4515-21-3Relevant articles and documents
Discovery of an Orally Active Small-Molecule Tumor Necrosis Factor-α Inhibitor
Sun, Weiguang,Wu, Yanli,Zheng, Mengzhu,Yang, Yueying,Liu, Yang,Wu, Canrong,Zhou, Yirong,Zhang, Yonghui,Chen, Lixia,Li, Hua
supporting information, p. 8146 - 8156 (2020/09/21)
Tumor necrosis factor α (TNF-α) is an important therapeutic target for rheumatoid arthritis, inflammatory bowel disease, and septic hepatitis. In this study, structure-based virtual ligand screening combined with in vitro and in vivo assays were applied.
Total synthesis of (-)-platensimycin by advancing oxocarbenium- and iminium-mediated catalytic methods
Eey, Stanley T.-C.,Lear, Martin J.
, p. 11556 - 11573 (2015/01/16)
(-)-Platensimycin is a potent inhibitor of fatty acid synthase that holds promise in the treatment of metabolic disorders (e.g., diabetes and "fatty liver") and pathogenic infections (e.g., those caused by drug-resistant bacteria). Herein, we describe its total synthesis through a four-step preparation of the aromatic amine fragment and an improved stereocontrolled assembly of the ketolide fragment, (-)-platensic acid. Key synthetic advances include 1) a modified Lieben haloform reaction to directly convert an aryl methyl ketone into its methyl ester within 30 seconds, 2) an experimentally improved dialkylation protocol to form platensic acid, 3) a sterically controlled chemo- and diastereoselective organocatalytic conjugate reduction of a spiro-cyclized cyclohexadienone by using the trifluoroacetic acid salt of α-amino di-tert-butyl malonate, 4) a tetrabutylammonium fluoride promoted spiro-alkylative para dearomatization of a free phenol to assemble the cagelike ketolide core with the moderate leaving-group ability of an early tosylate intermediate, and 5) a bismuth(III)-catalyzed Friedel-Crafts cyclization of a free lactol, with LiClO4 as an additive to liberate a more active oxocarbenium perchlorate species and suppress the Lewis basicity of the sulfonyloxy group. The longest linear sequence is 21 steps with an overall yield of 3.8% from commercially available eugenol. Relay tactics: The stereocontrolled assembly of the potent antibiotic (-)-platensimycin in 21 steps and 3.8% yield from eugenol is described (see scheme; TBAF: tetrabutylammonium fluoride; Ts: toluene-4-sulfonyl). Highlights are 1) a rapid oxidative esterification of an acyl aromatic, 2) a reliable dialkylation protocol to form platensic acid, 3) a π-facial conjugate reduction of a dienone, 4) a TBAF-promoted alkylative dearomatization of a free phenol, and 5) a Friedel-Crafts closure of a free lactol.
Syntheses of Polypeptides by Hidrogenolysis of N-Benzyloxycarbonyl-Amino Acid Anhydrides
Munegumi, Toratane,Meng, Yan-Quing,Harada, Kaoru
, p. 2748 - 2750 (2007/10/02)
When anhydrides of N-benzyloxycarbonyl-DL-aspartic acid (Z-DL-Asp), Z-L-Asp, N-Z-DL-glutamic acid (Z-DL-Glu), Z-L-Glu and N-Z-3-aminoglutaric acid (Z-β-Agl) were hydrogenolyzed in N,N-dimethylformamide (DMF), polypeptides were obtained in high yields.Hydrogenolyses of Z-DL-Glu and Z-L-Glu in dioxane gave pyroglutamic acid.
