Y-Pyrones

It may be regarded as the parent of a number of important classes of compounds derived from the y-pyrone skeleton (e.g. flavone, xan-thone) and the important chroman derivatives called the tocopherols (vitamin E). 

The synthesis of a large number of y-pyrones and y-pyranols from enamines has been brought about through the use of a wide variety of bifunctional molecules. These molecules include phenolic aldehydes (126,127), phenolic Mannich bases (128), ketal esters (129), and diketene (120-132). All of these molecules have an electrophilic carbonyl group and a nucleophilic oxygen center in relative 1,4 positions. This is illustrated by the reaction between salicylaldehyde (101) and the morpholine enamine of cyclohexanone to give pyranol 102 in a quantitative yield (127). 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

Baeyer and Piccard were the first to prepare crystalline monocyclic pyrylium salts without hydroxy or alkoxy substituents, from y-pyrones and Grignard reagents in 1911. They ascribed a correct structure to these salts, although the bonds in the ring and the valency of the oxygen heteroatom remained contested topics for the next 20 years. The discussions around the formula of pyrylium... 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

Preparation of y-pyrone by the reaction of methoxybutenone with formic acid esters (10°C, MeONa, CgHe, 1.5 h) has been reported (73 JPP7229512 80MI2). The intermediate 292 undergoes [3,3]-sigmatropic rearrangement to form methoxydi-hydropyrone 293 which further eliminates methanol, thus transforming to y-pyrone. 

Pyridoxal 157,158,253 Pyridoxamine 253 Pyridoxine 253 Pyrimidines 266,438, 439 Pyrocatechol see 1,2-Dihydroxybenzene I ocatecholsulfophthalein 398 I ocatechol violet reagent 398 Pyrolysis of organic compounds 92, 96 a,y-Pyrone derivatives 288 Pyrrole alkaloids 66 Pyrrole derivatives 266, 269, 270 Pyruvic acid 426... 

If c-QHnCOCI is used instead of the imidazolide, the yield of the y-pyrone is only 23%d1081 For an analogous reaction see also reference [109]. 

There continues to be interest in small-molecular scaffolds as good starting points for drug discovery [50]. Indoles [51], 2-oxindoles [52], 2-arylben-zothiazoles [53], rhodanines [54], quinolones [55], (3-D-glucose [56], and y-pyrones [57] have all recently been reviewed as "privileged" scaffolds. 

A derivative of the oxo form of a 3-hydroxyselenophene has been obtained by a quite different route.123 1,5-Diphenyl-1,4-pentadiyn-3-one (94) adds hydrogen selenide and gives a mixture of 2,6-diphenyl-1-seleno-y-pyrone (95) and 2-benzylidene-3-oxo-5-phenyl-2,3-dihydroselenophene (96). 

Instead of AH-pyran-4-one the simpler, equivalent term y-pyrone will be used throughout this article. 

These investigations shed considerable light on the synthesis of the Y-pyrone ring however, it is unlikely that any conclusions regarding the biosynthetic process could be drawn from them. 

Kojic acid is a -y-pyrone. The conventional way of numbering the atoms in the Y-pyrone ring of kojic acid is shown in structure II. For convenience... 

The cleavage of kojic acid by hot alkali, to fragments containing one to three carbon atoms, could not be definitely shown to commence at the ring oxygen atom, but what was said earlier about y-pyrones in general renders this conclusion probable. 

Shikimates, which include phenylalanine, tyrosine, tryptophan, and their derivatives, are represented by many aromatic natural products, including hydroquinones found inbrownalgae such as Sargassum (Segawaand Shirahama 1987). Flavonoids are a structural class of shikimates found in plants, including isoflavonoids or neo-flavonoids, as is the y-pyrone (coumarin) core structure (Knaggs 2003). 

The first report of a cycloaddition reaction in the presence of an optically active catalyst13 appeared in 198314a. The dienes 14 add to benzaldehyde in the presence of 1 mol% of the chiral lanthanide NMR shift reagent Eu (hfc)3, i.e. tris[3-(heptafluoropropyl-hydroxymethylene)-(+)-camphorato]-europium(III), to give, after treatment with trifluo-roacetic acid, the dihydro-y-pyrone 15 enriched in the (R)-enantiomer, the degree of... 

It has been shown22 that the reaction of the diene 4 with aldehydes RCHO in the presence of a catalyst prepared from (R)-BHMOL (33) and Ti(OPr-i)3, which affords the dihydro-y-pyrones 35 in good yields and high ee, proceeds by a two-step sequence via the open-chain adducts 34, which cyclize to the products on treatment with trifluoroacetic acid (equation 20). 

Or, alternatively (see Scheme 3.3), the immediate precursor of patulin could be iO, arriving through this new route to tetrahydro-y-pyrone 12, as the starting material, together with the synthon =CH-COOR, which conveniently elaborated gives either a glyoxylic ester, OCH-COOR, or an oxomalonic diester. 

The same product is obtained from 3-phenylchehdamic acid, the pyrone oxygen of which is already substituted by imino-nitrogen, only three molecules of biguanide being required for the formation of the final product (CXLVII). Similar reactions occur (464) with the parent chelidonic acid and with y-pyrone. 

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