Lactones 2-Pyrones

A number of 2-pyrone derivatives with aromatic substituents are widely distributed in several plant taxa, such as Lauraceae, Annonaceae, Leguminosae, or Piperaceae. Compounds of chemotaxonomic importance are described in the literature (47) and elsewhere in this book. In contrast, aliphatic 5-lactones are rather uncommon in plants and only a limited number of them have been isolated from woody plants. 

The simplest example of this type of compound, parasorbic acid (44), has long been known to occur only in the fruits of Sorbus aucuparia (Rosaceae) (30) before Cardellina and Meinwald isolated it from Vaccinium macrocarpon (Ericaceae) in 1980 (21). Parasorbic acid is known to inhibit fungal growth (16) and seed germination (17, 76). This may be responsible for the allelochemical nature of K macrocarpon (21). 

Massoilactone (45) is the major component of the bark oil of Cryptocarya massoia (Lauraceae) (1, 74). The absolute configuration of (-)-massoilactone is (R) at C-5, which is enantiomeric to parasorbic acid (29, 78). An analogous lactone (46) was also isolated from the same plant (22). Massoi bark has been used for many centuries as a constituent of native medicines. The sedative action expected from the structural similarity between massoilactone and active Kawa-type lactones is dubious (9). (-)-Massoilactone has been isolated from cane molasses as one of, and the most characteristic, sugary-flavor substances (48). This compound was also obtained from two species of formicine ants of the genus Cam-ponotus (22). This powerful skin-irritating compound might be responsible for the defensive factor secreted by the ants. 

The absolute stereochemistry has only been confirmed for boronolide as 6R-(l/ ,2/ ,3 )-5,6-dihydro-6-[l,2,3- n5(acetoxy)-heptyl]-2i/-pyran-2-one (62). 

Altholactone (56), found in the bark of unnamed Polyalthia (Annonaceae), has a unique tetrahydrofuro-pyrone structure (69). This compound is bioge-netically related to a number of a-pyrones with aromatic substituents, found in families of Lauraceae, Annonaceae, or Piperaceae. It can reasonably be regarded as an oxygenated and cyclized derivative of goniothalamin (57), distributed in several species of Goniothalamus (Annonaceae) (56, 69). 

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Queen pheromones ant alkaloids, lactones, pyrones, sesquiterpenes, pentadecene Cruz-Lopez etal. (2001)... 

Hundreds of compounds have been identified in the volatile flavor components of processed foods. Hydrocarbons, alcohols, ethers, aldehydes, ketones, acids, acid anhydrides, esters, aromatic, lactones, pyrones, furans, pyridines, pyrroles, n-alkylpyrrole-2-aldehydes, pyrazines, sulfides, disulfides, thiols, thiophenes, thiazoles, trithiolanes, thialdine. ..etc. 

Food, flavors consist of numerous compounds, none of which alone is characteristic of specific food. Classes of compounds which emcompass food flavors are - hydrocarbons (aliphatic, ali-cyclic, aromatic) carbonyls (aldehydes, ketones) carboxylic acids, esters, imides, anhydrides alcohols, phenols, ethers alkylamines, alkylimines aliphatic sulfur compounds (thiols, mono-, di- and tri-sulfides) nitrogen heterocyclics (pyrroles, pyrazines, pyridines) sulfur heterocylics (thiophenes, thiazoles, trithiolane, thialidine) and oxygen-heterocyclics (lactone, pyrone, furan). Discussion will be limited to striking developments in heterocyclics. 

Several metabolites from cnidaria-derived fungi are lactones, pyrones, and quinones. Here are some recent compounds among many others. 

For the preparation of 4-substituted coumarins, a phenol may be condensed with ethyl acetoacetate under the influence of sulphuric acid. Thus resorcinol (II) readily undergoes this condensation (which is represented diagrammatically above) to give 7-hydroxy-4-methyl-coumarin (III). Note that the coumarins, like all 2 pyrones, are systematically lactones. 

Barrelene was obtained via a double Diels-Alder reaction from a-pyrone with methyl acrylate (H.E. Zimmerman, I969A). The primarily forming bicyclic lactone decarboxylates in the heat, and the resulting cyclohexadiene rapidly undergoes another Diels-Alder cyclization. Standard reactions have then been used to eliminate the methoxycarbonyl groups and to introduce C—C double bonds. Irradiation of barrelene produces semibullvalene and cyclooctatetraene (H.E. Zimmerman. 1969B). 

