Keto-Acids hydrated

As shown in equation 12, the chemistry of this developer s oxidation and decomposition has been found to be less simple than first envisioned. One oxidation product, tetramethyl succinic acid (18), is not found under normal circumstances. Instead, the products are the a-hydroxyacid (20) and the a-ketoacid (22). When silver bromide is the oxidant, only the two-electron oxidation and hydrolysis occur to give (20). When silver chloride is the oxidant, a four-electron oxidation can occur to give (22). In model experiments the hydroxyacid was not converted to the keto acid. Therefore, it seemed that the two-electron intermediate triketone hydrate (19) in the presence of a stronger oxidant would reduce more silver, possibly involving a species such as (21) as a likely reactive intermediate. This mechanism was verified experimentally, using a controlled, constant electrochemical potential. At potentials like that of silver chloride, four electrons were used at lower potentials only two were used (104). 

Compound 2 is hydrolyzed in boiling water to form the hydrate of benzamidotrifluoroacetone (3) with loss of carbon dioxide. This behavior is readily understood in terms of a facile decarboxylation of the initially formed jS-keto acid. 

DAG (-)-2,3 4,6-di-0-isopropylidene-2-keto-L-gulonic acid hydrate [L-a /Zo-2-hexulosonic acid, bis-O-(l-methylethylidine)-]... 

A. fi(-)-a-(l-Naphthyl)ethylamine. A mixture of 58.44 g. (0.20 mole) of (-)-2,3 4,6-di-0-isopropylidene-2-keto-L-gulonic acid hydrate [(-)-DAG] (Note 1) and 1.7 1. of acetone (Note 2) is placed in a 3-1. Erlenmeyer flask. A boiling chip is added, and the mixture is heated to a gentle boil. To the resulting hot solution is added cautiously but rapidly, over a 1 minute period, 34.24 g. (0.20 mole) of racemic y.- 1 -naphthyl)et hylamine (Note 3) in 100 ml. of acetone. The mixture is allowed to stand at room temperature for approximately 4 hours. The (-)-amine (-)-DAG salt is filtered with suction, washed with 100 ml. of acetone, and dried in a vacuum oven at 60° to constant weight. The yield of the crude (-)-amine (-)DAG salt is 73-76 g., m.p. 205-207° (decomp.) (Note 4), [a]p —14.2° (c 1.01%, methanol). For crystallization, the crude salt and 4.2 1. of ethanol (Note 5) are placed in a 5-1. round-bottomed flask fitted with a reflux condenser and a mechanical stirrer. The mixture is stirred and heated at reflux... 

Benzopyran-3-one, l,4-dihydro-6,7-dimethoxy-], 55, 45 Isocyamde, benzyl-, 55, 98 Isocyanide, butyl-, 55, 98 ISOCYANIDE, tert-butyl- [Isocyamde, 1,1-dimethylethyl-], 55, 96 Isocyamde, cyclohexyl-, 55, 98 Isocyamde, dodecanyl-, 55, 98 Isocyamde, ethyl, 55,98 Isocyamde, methyl, 55, 98 Isocyamde, phenyl-, 55, 98 (-)-2,3 4,6-Di-0-isopropylidene-2-keto-L-gulomc acid, hydrate [L-jcy/o-2-Hex-ulosomc acid, bis-<9-( 1 -mcthylcthyl-ldene)-], 55,80, 81 ISOXAZOl F, 3-(4-chlorophenv1)-5-(4-methoxyphenyl)-, 55, 39 Isoxazole,5 -(4-chloropheny l)-3-(4-me th-oxyphenyl)-, 55,42... 

The RuClj/aq. HCl system is effective for hydration of phenylpropiolic acid to give acetophenone and carbon dioxide via the P-keto acid (Eq. 6.53) [86]. 

This arrangement of subgroups is due to the hypothetical biosynthetic sequence. It assumes that precursors for these alkaloids are the Af-methylphth-alideisoquinolinium salts, whose presence in plants is well documented. Enol lactones may be the initial degradation products formed in a Hofmann-type jft-elimination process. They could be hydrated to the keto acids and in the next step oxidated in air to the diketo acids. Diketo adds may undergo further oxidative cleavage to yield simple alkaloids of the fumariflorine (87) type 85,86), which seem to be the final products of the metabolism of phthalideiso-quinoline alkaloids. 

