1,2-benzopyrones

Three synthetic approaches for benzopyrones have been developed that use Gly as starting material. Hippuric acid was transformed with acetic anhydride into 2-phenyl-5(4//)oxazolone or further into its 4-ethoxy-methylene derivative, then reacted with cyclic 1,3-dicarbonyI compounds (such as like dimedone) to form 100 [90LA501 92H(33)843]. On the other hand, when hippuric acid was transformed into methyl 2-benzoyl-amino-3-dimethylaminopropenoate, it reacted with resorcinol to give a 7-hydroxybenzopyrone derivative (89JHC1273). 

4-Benzoquinone reacted with dialkyl aminocrotonate to give 3-amino-4-carbalkoxy-6-hydroxycoumarin (90J HCl 447). 

From diethyl acetamidomalonate and 2-(4-fluorophenoxy)ethyl bromide a spiro-benzopyranyl amino acid 101 could be prepared (88TL5493). 

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S I M O N I S Benzopyrone synthesis Benzopyrene synthesis Irem phenols and p ketoesters... 

Whereas benzopyrylium salts are resistant to electrophilic substitution, even in the benzene moiety, the benzopyrones [coumarins (81), isocoumar-ins (82), and chromones (83)] are readily halogenated in either ring, with... 

Balaiah V, Seshadri TR, Venkateswarlu V (1942) Visible fluorescence and chemical constitution of compounds of the benzopyrone group. Part III. Further study of structural influences in coumarins. Proc Ind Acad Sci 16A 68-82... 

The elucidation of the structure of 5,6-dihydrolamellarin37 38 served as the development vehicle for the entire family of ADEQUATE experiments. Hence, this work also represented the first reported application of the INADEQUATE experiment. Two important 1ADEQUATE correlations were observed in the benzopyrone portion of the molecule and are shown by 28. The C19 resonance was correlated via three bonds to the C23 carbonyl. The C22 carbon was correlated via three bonds to the C3 quaternary carbon adjacent to the C23 carbonyl. 

Coumarins belong to a group of compounds known as the benzopyrones, all of which consist of a benzene ring joined to a pyrone. They may also be found in nature, in combination with sugars, as glycosides. They can be categorized as simple fura-nocoumarins, pyranocoumarins, and coumarins substituted in the pyrone ring (Murray and others 1982). 

Hydrolysis of benzopyrones (for synthesis see elsewhere here) will produce compounds of type (III) which will work in this synthesis. The hydrolysis proceeds as follows (JCS 926(1927)) Add lOg of the benzopyrone to 20g 30% NaOH, cool and shake 1 hour with 19 ml methylsulfate. Extract the oil with ether and dry, evaporate in... 

An alternative method for removing Zn from the active site of zinc proteins is to use aromatic nitroso compounds such as 3-nitrosoben-zamide and 6-nitroso-l,2-benzopyrone (382). These agents can oxidize Zn-bound cysteine S and can inhibit HIV-1 infection in human lymphocytes. They also eject zinc from isolated HIV-1 nucleocapsid zinc-fingers and from intact HIV-1 virions. 

Nitrosobenzamide and 6-nitroso-l,2-benzopyrone are among the most active C-nitroso compounds that inactivate the eukariotic nuclear protein poly(ADP-ribose) polymerase at... 

Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289 2126—2128 Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107 137-148 Mabley JG, Suarez-Pinzon WL, Hasko G, Salzman AL, Rabinovitch A, Kun E, Szabo C (2001) Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition with 5-iodo-6-amino-l,2-benzopyrone protects mice from multiple-low-dose-streptozotocin-induced diabetes. Br J Pharmacol 133 909-919... 

Runkel M, Bourian M, Tegtmeier M, Legrum W (1997) The character of inhibition of the metabolism of 1,2-benzopyrone (coumarin) by grapefruit juice in human. Eur J Clin Pharmacol 53(3 ) 265-269... 

Synonyms 1,2-Benzopyrone 5,6-benzo-2-pyrone benzo-a-pyrone cis-ortho-co x-marinic acid lactone coumarinic anhydride ort/jo-hydroxyciimamic acid lactone... 

Beckley-Kartey, S.A.J., Hotchkiss, S.A.M. Capel, M. (1997) Comparative in vitro skin absorption and metabolism of coumarin (1,2-benzopyrone) in human, rat, and mouse. 

Cottrell, S., Oliver, K., Lake, B.G. Powell, C.J. (1996) Strain-specific enhancement or inhibition of coumarin hepatotoxicity in mice following pretreatment with two different liver enzyme-inducing agents. Fundam. appl. Toxicol, 34, 47-55 Cox, D., O Kennedy, R. Thornes, R.D. (1989) The rarity of liver toxicity inpatients treated with coumarin (1,2-benzopyrone). Hum. exp. Toxicol, 8, 501-506 Dexeus, E.H., Logothetis, C.J., Sella, A., Fitz, K., Amato, R., Reuben, J.M. Dozier, N. (1990) Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. J. din. Oncol, 8, 325-329... 

Gallicchio, V.S., Hulette, B.C., Harmon, C. Marshall, M.E. (1989) Toxicity of coumarin (1,2-benzopyrone) on human peripheral blood mononuclear cells and human and murine bone marrow progenitor stem cells. J. biol. Res. Modifiers, 8, 116-121 Gangolh, S.D., Shilling, W.H., Grasso, P. Gaunt, I F. (1974) Studies on the metabolism and hepatotoxicity of coumarin in the baboon. Biochem. Soc. Transact., 2, 310-312... 

Marshall, M.E., Butler, K. Hermansen, D. (1990) Treatment of hormone-refractory stage D carcinoma of prostate with coumarin (1,2-benzopyrone) and cimetidine a pilot study. 

Isoflavones (388) and dimethyloxosulfonium methylide gives 2,3-dihydro-2,3-methano-4-benzopyrones with 2-vinyl-3(2H)-benzofura-nones (389) as by-products.837... 

Coumarin is l, 2-benzopyrone. CyHf.0- or QH4OCOCH CH. a white solid. 

Acetoxybenzoic acid, AP05 4-Acetoxy-l,2-benzopyrone, AS98... 

Aminobenzoic acid, AK27 L-Aminobenzoic acid, AK28 -Aminobenzonitrile, AJ7 V-Amtno-ljU-benzopyrone, AP09... 

Benzopyrone, A070 o-Benzoquinone, AG07 -Benzoquinone, AG08... 

METHOXYCARBONYL-1,1,6-TRIMETHYL-1,4,4a,5,6,7,8,8a-OCTAHYDRO-2,3-BENZOPYRONE, an intramolecular Diels-Alder reaction is responsible for the diastereoselectivity. The stereoselective 1,4-functionalization of 1,3-dienes is exemplified by a two-step process leading to cis- and trans-1-ACETOXY-4-(DICARBOMETHOXYMETHYL)-2-CYCLOHEXENE. The effectiveness of a silyl hydride in providing a means for erythro-directed reduction of a p-keto amide is applied in a route to ERYTHRO-1 -(3-HYDROXY-2-METHYL-3-PHENYL-PROPANOYLJPIPERIDINE. This is followed by an asymmetric synthesis based on a chiral bicyclic lactam leading to (R)-4-ETHYL-4-ALLYL-2-CYCLOHEXEN-1-ONE. The stereoselectivity with which acetoxy migration can operate to an adjacent radical center is reflected in the one-step reaction that gives rise to 1,3,4,6-TETRA-O-ACETYL-2-DEOXY-a-D-GLUCOPYRANOSE. 

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