344-25-2Relevant articles and documents
Irreversible inhibitors of the proline racemase unveil innovative mechanism of action as antibacterial agents against Clostridioides difficile
Barbut, Frédéric,Blondel, Arnaud,Gateau, Cécile,Gouault, Nicolas,Melo, Guilherme D.,Minoprio, Paola,Renault, Jacques,Tasseau, Olivier,Uriac, Philippe
, (2022/01/11)
Proline racemases (PRAC), catalyzing the l-proline and d-proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T.?cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C.?difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4-oxopent-2-enoic acid TcPRAC irreversible inhibitors, we synthesized 4-aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C.?difficile. This study resulted in promising candidates and allowed for identification of (E)-4-(3-bromothiophen-2-yl)-4-oxobut-2-enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity.
Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce
Komatsu, Hidekazu,Shirakawa, Takashi,Uchiyama, Takeo,Hoshino, Tsutomu
, p. 299 - 309 (2019/02/20)
Pseudomonas cichorii, which causes varnish spots on lettuce and seriously damages lettuce production during the summer season in the highland areas of Japan (e.g., Nagano and Iwate prefectures) was isolated. The structure of a toxin produced by this organism was analyzed based on the detailed evaluation of its 2D NMR and FABMS spectra, and this compound has not been reported previously. We propose the name cichorinotoxin for this toxin. In conjunction with the D or L configurations of each amino acid, which were determined by Marfey’s method, we propose the structure of cichorinotoxin to be as follows: 3-hydroxydecanoyl-(Z)-dhThr1-D-Pro2-D-Ala3-D-Ala4-D-Ala5-D-Val6-D-Ala7-(Z)-dhThr8-Ala9-Val10-D-Ile11-Ser12-Ala13-Val14-Ala15-Val16-(Z)-dhThr17-D-alloThr18-Ala19-L-Dab20-Ser21-Val22, and an ester linkage is present between D-alloThr18 and Val22 (dhThr: 2-aminobut-2-enoic acid; Dab: 2,4-diaminobutanoic acid). Thus, the toxin is a lipodepsipeptide with 22 amino acids. The mono- and tetraacetate derivatives and two alkaline hydrolysates, compounds A and B, were prepared. We discuss here the structure–activity relationships between the derivatives and their necrotic activities toward lettuce.
Method for synthesizing D-proline
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Paragraph 0026; 0030-0032; 0035, (2018/07/30)
The invention belongs to the technical field of synthesis of chiral organic compounds, and especially relates to a method for synthesizing D-proline. The method comprises the following steps: taking pyrrolidine-2-carbaldehyde, dissolving the pyrrolidine-2-carbaldehyde in an organic solvent, adding a catalyst and an organic alkali potassium t-butoxide, and carrying out an asymmetric catalysis hydrogenation reaction to obtain an intermediate II; and carrying out an oxidation reaction on the intermediate II and an oxidant to obtain the product D-proline III. The method for synthesizing D-prolinehas the following advantages: the use amount of the catalyst is small, and the catalyst can be used repeatedly, so the cost is saved; the solvent used in the synthesis process is a common solvent, sothe method has the characteristics of low cost, non-toxicity, no pollution, greenness and environmental protection; and the synthesis method has a simple process, the yield in the invention is higherthan the yield in the prior art, and the optical purity of the obtained product is high, so the method is suitable for industrial production.