Of keto acids

Sorm" " found that when cholesterol acetate (67) is oxidized by chromic acid in acetic acid-water at 55°, crystalline keto seco-acid (69) is obtained in 25-30 % yield from the mother liquors after removal of successive crops of 7-ketocholesterol acetate (68). Reaction of keto acid (69) with benzoyl chloride in pyridine gives a dehydration product, shown" to be the )5-lactone... 

P-Acetoxy-5-hydroxy-B-mrcholestan-6-carboxylic Acid 5,6-Lactone (TO)."" A solution of 5 g (0.011 mole) of keto acid (69), 4.4 g of benzoyl chloride and 10 ml of anhydrous pyridine is allowed to stand for 3 days at room temperature. After a short period the mixture turns red-brown and at the end of the reaction the dark semi-solid mass is poured into 200 ml of water and extracted with two 100 ml portions of ether. The ethereal extracts are washed twice with equal portions of 5 % sodium hydroxide and water, dried and the ether evaporated. The red sirupy residue is mixed with 10 ml of methanol and a brown solid separates immediately. After standing for 1 hr the solid is removed by filtration and washed with methanol. A second crop is obtained upon concentration of the filtrate. The combined crops are recrystallized twice from methanol to give (70) as white needles mp 124-125° yield 2.8 g (58 %). 

Ring contraction by Baeyer-Villiger oxidation of 5-hydroxy-6-keto steroids—cyclization of keto acids 3/S-acetoxy-B-norandrost-5-en-17-one from 3/3-acetoxyandrost-5-en-17-one, 434... 

The reachons of -keto acid derivatives with tnfluoromethylsulfenyl chlonde give the a-tnfluoromethanesulfenyl substitution products [4 The products can be treated with a dunethyl sulfoxide-water soluhon to form tnfluoromethylthioke-tones or with potassium hydroxide solution to give tnfluoromethylthroacetic acid (equahon 3) (Table 2)... 

Of greater importance for the preparation of these substances is the reaction first observed by Locquin in 1906 and independently treated later by Bougault. These authors have shown that semi-carbazones of -keto acids (49) are cyclized under the influence of aqueous sodium hydroxide directly to the 6-substituted 2,5-dioxotetra-hydro-l,2,4-triazines (50). The reaction was usually carried out at... 

However, for the preparation of derivatives which contain a functional group directly attached to position 6, the application of the foregoing cyclization method is considerably limited by the availability or existence of the required derivatives of -keto acids and may also be affected by differences in their reactivity. Cyclization of thiosemicarbazones was, therefore, used for these substances only in the case of the 6-carboxylic acid (see also Section II,B,2,a). Of the other derivatives known, the 6-acetic acid ester should be mentioned. Recently some further derivatives of dioxotriazine-6-carboxylic acid were reported. ... 

The solubility of the resulting product may dictate the choice of solvent. Reductive alkylation of norepinephrine with a series of keto acids proceeded smoothly over platinum oxide in methanol-acetic acid mixtures. However, when n = 4 or 5, the product tended to precipitate from solution, making catalyst separation difficult. The problem was circumvented by using glacial acetic acid as solvent 38). 

Finally, 1-ethyl-2-methyl indole was reacted111 with pyromellitic anhydride to give a mixture of keto acids, as in Scheme 12, which was then treated with diphenylamines to yield bisphthalides such as 33 and 34. These color formers produce orange images on development, as also do those in which the indole residue is replaced by a 4-dialkylaminophenyl group. 

The reaction of keto acids with phenols is mainly used to prepare fluoran compounds developing colors from orange to red. 

Table 3 shows melting points of a few representative keto acids (72). The reaction of keto acids (66) with phenols (67) is usually carried out in 70-90% sulfuric acid at 50-150°C, or in an aromatic solvent such as benzene, toluene, or chlorobenzene at reflux in the presence... 

The reaction of keto acids (79) having no amino group with 3-alkoxy-diphenylamines (80) is used to synthesize 3 -anilinofluorans (81), especially near-infrared-absorbing fluoran compounds (Eq. 6). 

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). 

From the very successful developments of the alcohol dehydrogenase technology for production of secondary alcohols and enzymatic reductive amination of keto-acids for production of amino acids, it is expected that we will also soon see applications for other enzymatic redox chemistries for example, reduction of unsaturated carbonyl compounds with... 

Aldol reaction of keto-acid 21 with aldehyde 10 and esterification of the resulting acids with alcohol 22 led rapidly to cyclization precursor 23 and its 6S,7R-diastereomer (not shown). RCM using ruthenium initiator 3 (0.1 equiv) in dichloromethane (0.0015 M) at 25 °C afforded macrolactones 24a and 24b in a 1.2 1 ratio. Deprotection and epoxidation of the desired macrolactone, 24a, afforded epothilone A (4) via 25a (epothilone C) (Scheme 5). Varying a number of reaction parameters, such as solvent, temperature and concentration, failed to improve significantly the Z-selectivity of the RCM. However, in the context of the epothilone project, the formation of the E-isomer 24b could actually be viewed as beneficial since it allowed preparation of the epothilone A analog 26 for biological evaluation. 

Figure 1 shows the X-ray crystal structure of the (R)-(+)-l-phenylethyl-amine salt of keto-acid 37a prior to reaction and following 70% conversion to the corresponding cyclobutanol 38b. The structure of the mixed crystal is... 

Amides of keto acids were reduced to amides of hydroxy acids biochemically using Saccharomyces cerevisiae to give optically pure products [7059]. Refluxing with lithium aluminum hydride in ether for 6 hours reduced both the ketonic and the amidic carbonyl in A -methyl-5-phenyl-5-oxopentanamide and gave 82% yield of 5-methylamino-l-phenylpentanol [1134]. 

Nitriles of keto acids are reduced with lithium aluminum hydride at both functions. Benzoyl cyanide afforded 2-amino-1-phenylethanol in 86% yield... 

Phytochemical Reduction of Keto Acids and Keto Aldehydes. 85... 

Reaction between a long-chain ketone and a diol will lead to a surfactant that contains a ketal bond. The synthesis is analogous with those given in Figs. 13 and 14 for the preparation of acetal surfactants [52]. Ketal-based surfactants have also been prepared in good yields from esters of keto acids by either of two routes, as shown in Fig. 15 [53-55]. 

Synthesis of Keto-Acids. Action of Sodium Ethoxide on Diethylcyclo-pentanone-2-Carboxylate-2-Acetate. J. Indian chem. Soc. 17, I6l (1940). 

Exposure of keto acids 286 to ozone at low temperature followed by purging with excess ozone and the addition of silica gel and aqueous sulfuric acid led, over several days, to the clean formation of the desired tetracyclic artemisinin analogs 287 modified at C-3 and C-9 (Equation 35 Table 25) <1996JME2900>. 

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