Preparation and reactions of isoflavone heteroanalogs (a review)

Abstract

Methods for preparation of 3-hetarylchromones, which are isoflavone heteroanalogs, and the reactions of these compounds with either preservation or opening of the pyrone ring are reviewedThe 4H-[1]-benzo-4-pyranone (chromone) system is the basis of the chemical structure of a large group of biologically active natural products known as flavonoids and isoflavonoids. Replacement of the aryl residue in isoflavonoids by hetaryl residue leads to compounds having a broad range of biological activity arising from the combination of chromone and heterocyclic residues in a single molecule. Thus, 3-hetarylchromones, which have been termed isoflavonoid heteroanalogs, display strong antiallergenic [I-12], anticholesterol [13, 14], hypolipedimic [15, 16], antimicrobial [17, 18], anti-inflammatory [19], fungicidal [18], and antiblastic activity [20, 21] and are central nervous system stimulators [19,[22][23][24][25]. METHODS OF SYNTHESIS OF 3-HETARYLCHROMONESTwo major approaches have been developed for the synthesis of hetarylchromones. The first approach involves construction of the chromone system from substituted {x-hetaryl-2-hydroxyacetophenones, often using reagents such as ethoxalyl chloride, orthoformic ester, and acid anhydrides. The second method entails addition of the heterocycle to the prepared chromone system.The two approaches are examined in detail. Methods for the preparation of some starting substituted a-hetarylacetophenones are also given in Section 1.1. Examples of the synthesis of chromones containing completely or partially hydrogenated heterocyclic substituents are given in Section 1.2 (in light of their potential ability for conversion into 3-hetarylchromones by means of aromatization). Preparation of 3-hetaryichromones by construction of the chromone systemThienyl derivatives I--III have been obtained by cyclization of a-(2-thienyl)-2,4,6-trihydroxyacetophenone using ethoxalyl chloride [26]:Taras Shevchenko Kiev University, 252033 Kiev, Ukraine.

Cyclic Carboxylic Anhydrides as New Reagents for Formation of Chromone Ring

“…The nature of heterocyclic substituent in position 3 of chromone ring places some limitations on the use of standard methods for the synthesis of isoflavones, whereas other procedures are applicable only for synthesis of 3‐heteroarylchromones. Although ethyl oxalyl chloride reacts normally with 2,4‐dihydroxy‐α‐heteroarylacetophenones in pyridine , the use of ethoxycarbonylalkylcarbonyl chlorides was not previously reported. From this point of view, the development of facile method for the synthesis of 2‐carboxyalkyl‐3‐heteroarylchromones is of current importance for biological screening and is the subject of this report.…”

“…Isoflavone derivatives are useful intermediates for the synthesis of various 2‐hydroxyphenyl substituted pyrazoles , pyrimidines , pyrazolo[1,5‐ a ]pyrimidines , and isoxazoles , which can be obtained by cleavage of chromone ring with binucleophiles. These compounds are interesting targets because of their biological activity.…”

2-[6-Alkyl-3-hetaryl-4-oxo-9,10-dihydro-4H,8H-chromeno-[8,7-e][1,3]oxazin-9-yl]acetic acids

“…The 1 H, 13 (10a,b,11-14). A solution of glycine (0.3 g, 4 mmol) in water (5 ml) and 37% formalin solution (3 ml) were added to a solution of 2-R 1 -6-alkyl-3-hetaryl-7-hydroxychromone (1b,c, 4-8) (2 mmol) in ethanol (20 ml) and the mixture was boiled for 8-10 h (check by TLC).…”

“…It is known that the most reactive position for electrophilic attack in 7-hydroxychromones is position 8 [13]. If this is substituted aminomethylation by reactive agents occurs at position 6 [14].…”

Rapid synthetic approaches to libraries of diversified 1,2-dihydrochromeno[2,3-c]pyrrole-3,9-diones and 3-(2-hydroxyphenyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-ones

“…It should be noted that one-pot multicomponent reactions (MCRs) are some of the most efficient tools in modern synthetic organic chemistry for the preparation of highly functionalized organic compounds [40], including N-heterocycles [41,42]. Moreover, they have all the features of a perfect synthetic method: high efficiency and step economy, quick and simple implementation, time and energy reductions, environmental friendliness, and suitability for target and diversity-oriented synthesis [43].…”