Igor Gaon

Farnesyl and geranylgeranyl pyrophosphate analogs incorporating benzoylbenzyl ethers: Synthesis and inhibition of yeast protein farnesyltransferase

The syntheses of two photoactive analogs (1a and 1b) of farnesyl pyrophosphate that incorporate stable ether-linked benzophenones are described. Compounds 1a and 1b were prepared from geraniol in 17% overall yield. Both 1a and 1b are competitive inhibitors of yeast protein famesyltransferase with respect to farnesyl pyrophosphate and have K1 values of 45 nM and 49 nM. Upon photolysis for twelve hours, 1a and 1b both inactivate the enzyme by 40%

Electrochemical synthesis of heterocyclic compounds. XV: Anodic synthesis of s-triazolo[4,3-a]pyridine derivatives

Synthese des composes du titre, par oxydation de pyridyl-2 hydrazones de benzaldehydes substitues

Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

Abstract The syntheses of two photoactive prenyl pyrophosphate analogs (1a and 1b) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C5) unit between the pyrophosphate and benzophenone functionalities while 1b contains a geranyl (C10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have KI values of 6000 nM and 700 nM. Upon irradiation, [32P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.

Analogs of farnesyl pyrophosphate incorporating internal benzoylbenzoate esters: Synthesis, inhibition kinetics and photoinactivation of yeast protein farnesyltransferase

The syntheses of two analogs (1a and 1b) of farnesyl pyrophosphate incorporating photoactive benzoylbenzoate esters are described. Both 1a and 1b are competitive inhibitors of yeast protein farnesyltransferase with respect to farnesyl pyrophosphate and have Ki values of 3300 nM and 880 nM, respectively. Upon photolysis for two hours, 1a and 1b inactivate the enzyme by 46% and 11%, respectively. These compounds should be useful for a variety of studies of protein prenyltransferases.

A high current density electrosynthesis of amines from nitro compounds using metal powders as intermediates

Etude de la reduction du nitrobenzenes en presence de poudres metalliques (Cu, Fe, Sn, Zn) dans une solution aqueuse acide. Formation des amines correspondantes

Synthesis and rapid purification of 32P-labeled photoactive analogs of farnesyl pyrophosphate

To study the binding sites of protein prenyltransferases, we have synthesized photoaffinity labeling analogs that contain photoactive benzophenone units. Here we describe the syntheses and a method for the rapid purification of two 32P-labeled analogs; phosphorylation was accomplished by reacting the corresponding alcohols with CCl3CN and [32P]-H3PO4 in CH3CN and the purification was performed using C18 reversed-phase cartridges. Analog [32P]-3a was prepared from 2.4 mg of starting alcohol 4a and was obtained in 3.3% yield, 50% radiochemical purity and 480 Ci/mol specific activity. Further purification by preparative thin layer chromatography yielded material with a radiochemical purity of 90%. A second analog, [32P]-3b, was prepared from 1.2 mg of alcohol 4b and was obtained in 1.0% yield, 54% radiochemical purity and 700 Ci/mol specific activity. Further purification by preparative thin layer chromatography yielded material with a radiochemical purity of 91%.

Anodic oxidation of substituted [4-hydroxy-3-coumarinyl]-phenylthiomethanes in acetonitrile. Evidence for a cationic intermediate in carbon–sulfur bond fragmentation

Abstract The anodic oxidation of substituted [4-hydroxy-3-coumarinyl]-phenylthiomethanes, 1a–1c, in acetonitrile is shown to correspond to a one electron process. The radical cation produced undergoes carbon–sulfur bond fragmentation through loss of a phenylthio radical to give a cation which is trapped by Ritter reaction with acetonitrile to yield the final products 2a–2c in 64–82% yield. In the case of geranyl [4-hydroxy-3-coumarinyl]-phenylthiomethane, 1d, the intermediate allylic cation is attacked intramolecularly by a hydroxy nucleophile followed by loss of a proton, to give 2d in 40% yield.