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A facile method has been developed for the synthesis of chiral piperazines through Ir-catalyzed hydrogenation of pyrazines activated by alkyl halides, giving a wide range of chiral piperazines including 3-substituted as well as 2,3- and 3,5-disubstituted ones with up to 96% ee. The high enantioselectivity, easy scalability, and concise drug synthesis demonstrate the practical utility.
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http://dx.doi.org/10.1021/acs.orglett.6b01190 | DOI Listing |
Commun Chem
July 2025
Frontiers Science Center for New Organic Matter, State Key Laboratory of Advanced Chemical Power Sources, and Key Laboratory of Advanced Energy Materials Chemistry (MOE), College of Chemistry, Nankai University, Tianjin, China.
Chirality plays a pivotal role in the properties of biologically active molecules, with enantiomers exhibiting divergent pharmacological and toxicological profiles. Enantioselective recognition is thus crucial in drug development, asymmetric synthesis, and environmental monitoring. Luminescence sensing has emerged as a powerful strategy for enantioselective recognition due to its fast response and visual readout capabilities.
View Article and Find Full Text PDFSci Rep
July 2025
Department of Chemistry, Faculty of Science, Center of Excellence in Natural Products Chemistry, Chulalongkorn University, Pathum Wan, Bangkok, 10330, Thailand.
α-Glucosidase is an important target in treating type 2 diabetes, and thus, the inhibition of this enzyme could delay sugar digestion and avoid postprandial hyperglycemia. Previous studies revealed that some pyrimidine and piperazine derivatives showed good affinity towards α-glucosidase. In continuing efforts toward the development of α-glucosidase inhibitor, a series of pyrimidinyl-piperazine carboxamide 6-22 containing chiral center have been synthesized.
View Article and Find Full Text PDFACS Chem Neurosci
July 2025
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, United States.
We have characterized families of phenylpiperazine (PP) compounds, studying their relative activity with α7 and α9* nicotinic acetylcholine receptors (nAChRs) and focusing on the effects of side groups on the phenyl ring (R) and the effects of different alkyl groups on the base nitrogen. In this study, we evaluated the impact of methyl substitution on the piperazine ring, which introduced a chiral center, enabling the generation and separation of stereoisomers. Methyl groups were added to either the C2 or C3 positions on the piperazine of the α9α10 agonist/α7 partial agonist PA-EMPP.
View Article and Find Full Text PDFChirality
June 2025
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India.
In this research, estimation of enantioselective pharmacokinetics and biological interconversion of sotorasib were investigated. This is the first report for the novel chiral liquid chromatography-tandem mass spectrometry method for the enantioselective pharmacokinetics determination in biological matrix. Attempts were made to achieve separation in reverse phase mode with mass compatible mobile phase.
View Article and Find Full Text PDFChem Asian J
November 2024
Department of Chemistry, Università degli Studi di Milano and CNR-SCITEC, Via Golgi 19, 20133, Milano, Italy.
2,5-disubstituted N,N'-alkylpiperazines represent an interesting target in organic synthesis both for pharmaceutical or agrochemical applications and as a promising class of ligands in coordination chemistry. We report here a microwave-enhanced synthesis of these compounds starting from non-activated N-alkyl aziridines in the presence of catalytic amounts of simple ammonium metallates. A remarkable TOF of 2787.
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