The intramolecular reaction oF allcenes with various O and N functional groups offers useful synthetic methods for heterocycles[13,14,166]. The reaction of unsaturated carboxylic acids affords lactones by either exo- or endo-cyclization depending on the positions of the double bond. The reaction of sodium salts of the 3-alkenoic acid 143 and 4-alkenoic acid 144 with Li2PdCl4 affords mostly five-membcrcd lactones in 30-40% yields[167]. Both 5-hexe-noic acid (145) and 4-hexenoic acid (146) are converted to five- or six-mem-bered lactones depending on the solvents and bases[168]. Conjugated 2,4-pentadienoic acid (147) is cyclized with Li2PdCl4 to give 2-pyrone (148) in water[i69]. 

Additional applications are exemplified by the well-known Meystre-Miescher degradation of the bile acid side chain and, more recently, in the preparation of a-pyrones from a,iS-unsaturated lactones. ... 

The third synthetic scheme is employed when the phenylthio substituent is in the a-position of the lactone function, which interferes with the cyclization (90JOC5894). Acetylenic ketone 194 (95% yield) is readily transformed to the acetal 195 (with potassium carbonate in methanol) however, under the above conditions neither its hydrolysis nor cyclization to the spiroketal occurs. The spirocyclic pyrone 197 is formed in quantitative yield on treatment of 195 with p-toluenesulfonic acid in a 4 1 THF-H2O mixture at reflux for 12 h. 

A careful assessment of the constitution of compound 10 led to the development of a rather efficient strategy featuring the Diels-Alder reaction (see Scheme 3). Although the unassisted intermole-cular reaction between 3-hydroxy-2-pyrone (16)23 and a,/ -unsatu-rated ester 17 is unacceptable in terms of both regioselectivity and chemical yield, compounds 16 and 17 combine smoothly in refluxing benzene and in the presence of phenylboronic acid to give fused bicyclic lactone 12 (61% yield) after workup with 2,2-... 

Auch Natriumboranatgreift bei 2H-Pyronendie Ather-Bindungan (s. S. 445), wahrend 6-Trichlormethyl-2H-pyrone zu Diolen reduziert werden5. Bei der Reduktion polycycli-scher d-Enol-lactone mit komplexen Methallhydriden tritt oft Umlagerung ein6. 

Enol-lactone der 2H-Pyron-Reihe werden unter Hydrogenolyse der Enol-Bindung zu ungesattigten Carbonsauren reduziert. So erhalt man z. B. aus 4,6-Dimethyl-2H-pyron mit Lithiumalanat in 47%iger Ausbeute 3 -Melhyl-hexadien- (2,4) -satire11 ... 

Because of their low reactivity, a Diels-Alder reaction of 2-pyrones usually requires such a high temperature that the initial bicyclic lactone adducts often undergo cycloreversion [30,33] with loss of CO2. In some cases this limitation has been overcome by carrying out the reaction imder high pressure conditions. Posner and coworkers have shown [34-36] that the presence of a tolylthio group or a bromine atom at the 3- or 5-position increases the reactivity of 2-pyrones. 3-Bromo-2-pyrone (35) (Scheme 2.15), as well as its regioisomer 5-bromo (36)... 

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

The lactone-peroxides 17 are derived from the corresponding ot-pyrones. Singlet oxygenation at low temperature affords the unstable a-pyrone endoperoxides which, on warming up, readily decarboxylate into 1,2-diacylethylenes. However, subambient diimide reduction leads to the desired lactone peroxides 17 (Eq. 12)29). 

A similar mechanism could explain the elimination of the second molecule of benzoic acid, but formation of the triunsaturated lactone 154, obtained from the D-g/yccro-D-gw/o-heptonolactone perbenzoate, would require a different intermediate. The driving force in this case is the stability of the resulting furanone. An acid-base catalyzed process, such as that proposed for the formation of the a-pyrone 144a, could explain the formation of... 

Dideoxyhex-2-enono-1,5-lactone derivatives (penten-5-olides) have been prepared (255-258) and employed as starting compounds in synthesis. Thus, Michael addition of benzylhydroxylamine to racemic 6-0-acetyl-2,3,4-trideoxy-D,L-g/ycerohex-2-enono-1,5-lactone (267) took place ster-eoselectively to give the unstable benzyloxyamino-2-pyrone 268, which was readily converted into the /Mactam derivative 269, a precursor of thienamy-cin (259). / -Lactams were also obtained (260) by 1,3-dipolar cycloaddition of nitrone 270 to the unsaturated 1,5-lactone 267, followed by hydrogenoly-sis and subsequent cyclization to the /Mactam 271, having a polyol side-chain at the C-3 position. 

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