Keto acids, esterification reduction

Conversion of (107) into the dimethyl acetal (108) with trimethyl orthoformate and Rexyn 101, followed by pyrolytic elimination in refluxing o-xylene, gave (109). Treatment of (109) with n-butyl-lithium and C02 in THF, followed by hydrolysis, afforded the keto-acid (110). Reduction of (110) with borohydride, followed by dehydration with phosphoric acid and esterification, gave (111). 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

Keto acids can be dehydrated to enol lactones (Section III,A,1). They may also undergo esterification with alcohols e.g., /V-methylhydrasteine (104) in methanol at room temperature gave the expected keto ester 126 (R + R = CH2, R1 = CH3) (5,87). Sodium borohydride reduction of keto acid 104 supplies the saturated y-lactone 132 identical with that obtained from enol lactone 98 (5). 

Reductive Esterification. Organosilane reductions of y- or 5-keto acids and esters provide the corresponding lactones as the final products (Eqs. 226 and 227).69,79,402... 

The cyclobutanone (255) reacted with acid to furnish the keto-acid (259). Upon esterification, ketalization and reduction, (259) was converted to the alcohol (260). Mesylation of the alcohol (260) and then treatment of the mesylate with NaN3 in DMSO provided the azide (261). The azide (261) was then transformed to the urethane (262) by reduction and ethyl chloroformate reaction. The urethane (262) was deketalized by acid, nitrosated by N204—NaOAc and decomposed by NaOEt—EtOH to give the ketone (263) 89). The ketone (263) served as a starting material for the synthesis of veatchine (264)90). 

Lactones are cyclic compounds formed through the intramolecular esterification of a hydroxy fatty acid. 7-Lactones and 8-lactones, with fivesided and six-sided rings, respectively have been found in cheese (Jolly and Kosikowski, 1975 Wong et al., 1975 Collins et al., 2004). The origin of the precursor hydroxy fatty acids has been ascribed to a 8-oxidation system in the mammary gland of ruminants (see Fox et al., 2000), the reduction of keto acids (Wong et al., 1975) and/or the action of lipoxygenases and other enzymes present in members of the rumen microflora (Dufosse et al., 1994). Lactones have low flavor thresholds and while their aromas are not specifically cheese-like (their aromas have been described variously as peach, apricot and coconut ), they may contribute to the overall flavor of cheese (see Collins et al., 2004). 

The distribution of metabolites obtained after incubation of pineapple slices with keto acids and keto esters, potential precursors of the corresponding hydroxy compounds, is summarized in Table II. The metabolization steps comprise esterification, reduction to hydroxy compounds, formation of acetoxy esters, and cyclization to the corresponding lactones. Metabolization rate and distribution of formed products strongly depend on the structures of the precursors. The detection of these metabolites proves the enzymatic capability of pineapple tissue to catalyze these conversions, an aspect which might be interesting for future use of pineapple tissue cultures in the production of chiral compounds. 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

Route A Synthesis and Enantioselective Reduction of Keto Acid 3 with Immobilized Proteus vulgaris Followed by Esterification... 

The total synthesis of (+ )-dehydroheliotridine (4), a toxic metabolite of the pyrrolizidine alkaloids (e.g. lasiocarpine and heliotrine), has also been described.2 The pyrrole ring was obtained by reaction of l,6-dihydroxy-2,5-dicyanohexa-l,3,5-triene-l,6-dicarboxylic ester (5) with j3-alanine, which afforded the N-substituted pyrrole ester (6), together with the appropriate amide of oxalic acid. Careful hydrolysis of (6) with dilute alkali afforded the related tricarboxylic acid, which was converted, by Dieckmann cyclization, hydrolysis and decarboxylation, into the keto-acid (7). Esterification of (7) with diazomethane, followed by reduction with lithium aluminium hydride, finally afforded ( )-dehydroheliotridine (4), identical, except in optical rotation, with dehydroheliotridine obtained earlier by Culvenor et al.3... 

The keto ether (187) on treatment with diethyl carbonate in presence of sodium hydride in 1,2-dimethoxyethane afforded the keto ether (188), which was made to react with methyl-lithium in ether, to obtain the tertiary alcohol (189). This on being refluxed with methanolic hydrochloric acid yielded the phenol (190). It was methylated to yield(191) and heated with zinc, zinc iodide and acetic acid to produce pisiferol (192). Its methyl derivative (193) on oxidation with Jones reagent at room temperature, followed by esterification, furnished the keto ester (194). Reduction of (194) with metal hydride produced an alcohol whose tosyl derivative on heating with sodium iodide and zinc dust furnished the ester (195). Its identity was confirmed by comparing its spectral data and melting point with an authentic specimen [77]. The transformation of the ester (195) to pisiferic acid (196) was achieved by treatment with aluminium bromide and ethanethiol. The identity of the resulting pisiferic acid (196) was confirmed by comparison of its spectroscopic properties (IR and NMR) with an authentic specimen [77]. 

The reaction was carried out in a 22 L reactor with EDTA (3.35 g), mercaptoethanol (1.41g), ammonium formate (908 g), and sterile water (18.0 L), which was degassed prior to addition of keto acid sait 58 (800 g). The solution was filtered through a 0.2 p,m filter and transferred to a clean 22-L reactor. NAD+ (23.88 g) was added and the pH adjusted to 6.3 by adding 1 N HCI. This substrate solution was then fed into a membrane reactor with ultrafiltration membrane for enzymatic reduction. The reactor was previously filled with an aqueous mixture of enzymes (d-LDH, 400 units mL-1 with activity 20 units mg-1 and FDH, 20 units mL-1 with activity 76 units mL-1). An appropriate feed rate was used to maintain a conversion of > 90%. The circulation rate was kept between 15 and 30 times that of the feed rate. The aqueous effluent solution thus obtained was adjusted to pH 3.0 with 2 N HCI and extracted with MTBE (5 L). The organic layer was evaporated to obtain 972 g of acid 56 as an off-white solid in a yield of 88%, >90% purity and >99.9% ee. In this process a total of 14.5 kg of 56 was prepared with a productivity of approximately 560 gram per liter per day with good overall 72% yields [113]. To evaluate the optical purity, 56 was converted to methylester by esterification and the ee of methylester was found to be >99.9%. 

The combined action of lithium in liquid ammonia and carbon dioxide upon androst-4-en-3-one led to a synthesis of the /3-keto-ester (189), after esterification of the intermediate acid the reaction is one of reductive methoxycarbonyla-tion.82 Alkylation of the keto-ester (189) afforded a separable mixture of the 4/3-methyl steroid (190) as the major product (55%) and the corresponding 4a-methyl epimer. Reduction of the steroid (190) led to 4a-hydroxymethyl-4/3-methyl-5a-androstan-3/3-ol. Finally in this section, it has been noted that vinyl-magnesium bromide effects 1,4-addition to the a(3-unsaturated ketone 17/3-hydroxy-5a-androst-l-en-3-one to yield la-vinyl-5a-androstan-3-on-17/3-ol, which could be further reduced to the la-ethyl-3-ketone.83... 

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