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http://dx.doi.org/10.5012/jkcs.2015.59.6.488

Preparation of (S)-(+)-Pranidipine by Optical Resolution  

Baek, Du-Jong (Department of Chemistry, Sangmyung University)
Yoon, Ji Hye (Department of Chemistry, Sangmyung University)
Kim, Moon-Sik (Research Lab., M. C. Chem)
Publication Information
Journal of the Korean Chemical Society / v.59, no.6, 2015 , pp. 488-492 More about this Journal
Abstract
In this study, the effective preparation method of (S)-(+)-pranidipine, the active component of antihypertensive drug as a calcium channel blocker, was developed using optical resolution. The racemic monocarboxylic acid 5 obtained by the hydrolysis of (±)-pranidipine was mixed with optically active quinidine to form salts, and the insoluble diastereomeric salt was collected and successive treatment with base and acid furnished (R)-(-)-carboxylic acid 7. (S)-(+)-Pranidipine was prepared by esterification of this acid with cinnamyl alcohol, and the analysis by chiral HPLC showed 100% enantiomeric excess (ee). This process would be industrially very useful to prepare chiral (S)-(+)-pranidipine, since the use of strong base and anhydrous solvents, and ultra-low temperature condition were excluded in this process.
Keywords
(S)-(+)-Pranidipine; Calcium channel blocker; Antihypertensive drug; Optical resolution; Enantiomeric excess;
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  • Reference
1 Ahuja, S. Chiral Separation Methods for Pharmaceutical and Biotechnological Products; John Wiley & Sons: NewYork, U.S.A., 2011.
2 Fleckenstein, A. Circul. Res. 1983, 52, I3.
3 Hirano, T.; Mori, T.; Kido, M.; Toide, K.; Ohura, M.; Fujiki, H.; Orito, K.; Yoshida, K.; Ikezono, K.; Sumida, T.; Nakayama, N.; Yabuuchi, Y. Fundam. Clin. Pharmacol. 1999, 13, 650.   DOI
4 (c) Gjorstrup, P.; Harding, H.; Isaksson, R.; Westerlund, C. Eur. J. Pharmacol. 1986, 122, 357.   DOI
5 (b) Williams, J. S.; Grupp, I. L.; Grupp, G.; Vaghy, P. L.; Dumont, L.; Schwartz, A. Biochem. Biophys. Res. Commun. 1985, 131, 13.   DOI
6 (a) Franckowiak, G.; Bechem, M.; Schramm, M.; Thomas, G. Eur. J. Pharmacol. 1985, 114, 223.   DOI
7 (b) Hirano, T.; Ohura, M.; Orito, K.; Fujiki, H.; Miyakoda, G.; Mori, T. Eur. J. Pharmacol. 1997, 324, 201.   DOI
8 (a) Mori, T.; Takeuchi, T.; Ohura, M.; Miyakoda, G.; Fujiki, H.; Orito, K.; Yoshida, K.; Hirano, T.; Yamamura, Y.; Sumida,T.; Nakaya, Y.; Satake, H.; Hata, F. Mol. Cell. Biochem. 1998, 178, 335.   DOI
9 Nakayama, N.; Ikezono, K.; Ohura, M.; Yabuuchi, Y. Arzneimittelforschung-Drug Res. 1993, 43, 1266.
10 Ioan, P.; Carosati, E.; Micucci, M.; Cruciani, G.; Broccatelli, F.; Zhorov, B.; Chiarini, A.; Budriesi, R. Curr. Med. Chem. 2011, 18, 4901.   DOI
11 Shibanuma, T.; Iwanani, M.; Okuda, K.; Takenaka, T.; Murakami, M. Chem. Pharm. Bull. 1980, 28, 2809.   DOI
12 Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.   DOI
13 Kim, M.-S.; Ko, I. J. S-(+)-Pranidipine and methods of producing the same, KR Patent 10-0832659, May 20, 2008.
14 Ikawa, H.; Kadoiri, A.; Konagai, Y.; Yamaura, T.; Kase, N. 1,4-Dihydropyridine derivatives and methods of producing the same, U. S. Patent 5,763,614, Jun. 9, 1998.
15 Kadoiri, A.; Ikawa, H.; Kobayashi, N.; Isowa, Y. Optically active 1,4-dihydropyridine derivatives and methods of producing the same, JP 6,043,397B, Jun. 8, 1994.