these substrates, carbonium ions capable of alkylating nucleophilic groups are released in the active site.Nitroso lactams were also tested as substrates since they produce carbonium ions while still tethered to the enzyme at the acyl-enzyme stage.Kinetic studies indicated that at substrate/α-chymotrypsin ratios of 40:1 the acyclic substrates caused the following percent inhibition of α-chymotrypsin activity (substrate, percent inhibition): D-1a, 100; L-1a, 9; D-1c, 100; L-1c, 9.Nitroso lactams 2 and 3, in substrate/enzyme ratios of 54:1 and 20:1, respectively, caused 91 and 97percent inhibition of α-chymotrypsin activity.At low (6:1) substrate/enzyme ratios, the inhibition of nitroso lactam 3 was partially reversible.The extents of inhibition were decreased by the competitive inhibitor N-acetyl-L-tryptophan, indicating that the inhibitor substrates were acting at the active site.Radioactive analogues of D- and L-1a and of 3(14C) provided evidence that the inhibition was irreversible, since ca. 1.0 mol of the benzyl group of D-1a and ca. 1.6 mol of the aryl moiety in the case of 3 remained bound to the inhibited enzyme after dialysis or Sephadex G-25 chromatography (no alkylation occurred with L-1a).The enzymatic hydrolyses of the L isomers of phenylalanine substrates (1a,b) were faster than those of the D enantiomers, whereas in the alanine series (1c) the rate ratio was reversed.A model based on "reverse" binding of the two aromatic groups of substrates D-1a and D-1c in the enzyme active site is proposed to explain the hydrolysis rate and the preferential inhibition of α-chymotrypsin by the D antipodes.
Synthesis of Heterocycles via Lactones: Part VI Condensation of Bromo Esters with β-Phenethylamines, a New Route to Berbines: Synthesis of (+/-)-Xylopinine, (+/-)-Scoulerine, Isocoptisine and Pseudoepitetrahydroberberine
Pandey, G. D.,Tiwari, K. P.
, p. 272 - 275 (2007/10/02)
A new route involving the generation of a tricyclic lactam intermediate in one-step has been developed for the synthesis of 2,3,10,11-tetraoxygenated berbine alkaloids.Three such alkaloids have been synthesized besides scoulerine which is 2,9-dihydroxy-3,10-dimethoxyberbine (11).
Electrochemical Oxidation of Aromatic Ethers. Part 6. Oxidation of 4-(3,4-Dimethoxybenzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline and Attempted Synthesis of 4-(3,4-Dimethoxybenzyl)-6,7-dimethoxy-2-methyl-1,4-dihydro-3(2H)-isoquinoline
Carmody, Maurice P.,Sainsbury, Malcolm,Newton, Roger F.
, p. 2013 - 2020 (2007/10/02)
The cyclisation of 3-(2,4-dimethoxybenzyl)-2-(2-hydroxymethyl-4,5-dimethoxyphenyl)-N-methylpropionamide (5) and related compounds does not yield 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-methyl-1,4-dihydro-3(2H)-isoquinolone, but gives instead dibenzocycloheptane derivatives.Anodic oxidation of 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline affords the corresponding 3,4-dihydroisoquinolinium and 4-(3,4-dimethoxybenzylidene)-6,7-dimethoxy-2-methyl-1,4-dihydroisoquinolinium salts.No intramolecularly aryl-aryl coupled products are isolated and the implication of this result on the design of substrates for the synthesis of biphenyl derivatives is discussed.
