Dimethyl /?-ketoglutarate

To a mixture of 360 g 50% KOH and 138 ml methanol, add with stirring at -5° 70.5 g dimethyl ester of acetone dicarboxylic acid (dimethyl-beta-ketoglutarate — see method 3 for preparation) and let temperature rise to about 25° over V2 hour. Let stand ten minutes, cool to 0° and add 65 ml ether. Filter, wash precipitate with 65 ml ethanol and 150 ml ether at 0C to get 75 g (III). To 322 ml 1N HCI at 80c, add 41.1 g (I I) and stir twenty minutes cool to 10°, add 211 ml IN HCI, 98.2 g (Ml). 26.4 g Na acetate and 28.2 g methylamine HCI. Stir four hours at room temperature, cool to 10°, and saturate with 410 g KOH. Extract four times with methyl-Cl or benzene (75 ml each, fifteen minutes stirring) and evaporate in vacuum to get the methyl ester of tropan-3-one-2-COOH (IV), which precipitates from the oil (can distill 85/0,2). Test for activity. Dissolve 28.3 g (IV) in 170 ml 10% sulfuric acid cool to -5° and treat with 3.63 kg 1.5% Na-Hg amalgam with vigorous stirring at 0°. See below for easier methods of reducing (IV),... 

It has been shown that JHDMIA demethylates only mono- and dimethyl lysine of histone H3 (H3K36). This was rather unexpected given that the catalytic mechanism of a Jmj C domain does not require a protonated nitrogen, unlike LS D1, and therefore could also have the ability to remove the methyl in all three states. So far, two crystal structures have been deposited in the protein database but without any publication underlining the work. The crystal structures describe two forms of the human JHDMIA lysine demethylase, apo and in a complex with a-ketoglutarate (PDB codes 2yul and 2yu2). 

Other papers of interest in this section report transamination of camphor-3-carbothioamides with secondary cyclic amines, reaction of camphorquinone with dimethyl /S-ketoglutarate, the use of fenchone (212 X=0) in alkene formation from Grignard reagents, bromination of 2-e/itfo-6-endo-dibromobornane to yield 2,3,6-endo-tribromoborn-2-ene, and camphor-enol trimethylsilyl ether formation by quenching the reaction mixture of butyl-lithium and camphor tosyl-hydrazone with trimethylsilyl chloride. ... 

Alkyl-4-ketoglutaric acids 265, potential substrates of transaminases that are important for the nervous system, can be synthesized (from an enol ether 263 that was not isolated) by a Claisen-Johnson rearrangement affording a 2-ethylidene-4-methylglutarate 264 whose ozonolysis in CH2Cl2 at — 78 °G followed by reduction with dimethyl sulfide provided the final product (Scheme 81) <1999TL6577>. 

Recently, Kraus and Maeda have reported an elegant synthesis of the important C-4 o-anisyl derivative 26 in racemic form.85 This route involves pyrrolidine ring synthesis with key steps being Michael addition of the enolate of dimethyl a-ketoglutarate 174 to nitrostyrene derivative 175 followed by cyclization of the adduct 176 under reductive conditions to hemiaminal 177 (Scheme 63). 

A simpler and more versatile route to comparably functionalized bicyclooctanes has been developed more recently by Weiss and his co-workers.174-176 Specifically, the reaction of 1,2-dicarbonyl compounds with dimethyl 3-ketoglutarate (dimethyl acetonedicarboxylate) in aqueous solution at pH 5, or preferably in a citrate-phosphate buffer, followed by hydrolytic decarboxylation, affords 117 in good... 

By condensation of cyclopen tane-l,2-dione with dimethyl 0-ketoglutarate, Weiss and Edwards were able to prepare the [3.3.3]propellanedione 471,1 a molecule in which three cyclopentane rings are conjoined through a common carbon-carbon... 

Three tetracyclo[5.5.1.02,6.010,13]tridecanes are known at present. The reaction of glyoxal with dimethyl 3-ketoglutarate in aqueous solution at room temperature and pH 5 to give after treatment with acid c/,s-bicyclo[3.3.0]octane-3,7-dione has been discussed previously. More careful study of this condesation has led to the discovery that the two tetracyclic triketones 486 and 487 are also formed in low... 

