7608-06-2Relevant academic research and scientific papers
Direct transformation of aryl 2-pyridyl esters to secondary benzylic alcohols by nickel relay catalysis
Wu, Xianqing,Li, Xiaobin,Huang, Wenyi,Wang, Yun,Xu, Hui,Cai, Liangzhen,Qu, Jingping,Chen, Yifeng
supporting information, p. 2453 - 2458 (2019/03/29)
A direct transformation of aryl esters to secondary benzylic alcohols via tandem Ni-catalyzed cross-coupling reactions of aromatic 2-pyridyl esters with alkyl zinc reagents and carbonyl group reduction by Ni-H species is achieved. Preliminary mechanistic studies reveal that the Ni-H species is generated in situ via β-hydride elimination of the Negishi reagents. The reaction is catalyzed by bench-stable nickel salts under mild conditions with wide functional group tolerance.
Docking study and biological evaluation of pyrrolidine-based iminosugars as pharmacological chaperones for Gaucher disease
Kato, Atsushi,Nakagome, Izumi,Sato, Kasumi,Yamamoto, Arisa,Adachi, Isao,Nash, Robert J.,Fleet, George W. J.,Natori, Yoshihiro,Watanabe, Yasuka,Imahori, Tatsushi,Yoshimura, Yuichi,Takahata, Hiroki,Hirono, Shuichi
, p. 1039 - 1048 (2016/01/20)
We report on the synthesis and biological evaluation of a series of α-1-C-alkylated 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives as pharmacological chaperones for Gaucher disease. The parent compound, DAB, did not show inhibition of human β-glucocerebrosidase but showed moderate intestinal α-glucosidase inhibition; in contrast, extension of α-1-C-alkyl chain length gave a series of highly potent and selective inhibitors of the β-glucocerebrosidase. Our design of α-1-C-tridecyl-DAB (5j) produced a potent inhibitor of the β-glucocerebrosidase, with IC50 value of 0.77 μM. A molecular docking study revealed that the α-1-C-tridecyl group has a favorable interaction with the hydrophobic pocket and the sugar analogue part (DAB) interacted with essential hydrogen bonds formed to Asp127, Glu235 and Glu340. Furthermore, α-1-C-tridecyl-DAB (5j) displayed enhancement of activity at an effective concentration 10-times lower than isofagomine. α-1-C-Tridecyl-DAB therefore provides the first example of a pyrrolidine iminosugar as a new class of promising pharmacological chaperones with the potential for treatment of Gaucher disease. 2016 The Royal Society of Chemistry.
α-1-C-Butyl-1,4-Dideoxy-1,4-Imino-L-Arabinitol as a second-Generation iminosugar-based oral α-Glucosidase inhibitor for improving postprandial hyperglycemia
Kato, Atsushi,Hayashi, Erina,Miyauchi, Saori,Adachi, Isao,Imahori, Tatsushi,Natori, Yoshihiro,Yoshimura, Yuichi,Nash, Robert J.,Shimaoka, Hideyuki,Nakagome, Izumi,Koseki, Jun,Hirono, Shuichi,Takahata, Hiroki
, p. 10347 - 10362 (2013/02/23)
We report on the synthesis and the biological evaluation of a series of α-1-C-alkylated 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. α-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 μM, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of α-1-C-butyl-LAB and miglitol are clearly different. Furthermore, α-1-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. α-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.
