4-OXOHEXANOIC ACID ETHYL ESTER

Oxoethyl)-2-cycloalken-l-ones, 57,117 4-OXOHEXANOIC ACID ETHYL ESTER,... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

FROM a,a -DIBROMOKETONES AND ENAMINES 2,5-DI-METHYL-3-PHENYL-2-C Y CLOPENTEN-1 -ONE y-KETO-ESTER TO PREPARE CYCLIC DIKETONES 2-METHYL-1,3-CYCLOPENTANEDIONE, with the companion preparation y-KETOESTERS FROM ALDEHYDES VIA DIETHYL ARYLSUCCINATES 4-OXOHEXANOIC ACID ETHYL ESTER, which gives the procedure used to prepare the needed... 

AcetylaminoV2-deoxygalactopyranosyl]oxy]ethyl]amino]-6-oxohexanoic acid methyl ester, M-138... 

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 presence of at least two enzymes with different enantioselectivities depending on the structures of the substrates, comparable to the oxoacid ester reductases in baker s yeast (11), is indicated by the different optical purities obtained after incubation of 5-oxo-hexanoic acid, methyl 5-oxohexanoate, and ethyl 5-oxohexanoate (Table II). Variations of the concentrations of added precursors also resulted in different optical purities of metabolites (12). 

The (S)-enzyme (relative molecular mass 48000 -50000) reduced 3-oxoacid esters, 4-oxo and 5-oxoacids and esters enantioselectively to (S)-hydroxy compounds. The K -values for ethyl 3-oxobutanoate, ethyl 3-oxohexanoate, 4-oxopentanoic acid and 5-oxohexanoic acid were determined as 0.9 mM, 5.3 mM, 17.1 mM and 13.1 mM, respectively. 

Cinenic acid methyl ester, T3.10 tram-tran -Puleganolic acid, T15.1 3-Ethyl-3-methyl-6-oxoheptanoic acid, A55.10 2-Isopropyl-2-methyl-5-oxohexanoic acid, A55.3 C10H18O4... 

The (R)-enzyme (molecular mass 800000) was shown to be identical with a subunit of the fatty acid synthase complex. It reduced 3-oxoacid esters specifically to (R)-hydroxyacid esters. K -values for ethyl 3-oxobutanoate and ethyl 3-oxohexanoate were determined as 17.0 mM and 2.0 mM, respectively. Intact fatty acid synthase showed no activity in catalyzing the reduction of 3-oxoacid esters. 

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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