4- hydroxy-5,4-dihydro-2-pyrone

Hovorka SW, Hageman MJ, Schoneich C. Oxidative degradation of a sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrone in aqueous/organic cosolvent mixtures. Pharm Res 2002 19 538-545. 

The isomeric 6-hydroxy-2-pyrone (glutaconic anhydride) and its 4-methyl analog (47) react similarly with aryldiazonium salts and on hydrolysis with dilute alkali or acid the hydrazones (48) are transformed into l-aryl-6-oxo-l,6-dihydro-3-pyridazinecarboxylic acids or their 4-methyl analogs (49) in variable yields (28-74%). 

DIELS-ALDER REACTIONS Benzocyclopropene. 1,2-BisC3-tosyIethoxycarbonyl)-diazene. Cyclobutadiene iron tricarbonyl. 1,2-Dicyanocyclobutene. Diethyl ketomalonate. 1,3,4,6-Heptatetraene. 2-Hydroxy-5-oxo-5,6-dihydro-2/f-pyrone. 3-Hydroxy-2-pyrone. Isopropylidene isopropylidenemalonate. Lithium tetra-methylpiperidide. 4-Methoxy-5-acetoxymethyl-o-benzoquinone. 4-Methoxy-5-methyl-o-benzoquinone. frans-l-Methoxy-3-trimethyl-silyloxy-l,3-butadiene. Per-fluorotetramethylcyclopentadiene. 4-Phenyl-l, 2,4-triazoline-3,5-dione. Potassium f-butoxide. 

Romero, D.L., Tommasi, R.A., Janakiraman, M.N., Strohbach, J.W., Turner, S.R., et al. (1996) Structure-based design of HIV protease inhibitors 5,6-dihydro-4-hydroxy-2-pyrones as effective, nonpeptidic inhibitors. J. Med. Chem. 39 4630-4642. 

Figure 8.18 Scaffold progression in the discovery of the HIV protease inhibitor Aptivus (tipranavir). (Turner, S.R., et al. Tipranavir (PNU-140690) A potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone sulfonamide class. J. Med. Chem. 1998, 41, 3467-3476.)...

An aq. soln. of 5-carbethoxy-2- -hexyl-2,3-dihydro-6-methyl-4-pyrone and NaOH stirred 24 hrs. at 0-2°, then acidified with HCl -> 3-acetyl-6- -hexyl-5,6-dihydro-4-hydroxy-2-pyrone. Y 77.9%. K. Sato, S. Inoue, and M. Ohashi, Bull. Chem. Soc. Japan 46, 1288 (1973). 

Dihydro-2f/-pyran-2-one has been prepared by reductive cycliza-tion of 5-hydroxy-2-pentynoic acid [2-Pentynoic acid, 5-hydroxy-], which is obtained in two steps from acetylene [Ethyne] and ethylene oxide [Oxirane] 3 and by the reaction of dihydropyran [277-Pyran, 3,4-dihydro-] with singlet oxygen [Oxygen, singlet].4,5 2ff-Pyran-2-one has been prepared by pyrolysis of heavy metal salts of coumalic acid [2//-Pyran-5-carboxylic acid, 2-oxo-],8 by pyrolysis of a-pyrone-6-carboxylic acid [211 - Pyran-6-carboxyl ic acid, 2-oxo-] over copper,7 and by pyrolysis of coumalic acid over copper (66-70% yield).8... 

The Deng group identified QN-derived thiourea 121 and QD -derived thiourea 124 to be also efficient promoters of enantio- and diastereoselective Diels-Alder reactions between the 2-pyrone diene 3-hydroxypyran-2-one and the dienophiles fumaronitrile, maleonitrile as well as acrylonitrile, while various C9-hydroxy acylated and alkylated (dihydro)cupreines and (dihydro)cupreidines failed for the same reactions under identical conditions (e.g., 97% yield, 15% ee, 64 36 endoxxo) [289], Catalysts 121 and 124 (5mol% loading), however, produced the corresponding Diels-Alder adducts 1-3 with synthetically useful enantioselectivities (85-... 

Dimethoxyoxetanes.1 In the presence of ZnCl2, this ketal reacts with 0-hydroxy aldehydes to give 2,2-dimethoxyoxetanes, which can be converted into 4-hydroxy-3-methyl-8-lactones and 5,6-dihydro-2-pyrones. In one case, an optically active lactone was obtained in 80% ee from an optically active y-hydroxy aldehyde. 

