Synthesis and Characterization of new 2-substituted Isoindoline Derivatives of #alpha#-Amino Acids

摘要

Some isoindolines are important intermediates for the syntheses of novel multidrug resistance reversal agents;~1 they have also shown antiinflammatory~(2-4) and diuretic activity.~(5-6) They have been used for treating coronary vessel diseases~(7-8) and evaluated as alpha-adrenergic and adrenergic neuron blocking agents.~9 2-Substituted isoindolines have been prepared by a ) alkylation of isoindoline,~(3,4,7) b) alkylation and reduction of phthalimides~(7,8,10) and c) cyclocondensation of #alpha#,#alpha#'-dibromo-o-xylene with primary amines.~(1,2,7,11,12) To our knowledge, there are no reports concerning the synthesis of 2-substituted isoindoline derivatives of #alpha#-amino acids, which could have important biological properties and be used as ligands to obtain organometallic compounds with antitumor properties.~(13) Our current interest in 2-substituted isoindoline 4 derivatives of #alpha#-aminoacids prompted us to develop an easy methodology to obtain them from #alpha#-amino acid methyl ester hydrochlorides 2 and #alpha#,#alpha#'-dibromo-o-xylene. This paper describes the synthesis and characterization by spectroscopic methods of six new 2-substituted isoindolines 4a-f. The structure of compound 4b was further established by a single-crystal X-ray diffraction study.