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
3-Substituted Benzo[ e][1,2,4]triazines: Synthesis and Electronic Effects of the C(3) Substituent
Bodzioch, Agnieszka,Pomik?o, Dominika,Celeda, Ma?gorzata,Pietrzak, Anna,Kaszyński, Piotr
, p. 6377 - 6394 (2019/05/24)
A series of 19 structurally diverse C(3)-substituted derivatives of benzo[e][1,2,4]triazine were synthesized from 3-chloro- (1c) and 3-iodobenzo[e][1,2,4]triazine (1d) obtained in three steps from 2-nitroaniline in 37-55% yields. Nucleophilic aromatic substitution and metal-catalyzed (Pd, Cu) reactions led to functional derivatives that include alkyl (C5H11), (het)aryl (Ph, 2-thienyl, ferrocenyl), ArCC, amine (NHPh and morpholine), PO(OEt)2, sulfanyl (SBu-t), alkoxide (OEt, OMe), and CN. The synthesis of C(3)-CF3 derivative 1g via the Ruppert reaction with 1d and its 1-oxide analogue 2d led to the substitution followed by formal addition of HCF3 to the C?N bond. Pd-catalyzed carbonylation reactions of 1d and 2d did not give the corresponding C(3)-carboxylic acids. Therefore, acid 1f was obtained through hydrolysis of the CN. The substituent effect on the electronic structure of the benzo[e][1,2,4]triazine ring was investigated by spectroscopic methods (UV-vis and NMR) augmented with density functional theory calculations. Results show significant effect of the C(3) substituent on the (1) transition energy and good correlation of the 1H NMR chemical shift with the substituent constant σp. Molecular and crystal structures of six derivatives were established with the single-crystal X-ray diffraction method, and the substituent impact on the molecular geometry was investigated.
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.
A general strategy for the synthesis of enantiomerically pure azetidines and aziridines through nickel-catalyzed cross-coupling
Jensen, Kim L.,Nielsen, Dennis U.,Jamison, Timothy F.
supporting information, p. 7379 - 7383 (2015/05/13)
Abstract In this communication, we report a straightforward synthesis of enantiomerically pure 2-alkyl azetidines. The protocol is based on a highly regioselective nickel-catalyzed cross-coupling of aliphatic organozinc reagents with an aziridine that fea
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).
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.
Synthese et reactivite de quelques organozinciques dans des solvants peu courants en chimie organometallique
Grodin, Joseph,Sebban, Mohammed,Vottero, Philippe,Blancou, Hubert,Commeyras, Auguste
, p. 237 - 242 (2007/10/02)
The use of solvents strange to organometallic chemistry viz. carbonic or phosphoric esters, or sulfolane allows zinc to react with organic halides, which are usually unreactive towards this metal.The ractions of the organozinc compounds thus synthesised (
