Oxalacetate synthesis

Sucrow, studying the chemistry of the enehydrazines (83CB1520), has found several methods for the synthesis of pyrazoles. For example, he has described (79CB1712) the cyclization of monomethylhydrazones of dialkyl oxalacetates to 5-pyrazolones via an enehydrazine (Scheme 47). 

The method of synthesis described for chloropyruvic acid is essentially that reported. This procedure affords the product in excellent yields from readily available materials by a short, convenient route. Other less acceptable methods involve chlorination of pyruvic acid with sulfur dichloride or hypochlorous acid and the treatment of ethyl chloro(l-hydroxyheptyl)- or (o -hydroxybenzyl)oxalacetate 7-lactone with 50% hydrochloric acid. ... 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

Following the synthesis by Comforth and his associates18 of NeuAc from oxalacetate and 2-acetamido-2-deoxy-D-mannose, Ghalambor and Heath29,31 prepared KDO (isolated as the crystalline methyl 2,4,5,7,8-penta-0-acetyl-3-deoxy-D-manno-2-octulopyranosonate, 70) from D-arabinose and oxalacetate by an analogous reaction (see Scheme 20). 

The procedure that Kuhn and Baschang99 had reported for the synthesis of NeuAc was extended by Hershberger and Binkley100 to a synthesis of KDO, as follows. Condensation of di-ter -butyl oxalacetate (85 see Scheme 25) with D-arabinose gave the epimeric mixture of lactone esters, 86 and 87, which was separated by fractional recrystallization. When 86 was heated in aqueous solution, the enol lactone, 88, was produced from 87, an enol lactone diastereomeric with 88 was obtained under these conditions. Compound 88 was converted into ammonium KDO by treatment with aqueous ammonia. 

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

These syntlieses give no indication as to the structure of aspartic acid, the constitutional formula of which is based upon Kolbe s work, that it is amino-succinic acid the only synthesis of aspartic acid which confirms this constitution appears to be that by Piutti in 1887. Sodium oxalacetic ester, prepared from oxalic ester and acetic ester in the presence of sodium ethylate —... 

The synthesis of l-carbethoxy-2,3-dioxopyrrolizidine (cf. refs. 61 and 62) starting with d -pyrroline and ethyl oxalacetate has been reported.97... 

The basic starting substrate for fatty acid synthesis is acetyl-CoA (see below). In ruminants, the provision of this substrate is straightfoward. Acetate from blood (+ CoA + ATP) is converted by the cytosolic acetyl-CoA synthase (EC 2.3.1.169) to AMP and acetyl-CoA, which can then be used for fatty acid synthesis. In non-ruminants, glucose is converted via the glycolytic pathway to pyruvate, which is, in turn, converted to acetyl-CoA in mitochondria. Acetyl-CoA thus formed is converted to citrate which passes out to the cytosol where it is cleaved by ATP-citrate lyase (EC 2.3.3.8) to acetyl-CoA + oxalacetate (OAA). This transport of acetyl-CoA from... 

Both of the N-acylated neuraminic acids mentioned have been synthesized. Comforth, Daines, and Gottschalk192 made the first synthesis of N-acetylneuraminic acid. They condensed 2-acetamido-2-deoxy-D-glucose with oxalacetic acid at pH 11, and obtained a low yield (about 2%). Carroll and Comforth193 obtained a higher yield from 2-acetamido-2-deoxy-D-mannose and oxalacetic acid. 

Kuhn and Baschang194 used the same principle for the synthesis of N-acylated neuraminic acids by condensing the potassium salt of di-ferf-butyl oxalacetate (64) with 2-acetamido-2-deoxy-D-mannose (63) (or with 2-acetamido-4,6-0-benzylidene-2-deoxy-D-glucose), they obtained the corresponding lactone (65). This was hydrolyzed with water at 90-100° to give N-acetylneuraminic lactone (66) in a yield of 34%. 

