595-37-9Relevant academic research and scientific papers
Identification of 2,2-Dimethylbutanoic Acid (HST5040), a Clinical Development Candidate for the Treatment of Propionic Acidemia and Methylmalonic Acidemia
Armstrong, Allison J.,Henke, Brad R.,Collado, Maria Sol,Taylor, Justin M.,Pourtaheri, Taylor D.,Dillberger, John E.,Roper, Thomas D.,Wamhoff, Brian R.,Olson, Matthew W.,Figler, Robert A.,Hoang, Stephen A.,Reardon, John E.,Johns, Brian A.
, p. 5037 - 5048 (2021)
Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive disorders of propionyl-CoA (P-CoA) catabolism, caused by a deficiency in the enzymes P-CoA carboxylase and methylmalonyl-CoA (M-CoA) mutase, respectively. PA and MMA are classified as intoxication-type inborn errors of metabolism because the intramitochondrial accumulation of P-CoA, M-CoA, and other metabolites results in secondary inhibition of multiple pathways of intermediary metabolism, leading to organ dysfunction and failure. Herein, we describe the structure-activity relationships of a series of short-chain carboxylic acids which reduce disease-related metabolites in PA and MMA primary hepatocyte disease models. These studies culminated in the identification of 2,2-dimethylbutanoic acid (10, HST5040) as a clinical candidate for the treatment of PA and MMA. Additionally, we describe the in vitro and in vivo absorption, distribution, metabolism, and excretion profile of HST5040, data from preclinical studies, and the synthesis of the sodium salt of HST5040 for clinical trials.
Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes
Corbin, Nathan,Lazouski, Nikifar,Manthiram, Karthish,Steinberg, Katherine,Yang, Deng-Tao
, p. 12365 - 12376 (2021/10/08)
Although electrocarboxylation reactions use CO2as a renewable synthon and can incorporate renewable electricity as a driving force, the overall sustainability and practicality of this process is limited by the use of sacrificial anodes such as magnesium and aluminum. Replacing these anodes for the carboxylation of organic halides is not trivial because the cations produced from their oxidation inhibit a variety of undesired nucleophilic reactions that form esters, carbonates, and alcohols. Herein, a strategy to maintain selectivity without a sacrificial anode is developed by adding a salt with an inorganic cation that blocks nucleophilic reactions. Using anhydrous MgBr2as a low-cost, soluble source of Mg2+cations, carboxylation of a variety of aliphatic, benzylic, and aromatic halides was achieved with moderate to good (34-78%) yields without a sacrificial anode. Moreover, the yields from the sacrificial-anode-free process were often comparable or better than those from a traditional sacrificial-anode process. Examining a wide variety of substrates shows a correlation between known nucleophilic susceptibilities of carbon-halide bonds and selectivity loss in the absence of a Mg2+source. The carboxylate anion product was also discovered to mitigate cathodic passivation by insoluble carbonates produced as byproducts from concomitant CO2reduction to CO, although this protection can eventually become insufficient when sacrificial anodes are used. These results are a key step toward sustainable and practical carboxylation by providing an electrolyte design guideline to obviate the need for sacrificial anodes.
A process for preparing 2, 2 - dimethyl butyric acid (by machine translation)
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Paragraph 0044; 0045; 0046; 0047; 0048; 0049; 0050-0074, (2019/04/26)
A 2, 2 - dimethyl butyric acid preparation process, relates to the field of chemical synthesis. The 2, 2 - dimethyl butyric acid and the preparing process comprises: will be ert-amyl halogen magnesium format after the addition reaction of the reagent with the carbon dioxide obtained by the hydrolysis, it adopts ert-amyl halogen magnesium format reagent with the carbon dioxide to carbonyl addition reaction, the preparation process is simple in operation, easily available raw materials, high yield, while at the same time the finished product made easy to purify, after the purification can be up to 99% and above, has better application prospect. (by machine translation)
A 2, 2 - dimethyl butyric acid
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, (2019/04/13)
The invention relates to a pesticide synthesis technology field, discloses a 2, 2 - dimethyl butyric acid, use chloro- uncle pentane preparing Grignard reagent, then with the ester compound produced by the reaction of 2, 2 - dimethyl ester, followed by hydrolysis to obtain 2, 2 - dimethyl butyric acid. To avoid the traditional production of large amount of sulfuric acid used in the method of defect, reducing the risk of the working personnel, and the use of some conventional chemical reagent can prepare 2, 2 - dimethyl butyric acid, convenient to make the 2, 2 - dimethyl butyric acid.
