Synthesis of m-carborane-C-carboxylic acid hexahydrobenzo[a]acridine esters

Abstract

The possibility was demonstrated of selective preparation of m-carborane-C-carboxylic acid hexahydrobenzo[a]acridine esters both by the reaction of 1,3-diketones with azomethines obtained by condensation of m-carborane-C-carboxylic acid vanillin and vanillal esters with 1-or 2-naphthylamine and by the cascade heterocyclization of 1-or 2-naphthylamine, m-carborane-C-carboxylic acid vanillin and vanillal esters, and CHacids.Derivatives of carborane polyhedral claster systems are of interest for pharmacokinetic studies in the field of boron neutron capture therapy of tumors, radionuclides diagnostics and therapy [1,2]. We formerly reported on the synthesis of esters of o-and m-carborane-C-carboxylic acid with a series of naturally occurring hydroxycontaining compounds [3,4].The target of this study was the preparation of new hexahydrobenzo[a]acridine esters of m-carborane-Ccarboxylic acid for their further investigation and screening as antitumor pharmaceuticals.The cascade heterocyclization (cyclocondensation) involving aromatic aldehydes, amine, and cyclic β-diketones is a convenient method of synthesis of derivatives of benzo[a]acridine, 4,7-pnenanthroline, and other fused azaheterocycles [5][6][7]]. Yet no published information exists on the condensation with diketones of azomethines obtained from m-carborane-C-carboxylic acid vanillin and vanillal esters with 1-or 2-naphthylamines. Analogs of compounds of the hexahydrobenzo[f]quinoline series obtained by this condensation and containing as the main structural fragment a partially or completely hydrogenated phenanthrene or quinoline frameworks are extensively studied due to the carcinogenic, teratogenic, and mutagenic properties of the polycyclic aromatic hydrocarbons [8,9].In this study the reaction was investigated between the azomethines obtained from m-carborane-C-carboxylic acid vanillin and vanillal esters I and II with 1-or 2-naphthylamines and 1,3-diketones. The feasibility of the application in this reaction as an aldehyde component of compounds I and II is due to the following reasons: the natural plant phenols (vanillin and vanillal) are convenient synthons for building up biologically active compound and for purposeful incorporating them into pharmacophoric fragments [10][11][12][13], the ester fragment of the m-carborane-C-carboxylic acid also provides a possibility of a successful synthesis of high-molecular polycyclic compounds containing diverse functional groups [14,15].Schiff bases III-VI were prepared by the standard procedure: boiling of equimolar amounts of m-carborane-C-carboxylic acid vanillin and vanillal esters with 1-or 2-naphthylamines in the methanol solution [16].Azomethines III-VI were brought into the reaction with CH-acids [1,3-cyclohexanedione and 5,5-dimethyl-1,3-cyclohexanedione (dimedone)] obtaining as a result the corresponding m-carborane-C-carboxylic acid 4-(10,10-di-R 2 -8- oxo-7,8,9,10,11,12-hexahydrobenzo[c]acridin-7-yl)-2-R 1 -phenyl esters VII, IX, XI, XII and 4-(9,9-di-R 2 -11-oxo-7,8,9,10,11,12-hexahydrobenzo[a]-acri...