Published data on the synthesis of chromones annelated at the C(7)-C(8) bond with nitrogen-, oxygen-, and sulfur-containing heterocycles of various sizes, including those with two and three heteroatoms, are discussed. Data on the biological activity of chromone derivatives isolated from natural sources and obtained synthetically are presented.

Prenyl group is a ubiquitous structural moiety in natural compounds showing a wide spectrum of different biological activities with potential benefits for human health. This review presents the current knowledge on the prenylation of aromatic compounds such as flavonoids and coumarins. The references to the ‘classical’ methods that encompass Friedel‐Crafts reaction using prenyl alcohol and boron trifluoride, and alkylation with prenyl bromide in the presence of strong bases are given in comparison with the most state‐of‐the‐art prenylation methods. This review highlights the marked advance that has been achieved so far and makes prenyl group installment a versatile tool in the synthesis of drug candidates, natural compounds, and building blocks. Different aspects of prenyl group assembling methods are reported in more than 30 syntheses of natural substances and their analogues. The last part highlights a role of prenylation in flavonoid bioavailability and bioactivity modulation especially regarding their estrogenicity.

UDC 547.814.5 7-Hydroxy-3-phenoxy-8-formylchromones were synthesized using the Duff reaction and were reacted with 2,4-dinitrophenylhydrazine to produce hydrazones and with an excess of hydrazine hydrate to produce the pyrazole recyclization products. Derivatives of α-pyrono[2,3-f]chromones were synthesized using the Knoevenagel condensation with 2-azahetarylacetonitriles and the Perkin reaction.Few 7-hydroxy-8-formylchromones (isounonal 1) and their partially hydrogenated derivatives, lavinal (2), and 4,7-dihydroxy-6-methyl-5-methoxy-8-formylflavan (3) have been discovered within the broad class of natural flavonoids. The first two occur together in plants of the family Annonaceae [1-6] such as Dasymaschalon rostratum [1], Desmos chinensis Lour [2], Desmos cochinchinensis [3], and Unona lawii Hook. f. & Thoms [4]. The last is found in roots of Desmos cochinchinensis [3]. A mixture of all three flavonoids isolated from D. cochinchinensis [3] exhibited antimalarial activity whereas lavinal itself was viewed as a potential AIDS agent [7]. Phenoxychromones are also found in nature [8]. This enabled us to combine these two classes into one in order to study properties different from those of each class individually but characteristic of the system as a whole.The classical method for synthesizing 7-hydroxy-8-formylchromones is the Duff reaction [9-15]. Starting 7-hydroxy-3-phenoxy-8-formylchromones 4-10 were synthesized using the Duff reaction by heating chromones 11-17 with urotropine in acetic acid with subsequent work up of the reaction mixture by HCl solution. PMR spectra of these compounds in DMSO-d 6 showed a singlet for the formyl group near 10.5 ppm and a broad singlet for the hydroxyl proton that was shifted to weak field relative to the resonance of the hydroxyl in the starting chromone by 1.6-1.7 ppm as a result of the formation of an intramolecular H-bond.The presence of the formyl group was also confirmed by formation of the 2,4-dinitrophenylhydrazone 18 upon reaction of 8 with 2,4-dinitrophenylhydrazine. The PMR spectrum of 18 exhibited resonances for aromatic protons characteristic of starting chromone 8; 1H doublets for H-5′′ and H-6′′ at 8.39 and 7.89 ppm, respectively; and a singlet for H-3′′ of the 2,4-dinitrophenyl group at 8.90 ppm.The reaction of 8-formylchromone 6 with an excess of hydrazine hydrate did not stop at the formation of the hydrazone but led to recyclization of theγ-pyrone ring to form pyrazole 19. This was confirmed by a broad singlet typical of the pyrazole NH proton at 12.90 ppm, singlets for two hydroxyls at 11.78 and 12.07, and a 2H singlet at 6.69 for the hydrazone amino group in the PMR spectrum recorded in DMSO-d 6 .

The present review highlights advanced strategies to the synthesis of the chromones annulated with O-and N-containing heterocycles at C(7)-C(8) bond. Due to the prevalence of such motives in different kinds of natural flavonoids and some alkaloids, fused chromones have attracted a great deal of attention so far. On the other hand a wide range of biological activities is displayed by the compounds of this type both among naturally occurring flavonoids and their synthetic analogues. 8-Carbonyl-7-hydroxychromones proved to be versatile synthones for the synthesis of angular hetarenochromones via approach of annulation of a heterocycle to the chromone core. It also addresses the question of the biological activity of naturally occurring and fused synthetic hetarenochromones. ________________________________________________________________________________