Steric hindrances may also be the reason why quaternary salts of 8-alkylnarcotoline (130) were transformed during Hofmann degradation to analogous keto acids (131) (111,112) and not to the enol lactones (Scheme 24). In some cases (5,87) the keto acids and their esters have been synthesized from the corresponding enol lactones by hydration (Section III,A,2). Nornarceine (107) was prepared from JV-benzyl-(—)-a-narcotinium bromide (139, X = Br) by Hofmann degradation followed by N-debenzylation and ester hydrolysis (109). 

Stacey and Turton61 showed that 2,3,4,6-tetra-O-acetyl-D-glucosone hydrate can be used in two of the established methods for the production of analogs of ascorbic acid. Methods of preparation, reactions, and importance of this class of compound have been reviewed previously.62 Addition of hydrogen cyanide to 2,3,4,6-tetra-O-acetyl-D-glucosone hydrate, and hydrolysis by the usual methods, led to a keto-acid (not isolated) which was converted by enolization and lactonization to D-gluco-ascorbic acid monohydrate, isolated in 50% yield. The product was identified by its (52) F. Smith, Advances in Carbohydrate Chem., 2, 79 (1946). 

Isoleucine and valine. The first four reactions in the degradation of isoleucine and valine are identical. Initially, both amino acids undergo transamination reactions to form a-keto-/T methyl valerate and a-ketoiso valerate, respectively. This is followed by the formation of CoA derivatives, and oxidative decarboxylation, oxidation, and dehydration reactions. The product of the isoleucine pathway is then hydrated, dehydrogenated, and cleaved to form acetyl-CoA and propionyl-CoA. In the valine degradative pathway the a-keto acid intermediate is converted into propionyl-CoA after a double bond is hydrated and CoA is removed by hydrolysis. After the formation of an aldehyde by the oxidation of the hydroxyl group, propionyl-CoA is produced as a new thioester is formed during an oxidative decarboxylation. 

The second method involves staining larval entry holes in pulse seeds. In the third method, ninhydrin (triketohydrindene hydrate) has been used to react with the body fluids of insects developing inside grains. A purple spot develops when ninhydrin reacts with the free amino acids (and keto acids) present in the body fluids of insects (Dennis and Decker, 1962). Ninhydrin at a 0.3% level in acetone is impregnated into filter paper. When infested grains are crushed between the folds of ninhydrin-treated paper, the body fluids from the crushed insect bodies react with ninhydrin in the paper. Purple spots develop in the paper in 20-30 minutes at room temperature (20-25 °C), the number of spots indicating the number of insects present. 

S-keto-L-ascorbic acid (hydrated form isolated)... 

A soln. of l-keto-l,2,3,4-tetrahydrophenanthrene in acetic anhydride treated dropwise -with swirling in an ice bath with a soln. of coned. H2S04 in acetic anhydride, allowed to stand 2 hrs. at room temp., worked up, and the process repeated - l-keto-l,2,3,4-tetrahydrophen-anthrene-2-sulfonic acid hydrate (startg. m. f. 183). Y 85%. (F. e. s. C. Djerassi, J. Org. Chem. 13, 848 (1948).)... 

Citrate is not a good substrate for decarboxylation. Decarboxylation is usually carried out on alpha-keto acids (like pyruvate, above) or alpha-hydroxy acids. Conversion of citrate into an alpha-hydroxy acid involves a two-step process of water removal (dehydration), making a double bond, and readdition (hydration) of the intermediate—aconitate as Figure 10-4 shows. The enzyme responsible for this isomerization is aconitase. 

DH>-isopropylidene-2-keto-L-gulonic acid hydrate. 113 Diisopropyl sulfide. 283... 

Di-0-isopropyUdene-2-keto-L-gulonic acid hydrate, (-)-DAG, (1). Available from Commercial Development Dept., HoiTman-LaRoche, Inc. 

RESOLUTION Cupric perchlorate. 2,3 4,5-Di-0-tsopropylidenc-2-keto-L-gulomc acid hydrate. Tartaric acid. 

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