Esters 3-oxoglutaric acid

A biomimetic synthesis of solerone (5-oxo-4-hexanolide) 1 using both enzymatic and acid-catalyzed reactions was performed. Starting from L-glutamic acid 5-ethyl ester 2 enzymatic oxidative deamination followed by subsequent decarboxylation of the corresponding 2-oxoglutaric acid 5-ethyl ester 3 led to ethyl 4-oxobutanoate 4. In the presence of pyruvate,... 

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). 

The sodium salt of the stabilized enolate derived from the heteroaryl-substituted 2-oxoglutaric acid ester (186) is reported to have the alkene geometry as shown in formula (187). Hnally, Collum et al. have reported the structure of the lithiated anion derived from the A, A -dimethylhydrazone of 2-methoxy-carbonylcyclohexanone (188). This enolate crystallizes as the dimeric, bis-THF-solvated aggregate (189). 

Carboxyalkyl-Y-but5U olactone has also been S5mthesized by combining pure enz5mies and whole microbial cells in the same process. Thus, the corresponding 2-hydroxy esters and lactones were obtained from 2-oxoglutaric acid [219]. Low ee values, however, were obtained for the reduction of a,y-diketo esters and keto a,y-diesters [220-224]. 

On heating the parent acid of ester VI (from condensation of D-glucose with diethyl 3-oxoglutarate) in aqueous solution,11 following the procedure employed to obtain the corresponding derivative of ethyl acetoacetate XXVI, a sirup results. However, its change in optical activity shows a parallelism with that in analogous cases where crystalline products are isolated, and apparently indicates anhydride formation (see the last line in Table V). 

The 3-oxo-2//-furans (260) obtained from the reaction of a-halogenoacyl halides with /3-ketonic esters at -20 °C show no tendency to enolize to the hydroxyfurans (261) but rather behave as unsaturated ketones (Scheme 71) (73RTC731). 2,4-Dialkylfurans (262) are obtained by condensation of acyl halides with allyl halides catalyzed by aluminum chloride (73KGS1434). The acid catalyzed condensation of 2-chlorocyclopentanone with dimethyl /3-oxoglutarate leads to the furan ester (263) (77JHC711). 

The phosphate ester of the aldehyde form of vitamin B6, pyridoxal phosphate (pyridoxal-P or PLP), is required by many enzymes catalyzing reactions of amino acids and amines. The reactions are numerous, and pyridoxal phosphate is surely one of nature s most versatile catalysts. The story begins with biochemical transamination, a process of central importance in nitrogen metabolism. In 1937, Alexander Braunstein and Maria Kritzmann, in Moscow, described the transamination reaction by which amino groups can be transferred from one carbon skeleton to another.139 140 For example, the amino group of glutamate can be transferred to the carbon skeleton of oxaloacetate to form aspartate and 2-oxoglutarate (Eq. 14-24). 

The biogenesis of solerone 1 and related compounds was successfully rationalized by biomimetic model reactions. As key step we established the pyruvate decarboxylase catalyzed acyloin condensation of pyruvic acid with ethyl 4-oxobutanoate 4 or ethyl 2-oxoglutarate 3 with acetaldehyde. The importance of the ethyl ester function in 3 and 4 serving as substrates for the enzymatic formation of a-hydroxy ketones 5 and 6 was demonstrated. The identification of six yet unknown sherry compounds including acyloins 5 and 6, which have been synthesized for the first time, confirmed the relevance of the biosynthetic pathway. Application of MDGC-MS allowed the enantiodifferentiation of a-ketols and related lactones in complex sherry samples and disclosed details of their biogenetic relationship. 

The reaction, under the same conditions, has been extended to other /3-keto esters. Ethyl 3-oxovalerate, ethyl 3-oxohexanoate, and diethyl 3-oxoglutarate react with 2-amino-2-deoxy-D-glucose to give compounds (11), (12), and (13), respectively, whose oxidations with lead tetraacetate or periodic acid furnish the corresponding aldehydes (14), (IS), and (16). 

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