31329-57-4Relevant academic research and scientific papers
Separation of Stereoisomeric Mixtures of Nafronyl as a Representative of Compounds Possessing Two Stereogenic Centers by Coupling Crystallization, Diastereoisomeric Conversion and Chromatography
Kiwala, Dawid,Olbrycht, Maksymilian,Balawejder, Maciej,Piatkowski, Wojciech,Seidel-Morgenstern, Andreas,Antos, Dorota
, p. 615 - 625 (2016/04/04)
A procedure for the isolation of the most biologically active component of a stereoisomeric mixture of nafronyl-2-(diethylamino)ethyl 3-(naphthalen-1-yl)-2-((tetrahydrofuran-2-yl)methyl)propanoate has been proposed. The molecule of nafronyl is a representative of compounds possessing two stereogenic centers, which may be produced in the form of a quaternary mixture that contains two pairs of racemates being diastereoisomers of one another. The components of such stereoisomeric mixtures usually differ in pharmacological activity; therefore, there is an interest in developing efficient methods for their resolution. The method suggested in this study comprised two sequential separation processes, including multistage cross-current crystallization and chiral chromatography. Crystallization was employed to enrich the raw material mixture with the target racemate, which contained the stereoisomer exhibiting the highest biological activity. To intensify the process, the mother liquors depleted with the target racemate were subjected to fast base-catalyzed diastereoisomeric conversion in the melt, which provided equimolar mixtures of all four stereoisomers. The coupling of cross-current crystallization and diastereoisomeric conversion could improve yield of crystallization from 29% up to 84%. The purified racemate was further processed by chromatography to isolate finally the most active stereoisomer with 99% purity and total yield of 84%, at a relatively high throughput.
Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor
Hao, Jia,Chen, Bo,Yao, Yiwu,Hossain, Murad,Nagatomo, Takafumi,Yao, Hequan,Kong, Lingyi,Sun, Hongbin
, p. 3441 - 3444 (2012/06/18)
Naftidrofuryl oxalate (Praxilene, 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2′ configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents.
2-DIETHYLAMINOETHYL ESTERS OF 1,3-DISUBSTITUTED PROPANE-2-CARBOXYLIC ACIDS
Valenta, Vladimir,Holubek, Jiri,Svatek, Emil,Miller, Vladimir,Vlkova, Marie,Protiva, Miroslav
, p. 2534 - 2544 (2007/10/02)
Alkaline hydrolysis of diethyl 1-(tetrahydro-2-furyl)-3-(1-naphthyl)propane-2,2-dicarboxylate (IV) gave the crude acid V which was purified via the dipotassium salt and was obtained as the homogenous higher melting crystal form.Its thermic decarboxylation yielded the acid II as a mixture of two racemates (38:62); crystallization led to almost homogenous racemate B (10:90).Reaction of the sodium salt of II with dimethyl sulfate in methanol gave the methyl ester III which afforded by ester exchange with 2-diethylaminoethanol the ester I (mixture of two racemates 34:66). 2-Diethylaminoethyl 1,3-bis(1-naphthyl)propane-2-carboxylate (VII) was synthetized in three steps from diethyl (1-naphthylmethyl)malonate.Ester X was obtained from 1,3-bis(tetrahydro-2-furyl)propane-2-carboxylic acid by treatment with 2-diethylaminoethyl chloride in boiling 2-propanol in the presence of potassium carbonate.The acid V gave similarly the diester VI. 2-Diethylaminoethyl esters I, VI, VII, and X were transformed to the hydrogen oxalates.Pharmacological screening showed for the diester VI hypotensive, spasmolytic, antiarrhythmic, and antitussic activity.
