Ізокумарини. Методи синтезу

Abstract

Розглянуто праці, які стосуються способів одержання похідних ізокумарину та їхніх 3,4-дигідроаналогів. Обговорено синтетичні можливості і практичне застосування різних методів. Ключові слова: ізокумарини, 3,4-дигідроізокумарини, синтез.

The paper reviews methods of isocoumarins and 3,4-dihydroisocoumarins synthesis. These compounds are important class of organic compounds that are widespread in nature and exhibit a wide spectrum of biological activity. Isocoumarins often are synthetic precursors of isoquinoline alkaloids. Analysis of literature data shows that there are several basic approaches to designing of isocoumarins skeleton. The most of them are based on using of homophthalic acid derivatives in various types of condensation reactions. Diene synthesis and different catalytic reactions (transition metal catalysis, organometalic reagents, etc.) are also useful to the isocoumarins rings construction. Condensation of homophthalic acid derivatives, such as esters, nitriles, anhydride, with carbonyl compounds were used in various types of the reactions (e.g. Shtobbe, Claisen, Perkin, types), due to the reactivity of the CH2 group. Carbonyl components in this synthesis were aldehydes, ketones, esters of formic and oxalic acids, aromatic anhydrides. Acylation of homophthalic acid derivatives by the various acyl chloride are general synthetical method of isocoumarins ring constraction. Homophthalic acid are also utilized for the synthesis of 3,4-dyhidroisocoumarins through oxidation to isochromans. Oxidants utilized in this reaction are CrO3, HNO3, O2, dymethyldioxyran (DMD), systems of SeO2/xylene and KMnO4/acetone. In addition, spontaneous or initiated by various reagents cyclizations of 2-carboxybenzyl ketones are convenient method for synthesis of a 3-isocoumarins. Mineral acids, Lewis acids, sodium acetate, LDA in THF are catalysts of in these reactions. If ketogroup was reduced to the hydroxyl, the substituted 3,4-dyhidroisocoumarins may be obtained by the intramolecular etherification. 2-Vinylbenzoic acid under the action of concentrated mineral acids, peroxide compounds or reactions halolactonization gives either γ-lactones or δ-lactones. Formation of different lactones, or its mixtures are determined by steric and electronic factors. Direction of lactonization depends on the center of the lowest electronic density. Using of organometalic reagents and transition metal complexes are a convenient method of synthesis of acyclic isocoumarins precursors. Although organometalic reagents and catalysts are effective in this synthesis, but using of special conditions (low temperature, high purity solvents, etc.) causes some complications. Diels-Alder [4+2]-cycloaddition are convenient method for obtaining of isocoumarin precursors. This reaction is especially often used when it is necessary to reproduce the natural structure of isocoumarins. We also described the utilizing of diazonium salts, obtained from anthranylic acid derivatives in synthesis of isocoumarins. Keywords: isocoumarins, 3,4-dihydroisocoumarins, synthesis.

Рассмотрено работы, касающиеся способов получения производных изокумарина и их 3,4-дигидроаналогов. Обсуждено синтетические возможности и практическое применение различных методов. Ключевые слова: изокумарины, 3,4-дигидроизокумарины, синтез.