Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 18, 2008, Pages 4978-4981

  Fujii, Hideaki ^a   Osa, Yumiko ^a   Ishihara, Marina ^a   Hanamura, Shinichi ^a   Nemoto, Toru ^a   Nakajima, Mayumi ^b   Hasebe, Ko ^b   Mochizuki, Hidenori ^b   Nagase, Hiroshi ^a  

^a KITASATO UNIVERSITY   (Japan)

^b TORAY INDUSTRIES INC   (Japan)

Author keywords

Cyclopropylcarbinyl cation; Hydrogenolysis; Opioid; Platinum (IV) oxide

Indexed keywords

ACETIC ACID; CYCLOPROPANE DERIVATIVE; HYDROBROMIC ACID; MORPHINAN DERIVATIVE; N ISOBUTYLNOROXYMORPHONE; NALOXONE; NALTREXONE; OPIATE AGONIST; OPIATE ANTAGONIST; OPIATE RECEPTOR; OXYMORPHONE; PLATINUM; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG BINDING; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROGENATION; MOUSE; NONHUMAN; RING OPENING; STRUCTURE ACTIVITY RELATION; WRITHING TEST;

ACETIC ACID; ANALGESICS, OPIOID; ANIMALS; CYCLOPROPANES; DOSE-RESPONSE RELATIONSHIP, DRUG; MICE; MOLECULAR STRUCTURE; MORPHINANS; NALTREXONE; RECEPTORS, OPIOID;

EID: 51349104143     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.08.019     Document Type: Article

References (25)

1. Casy A.F., and Parfitt R.T. Opioid Analgesics: Chemistry and Receptors (1986), Plenum Press, New York 9-104
2. Zimmerman D.M., and Leander J.D. NIDA Res. Monogr. 96 (1990) 50
3. Fries D.S. In: Williams D.A., and Lemke T.L. (Eds). FOYE'S Principles of Medicinal Chemistry. 6th ed. (2008), Lippincott Williams & Wilkins, Philadelphia 652-678
4. Nemoto T., Fujii H., Sato N., and Nagase H. Tetrahedron Lett. 48 (2007) 7413
5. Casy et al. described in the reference (1a) as follows: It would seem that an N-substituent with a straight chain of three carbons affords optimum antagonist activity. Extending the chain by one carbon lowers activity, whereas a five-carbon chain or slightly more restores agonist activity.
6. Hagemen H.A. Org. React. 7 (1953) 198
7. Cooley J.H., and Evain E.J. Synthesis (1989) 1
8. Montzka T.A., Matiskella J.D., and Partyka R.A. Tetrahedron Lett. 15 (1974) 1325
9. Olofson A.R., Schnur R.C., Bunes L., and Pepe J.P. Tetrahedron Lett. 18 (1977) 1567
10. Olofson R.A., Martz J.T., Senet J.P., Piteau M., and Malfroot T. J. Org. Chem. 49 (1984) 2081
11. Fujii, H.; Nagase, H. unpublished results.
12. Nagase H., Abe A., and Portoghese P.S. J. Org. Chem. 54 (1989) 4120
13. Freifelder M. Practical Catalytic Hydrogenation (1971), Wiley & Sons, New York 254-530
14. Larson D.L., Jones R.M., Hjorth S.A., Schwartz T.W., and Portoghese P.S. J. Med. Chem. 43 (2000) 1573
15. Nagase, H.; Yamamoto, N.; Nemoto, T.; Yoza, K.; Kamiya, K.; Hirono, S.; Momen, S.; Izumimoto, N.; Hasebe, K.; Mochizuki, H.; Fujii, H. J. Org. Chem., in press.
16. Gould E.S. Mechanism and Structure in Organic Chemistry (1959), Henry Holt and Company, New York 561-617
17. Richey Jr. H.G. In: Olah G.A., and Schleyer P.R. (Eds). Carbonium Ions (1972), John Wiley & Sons, Canada 1201-1294
18. Olah G.A., Prakash Reddy V., and Surya Prakash G.K. Chem. Rev. 92 (1992) 69
19. 6 faster than the isobutyl tosylate because the tosylate ion could solvolitically eliminate from the cyclopropylmethyl tosylate to afford the stable cyclopropylcarbinyl cation. Lowry, T. H.; Richardson, K. S. In Mechanism and Theory in Organic Chemistry, 3rd ed; Harper & Row Publishers: New York, 1987; pp. 425-515.
20. MaloneyHuss K.E., and Portoghese P.S. J. Org. Chem. 55 (1990) 2957
21. Gates M., and Montzka T.A. J. Med. Chem. 7 (1964) 127
22. Osa Y., Ida Y., Yano Y., Furuhata K., and Nagase H. Heterocycles 69 (2006) 271
23. Casy A.F., and Beckett A.H. J. Pharm. Pharmacol. 6 (1954) 986
24. Beckett A.H. J. Pharm. Pharmacol. 8 (1956) 848
25. In general, partial agonists cannot completely attenuate the number of writhes. Compound 10 suppressed almost completely the number of writhes, suggesting that it would be a full agonist. Further assessment of compound 10 is now carried out, and its results will be reported as a full paper in the near future.