153750-10-8Relevant articles and documents
Increased catalyst productivity in α-hydroxy acids resolution by esterase mutation and substrate modification
Ma, Bao-Di,Kong, Xu-Dong,Yu, Hui-Lei,Zhang, Zhi-Jun,Dou, Shuai,Xu, Yan-Peng,Ni, Yan,Xu, Jian-He
, p. 1026 - 1031 (2014/04/03)
Optically pure α-hydroxy acids and their derivatives are versatile chiral building blocks in the pharmaceutical industry. In this study, the potential of a recombinant Pseudomonas putida esterase (rPPE01) for the enzymatic resolution of α-acetoxy acids was significantly improved by combinatorial engineering of both the biocatalyst and substrate. Semirational design based on homologous modeling and molecular docking provided a single-point variant, W187H, whose kcat/KM for sodium 2-acetoxy-2-(2′-chlorophenyl)acetate (Ac-CPA-Na) was increased 100-fold, from 0.0611 to 6.20 mM-1 s-1, while retaining its excellent enantioselectivity and broad substrate spectrum. Biocatalyst deactivation under the operating conditions was decreased by using the potassium salt of Ac-CPA instead of Ac-CPA-Na. With 0.5 g L-1 of lyophilized cells containing rPPE01-W187H, 500 mM (R,S)-Ac-CPA-K was selectively deacylated with 49.9% conversion within 15 h, giving satisfactory enantiomeric excesses (ee) for both the S product (>99% ee) and the remaining R substrate (98.7% ee). Consequently, the amount of (S)-2-hydroxy-2-(2′-chlorophenyl)acetate prepared per unit weight of lyophilized cells was improved by a factor of 18.9 compared with the original productivity of the wild-type esterase. Further enzymatic resolution of other important hydroxy acids at the 100 mL scale demonstrated that the rPPE01-W187H-based bioprocess is versatile and practical for the large-scale preparation of chiral α-hydroxy acids.
Synthesis and pharmacological evaluation of indolinone derivatives as novel ghrelin receptor antagonists
Puleo, Letizia,Marini, Pietro,Avallone, Roberta,Zanchet, Marco,Bandiera, Silvio,Baroni, Marco,Croci, Tiziano
, p. 5623 - 5636 (2012/10/29)
The ghrelin receptor is a G-protein-coupled receptor (GPCR) widely expressed in the brain, stomach and the intestine. It was firstly identified during studies aimed to find synthetic modulators of growth hormone (GH) secretion. GHSR and its endogenous ligand ghrelin were found to be involved in hunger response. Through food intake regulation, they could affect body weight and adiposity. Thus GHSR antagonists rapidly became an attractive target to treat obesity and feeding disorders. In this study we describe the biological properties of new indolinone derivatives identified as a new, chiral class of ghrelin antagonists. Their synthesis as well as the structure-activity relationship will be discussed herein. The in vitro identified compound 14f was a potent GHSR1a antagonist (IC50 = 7 nM). When tested in vivo, on gastric emptying model, 14f showed an inhibitory intrinsic effect when given alone and it dose dependently inhibited ghrelin stimulation. Compound 14f also reduced food intake stimulated both by fasting condition (high level of endogenous ghrelin) and by icv ghrelin. Moreover this compound improved glucose tolerance in ipGTT test.
Synthesis of arylglycine and mandelic acid derivatives through carboxylations of α-amido and α-acetoxy stannanes with carbon dioxide
Mita, Tsuyoshi,Sugawara, Masumi,Hasegawa, Hiroyuki,Sato, Yoshihiro
experimental part, p. 2159 - 2168 (2012/06/01)
Incorporation reactions of carbon dioxide (CO2) with N-Boc-α-amido and α-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected α-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO2 pressure. α-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO2 pressure. Both transformations enabled the synthesis of α-tertiary and α-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-α- amido stannanes was transferred with up to 90% inversion of configuration at 100 °C.
Phenyl alpha acyloxyalkanoic acids, derivatives and their therapeutic use
-
, (2008/06/13)
Therapeutic as well as preventative measures to improve the cosmetic conditions or to alleviate the symptoms of dermatologic disorders with phenyl alpha acyloxyalkanoic acids and derivatives is disclosed. The cosmetic conditions and dermatologic disorders
Electron-transfer Processes: Oxidation of Arylacetic Acids by Peroxydisulphate in Acetic Acid
Giordano, Claudio,Beili, Aldo,Citterio, Attilio,Minisci, Francesco
, p. 1574 - 1576 (2007/10/02)
The oxidation of arylacetic acids by peroxydisulphate in acetic acid media in the presence of potassium and copper(II) acetates leads to the corresponding benzylacetates.The mechanism of the reaction is rationalized by the occurrence of two pathways: the intermediate formation of aromatic radical cations or the direct decarboxylation of the arylacetate ion.The importance of acetic acid as reaction medium is stressed.