Synthesis of N-glycoloylneuraminic acid was achieved by Faillard and Blohm.198 By the general procedure of Gault1 7 and Kuhn and Baschang,194 2-deoxy-2-glycoloylamido-D-glucose was condensed with the potassium salt of di-tert-butyl oxalacetate. The tert-butyloxy lactone obtained was converted into N-glycoloylneuraminic lactone. 

Kumagai and coworkers11131 developed an enzymatic procedure to produce d-alanine from fumarate by means of aspartase (E. C. 4.3.1.1), aspartate racemase, and D-amino acid aminotransferase (Fig. 17-12). Aspartase catalyzes conversion of fumarate into L-aspartate, which is racemized to form D-aspartate. D-Amino acid aminotransferase catalyzes transamination between D-aspartate and pyruvate to produce D-alanine and oxalacetate. This 2-oxo acid is easily decarboxylated spontaneously to form pyruvate in the presence of metals. Thus, the transamination proceeds exclusively toward the direction of D-alanine synthesis, and total conversion of fumarate into D-alanine was achieved. 

The essential starting material for the total synthesis of ( )-aku-ammigine (21) and (+ )-tetrahydroalstonine (22) was the tetracyclic unsaturated ketone 23 (3). This was prepared by condensation of tryp-tamine hydrochloride with oxalacetic acid monomethyl ester which gave the tetrahydro- 8-carboline 24. 

Aldol reactions of this type, involving 2-acetamido-2-deoxyaldohexoses, have been studied in connection with the chemical synthesis of A -acetyl-neuraminic acid (50) and related substances, and, for this reason, the choice of the dicarbonyl compound has thus far been limited to oxalacetic acid and its esters. Oxalacetic acid condenses readily with 2-acetamido-2-deoxyaldohexoses in aqueous solution at pH 11. Under these conditions, acetamido sugars partially epimerize, and the aldol reaction takes place for both of the 2-acetamido-2-deoxyaldohexoses present. The complexity of the reaction is further increased by the formation of asymmetric centers at carbon atoms 3 and 4 of the condensation products, namely, diacids (45) and (48), and this can result in the formation of four diastereo-isomers from each sugar. The reaction using 2-acetamido-2-deoxy-o-rnannose (47) has been the one most extensively studied. In this... 

The introduction of the a-keto acid function on the way to the ulosonic acids is a main problem of their syntheses. By analogy with the biosynthetic pathway, the aldol reaction between sugar aldehydes and a pyruvate equivalents seems to be the most simple and versatile. As it has been demonstrated by Comforth [74] in the first chemical synthesis, the reaction of arabinose and oxalacetic acid as pyruvate equivalent, followed by decarboxylation afforded KDO, albeit in low yield. This condensation has been optimized by use of Ni(II) catalyst for the decarboxylation [75], In this case, reaction of D-mannose and oxalacetic acid gave KDN (11) and its D-manno epimer 37 in 70% yield [75] (Scheme 12). 

However, the lack of stereochemical control at C-4 of newly created asymmetric center, resulting in the formation of two diastereomers, is the great disadvantage. Despite this, Comforth s methodology remains still the best choice for preparation of the selected ulosonic acids. It is a case of synthesis of nine stereoisomeric 5,7-diacetamido-3,5,7,9-tetradeoxy-2-nonulosonic acids [76]. The synthesis was performed by condensation of an appropriate 2,4-diacetamido-2,4,6-trideoxy-hexopiranoses with oxalacetic acid under basic conditions (Scheme 13), used previously in the preparation of Neu5Ac [77]. 

The synthesis of barbituric acid can be best accomplished from diethyl malonate and urea, with an alkaline catalyst, such as sodium ethoxide in ethanol [113]. Barbituric acid-2- C has been prepared from urea- C and diethyl malonate [114]. The 4- C and 5- C compounds have been obtained by the pyrolysis of diethyl oxalacetate-3- C, which produced an equimolar mixture of 4- and 5- C barbituric acid after a rather lengthy procedure [115]. 

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