Hydrogenolysis of 2-pyrone derivatives to give open-chain products occurs especially readily when phenyl group is substituted in the 6 position.237,238 4-Ethoxy- and 4-hy-droxy-6-phenyl-5,6-dihydro-2-pyrones were hydrogenated to give 3-ethoxy-5-phenyl-2-pentenoic acid and 3-hydroxy-5-phenylvaleric acid, respectively, over Raney Ni at room temperature and 0.3 MPa H2 (eq. 12.126).237... 

The reaction of benzaldehyde with the stabilized allyl anion 205 (cf. equation 15) affords the hydroxy ester 206, which cyclizes to the dihydro-a-pyrone 207 on distillation (equation 87)34. 

Kojic acid (J2-dihydro-3-hydroxy-6-hydroxymethyl-y-pyrone) ... 

The most common method for the preparation of pyrazoles from other heterocycles is from pyranone-type compounds. Condensation of 2,3-dihydro /7-pyran -ones 787 with various aryl hydrazines in the presence of montmorillonite KSF clay under mild conditions proceeded rapidly to afford enantiomerically pure 5-substituted pyrazoles 788 (Equation 172) <2004TL6033>. Comparable results were obtained when arylhydrazines were reacted with 2-formyl glycals under microwave irradiation <2004TL8587>. Phenylhydrazine and hydrazine were reacted with 3-acetyl-4-hydroxy-6-methyl-2/7-pyran-2-one to afford 4-acetoacetyl-3-methylpyrazolin-5-ones, which were employed in the synthesis of bipyrazoles and pyrazoloisoxazoles <1999JHC1291>. Reaction of 3,3-dialkyl-6-(trifluoromethyl)-2,3-dihy-dro -pyrones with hydrazine hydrate afforded 3-(trifluoromethyl)-5-substituted-pyrazoles <1998RCB1365>. 

Ehnenhorst, H. Dihydro-y-pyrones in tobacco smoke. Identification of 2,3-dihydro-5-hydroxy-6-methyM//-pyran -one in cigarette smoke CORESTA 1978 Symp., Sofia, Bulgaria, CORESTA Inf. Bull., Spec. Edition 1978 Paper S05, 114—115. 

Ehnenhorst, H. and G. Nicolaus Dihydro-y-pyrone im Tabakrauch. Nachweis von 2,3-Dihydro-5-hydroxy-6 -methyl-4//-pyran-4-one in Rauch von Cigaretten aus Burley-, Vhginia-, und Orienttabaken [Dihydro-y-pyrones... 

Hydroxy-6-propenyl-2-pyrone heated 3 hrs. at 100° with crotonoyl diloride in tetrachlorethane in the presence of TiCl4 3,4-dihydro-2-methyl-7-propenyl-2H,5H-pyrano[4,3-b]pyran-4,5-dione. Y 70%. K. Kato, Y. Hirata, and S. Yama-mura, Chem. Commun. 1969, 95. 

Nagumo, S.T., T. Toyonaga, T. Inoue, and M. Nagai New Glucosides of a 4-Hydroxy-5-methylcoumarin and a Dihydro-a-pyrone from Gerbera jamesonii hybrida. Chem. Pharm. Bull. (Japan), 37, 2621 (1989). 

Crude methyl 6-benzyloxy-5-hydroxy-2-decynoate added to a soln. of Na in methanol and stirred 22 hrs. at 25° -> 4-methoxy-5,6-dihydro-6-(l-benzyloxy-pent-l-yl)-2H-pyran-2-one. Y 82%. F. e., also from the acids, s. R. M. Carlson and A. R. Oyler, Tetrah. Let. 1974, 2615 5,6-dihydro-2-pyrones s. a. J. Org. Chem. 40,1610 (1975). 

Chloro ulfonyl isocyanate and isoprene in ether give 5-hydroxy-3-methyl-2-pentenoic acid lactone (4-methyl-5,6-dihydro-2-pyrone, XII-98) and 5-amino-3-methyl-3-pentenoic acid lactam (4-methyl-3,6-dihydro-2-pyridone, XII-99) by hydrolysis of intermediate N-sulfochlorides that were not isolated ... 

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