Ketones interconversions

In this chapter, we have examined the use of cells and enzymes to chemically transform lipids. We have had to be selective and have predominantly focused attention on the transformation of sterols and steroids. We first explained why these compounds were commercially important and why they only occur in low concentrations in natural systems. We pointed out that a very large number of reaction types are possible, but those which have found greatest use include stereospedfic hydroxylations, alcohol/ketone interconversion, hydrolysis, conjugation and isomerisation. 

Scheme 17 Mechanism of alcohol-ketone interconversion coupled with the hydrogen evolution step." ...

Enols aie related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto-enol tautomerism. (Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group.)... 

This election delocalization stabilizes a conjugated system. Under conditions chosen to bring about their interconversion, the equilibrium between a p,7-unsaturated ketone and an a,p-unsaturated analog favors the conjugated isomer. 

The interconversion of alcohols to ketones is a common biochemical reaction. The introduction of hydroxyl groups into toe steroid nucleus and side chain creates a variety of secondary alcohols. Some of these, especially at positions 3, 7, 11 and 17 are frequently oxidised to ketones. 

This chapter covers not only nuclear and extranuclear quinoxahnecarboxylic acids (and anhydrides) but also the carboxylic esters, acyl halides, carboxamides, carbohydrazides, carbonitriles, carbaldehydes, and (ketonic) acyl derivatives of quinoxaline a few related speceis are also included. To avoid repetition, the interconversions of these quinoxaline derivatives are discussed only at the first opportunity thus the esterification of quinoxalinecarboxylic acids in covered as a reaction of carboxylic acids rather than as a preparative route to carboxylic esters, simply because the section on carboxylic acids precedes that on carboxylic esters. To minimize any confusion, appropriate cross-references have been inserted. 

The most plausible mechanism for the interconversion of la and Ih is shown in Scheme 2. Similar mechanism has been put forward for epimerization of a-substituted ketones under basic conditions and for the equilibration via an enolate prior to nucleophilic substitution was observed by Numazawa et al. (ref. 13). The same mechanism seems to operate in the reduction of some steroid a-haloketones (ref. 14) or tra/ty-3-chloroflavanone (ref. 15) with sodium borohydride where an inversion of configuration takes place at the a carbon parallel to the reduction of the... 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

These catalysts facilitate the interconversion of isomeric compounds and include racemases, optimerases, cis-trans isomerases, intramolecular oxidoreductases and intramolecular transferases. Scheme 10.14 shows the conversion of an aldehyde to a ketone by triose phosphate isomerase. 

In addition to these interconversions, the metabolism of fat and the metabolism of carbohydrate are inseparably related. This fact is most clearly demonstrated by the appearance of such abnormal products of fat oxidation as the so-called ketone bodies in the blood and urine whenever the supply of carbohydrate is deficient or in cases where the organism is unable to metabolize this foodstuff. Whether ketonuria results because the metabolism of fat must occur concomitantly with that of D-glucose (ketolysis), or whether the presence of D-glucose prevents any fat breakdown because it is preferentially oxidized (antiketogenesis) is still a moot question. 

Hydroxyaminobenzo-furan and -thiophene (32a X = O, S) are the unstable enam-ine tautomers of the corresponding oximes (32b). Kinetics of the tautomeric interconversions have been measured, yielding tautomeric constants the latter have been compared with the corresponding keto-enol constants. The enamines are ca 40 times less stable, relative to the oximes, than are the enols, relative to the ketones. The minor tautomers are ca 100 times more stable (relative to the major) for the benzothiophene system. 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

The active site also facilitates the ketone-hemiketal interconversion, so that the product liberated is the hemiketal form of fructose 1,6-diphosphate. 

Formation of mevalonate. The conversion of acetyl CoA to acetoacetyl CoA and then to 3-hydroxy-3-methylglutaryl CoA (3-HMG CoA) corresponds to the biosynthetic pathway for ketone bodies (details on p. 312). In this case, however, the synthesis occurs not in the mitochondria as in ketone body synthesis, but in the smooth endoplasmic reticulum. In the next step, the 3-HMG group is cleaved from the CoA and at the same time reduced to mevalonate with the help of NADPH+H 3-HMG CoA reductase is the key enzyme in cholesterol biosynthesis. It is regulated by repression of transcription (effectors oxysterols such as cholesterol) and by interconversion... 

The word enamine was coined in 1927 by Wittig [27], However, at that time, enamines were usually not considered as reactive intermediates. An early example of enamine catalysis that was not explicitly recognized as enamine-based reaction was the reaction of isatin with ketone nucleophiles (acetone and acetophenone), first pnblished by Lindwall and coworkers in 1932 [28, 31]. Later, the interconversion of imininm ions and enamines in enzymatic reactions was recognized by Westheimer [32, 354]. The first person to propose a modem enamine-based... 

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