A-Oximino acids

Curtius rearrangement of a-oximino acid azides is reported as a new method of synthesis for 3-substituted 5-hydroxyoxadiazoles. In this method, the oxime of an a-ketoester is converted to the acid hydrazide, which in turn is converted to the azide by reaction with nitrous acid 115a). 

Curtius rearrangement of a-oximino acid azides 115a) (see p. 817). 

The reduction of a-oximino acids to a-amino acids is accomplished by catalytic hydrogenation with a Raney nickel or palladium-charcoal catalyst or by the action of sodium or aluminum amalgam. ... 

Several procedures involving the formation of a-oximino acid intermediates for the synthesis of a-amino acids have been described ... 

Nitriles. a-Oximino acids react with phenyl isocyanate in benzene solution at ambient temperatures to form nitriles (equation 1). ... 

This method (Scheme 23) was proposed in 1974 by Ahmad (144) who used excess lithium cyanoborohydride as the reducing agent, a-Oximino acids (80) or equimolar quantities of a-keto acid and hydrox-ylamine were reduced at pH 5 in aqueous solution. This procedure was also successfully applied to the synthesis of N-hydroxytyrosine (35) (95) (Scheme 23). 

However, it seems more likely that the amide (82), and the other bromo-nietabolites of Verongia, are most probably formed directly from an epoxide (85), in which the epoxide ring is derived from the tertiary OH group by nucleophilic attack on the enone system in (84). In addition, since there is considerable evidence, both from in vivo and in vitro studies, that nitriles can be derived in vivo from a-amino-acids by way of a-oximino-acids, it seems most probable that epoxide (86) is the likely precursor of (76). 

Examination of the structure of nocardicin A (1) reveals that the compound contains three a-amino acid units and one a-oximino acid, residue and suggests that the compound is probably derived from a peptide. 

Moreover, it has been demonstrated that a-oximino acids undergo facile dehydration/decarboxylation to give nitriles in vitro (180) and in vivo (181),... 

In the present preparation, ethyl acetoacetate is treated with sufficient nitrous acid to convert half into the a-nitroso (or a-oximino) ester, which is reduced by zinc and acetic acid to the a-amino ester (I). The latter then condenses with... 

An interesting comparison between a catalytic hydrogenation and a zinc and acetic acid reduction is observed in the case of the oximino acid (49). The cw-fused hydroxamic acid (50) was the sole... 

The same oximino acid (49) underwent a cyclodehydration on treatment with dicyclohexyl carbodiimide to form the unsaturated hydroxamic acid (52) in almost quantitative yield. 

An analogous result was obtained by the hydrogenation of five-membered cyclic nitronate. The latter reaction afforded a-oximino-Y-hydroxypentane-1,5-dicarboxylic acid derivative (Scheme 3.116, Eq. 2) in high yield (83%) (319). 

This compound, when treated with nitrosyl sulphate was decomposed into a-oximino-sec-butylacetic acid, which, on reduction with zinc dust and hydi ochloric acid in alcohol, gave a 60 per cent, yield of dl-isoleucine —... 

Construction of pyrazine rings from a-amino nitriles has been sometimes completed through multistep reactions. For example, 2-aminopyrazine 1-oxide 163 is synthesized via amide intermediate 162 formed by reaction of methyl a-aminocyanoacetate with a-oximino carboxylic acid (Scheme 45) <1994H(38)1581>. 

There are very few reactions of real synthetic significance which proceed via condensation of two 1,3-electrophile-nucleophile species. Probably the most important of this latter type of reaction is the synthesis of pyrazines by self-condensation of an a-acylamino compound to the dihydropyrazine followed by aromatization (equation 132). The a-acylamino compounds, which dimerize spontaneously, are normally generated in situ, for example by treatment of a- hydroxy carbonyl compounds with ammonium acetate or by reduction of a-azido, -nitro or -oximino carbonyl compounds. Cyclodimerization of a-amino acids gives 2,5-dioxopiperazines (equation 133), many derivatives of which occur as natural products. Two further reactions which illustrate the 1,3-electrophile-nucleophile approach are outlined in equations (134) and (135), but su i processes are of little general utility. 

After development has taken place in a layer containing silver halide, two images are present a negative one in metallic silver and a positive one in silver halide. The silver halide can be converted to a silver salt of a thiobarbituric acid, which is less soluble than the silver halide. Nitrosation of this insoluble silver salt produces an a-oximino ketone, which when treated with iron(II) ion yields a positive image in blue-green iron chelate.136... 

Reduction of a-oximino esters.1 This combination (3.15 2.8) reduces a-ox-imino esters (1 equiv.) to a-amino esters in a buffered solution (pH 7). L-Tartaric acid is a useful buffer it does not induce any enantiomeric selectivity, but affords clean reactions. 

Nitriles are also formed in excellent yields by the decarboxylation and dehydration of oximino acids with warm acetic anhydride. A good route for obtaining the starting materials consists in the condensation of aldehydes with rhodanine followed by cleavage of the product with alkali and treatment with hydroxylamine. 

Similarly, the a-methylene group of acetoacetic ester is oximinated by the action of sodium nitrite in glacial acetic acid (63%). Nitrosation of alkylated malonic, acetoacetic, and benzoyl acetic esters with subsequent cleavage affords an excellent synthesis for a-oximino esters, RC(=-NOH)COjC2Hj. A survey of several possible procedures for this conversion has been made." If a /3-keto acid is nitrosated, then the Carboxyl group is lost and an a-oximino ketone is formed, viz.,... 

A closely related reaction involves the conversion of a-oximino ketones to nitriles by pyrolysis or by the action of thionyl chloride (75%). This reaction constitutes a step in a series for the synthesis of aliphatic acids from valeric to lauric acids. 

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