Lactone formation hydroxyester

While in the presence of 2-oxoglutaric acid neither decarboxylation nor acyloin condensation had been observed, as expected from previously published results (75), we succeeded in the enzymatic conversion of the mono ethyl ester 3 to ethyl 4-oxobutanoate 4, using both whole yeast cells (Saccharomyces cerevisiae) and purified PDC. The oxo ester 4 served as substrate for a second reaction catalyzed by PDC. Formation of a new carbon-carbon bond was accomplished in the presence of pyruvic acid which acted as donor of a C2-unit. Thus, ethyl 4-hydroxy-5-oxohexanoate 5 was obtained for the first time as the result of an enzymatic acyloin condensation. Finally, traces of acid induced the lactonization of hydroxyester 5, indicating it as direct precursor of solerone 1 (Figure 1). 

Heilmann, J. Maier, W.F. Problems in selective catalysis with molecular imprints in silica—selective lactones formation from hydroxyesters in micropores. Z Naturforsch 1995, 50b, 460-468. 

Similar results have come from studies of the DEBS 1-i-TE system in vitro [53]. When DEBS 1 -I- TE was incubated with appropriate precursors in the absence of the reducing agent NADPH the keto 27 and the pyrone 28 analogues of the triketide lactone were obtained (Scheme 13) [53,54]. This latter result resembles the similar formation of a pyrone product by the animal PAS and the 6-methyl-salicylic acid PKS under similar conditions [55]. Clearly, the /Tketoester intermediates can be transferred from one module to the next without further processing, even in modules which are geared to the production of a hydroxyester intermediate. 

The protection of carboxylic acids as their phenacyl esters has been described regeneration is effected with great facility at room temperature by zinc in glacial or dilute aqueous acetic acid. Of notable applicability is the formation of y-hydroxyesters from y-lactones, an otherwise indirect transformation an example is the obtention of the ester (13) from the sodium salt of santonin (12). This protection can be extended to phenols. 

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