Optical Resolution of Rimantadine

Han, Jianlin; Takeda, Ryosuke; Sato, T.; Moriwaki, Hiroki; Abe, Hidenori; Izawa, Kunisuke; Soloshonok, Vadim A.

doi:10.3390/molecules24091828

Cited by 7 publications

(5 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to further improve the ee, (scl)-flurbiprofen was also subjected to diastereomeric salt crystallization [57,58] using either 1-cyclohexyl ethylamine or 1-phenyl ethylamine as the base and ethanol as the solvent for crystallization (Figure 2). For example, the ee of (S)-flurbiprofen was increased from 77% to 95% by this mean.…”

Section: Resolution Of (Rac)-flurbiprofenmentioning

confidence: 99%

Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR

et al. 2021

Self Cite

View full text Add to dashboard Cite

2-(2-Fluoro-4-biphenyl) propionic acid (flurbiprofen), from the phenylalkanoic acid family of nonsteroidal anti-inflammatory drugs (NSAID’s), is currently on the pharmaceutical market as a racemate. This racemic compound was tested for its propensity to undergo the self-disproportionation of enantiomers (SDE) phenomenon by various forms of chromatography (SDEvC), such as routine gravity-driven column chromatography, medium-pressure liquid chromatography (MPLC), preparative thin-layer chromatography (PTLC), and size-exclusion chromatography (SEC), as well as by sublimation (SDEvS). Furthermore, examination by nuclear magnetic resonance (NMR) in various solvents found that flurbiprofen exhibited the phenomenon of self-induced diastereomeric anisochronism (SIDA). By measurement of the diffusion coefficient (D), the longitudinal relaxation time (T1), and the transverse relaxation time (T2) using NMR, as well as by electrospray ionization-mass spectrometry (ESI-MS) examinations, the preferred intermolecular association was found to be solvent dependent, e.g., heterochiral association was preferred in toluene, while homochiral association was preferred in more polar solvents. This study also attempted, unsuccessfully, to correlate the NMR measurements of flurbiprofen with chromatographic outcomes for the rationalization and prediction of chromatographic results based on NMR measurements. Because the intermolecular hydrogen bonding of the acid groups in flurbiprofen overwhelmingly predominates over other intermolecular interactions, flurbiprofen seemed to represent a good test case for this idea. The behavior of scalemic samples of flurbiprofen is important, as, although it is currently dispensed as a racemate, clinical applications of the R enantiomer have been investigated. SDEvC and SDEvS both have ramifications for the preparation, handling, and storage of enantioenriched flurbiprofen, and this concern applies to other chiral drugs as well.

show abstract

Section: Resolution Of (Rac)-flurbiprofenmentioning

confidence: 99%

Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the context of synthetic methodology, the chemistry of Ni(II) complexes of AA Schiff bases (Scheme 1) [99][100][101][102] has emerged as a dominant, most commonly used approach for asymmetric synthesis of tailor-made AAs. Using the modular approach for the design of chiral Ni(II) complexes of glycine Schiff bases [103,104], the recent research activity has been focusing around four structural types of chiral nucleophilic glycine equivalents 3-6 possessing elements of axial 3 [105], both axial and central 4 [106,107] chirality, carbon and nitrogen stereogenic centers 5 [108][109][110], and a proline-derived complex 6 bearing electron-deficient benzyl moiety [111,112]. The Ni(II) complex methodology can be used for direct dynamic kinetic resolution of racemic α- [113][114][115] and β-AAs [116], provided that the corresponding racemic AAs are readily commercially available.…”

Section: Resultsmentioning

confidence: 99%

“…Derivatives 8 are conveniently disassembled to release the target AAs 9, along with recycling of the corresponding chiral ligands, rendering the process commercially attractive. and nitrogen stereogenic centers 5 [108][109][110], and a proline-derived complex 6 bearing electrondeficient benzyl moiety [111,112]. The Ni(II) complex methodology can be used for direct dynamic kinetic resolution of racemic α- [113][114][115] and β-AAs [116], provided that the corresponding racemic AAs are readily commercially available.…”

Section: Resultsmentioning

confidence: 99%

Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid

et al. 2019

Self Cite

View full text Add to dashboard Cite

Enantiomerically pure derivatives of 2-amino-4,4,4-trifluorobutanoic acid are in great demand as bioisostere of leucine moiety in the drug design. Here, we disclose a method specifically developed for large-scale (>150 g) preparation of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid. The method employs a recyclable chiral auxiliary to form the corresponding Ni(II) complex with glycine Schiff base, which is alkylated with CF3–CH2–I under basic conditions. The resultant alkylated Ni(II) complex is disassembled to reclaim the chiral auxiliary and 2-amino-4,4,4-trifluorobutanoic acid, which is in situ converted to the N-Fmoc derivative. The whole procedure was reproduced several times for consecutive preparation of over 300 g of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid.

show abstract

“…In this contest, adamantane derivatives are known to exhibit considerable biological significance, which includes antiviral [23], antibacterial [24,25], anti-inflammatory [26,27] activities, and the inhibition of 11β-hydroxysteriod dehydrogenase type I [28]. A recent study discussed the uses of adamantine in resolution of racemic rimantadine hydrocholide [29]. In spite of biological importance of metal ions, only few Co(II), Cd(II) and Cu(II) complexes with hydrazone ligands incorporating adamantane were synthesized [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

et al. 2020

View full text Add to dashboard Cite

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

show abstract

Optical Resolution of Rimantadine

Cited by 7 publications

References 64 publications

Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR

Flurbiprofen: A Study of the Behavior of the Scalemate by Chromatography, Sublimation, and NMR

Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid

Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Contact Info

Product

Resources

About