Palladium-catalyzed 2-pyridylmethyl-directed β-C(sp3)–H activation and cyclization of aliphatic amides with gem-dibromoolefins: A rapid access to γ-lactams
Zhou, Danni,Wang, Chunxia,Li, Mingliang,Long, Zheng,Lan, Jingbo
supporting information, p. 191 - 193 (2017/11/17)
The direct Pd-catalyzed β-C(sp3)–H activation and cyclization of aliphatic amides bearing a removable 2-pyridylmethyl directing group with gem-dibromoolefins is described for the first time to construct a variety of γ-lactams. The resulting products with Z- and E-configurations can be easily separated and purified after the reaction, demonstrating the effectiveness and applicability of the method herein developed.
Structure and reactivity in the hydrolyses of aliphatic carboxylic acid esters and chlorides
Regan, Andrew C.,Watt, C. Ian F.
, p. 180 - 189 (2008/02/06)
For hexanoic acid and its seven isomers, relative rates have been determined for acid catalysed esterification with methanol, and compared with those for saponification of the methyl esters. A good correlation between logarithms of relative rates for the two reactions is obtained, and it is suggested that the eight isomers provide a test set of compounds in which steric effects alone act on reactivity at the acyl carbon. A full set of steric parameters (Es′ values) are presented. Rates of solvolyses of the acid chlorides- of the isomers have been determined conductometrically in 3:1 wt:wt acetonitrile water. Logarithms of relative rates show a poor correlation with Es′, and, taking into account the solvent dependence of the rates, the pattern excludes both rate-limiting formation of a tetrahedral intermediate and rate-limiting dissociation of chloride to form acylium ions. The remaining possibilities, a concerted process (ANDN?) and rapid reversible formation of a hydrate followed by rate-limiting dissociation of chloride (AN + DN?,) are considered. Copyright
Koch carbonylation using silver trifluoromethanesulfonate
Mori, Hajime,Mori, Aya,Xu, Qiang,Souma, Yoshie
, p. 7871 - 7874 (2007/10/03)
Koch carbonylation was carried out using silver trifluoromethanesulfonate (AgOTf). Tertiary alcohols were transformed into the corresponding carboxylic acids in good yield under carbon monoxide atmosphere (5 MPa: initial pressure) at 150°C. It can be assumed that under these reaction conditions, a strong acid, in which a silver(I) cation participates, would be generated from AgOTf.
n-pentane carbonylation with CO on sulfated zirconia: An in situ solid-state 13C NMR study
Luzgin,Stepanov,Shmachkova,Kotsarenko
, p. 23 - 25 (2007/10/03)
Using 13C CP/MAS NMR, the first evidence has been obtained for n-pentane carbonylation with carbon monoxide into C6 aldehydes, ketones and carboxylic acids on a sulfated zirconia catalyst.
The autoxidation of aliphatic esters. Part 2. The autoxidation of neopentyl esters
Lindsay Smith, John R.,Nagatomi, Eiji,Waddington, David J.
, p. 2248 - 2258 (2007/10/03)
The autoxidation of six esters, neopentyl butanoate, 2,2-dimethylpropanoate, 3,3-dimethylbutanoate, 2,2-dimethylbutanoate, 2-methylbutanoate and 1,1-[2H2]-neopentyl butanoate, has been studied at 438 K. The reaction products were determined for each system and key reactions leading to the formation and further reactions of the primary products have been identified. Primary products include a range of hydroperoxides which lead to the formation of keto- and hydroxy-esters. Large amounts of neopentanol and the parent carboxylic acid are formed from each ester. It is shown that these are principally oxidation, and not hydrolysis, products. The relative rates of autoxidation of the first five esters mirror the relative rates of attack that occur on reaction with alkoxyl radicals; the sites of attack are on both the alkyl and acyl groups, with the α-alkyl hydrogen atoms on the ester showing particular vulnerability compared to the acyl hydrogen atoms. The analysis of products from the deuterated ester supports this conclusion.
Novel application of a solid super acid, sulfated zirconia, as a catalyst for Koch carbonylation reaction
Mori, Hajime,Wada, Aya,Xu, Qiang,Souma, Yoshie
, p. 136 - 137 (2007/10/03)
A solid superacid, sulfated zirconia, worked well in the Koch reaction. Under optimized conditions, tertiary alcohols were selectively transformed to the corresponding carboxylic acids (34-72%), while primary alcohols were transformed to the corresponding ethers (58-72%).
