308796-10-3Relevant articles and documents
Enantio- and Regioconvergent Nickel-Catalyzed C(sp3)?C(sp3) Cross-Coupling of Allylic Electrophiles Steered by a Silyl Group
Kranidiotis-Hisatomi, Nektarios,Oestreich, Martin,Yi, Hong
supporting information, p. 13652 - 13655 (2021/05/10)
A two-step sequence for the enantio- and diastereoselective synthesis of exclusively alkyl-substituted acyclic allylic systems with a stereocenter in the allylic position is reported. The asymmetric induction and the site selectivity are controlled in an
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.
Highly regioselective nickel-catalyzed cross-coupling of N -tosylaziridines and alkylzinc reagents
Jensen, Kim L.,Standley, Eric A.,Jamison, Timothy F.
supporting information, p. 11145 - 11152 (2014/08/18)
Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with aliphatic organozinc reagents. The reaction protocol displays complete regioselectivity for reaction at the less hindered C-N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. Moreover, we have developed an air-stable nickel(II) chloride/ligand precatalyst that can be handled and stored outside a glovebox. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni(cod)2 is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetalation (retention), and reductive elimination (retention).
