Enantiopure methoxetamine stereoisomers: chiral resolution, conformational analysis, UV-circular dichroism spectroscopy and electronic circular dichroism
| Autor: | Seung-Hwan Kim, Jae Hoon Cheong, Kun Won Lee, Hye Rim Jeon, Jiyoung Kim, Yong Sup Lee, Suk Woo Chang, Dae Sik Jang, Hee Jin Kim, Seolmin Yoon, Youngdo Jeong, Cheol Jung Lee, Ahmed H.E. Hassan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Circular dichroism
Chemistry Stereochemistry Absolute configuration Free base General Chemistry 010402 general chemistry 01 natural sciences Catalysis Chiral resolution 0104 chemical sciences 03 medical and health sciences 0302 clinical medicine Enantiopure drug Materials Chemistry Optical rotation Enantiomer Conformational isomerism 030217 neurology & neurosurgery |
| Zdroj: | New Journal of Chemistry. 45:4354-4364 |
| ISSN: | 1369-9261 1144-0546 |
| DOI: | 10.1039/d0nj05192f |
| Popis: | The chiral molecule, methoxetamine (MXE), demonstrated promising biological effects in management of treatment-resistant depression patients. To satisfy the need for a method capable of providing gram quantities of each enantiopure stereoisomer of MXE to enable advanced biological studies of enantiomers, a protocol was developed to access gram scale quantities of (R)- and (S)-MXE in the form of pharmaceutically acceptable HCl salts employing L-(−)-DTTA and D-(+)-DTTA ((−)-O,O′-di-p-toluoyl-L-tartaric acid and (+)-O,O′-di-p-toluoyl-D-tartaric acid, respectively) as two chiral resolving agents. In contrast to ketamine, the measured specific optical rotation and conformational analysis indicated that the most abundant conformers possess a common axial-methoxyphenyl conformation responsible for the conserved direction of optical rotation in both free base and HCl salt forms of the MXE stereoisomers. Finally, the absolute configuration was unambiguously assigned through matching experimental and calculated ECD spectra. This report offers a gateway to obtain gram scale amounts of enantiopure MXE stereoisomers needed to advance the current knowledge on MXE biology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|