65-49-6Relevant articles and documents
P-aminosalicylic acid production by enzymatic kolbeschmitt reaction using salicylic acid decarboxylases improved through site-directed mutagenesis
Ienaga, Saori,Kosaka, Sachiyo,Honda, Yuki,Ishii, Yoshitaka,Kirimura, Kohtaro
, p. 628 - 634 (2013)
A reversible salicylic acid decarboxylase (Sdc) catalyzes the carboxylation of m-aminophenol (m-AP) to paminosalicylic acid (PAS) as an antituberculous agent, through an enzymatic KolbeSchmitt reaction. To develop a highyield PAS production system through such an enzymatic reaction, we generated Sdc mutants by site-directed mutagenesis and succeeded in generating several mutants showing increased carboxylation specific activities. Among them, a Y64T-F195Y-Sdc mutant showed a 12-fold higher carboxylation specific activity toward m-AP than wild-type Sdc. By the whole-cell reaction of recombinant Escherichia coli BL21(DE3) expressing the gene encoding Y64T-F195Y-Sdc, 70mM PAS was produced from 100 mM m-AP within 2 h. This reaction time was shortened to one-twelfth that of the PAS production using E. coli BL21(DE3) expressing the gene encoding wild-type Sdc (24 h). Moreover, 140 mM PAS was produced from 200 mM m-AP within 9 h by the whole-cell reaction of recombinant E. coli BL21(DE3) expressing the gene encoding Y64T-F195Y-Sdc.
Production of p-aminosalicylic acid through enzymatic kolbeschmitt reaction catalyzed by reversible salicylic acid decarboxylase
Kirimura, Kohtaro,Yanaso, Satomi,Kosaka, Sachiyo,Koyama, Keiko,Hattori, Takasumi,Ishii, Yoshitaka
, p. 206 - 208 (2011)
A reversible salicylic acid decarboxylase (Sdc), found in the yeast Trichosporon moniliiforme WU-0401, is applicable for the production of p-aminosalicylic acid (PAS) from m-aminophenol (m-AP). For the high-yield production of PAS, used as an antituberculous agent, we developed F195Y, a genetically engineered Sdc mutant. We succeeded in selectively producing PAS from m-AP through an enzymatic KolbeSchmitt reaction in aqueous solution by using recombinant Escherichia coli cells expressing the gene encoding F195Y. We found that 70mM PAS was produced at 30 °C in 15h with a conversion yield of 70% (mol/mol).
Cyclic (Alkyl)(amino)carbene Ligand-Promoted Nitro Deoxygenative Hydroboration with Chromium Catalysis: Scope, Mechanism, and Applications
Zhao, Lixing,Hu, Chenyang,Cong, Xuefeng,Deng, Gongda,Liu, Liu Leo,Luo, Meiming,Zeng, Xiaoming
supporting information, p. 1618 - 1629 (2021/01/25)
Transition metal catalysis that utilizes N-heterocyclic carbenes as noninnocent ligands in promoting transformations has not been well studied. We report here a cyclic (alkyl)(amino)carbene (CAAC) ligand-promoted nitro deoxygenative hydroboration with cost-effective chromium catalysis. Using 1 mol % of CAAC-Cr precatalyst, the addition of HBpin to nitro scaffolds leads to deoxygenation, allowing for the retention of various reducible functionalities and the compatibility of sensitive groups toward hydroboration, thereby providing a mild, chemoselective, and facile strategy to form anilines, as well as heteroaryl and aliphatic amine derivatives, with broad scope and particularly high turnover numbers (up to 1.8 × 106). Mechanistic studies, based on theoretical calculations, indicate that the CAAC ligand plays an important role in promoting polarity reversal of hydride of HBpin; it serves as an H-shuttle to facilitate deoxygenative hydroboration. The preparation of several commercially available pharmaceuticals by means of this strategy highlights its potential application in medicinal chemistry.
For amino salicylic acid crystal form and its preparation method and application
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Paragraph 0057-0059, (2017/08/25)
The invention relates to the field of pharmaceutical chemistry, in particular to a novel crystal form of p-aminosalicylic acid and a preparation method thereof. A crystal in the novel crystal form is subjected to X-ray powder diffraction, diffraction peak positions 2theta are used as spectrogram characteristic parameters, and 2theta are 7.36+/-0.2, 14.61+/-0.2, 17.01+/-0.2, 21.91+/-0.2 and 29.28+/-0.2 sequentially. The preparation of the crystal comprises steps of mixing p-aminosalicylic acid and an organic solvent, then utilizing a temperature differential method for crystallization, carrying out solid-liquid separation, drying solid, and obtaining the crystal in the novel crystal form. The invention further relates to preparations or compositions containing the novel crystal form, and applications of the novel crystal form to preparations of drugs for treating tuberculosis. The novel crystal form of p-aminosalicylic acid is good in stability, and not only has storage and transportation advantages, but also greatly facilitates industrial production.
Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: A biocatalytic equivalent to the Kolbe-Schmitt reaction
Wuensch, Christiane,Gross, Johannes,Steinkellner, Georg,Lyskowski, Andrzej,Gruber, Karl,Glueck, Silvia M.,Faber, Kurt
, p. 9673 - 9679 (2014/03/21)
The enzyme catalyzed carboxylation of electron-rich phenol derivatives employing recombinant benzoic acid decarboxylases at the expense of bicarbonate as CO2 source is reported. In contrast to the classic Kolbe-Schmitt reaction, the biocatalytic equivalent proceeded in a highly regioselective fashion exclusively at the ortho-position of the phenolic directing group in up to 80% conversion. Several enzymes were identified, which displayed a remarkably broad substrate scope encompassing alkyl, alkoxy, halo and amino- functionalities. Based on the crystal structure and molecular docking simulations, a mechanistic proposal for 2,6-dihydroxybenzoic acid decarboxylase is presented.
4-aminosalicylic acid adducts
Cherukuvada, Suryanarayan,Bolla, Geetha,Sikligar, Kanishka,Nangia, Ashwini
, p. 1551 - 1557 (2013/05/21)
4-Aminosalicylic acid (p-aminosalicylic acid, PAS), an antituberculosis drug, is a model active pharmaceutical ingredient to study salt and cocrystal formation in a multiple hydrogen-bonding functionality molecule with carboxylic acid, amine, and phenol groups. A cytosine salt CYT+-PAS-, salt cocrystal hydrate CYT+-PAS--CYT-H2O, and nicotinamide cocrystal hydrate PAS-NAM-H2O, are described in this article. Furthermore, X-ray crystal structures of PAS sodium dihydrate, sulfate, and mesylate salts and dehydration/rehydration behavior of the sodium salt by powder X-ray diffraction are discussed.
NEW ORGANOSILICON COMPOUND, THERMOSETTING RESIN COMPOSITION CONTAINING THE ORGANOSILICON COMPOUND, HARDENING RESIN AND ENCAPSULATION MATERIAL FOR OPTICAL SEMICONDUCTOR
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Page/Page column, (2013/04/24)
A solution is a liquid organosilicon compound represented by general formula (1) as described below: wherein, X is each independently a group represented by formula (I), formula (II) or formula (III) as described below, and when the number of the group represented by formula (I) per one molecule of the liquid organosilicon compound represented by general formula (1) is defined as a, the number of the group represented by formula (II) per one molecule thereof is defined as b, and the number of the group represented by formula (III) per one molecule thereof is defined as c, 0≦a≦3.5, 0≦b≦3.5, and 0≦c≦1 are obtained, and also a+b+2c=4 is obtained:
Regioselective enzymatic carboxylation of phenols and hydroxystyrene derivatives
Wuensch, Christiane,Glueck, Silvia M.,Gross, Johannes,Koszelewski, Dominik,Schober, Markus,Faber, Kurt
supporting information; experimental part, p. 1974 - 1977 (2012/06/15)
The enzymatic carboxylation of phenol and styrene derivatives using (de)carboxylases in carbonate buffer proceeded in a highly regioselective fashion: Benzoic acid (de)carboxylases selectively formed o-hydroxybenzoic acid derivatives, phenolic acid (de)carboxylases selectively acted at the β-carbon atom of styrenes forming (E)-cinnamic acids.
Enzymatic Kolbe-Schmitt reaction to form salicylic acid from phenol: Enzymatic characterization and gene identification of a novel enzyme, Trichosporon moniliiforme salicylic acid decarboxylase
Kirimura, Kohtaro,Gunji, Hiroaki,Wakayama, Rumiko,Hattori, Takasumi,Ishii, Yoshitaka
experimental part, p. 279 - 284 (2011/11/14)
Salicylic acid decarboxylase (Sdc) can produce salicylic acid from phenol; it was found in the yeast Trichosporon moniliiforme WU-0401 and was for the first time enzymatically characterized, with the sdc gene heterologously expressed. Sdc catalyzed both reactions: decarboxylation of salicylic acid to phenol and the carboxylation of phenol to form salicylic acid without any byproducts. Both reactions were detected without the addition of any cofactors and occurred even in the presence of oxygen, suggesting that this Sdc is reversible, nonoxidative, and oxygen insensitive. Therefore, it is readily applicable in the selective production of salicylic acid from phenol, the enzymatic Kolbe-Schmitt reaction. The deduced amino acid sequence of the gene, sdc, encoding Sdc comprises 350 amino acid residues corresponding to a 40-kDa protein. The recombinant Escherichia coli BL21(DE3) expressing sdc converted phenol to salicylic acid with a 27% (mol/mol) yield at 30 °C for 9 h.
Colon-specific mutual amide prodrugs of 4-aminosalicylic acid for their mitigating effect on experimental colitis in rats
Dhaneshwar, Suneela S.,Chail, Mukta,Patil, Mahavir,Naqvi, Salma,Vadnerkar, Gaurav
experimental part, p. 131 - 142 (2009/04/07)
Mutual amide prodrugs of 4-aminosalicylic acid with d-phenylalanine and l-tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10 h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86-91% over a period of 20 h, with half-lives ranging between 343 and 412 min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.
