Lactone forming reactions

Activation parameters for the lactone-forming reaction and the Ruzicka hypothesis... 

In addition to the lactone-forming reaction (44), there has been in the last decade a substantial accumulation of accurate kinetic measurements for ring-closure reactions, parts of which have been discussed by Illuminati and Mandolini (1981) and by Winnik (1981a). 

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... 

This Chapter is subdivided into carbocycle, lactam, and lactone forming reactions according to the structural classes of the products formed by the ring enlargement. 

A confirmation of the essential correctness of the Ruzicka hypothesis is provided by the available parameters of activation for the lactone-forming reaction (44) (Galli et al., 1977 Mandolini, 1978b), shown in Figs 8 and 9 as AH and vs ring-size profiles respectively. In the large-ring... 

Radicals in y or 6 positions relative to acylperoxy groups also lead to lactone formation (eq. 9-12). In these lactone-forming reactions homolytic attack could occur either at carbonyl or peroxidic oxygen (eq. 13) but apparently this has yet to be determined for the examples noted in eq. 9-12. 

Some related lactone forming reactions have been observed in the reactions of acylperoxy alkenes in which the double bond participates in the homolysis (eq. 14,15). In the first case (eq. 14), the position of bond scission has been elucidated and found to occur at the peroxidic oxygen (27), in agreement with the results for benzoyl peroxide and tert-butyl perbenzoate which are attacked on peroxidic oxygen by a variety of radicals ( 5,30-32). 

Ishihara s group [8] also reported valuable kinetic resolution of xmsaturated carboxylic acid 1 based on chiral phosphonium acid-catalyzed lactone-forming reaction (Scheme 2). Unfortunately, tiiis reaction was going well in a case of 6-membered lactone formation. 

SCHEME 6 Oxidative lactone-forming reactions catalyzed by in situ-generated hypervalent iodine species. 

SCHEME 7 Oxidative lactone-forming reaction by Dohi and Kita. 

SC HEME 21 Au-catalyzed lactone-forming reaction of homopropargyl alcohols. 

SCHEME 26 Liu s lactone-forming reaction using gold catalyst. 

SCHEME 30 Pd(n/IV) catalysis in lactone-forming reaction of enyne. 

SCHEME 46 N-Heterocyclic carbene (NHC)-catalyzed lactone-forming reaction. 

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