Keto methyl ester

The progress of the reaction is followed by HPLC (Zorbax RX-C8 column, 1.5 mL/min, gradient elution of 20 80 to 70 30 CH3CN 0.01 M H3P04 in water over 10 min, held for 20 min, room temperature, detection at 200 nm, retention times P-keto t-butyl ester 2 8.31 min, hydroxy fcrt-butyl ester 3 7.10 min, hydroxy methyl ester 4.45 min, P-keto methyl ester 5.47 min). 

The Bristol group of Christine Willis, in collaboration with Amersham International, developed a procedure for deuterium (or labeling of nonpolar amino acids." In the chemical steps, a selectively methyl-labeled oxazolidinone is converted first into a 2-methyl carboxylic acid and then lengthened by two carbon atoms without racemization to yield an a-keto methyl ester (Scheme 9). 

In the enzymatic part of the process, a one-pot conversion was achieved by using Candida lipase (Lip) to hydrolyze the ester and then LeuDH to catalyze the reductive amination (with or without N labeling). In this case, the coenzyme recycling was accomplished by adding FDH and formate. The same group used a similar enzymatic strategy to prepare labeled L-threonine and L-allothreonine starting from the a-keto methyl ester. ... 

With these results in hand, we turned our attention to the rational design of enantio-merically pure complexes [23, 24] that might direct the absolute sense of the cyclization of 47 to 48 (Eq. 2). The best catalyst reported to date for the cyclization of a /9-keto methyl ester such as 47 is that of Hashimoto [25], which effects C-H insertion with up... 

D-Erythroascorbic acid (D-g/vccro-2-pentenono-1,4-lactone, 142), was prepared from D-glucose by degradative oxidation to potassium D-arabinonate, which was acidified and lactonized. The lactone 143 was converted in one step into the 2-keto methyl ester 144, which finally was tautomerized in hot methanolic sodium acetate, affording D-erythroascorbic acid (142) as a crystalline solid.328... 

In an alternate approach, the enantioselective microbial reduction of methyl-4-(2 -acetyl-5 -fluorophenyl) butanoates 80 (Figure 16.19B) was demonstrated using strains of Candida and Pichia. Reaction yields of 40%-53% and EEs of 90%-99% were obtained for the corresponding (5)-hydroxy esters 77. The reductase that catalyzed the enantioselective reduction of ketoesters was purified to homogeneity from cell extracts of Pichia methanolica SC 13825. It was cloned and expressed in E. coli, and recombinant cultures were used for the enantioselective reduction of the keto-methyl ester 80 to the corresponding (5)-hydroxy methyl ester 77. On a preparative scale, a reaction yield of 98% with an EE of 99% was obtained [99]. 

The Ru-porphyrin catalyst immobilized on PEG was also useful in catalytic cyclopropanations, carbene insertion chemistry, and aziridination reactions. While the TONs in the aziridination reaction were only modest, catalyst 43 was substantially more efficient in the formation of (Z)-2-phenyl-4-(methoxy-carbonylmethylene)-l,3-dioxolanes from y-benzyloxy-a-diazo-jS-keto methyl esters than the corresponding low molecular weight Ru-porphyrin (Eq. 16). Adding ether to the reaction mixture quantitatively precipitated the catalyst 43, eliminating the need for column chromatography to separate the catalyst and reaction products. 

Allyl alcohol (0.60 mL, 8.81 mmol) and DMAP (538 mg, 4.41 mmol) were successively added to a solution of the P-keto methyl ester (18) (500 mg, 2.94 mmol) suspended in toluene (5 mL) and 3 A molecular sieves (500 mg). The reaction mixture was heated to reflux and stirred for 14 h. The reaction mixture was allowed to cool to room temperature, quenched by the slow addition of 1 M HCl (5 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (40 mL) and dried over anhydrous Na2S04. The solvent was removed in vacuo and the resulting oil was purified by silica gel column chromatography (20 % EtOAc in pentane) to yield the product as a colourless oil (311 mg, 54 %). 

The 3/3-epimer of deoxycholic acid has been detected as a component of rabbit and human feces (50,52,62,74,87). It has not been detected elsewhere as a naturally occurring substance. The acid was prepared by reduction of the corresponding 3-keto methyl ester followed by hydrolysis (87). It has also been prepared in good yield by inversion of the 3-tosylate of methyl deoxy-cholate (112). 

S5mthesis of benzimidazole N-oxides on SynPhase Lanterns was discovered by Wu et al. [34] via tin(ll)-pro-moted reduction-cyclization of aryl nitro 3-keto methyl esters. The focal point of this synthesis involves the reduc-hon of an aryl nitro to a hydroxyamino intermediate, which subsequently condenses with an internal carbonyl group to produce benzimidazole N-oxide with minor quantity of benzimidazole as a side product (Scheme 12). 

Standard retrosynthetic manipulation of PGA2 (1) converts it to 5 (see Scheme 2). A conspicuous feature of the five-membered ring of intermediate 5 is the /(-keto ester moiety. Retrosynthetic cleavage of the indicated bond in 5 furnishes triester 6 as a potential precursor. Under basic conditions and in the synthetic direction, a Dieck-mann condensation4 could accomplish the formation of a bond between carbon atoms 9 and 10 in 6 to give intermediate 5. The action of sodium hydroxide on intermediate 5 could then accomplish saponification of both methyl esters, decarboxylation, and epi-merization adjacent to the ketone carbonyl to establish the necessary, and thermodynamically most stable, trans relationship between the two unsaturated side-chain appendages. 

From intermediate 43, the path to monensin would seemingly be straightforward. A significant task which would remain would be the construction of the l,6-dioxaspiro[4.5]decane substructure of monensin. You will note that the oxygen atoms affixed to carbons 5 and 12 in 43 reside in proximity to the ketone carbonyl at C-9. In such a favorable setting, it is conceivable that the action of acid on 43 could induce cleavage of both triethylsilyl ethers to give a keto triol which could then participate in a spontaneous, thermodynamically controlled spiroketalization reaction. Saponification of the C-l methyl ester would then complete the synthesis of monensin. 

The present method9 affords the methyl ester directly in high yields from 2-pyrazolin-5-ones, which are readily prepared in nearly quantitative yields from readily accessible, /3-keto-esters. In addition, the reaction is simple to carry out, conditions are mild, and the product is easily isolated in a high state of purity. A limitation of the reaction is that only the methyl ester can be made, as other alcohols have been found to give poor yields and undesirable mixtures of products. Table I illustrates other examples of the reaction.10... 

Starting /3-keto ester and the product were 2 1 mixtures of ethyl and methyl esters. 

The phosphonate (176) has been used for the addition to aldehydes of a masked jS-keto-ester function and applied in the synthesis of ( )-7(f),9(t)-trisporic acid B methyl ester. The isomerically pure phosphonate (177) has been used in a synthesis of dehydro-Cig juvenile hormone," the anion being generated by treatment with lithium di-isopro-pylamide in THF-HMPT at - 65 °C for 1 min. 

Hydrolysis of 20 with the aid of butanol followed by syn-selective reduction of jS-keto ester 21 and protection as the isopropylidene acetal was accomplished in 87% yield. L1A1H4 reduction and TBS protection of the primary alcohol gave 22 in very good yields. In this strategy, the furan residue serves as an aldehyde synthon and ozonolysis followed by esterification gave the corresponding methyl ester. Reduction and consecutive oxidation established aldehyde 23 in 71% yield. 

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