Coumarins are naturally occurring oxygen heterocyclic compounds having multifarious medicinal properties, hence used as lead compounds for designing new potent analogs. The chromene butenoic acid 3 and the benzochromene butenoic acid 4 which are derived from the reaction of glyoxalic acid with 3-acetylcoumarin and 3-acetylbenzocoumarin, respectively, were reacted with different nitrogen and carbon nucleophiles to give new heterocyclic compounds. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, and mass spectroscopy. Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity.

https://www.mdpi.com/1420-3049/21/2/249/pdf

Synthesis and Characterization of Some New Coumarins with in Vitro Antitumor and Antioxidant Activity and High Protective Effects against DNA Damage

Syntheses and Biological Activities of Chroman-2-ones. A Review

Carbodiimide that was generated from the condensation reaction of iminophosphorane with phenylisocyanate was allowed to react with different phosphorus nucleophiles. Thus, the in situ resulted heterocumulene reacted with dialkylhydrogenphosphonates in tetrahydrofuran (THF)/FeCl(3) /H(2) O system to give fused pyrrole- (≈14%) and pyrimidinephosphonates (≈57%). On the other hand, with tris-(dialkyl)aminophosphines, the reaction afforded the corresponding hexaalkylphosphinic diamides as a water-sensitive fine powder, quite stable for a few days in a desiccator. When a protonating agent was present in the reaction medium, the reaction was markedly accelerated leading to the formation of the phosphamides. Next, some saturated and unsaturated Horner-Emmons reagents were applied in situ to the same carbodiimide to obtain more phosphorylated N-heterocycles. The analgesic and antiinflammatory activities of the newly synthesized compounds were investigated and showed significant activities. Finally, we further estimated the antitumor activity of five new phosphonates against four carcinoma cell lines.

Carbodiimides in the synthesis of enamino- and α-aminophosphonates as peptidomimetics of analgesic/antiinflammatory and anticancer agents.

Chromone and coumarin derivatives exhibit a wide spectrum of biological activity, including spasmolytic, antiarrhythmic, cardiothonic, antiviral, and anticancer properties. Phosphorus-containing chromone and coumarin derivatives form a novel group of compounds, possessing remarkable cytotoxicity and alkylating and anticancer activity against selected tumor cell lines. Derivatives containing a phosphorus atom at position 2 of a γ-pyrone ring are known to be efficient antibacterial agents. This review presents methods developed for the synthesis of derivatives of chromone and coumarin that contain a phosphonate moiety. Among them, the reaction of derivatives of 2-hydroxyacetophenone with phosphonic compounds is the one most frequently used. Some analogues were characterized by X-ray crystallography.

Synthesis, reactions and biological activity of phosphorus-containing derivatives of chromone and coumarin

William Pitt and co-workers have created a virtual exploratory heterocyclic library ‘VEHICLe’ containing over 200 unconquered bicyclic heteroaromatic rings, synthetically feasible with potential medicinal interest. Since the publication of the 22 ‘heteroaromatic rings of the future’ by Pitt in 2009, 15 of them have been successfully synthesized as bicyclic or polycyclic forms and evaluated for applications in both biology and material science. This short review presents the critical synthesis associated with innovative synthetic methodologies of the synthetically conquered ring scaffolds from the list of 22 with a spotlight on the scientific contribution of this fascinating article for the expansion of the chemical diversity. 1 	Introduction 2 	Heteroaromatic Rings of the Future: The Synthetic challenge? 2.1 	4 -Pyrido[1,3]oxazin-4-one-P1
 2.2 	Pyrrolo[2,1-b][1,3]oxazin-4-one-P4
 2.3 	Furo[2,1-e]pyridazin-4(1H)-one-P5
 2.4 	Isoxazolo[3,4-c]pyridin-7-one-P6
 2.5 	5H,6H-[1,2]Thiazolo[5,4-c]pyridin-5-one-P7
 2.6 	4H,5H-Furo[3,2-b]pyridin-5-one-P8
 2.7 	1H,5H,6H-Pyrazolo[3,4-c]pyridin-5-one-P9
 2.8 	Thieno[3,4-c]pyridazine-P10
 2.9 	Pyrrolo[1,2-c][1,2,3]triazine-P11
 2.10 	Thieno[3,4-a]oxazole-P12
 2.11 	2,4-Dihydropyrrolo[3,2-c]pyrazole-P13
 2.12 	Pyrazolo[1,5-b]isoxazole-P14
 2.13	Imidazo[1,5-c]pyrimidin-3(2H)-one-P16
 2.14 	Cyclopenta[b][1,4]oxazin-5(4H)-one-P17
 2.15 	2,3-Dihydro-2,6-naphthyridin-3-one-P18
 3 	Conclusion

