6-Aryl-4-hydroxy-2-pyrones

The retrosynthetic analysis of arisugacin is shown in Scheme 12.2. It is clear to us that this formal [3+3] cycloaddition method could be invaluable to achieve a practical total synthesis of arisugacin A 6 or other family members and their analogs [20]. Specifically, the reaction of a,(3-unsaturated iminium salts 13 with 6-aryl-4-hydroxy-2-pyrones 14 should provide a facile access to the advanced pentacyclic intermediate 12. 

Structurally related to the triarylmethanes is the xanthene chromogen (1.30), in which two of the aryl nuclei are linked by an oxygen atom to form a pyrone ring. Similar terminal groupings (amino, hydroxy, or both) are usually present. Xanthene dyes have mainly... 

The 4-hydroxy-2H-pyran-2-one moiety is a key structural feature in a recently discovered new class of non-peptidic HIV protease inhibitors. Therefore, the synthetic methodologies were extended to allow the functionalization of commercially available chemicals. Direct arylation of the pyrone ring at the C-3 and C-5 positions had not been reported until the re-... 

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%). 

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>. 

The reactions of amidines or guanidines with a-functionalized carbonyl compounds continue to be utilized for the synthesis of imidazoles. Thus, the mixed anhydride of acetic and chloroacetic acids reacts with symmetrical diarylguanidines to give l-aryl-2-arylaminoimidazolin-4-ones, and there is competitive formation of imidazoles and pyrimidines in the reaction of benzamidine with 3-bromobenzo-4-pyrones (18). Imidazoles are minor products, but are favored in nonpolar solvents. The use of a-dicarbonyl compounds with guanidine gives 2-amino-4-hydroxy-4-methyl-4//-imid-azoles, which give excellent yields of 2-aminoimidazoles on catalytic hydrogenation. " ... 

Treatment of MI-220 or MI-221 (R = H, CH3) with aromatic amines in water gives l-aryl-5-hydroxy(or methoxy)-4-pyridone-2-carboxylic acids, which are readily decarboxylated to XII-223, (R = H, CH3) or converted to ethyl esters."" 2-Hydroxymethyl-S-methoxy-4-pyrone, a monomethyl ether of kojic acid, and 2-dialkylaminoethylamines in water give l-(2-dialkylaminoethyl)-2-hydroxymethyl-5-methoxy-4-pyridones (MI-224 R = CH3,C2Hs). Natural maltol glucoside and ammonia or primary amines give the corresponding pyridones (XU-225) when boiled in methanol. ... 

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