Asymmetric synthesis of (+)-morphine. The phenanthrene route revisited

Journal of Organic Chemistry

Volumn 62, Issue 16, 1997, Pages 5250-5251

  White, James D ^a   Hrnciar, Peter ^a   Stappenbeck, Frank ^a  

^a OREGON STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MORPHINE; PHENANTHRENE;

ANALGESIA; ARTICLE; DRUG SYNTHESIS; ENANTIOMER; PAIN; STEREOCHEMISTRY;

EID: 0030837809     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9710994     Document Type: Article

References (26)

1. For a concise history of morphine and its development as an analgesic, see Lednicer, D. Analgesics; Wiley: New York, 1982; pp 137-213.
2. (a) Gulland, J. M.; Robinson, R. Mem. Proc. Manch. Lit. Soc. 1925, 69, 79.
3. (b) Robinson, R.; Sugasawa, S. J. Chem. Soc. 1933, 1079.
4. These early endeavors were heavily influenced by degradative experiments with morphine which yielded a phenanthrene system after exhaustive dehydrogenation. For a recent successful approach to morphine along these lines, see Mulzer, J.; Durner, G.; Trauner, D. Angew. Chem., Int. Ed. Engl. 1996, 35, 2830.
5. For a recent review, see Hudlicky, T.; Butora, G.; Fearnley, S. P.; Gum, A. G.; Stabile, M. R. Studies in Natural Products Chemistry; Rahman, A-u., Ed.; Elsevier: Amsterdam, 1996; pp 43-154.
6. For example, see Schwartz, M. A.; Pham, P. T. K. J. Org. Chem. 1988, 53, 2318.
7. Hong, C. Y.; Kado, N.; Overman, L. E. J. Am. Chem. Soc. 1993, 115, 11028.
8. (a) Pschorr, A. T. Ber. 1896, 29, 296.
9. (b) Fieser, L. F.; Holmes, H. L. J. Am. Chem. Soc. 1936, 58, 2319.
10. (c) Robinson, R.; Gosh, R. J. J. Chem. Soc. 1944, 506.
11. For a recent approach to the unnatural enantiomer of morphine, see Butora, G.; Hudlicky, T.; Fearnley, S. P.; Gunn, A. G.; Stabile, M. R.; Abboud, K. Tetrahedron Lett. 1996, 37, 8155.
12. Of the 16 completed morphine syntheses only one, that of Ginsburg, attacks the morphine problem from this direction (a) Ginsburg, D.; Pappo, R. J. Chem. Soc. 1953, 1524. (b) Ginsburg, D.; Elad, D. J. Chem. Soc. 1954, 3052.
13. Of the 16 completed morphine syntheses only one, that of Ginsburg, attacks the morphine problem from this direction (a) Ginsburg, D.; Pappo, R. J. Chem. Soc. 1953, 1524. (b) Ginsburg, D.; Elad, D. J. Chem. Soc. 1954, 3052.
14. Harada, K. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, 1985; Vol. 5, p 345.
15. Johnson, W. S.; Daub, G. Org. React. 1951, 6, 1.
16. Morimoto, T.; Chiba, M.; Achiwa, K. Tetrahedron Lett. 1989, 30, 735.
17. Enantiomeric excess of 4 was determined by chiral HPLC using a Chiralpak AD column and 9:1 hexane-2-propanol (containing 5% trifluoroacetic acid) as eluent.
18. For a previous application of this tactic, see White, J. D.; Caravatti, G.; Kline, T. B.; Edstrom, E.; Rice, K. C.; Brossi, A. Tetrahedron 1983, 39, 2393.
19. Banwell, M. G.; Lambert, J. N.; Corbett, M; Greenwood, R. J.; Gulbis, J. M.; Mackay, M. F. J. Chem. Soc., Perkin Trans. 1 1992, 1415. Saponification of the methyl ester of 5 is necessary in order to avoid racemization in this step.
20. Cyclization probably occurs via the isomeric βγ-unsaturated ketone.
21. Taber, D. F. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon, Oxford, U.K., 1991; Vol. 3, p 1045.
22. The two byproducts (ca. 15% each) have been identified as i and ii, respectively: Equation presented.
23. Gawley, R. E. Org. React. 1988, 35, 1. The principal reaction pathway is believed to involve Beckmann fragmentation.
24. Iijima, I.; Rice, K. C. Heterocycles 1977, 6, 1157.
25. Weller, D. D.; Rapoport, H. J. Med. Chem. 1976, 19, 1171.
26. Rice, K. C. J. Med. Chem. 1977, 20, 164.