‘Heteroaromatic Rings of the Future’: Exploration of Unconquered Chemical Space

Treatment of triketoindan-2-oxime with α-phosphonyl carbanions in sodium ethanolate solution at reflux temperature led to a number of the corresponding substituted spiroisooxazole-, fused 1,3-oxazole, and 1,4-oxazine phosphor esters in moderate to high yields. Mechanisms for the formation of five- and six-membered rings are provided. A comparison of Wittig-Horner and Wittig reagent counterparts in reactions with the oxime is discussed. The various biological properties of selected examples of the synthesized products were studied.

An efficient method for the synthesis of spiro and fused N-heterocyclic phosphor esters. Reactions of triketoindan-2-oxime with α-phosphonyl carbanions

Synthesis and reactions of phosphino- and phosphono substituted-coumarins

Treatment of 5,6-di(2-furyl)-3-thioxo-2,3-dihydropyridazine-4-carbonitrile with phosphonate carboanions stabilised with electron withdrawing group (CO 2 R, CN, SR') led, under microwave irradiation and the effect of basic catalysis, to excellent yields of a variety of condensed sulfur, nitrogen and phosphorus-containing heterocycles as major products, along with fused thieno- and thiazole ring systems bearing a phosphonate moiety. On the other hand, fused thiazaphosphinine oxide and thiopyranone phosphonate were obtained in equal yields from the reaction of 5,6-di(2-furyl)-3-thioxo-2,3-dihydropyridazine-4-carbonitrile with diethyl vinylphosphonate. Screening results of antimicrobial potency for the products were discussed in terms of structure-activity relationships (SAR), and an attempt was made to define the structural features for lead compounds.

Antimicrobial activity of novel fused nitrogen, sulfur and phosphorus containing-heterocycles and relevant phosphonates with difurylpyridazine species

Reactions of alkylidenephosphoranes with symmetrically substituted p-quinones

Treatment of 2-acetyl (3H)naphtho[2,l-6] pyran-3-one I with ylides 2aJ) led to the formation of the corresponding [2, l i]-fused substituted benzene 6a.b and the Wittig products 3a,b. with ylides Zc.d afforded, again the corresponding [2,l-o]-fused cyclopentadienes 9a,b and the olefination products 7a,b. Conversely, compound 1 undergoes conjugated addition reaction with both ylides 10 and 12 to give 1_1 and 13, respectively. Introduction Polyfunctionally substituted heteroaromatics are of immense importance in biochemistry (1-3). Thus, despite coumann itself, has very little physiological action upon human being, it has long been recognized the versatile applications of naturally occurring-and synthesized coumaran derivatives (4,5). Previously mentioned fact has encouraged us to synthesize and study the reactions of some novel pyrans by making use of 2-acetyl (3H)naphtho[2,l-6]pyran-3-one 1. (also known as 3-acetyl 5,6-benzocoumarin) and some methylenetriphenylphosphoranes (Wittig reagents) 2a-d, 10 and 12.

Ashraf A. Sediek

Papers

An efficient method for the synthesis of spiro and fused N-heterocyclic phosphor esters. Reactions of triketoindan-2-oxime with α-phosphonyl carbanions

Synthesis and reactions of phosphino- and phosphono substituted-coumarins

Antimicrobial activity of novel fused nitrogen, sulfur and phosphorus containing-heterocycles and relevant phosphonates with difurylpyridazine species

Reactions of alkylidenephosphoranes with symmetrically substituted p-quinones

THE REACTIVITY OF 2-ACETYL(3H)NAPHTHO(2,1-b]-PYRAN-3-ONE TOWARDS SOME PHOSPHORUS YLIDES: SYNTHESIS OF COUMARINYL[2,1-b]-FUSED CYCLIC COMPOUNDS