Unsaturated ketoacids

However, the key disadvantage of the reaction described in [199] is observed in the first step—synthesis of unsaturated ketoacids 236 with very low yields (20-30%) [200]. The same authors [201] proposed a multicomponent approach to azolopyr-imidinecarboxylic acids. The reactions of pyruvic acid 239 and aromatic aldehydes 240 with 2-aminobenzimidazole, 5-aminotetrazole 156 and 3-amino-1,2,4-triazole 147 in alcohols, DMF and acetic acid were studied (Scheme 3.67). 

The different reaction pathways described in [202] were rationalized from a mechanistic point of view. The reactions of arylidenepyruvic acids 236 with 3-substituted 5-aminopyrazoles most likely start with nucleophilic attack of the enone system of the unsaturated ketoacid at the (3-position to the carbonyl group (Scheme 3.71). In the case of amines 220 and 221, the nucleophilic center CH group at position 4 of aminopyrazole causes the formation of... 

The interaction of arylidenepyruvic acids with 5-aminotetrazole and 2-aminobenzimidazole most likely involves the nucleophilic attack of the enone fragment of the unsaturated ketoacid 236 by the endocyclic nitrogen atom. 

Use of the related unsaturated ketoacid LX VIII in the initial condensation gave the tetracyclic lactam LXIX in which the double bond has shifted from its original position. An attempt to introduce additional... 

Since both inhibitors must be converted into the active form 4 by the enzyme, neither one inhibits the holoenzyme in the pyridoxamine form or the apoenzyme. The reactive enzyme product itself must be an aflSnity labeling agent of the enzyme. As expected, p, y-unsaturated -ketoacids are irreversible inhibitors of the enzyme iii the pyridoxamine form. Finally, the pH rate profile for the inhibitor is the same as that for substrate turnover this need not be the case, but does obtain in this example. 

The 9,10-phosphonostearic acid in form of its sodium salt shows a good thermal stability and was efficient as an inhibitor in rust protection. The diethyl-phosphonoacetoxystearic acid methyl ester is used as additive in high-pressure lubricants. Rust protection properties are also shown by 9,10-phosphonostearyl alcohol [157]. Trisodium 9,10-phosphonostearate possesses the best surface activity in an 0.2% aqueous solution showing 33 mN/m at 30°C and a pH value of 10.5 [156]. By the addition of dialkyl phosphite to a,p-unsaturated ketones the y-oxophosphonic acids are available [159]. Addition of dialkyl phosphite to y-ketoacids leads to a-hydroxy-y-carboxyphosphonates see Eq. (86) ... 

A very simple synthesis of the pheromone exo-brevicomin (4i) proceeds via an electrochemical Kolbe condensation between the unsaturated carboxylic acid 39 and the ketoacid 40, followed by hydroxylation of the double bond with OSO4, as... 

Values of rate constants in reaction (18 a) have been calculated (40) by means of this and similar treatments for a-ketoacids (44, 45), pyri-dinecarboxylic acids (46, 47), unsaturated acids (48, 49), phthalic acid (50), carbonyl compounds (51,52), iodobenzenes bearing ionisable groupings (53), etc. 

Acids of low molecular weight form readily with IOB [bis(acyloxy)iodo]benzenes, PhI(OOCR)2, in solution. However, a-ketoacids did not afford the corresponding compounds, because they were readily decarboxylated, in dioxane, at room temperature. Decarboxylation also occurred with a,/i-unsaturated acids, especially those having an aryl group at the /3-position. The reaction started with the acid and IOB the intermediate formed reacted further with A-chloro-, A-bromo-, or A-iodosuccinimide to afford the decarboxylated products, i.e. haloalkenes the stereochemistry of the double bond was largely retained and best results were obtained with A-bromosuccinimide (NBS). 

Lewis295 300 considers that the main intermediate in the rearrangement to the y-ketoacid is the unsaturated acetal 35, which can give methyl levulate in the following way ... 

Less frequently, unsaturated 1,4-ketoacids were employed and these 207-209 qj. hydrazones afford 12 directly. Synthesis of 12 is also possible from unsaturated y-lactones 210-21S S-bromo-, " 3-alkylthio-, or 2-hydroxy-l,4-ketoacids. The reaction takes place with simultaneous elimination of water or other residues, although it is claimed that in some cases the elimination of water is slower since the corresponding 4-hydroxy derivatives (13) were isolated.However, the structure of the latter compounds... 

