Triacetic acid lactone, formation

When the catalytic reaction of 6-hydroxymellein synthase is carried out in the absence of NADPH or with monomeric enzyme, keto-reduction of the carbonyl group of the triketomethylene chain does not take place, and the synthase liberates triacetic acid lactone instead of 6-hydroxymellein [64, 71]. However, the efficiencies of product formation are markedly lower than for the normal reaction. Two mechanisms could account for the low efficiency of triacetic acid lactone formation observed in the monomeric and the NADPH-depleted dimeric forms of 6-hydroxymellein synthase. These are 1) Reduced affinity of the cosubstrates acetyl-CoA and/or malonyl-CoA for the enzyme protein with the incomplete reaction centers 2) Reduced rate of reaction of acyl-CoA condensation and/or product liberation. To examine these possibilities, kinetic parameters of the two triacetic acid lactone-forming reactions were compared with those of the normal reaction which produces 6-hydroxymellein. The Km value of 6-hydroxymellein synthase for acetyl-CoA in the normal reaction was estimated to be 22 pM, while in both the NADPH-depleted dimer and the monomer reactions the affinity of 6-hydroxymellein synthase protein for acetyl-CoA was markedly lower at 284 and 318 pM respectively. By contrast the Km values for malonyl-CoA in the normal and the two abnormal reactions were essentially the same (40 - 43 pM), indicating that the affinity of 6-hydroxymellein... 

Divergent reports are available regarding the action of diazomethane on triacetic acid lactone (83). In the first investigations the sole formation of 6-methyl-2-methoxypyran-4-one (85) or of 6-methyl-4-methoxypyran-2-one (84) " w as reported. Later it was shown that a mixture of both compounds is formed albeit the 2-methoxy derivative (85) in small yield. The discrepancies are in... 

Triacetic acid lactone (1) is one of the simplest polyketides, and its formation from acetyl-CoA and malonyl-CoA has been proved (68JBC5471). Biogenetic formation of triacetic acid lactone has been considered a derailment from fatty acid biosynthesis promoted by the absence of the reductant NADPH (69MII). Pyrone 1 has been isolated from microorganisms (67JA676) and is transformed into tropolone derivatives by Penicillium stipitatum (67JA681). 

C. Formation of Triacetic Acid Lactone and Tetraacetic Acid Lactone... 

Triacetic acid lactone is the simplest of all polyacetate structures. Its formation incorporates an essential feature of the synthesis of acetate-derived phenols, since it is formed by condensation from acetyl-CoA and malonyl-CoA via an intermediate acetoacetyl-enzyme (Nixon et al., 1968 Yalpani et al., 1969) or acetoacetyl-ACP stage (Brock and Bloch, 1966), at which point... 

For more complex metabolites (phenols and tetraacetic acid lactone), further condensation of the triacetyl residue must take place and can only proceed if the priming acetyl residue, with its C-5 oxygen function, is stabilized away from the thioester region of the acyl-enzyme intermediate at this time. Possibly, the presence of NADPH assists in this process, in appropriate enzymes, since the ability to form triacetic acid lactone has been demonstrated by fatty acid and 6-methylsalicylate synthetases when deprived of this nucleotide, but other synthetases have not been tested for this effect. Moreover, the analogous formation of the styrylpyrone bisnoryangonin by flavan-one synthase (Kreuzaler and Hahlbrock, 1975a,b) confirms that the potential for synthesis of stable products with shorter chains does exist. 

Reactions between triacetic acid lactone (MI-243) and ammonia or amines to give 4-hydroxy-6-methyl-2-pyridones are well known. For example, glycine and XII-243 give l-carboxymethylene-4-hydroxy-6-methyl-2-pyii-done. This latter 4-hydroxy-2-pyridone has also been formed from diketene and glycine in aqueous base via XU-244, which can be deacetylated in concentrated sulfuric acid. Dehydroacetic acid does not appear to be an intermediate in the formation of xn-244. Under these conditions it reacted with glycine to form an isomeric product, which, however, was not characterized. ... 

The Chinese plant Amoora yunnanensis contains dammaranes 642 and 643 (746), and oleanane 644 was isolated as a triacetate from Mentha villosa (747). It is conceivable that 644 is an artifact formed by HC1 acting on the corresponding unsaturated carboxylic acid, since this type of acid-catalyzed lactone formation is well known (748). 

One-electron oxidation systems can also generate radical species in non-chain processes. The manganese(III)-induced oxidation of C-H bonds of enolizable carbonyl compounds [74], which leads to the generation of electrophilic radicals, has found some applications in multicomponent reactions involving carbon monoxide. In the first transformation given in Scheme 6.49, a one-electron oxidation of ethyl acetoacetate by manganese triacetate, yields a radical, which then consecutively adds to 1-decene and CO to form an acyl radical [75]. The subsequent one-electron oxidation of an acyl radical to an acyl cation leads to a carboxylic acid. The formation of a y-lactone is due to the further oxidation of a carboxylic acid having an active C-H bond. As shown in the second equation, alkynes can also be used as substrates for similar three-component reactions, in which further oxidation is not observed [76]. 

Figure 1. Proposed mechanism for the formation of (A) naringenin chalcone from 4-coumaroyl-CoA and three molecules of malonyUCoA by CHS, (B) triacetic lactone from acetyl-CoA and two molecules of malortyUCoA by 2PS, (C) aloesone from acetyl-CoA and six molecules of malonyUCoA by ALS, (D) 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA by PCS, and (E) SEK4 and SEK4b from eight molecules of malonyl-CoA by OKS. Bis-noryangonin (BNY) and 4-coumaroyltriacetic acid lactone (CTAL) are derailment by-products of the CHS reactions in vitro when the reaction mixtures are acidified before extraction. In A. arborescens PCS and OKS, acetyl-CoA, resulting from decarboxylation of malonyl-CoA, is also accepted as a starter but not so efficiently as in the case ofR. palmatum ALS.

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