17604-74-9Relevant articles and documents
A Methyl Scan of the Pyrrolidinium Ring of Nicotine Reveals Significant Differences in Its Interactions with a7 and a4b2 Nicotinic Acetylcholine Receptors
Xing, Hong,Andrud, Kristin W.,Soti, Ferenc,Rouchaud, Anne,Jahn, Stephan C.,Lu, Ziang,Cho, Yeh-Hyon,Habibi, Sophia,Corsino, Patrick,Slavov, Svetoslav,Rocca, James R.,Lindstrom, Jon M.,Lukas, Ron J.,Kem, William R.
supporting information, p. 168 - 180 (2020/09/12)
The two major nicotinic acetylcholine receptors (nAChRs) in the brain are the a4b2 and a7 subtypes. A "methyl scan" of the pyrrolidinium ring was used to detect differences in nicotine's interactions with these two receptors. Each methylnicotine was investigated using voltage-clamp and radioligand binding techniques. Methylation at each ring carbon elicited unique changes in nicotine's receptor interactions. Replacing the 19-N-methyl with an ethyl group or adding a second 19-N-methyl group significantly reduced interaction with a4b2 but not a7 receptors. The 29-methylation uniquely enhanced binding and agonist potency at a7 receptors. Although 39- A nd 59-trans-methylations were much better tolerated by a7 receptors than a4b2 receptors, 49-methylation decreased potency and efficacy at a7 receptors much more than at a4b2 receptors. Whereas cis-59-methylnicotine lacked agonist activity and displayed a low affinity at both receptors, trans-59-methylnicotine retained considerable a7 receptor activity. Differences between the two 59-methylated analogs of the potent pyridyl oxymethylene-bridged nicotine analog A84543 were consistent with what was found for the 59-methylnicotines. Computer docking of the methylnicotines to the Lymnaea acetylcholine binding protein crystal structure containing two persistent waters predicted most of the changes in receptor affinity that were observed with methylation, particularly the lower affinities of the cis-methylnicotines. The much smaller effects of 19-, 39-, and 59-methylations and the greater effects of 29- A nd 49-methylations on nicotine a7 nAChR interaction might be exploited for the design of new drugs based on the nicotine scaffold.
Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
Zheng, Yu-Cong,Xu, Jian-He,Wang, Hui,Lin, Guo-Qiang,Hong, Ran,Yu, Hui-Lei
, p. 1185 - 1193 (2017/04/13)
Biocatalysts originating from Badamu (Prunus communis) have been applied to catalyze the asymmetric synthesis of (R)-4-methylsulfanylmandelonitrile, a key building block of thiamphenicol and florfenicol. Here, four hydroxynitrile lyase (HNL) isozymes from Badamu were cloned and heterologously expressed in Pichia pastoris. The biochemical properties and catalytic performances of these isozymes were comprehensively explored to evaluate their efficiency and selectivity in asymmetric synthesis. Among then, PcHNL5 was identified with outstanding activity and enantioselectivity in asymmetric hydrocyanation. Under the optimized mild biphasic reaction conditions, seventeen prochiral aromatic aldehydes were converted to valuable chiral cyanohydrins with good yields (up to 94%) and excellent optical purities (up to >99.9% ee), which provide a facile access to numerous chiral amino alcohols, hypoglycemic agents, angiotension converting enzyme (ACE) inhibitors and β-blockers. This work therefore underlines the importance of discovering the most potent biocatalyst among a group of isozymes for converting unnatural substrates into value-added products. (Figure presented.).
Direct crystallographic observation of catalytic reactions inside the pores of a flexible coordination polymer
Das, Raj Kumar,Aijaz, Arshad,Sharma, Manish K.,Lama, Prem,Bharadwaj, Parimal K.
experimental part, p. 6866 - 6872 (2012/07/31)
A new flexible porous coordination polymer (PCP), {[Gd2(L) 3(dmf)4]·4 DMF·3 H2O}n (1), was synthesized under solvothermal condition by reacting [Gd(NO 3)3]·6 H2O with the ligand 2,6,2',6'-tetranitro-biphenyl-4,4'-dicarboxylic acid (H2L). Compound 1 had a 3D coordination polymeric structure with two types of 1D channels (A and B) that were occupied by DMF and water molecules. When crystals of 1 were separately exposed to vapors of various aromatic aldehydes, either the lattice or both the lattice and metal-bound solvent molecules were replaced by aldehyde molecules. The aldehyde molecules inside the pores spontaneously underwent cyanosilylation and Knoevenagel condensation reactions upon exposure to vapors of trimethylsilyl cyanide and malononitrile, respectively. These reactions took place at ambient temperature and pressure. Moreover, both the reactants and the products translocated from one cavity to another. The products that occupied the cavity were expunged upon exposure to the vapors of an aldehyde. Because crystallinity was maintained during these chemical transformations, direct crystallographic observation was possible. Herein, we showed that confinement of the reactants inside the void spaces of the PCP led to the products; we also assessed catalytic activities of this PCP in bulk quantities. Copyright