The retro-ene reaction cleaves an unsaturated compound into two unsaturated fragments. A common example of a retro-ene reaction in organic synthesis is the acid-catalyzed decarboxylation of a (B-ketoester. The ester is hydrolyzed to the (3-ketoacid by the aqueous acid, which rapidly loses carbon dioxide to form enol. The loss of CO2 drives the reaction to the right-hand side. The enol rapidly tautomerizes to the methyl ketone (Scheme 8.17). 

The same allylic alcohols (142) undergo regiospecific oxidative cleavage with pyridinium chloro-chromate at the ethylenic bond to give, after saponification, a-hydroxyacids (145). Extension of this reaction to a -unsaturated ketones (146), obtained by oxidation of secondary alcohols with silver carbonate on celite, affords a-ketoacids (147) <88TL626l>. 

In analogy to allyl halogenides, iodobenzene and other aromatic iodo derivatives can be reacted with Ni(CO)4 and acetylene at reaction temperatures above 100 °C with formation of y-ketoacids or their esters [418, 442], which may be considered as hydrolysis products of p,y-unsaturated y-lac-tones or as hydrogenation products of a,p-unsaturated y-ketoacids or -esters. a,p-Unsaturated y-ketoacids or -esters will be hydrogenated under the reaction conditions, but do not take up carbon monoxide because of the presence of electrophilic substituents. Besides allyl halogenides, allyl alcohols, -ethers and -esters may also be reacted to give unsaturated acids or esters. 

The demonstration that acetyl-CoA is a relatively stable thiolester as well as later reports from Lynen s laboratory showing, (a) that thiolester derivatives of saturated, unsaturated and j8-ketoacids could be differentiated from one another by differences in their ultraviolet absorption spectra, and (b) that acyl-CoA analogs (i.e. thiolesters of A-acetylthioethano-lamine and panthetheine) are catalytically active substrates for sheep liver enzymes, provided the much needed tools for more definitive studies on the role of acyl-CoA derivatives in intermediary metabolism. These studies were facilitated also by the eventual development of reliable methods for the isolation of substrate quantities of CoA of relatively high purity.8... 

Oxoacids (ketoacids) are less common than hydroxy acids. Saturated oxoacids with 10-24 carbon atoms and unsaturated oxoacids Fatty Melting point Fatty Melting point... 

Stetter and Lorenz reported in 1985 that a thiazolylidine catalyst could promote the addition of a-ketoacid derivatives (17) to activated olefins (18) with loss of CO2 to give 1,4-diketones (19)7 The reaction has been called biomimetic because of its resemblance to the family of biochemical transformations effected by thiamine diphosphate-dependent enzymes acting on pyruvate While the original report was limited to alkyl vinyl ketones, more recent work by Scheldt and co-workers has greatly expanded the scope of this reaction by employing a, 3-unsaturated 2-acylimidazoles as the activated olefin component. ... 

Cossio and coworkers found a route to 3-pyrrohn-2-ones by condensation of amines with y-ketoacids (1,4-dicarbonyls) (Scheme 83 2010JOC7435). For example, microwave irradiation of ketoadd 325 and benzylamine (326) in the presence of acetic acid gives 3-pyrroHn-2-one 327 this reaction did not proceed in the absence of microwave irradiation. Montforts and Schwartz used a condensation of an aldehyde-ester 1,4-dicarbonyl to prepare a 3-pyrroUn-2-one building block en route to boneUin dimethyl ester (o%o-pyrrole bile pigment) (1991LAC709). Peterson and coworkers obtained simple 3-pyrrolin-2-ones by condensation of unsaturated 1,4-dialdehydes with primary amines (1997MI3). 

Trost and Salzmann 168) were able to stereoselectively introduce an E double bond by their sulfenylation-dehydrosulfenylation method (Scheme 64). Palladium catalyzed telomerization of butadiene (358) by Tsuji et al. 169) afforded diene (360) (Scheme 65). Ketoacid ester (363), obtained by terminal olefin oxidation and subsequent reduction, was treated with diphenyldiselenide and the resultant phenylselenyl group oxidatively removed to give the E a,P-unsaturated keto ester (365). 

Unsaturated organic acids (e.g., acrylic acid) represent an exception, however, as the presence of the C=C double bond in these molecules provides a site for reasonably rapid OH addition and thus shorter gas-phase lifetimes. Furthermore, limited data on the ketoacids [e.g., pyruvic acid, CH3C(0)C(0)0H] suggested that these species undergo rapid photolysis see section IX-F-9. 

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