Synthesis of (+)- and (-)-milnaciprans and their conformationally restricted analogs

Tetrahedron Letters

Volumn 37, Issue 5, 1996, Pages 641-644

  Shuto, Satoshi ^a   Ono, Shizuka ^a   Hase, Yukako ^a   Kamiyama, Noriko ^a   Matsuda, Akira ^a  

^a HOKKAIDO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPROPANE DERIVATIVE; MILNACIPRAN;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030031276     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02221-X     Document Type: Article

References (24)

1. Collingridge, G. L. Watkins, J. C.; "The NMDA Receptor", eds, IRL Press at Oxford Univ. Press; Oxford, UK, 1994.
2. a) Brukey, M. Drugs future 1986, 11, 21-23.
3. b) Moret, C.; Charveron, M.; Finberg, J. P. M.; Cozinier, J.; M. Brukey, M. Neuropharmacology 1985, 24, 1211-1219.
4. Shuto, S.; Takada, H.; Mochizuki, D.; Tsujita, R.: Hase, Y.; Ono, S.; Shibuya, N.; Matsuda, A. J. Med. Chem. 1995, 38, 2964-2968.
5. Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in an eclipsed conformation to each other. Consequently, conformations of the substituents on a cyclopropane can be restricted by the steric effect of adjacent substituents. Therefore, depend on the configuration of the alkyl group introduced, the conformation of the aminomethyl moiety which is essential for the activity of (±)-1, can be restricted; conformer B would be predominant in 2 and ent-2, conversely, conformer A would be predominant in 3 and ent-3 as shown here. (equation presented)
6. Mouzin, G.; Cousse, H.; Bonnaud, B. A. Synthesis 1978, 304-305.
7. From a inflate of 92 % e.e., the corresponding cyclopropane derivative of 91% e.e. was synthesized in 50% yield: Burgess, K.; Ho, K-K. J. Org. Chem. 1992, 57, 5931-5936.
8. Hanson, R. M. Chem. Rev. 1991, 91, 437-475
9. (a) Reaction of (S)-5 of 88% e.e. and heptynyllithium gave the corresponding epoxide of 76% e.e.: Russell, S. W.; Pabon, H. J. J., J. Chem Soc. Perkin I 1982, 545-552.
10. (b) Reaction of (R)-5 and sodium dimethyl malonate gave the corresponding cyclopropane product of 93% e.e. in 36% yield: Pirrung, M. C.; Dunlap, S. E.; Trinks, U. P. Helv. Chim. Acta 1989, 72, 1301-1310.
11. Available from Daiso Co., Ltd.
12. Enantiomeric purity was measured by HPLC with Chiralcel-OJ column (Daicel Chemical Co., Ltd.).
13. When the other solvents or bases were used, the yield and/or the enantiomeric purity were decreased.
14. 2O·HCl : C, 63.72; H, 8.14; N, 9.91. Found; C. 63.43; H, 8.15; N, 9.58.
15. Although (+)-and (-)-milnaciprans have been prepared using optical resolution method with (R)-1-phenylethylamine, the optical purity was low (75% e.e. and 80% e.e., respectively): Bonnaud, R.; Calmel, R., Patoiseau, J-F.; N'Guyen, N-T.; Cousse, H. J. Chromatogr. 1985, 318, 398-403.
16. On the facial selectivity of the reaction see: Ono, S.; Shuto, S. Matsuda, A. Tetrahedron Lett. in press.
17. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113, 4092-4096.
18. Successive treatment of 10 with KOH/glycerol and DCC/MeOH also gave 12.
19. The absolute stereochemistry was also confirmed from the X-ray crystallographic analysis of the corresponding O-p-iodobenzoate of 10.
20. Yamamoto, I.; Sekine, M.; Hata, T. J. Chem. Soc. Perkin I 1983, 306-310.
21. 2,2′ value was 5.9 Hz.
22. a) Salaun, J. Chem. Rev. 1989, 89, 1247-1270
23. b) Wong, H. N. C.; Hon, M-Y.; Tse, C-Y.; Yip, Y-C. Chem. Rev., 1989, 89, 165-198.
24. More than 30 g of chiral cyclopropane derivative 4 or ent-4 can be prepared at once.