48179-00-6Relevant articles and documents
Heck-mediated synthesis and photochemically induced cyclization of [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters and 2-styryl-benzoic acid methyl esters: Total synthesis of naphtho[2,1f]isoquinolines (2-azachrysenes)
Pampín, M. Carme,Estévez, Juan C.,Estévez, Ramón J.,Maestro, Miguel,Castedo, Luis
, p. 7231 - 7243 (2007/10/03)
We describe two new closely related total syntheses of naphtho[2,1-f]isoquinolines. The first synthesis consists of a Heck coupling reaction between trifluoromethanesulfonic acid 2-(2-ethoxycarbonylaminoethyl)phenyl esters and styrenes to give [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters. These compounds cyclize to give (2-phenanthren-1-yl-ethyl)carbamic acid ethyl esters, from which 2-azachrysenes can be obtained in a three-step sequence. The second synthesis includes a new total synthesis of 2-styrylbenzoic acid methyl esters by Heck coupling of methyl o-iodobenzoates to styrenes, followed by the transformation of the resulting benzoic acid derivatives into phenanthrene-1-carboxylic acid methyl esters and then into the target compounds by a six-step sequence including a Bischler-Napieralski cyclization.
Synthesis and physicochemical assessment of novel 2-substituted 3-hydroxypyridin-4-ones, novel iron chelators
Moridani, Majid Y.,Tilbrook, Gary S.,Khodr, Hicham H.,Hider, Robert C.
, p. 349 - 364 (2007/10/03)
Novel 3-hydroxypyridin-4-one containing tridentate ligands were synthesised and their physicochemical properties characterised, including ionisation constants and stoichiometric titration with Fe(III). There is an urgent demand for orally active iron chelators with potential for the treatment of thalassaemia. In principle, tridentate ligands are likely to be more kinetically stable than bidentate molecules, but to date no satisfactory molecules have been identified. Fe(III) stability constants were assessed by competition with the hexadentate ligand EDTA. In all cases no evidence was found for a tridentate mode of iron chelation; instead the ligands behaved as bidentate hydroxypyridinones. As a consequence they provide no advantage over the more simple alkyl hydroxypyridinones.
The Lactonization of 2'-Hydroxyhydrocinnamic Acid Amides: A Potential Prodrug for Amines
Amsberry, Kent L.,Borchardt, Ronald T.
, p. 5867 - 5877 (2007/10/02)
The lactoniaztion of two hydroxy amides - 4-methoxyaniline 3-(2'-hydroxyphenyl)-3,3-dimethylpropionic acid amide (2b) and 4-methoxyaniline 3-(2'-hydroxy-4',6'-dimethylphenyl)-3,3-dimethylpropionic acid amide (3b) - was studied over a pH range of 1-8.Due to the slowness of its reaction, a third hydroxy amide - 4-methoxyaniline 3-(2'-hydroxyphenyl)propionic acid amide (1b) - was investigated only at pH values of 7.5 and 10.The lactonization of 2b and 3b, which was found to be subject to general catalysis by buffer components, was observed to be catalyzed concurrently but not concertedly by both the acidic and basic forms of the buffer.The buffer-independent pH rate profiles for the lactonization of 2b and 3b were found to obey the equation k0 = kH++> + kH2O + kOH-->, indicating that the reaction is also subject to specific catalysis by hydronium and hydroxide ions.A Broenstedt analysis of the rate constants for buffer catalysis gave α and β values of 0.30 +/- 0.02 and 0.54 +/- 0.04, respectively, for 3b.The rate constants for the accelerated lactonization of 1b at 50, 70, and 90 deg C and pH 10 were used to calculate values of 14.7 +/- 0.8 kcal/mol and -9.5 +/- 2.3 eu for the activation parameters, ΔH(excit.) and ΔS(excit.), respectively.Comparison of the observed rates of lactonization at pH 7.5 and 30 deg C for the three hydroxy amides allowed an estimate of the extent of rate enhancement provided by addition of a partial or total "trimethyl lock" for the hydroxy amide lactonization reaction under near physiological conditions.The order of reactivity of the three hydroxy amides was found to be 3b >> 2b > 1b with rate enhancement factors of 2.5E4, 44, and 1, respectively.This study was begun with the objective of generating a hydroxy amide of very high reactivity at physiological pH for development into amine prodrug forms. 3b, which exhibited a half-life of 65 s at pH 7.5, has been chosen for further development as an amine prodrug.