Add with stirring over 1 Vz hours 192 g powdered anhydrous citric acid in 32 g portions to 202 ml (383 g) fuming sulfuric acid (21%). Make the first two additions at 0° carefully the other four at 15 . Stir one hour at room temperature, and for three hours at 35° and 17 hours at 25°. Add dropwise with stirring below 0°, 500 ml methanol over three hours. Keep about fifteen hours at room temperature and add to a stirred mixture of 700 g NaHCOj, 500 g ice and 200 ml water. Filter, wash precipitate with 150 ml 50% aqueous methanol and extract the filtrate with 7X400 ml ether. Dry and evaporate in vacuum (can distill 85/1) to get 110 g oily dimethyl-beta-ketoglutarate (1). Use this in method 1 or as follows. Dissolve 33.6 g KOH in 150 ml methanol and add dropwise at 0° over Vz hour (or at room temperature over one hour) to 43.5 ml (1) in 10 ml methanol. Let stand three hours at room temperature, add 50 ml ether and refrigerate twelve hours to precipitate the dipotassium salt of monomethyl-beta-ketoglutarate (II). Dissolve 10 g succindialdehyde in 200 ml water at -5° and add 41 g (II) and... 

A number of steps are required for the conversion of rac-12 into the cyclic hemiacetal rac-14 (Scheme 3). This compound is important to the rest of the synthesis, since it cannot only be prepared from tryptamine (3) and dimethyl 2-ketoglutarate (4), but can also be obtained readily in substantial amounts and in enantiomerically pure form by degradation of strychnine. As soon as enough of this relay hemiacetal has been secured, assembly of the G ring can be tackled. 

Another version of the Pictet-Spengler reaction uses 2-carboxytryptamines. The reaction is carried out in organic solvent mixtures with TFA as the acid catalyst. The reactions proceed by ipso substitution at C-2, followed by decarboxylation. When used with the dimethyl ester of a-ketoglutaric acid, lactams that are useful intermediates in alkaloid synthesis are formed [348]. 

Acetone, acetonyl-. See 2,5-Hexanedione Acetone chloroform. See Chlorobutanol hemihydrate Chlorobutanol Acetone cyanhydrin Acetone cyanohydrin. See 2-Hydroxy-2-methylpropanenitrile Acetonedicarboxylic acid Acetone-1,3-dicarboxylic acid. See P-Ketoglutaric acid Acetone dimethyl acetal. See Dimethoxypropane Acetone/diphenylamine condensate Acetone/diphenylamine condensates. See Di phenylam i ne-acetone Acetone/formaldehyde condensate CAS 25619-09-4 Uses In food-pkg. adhesives Regulatory FDA 21CFR 175.105... 

Reaction of dimethyl P-ketoglutarate with glyoxal at pH 7 followed by acidification with HCl to pH 2 yields a precipitate containing (705)—(107). Under different condition (e.g. pH 6) the product balance is somewhat altered and a compound possessing the bicyclo[2,2,l]heptane moiety can be made to predominate. ... 

The utility of the method of synthesis of fused five-membered rings by reactions between dimethyl 3-ketoglutarate and 1,2-dicarbonyl compounds is further illustrated this year, with syntheses of the tetraketone (105) from the keto-aldehyde (104) and of the propellane (107) from cyclopentane-1,2-dione (106). ... 

To prepare stock solutions of the a-keto acids and the monoester studied the required amount of the compound was dissolved in distilled water, and then diluted to the mark. The stock solutions of diethyl esters were prepared in dimethyl sulfoxide or freshly distilled acetonitrile. Stock solutions of all compounds were stored at 5 C and kept in an ice bath during use. Oxalacetic acid stock solutions were only stable for a day, the diethyl ester stock solutions, in dimethyl sulfoxide or acetonitrile, were stable for four days. Stock solutions of all other a-keto acids were found to be stable for at least one week and were prepared freshly every week. Concentrated stock solutions of a-ketoglutaric acid (greater than 0.5 M) were found to undergo measurable changes in about four hours. 

Fig. 3.4 Chromatogram of methyl esters obtained from a solution of pure adds and salts, separated on a 6 ft (0.004 m i.d.) glass column packed with 12.5 per cent di(ethylene glyclol) succinate on AW Chromosorb W (45-60 mesh), using temperature programming as follows 80°C for 1 min, 80-100 C at 2.9°C min S 100-133°C at 4.7 C min S 133 220°C at 4.8°C min and 220°C for 2.5 min. Peak identifications are 1, solvent 2, methyl pyruvate 3, methyl lactate 4, methyl 2,2-dimethoxypropionate 5, dimethyl-fumarate 6, methyl benzoate 7, dimethyl succinate 8, methyl laurate 9, dimethyl malate 10, dimethyl 2-ketoglutarate 11, dimethyl 2,2-dimethoxyglutarate 12, trimethyl citrate. (Redrawn with modifications from Zaura and Metcoff, 1969)...

---