A unified strategy for the synthesis of phenanthroizidine alkaloids: Preparation of sterically congested pyridines

Journal of the American Chemical Society

Volumn 118, Issue 48, 1996, Pages 12082-12089

  Ciufolini, Marco A ^a   Roschangar, Frank ^a  

^a RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; ANTOFINE; JULANDINE; SEPTICINE; TYLOPHORINE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; INFRARED SPECTROPHOTOMETRY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY; TECHNIQUE;

EID: 0030474491     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja962757p     Document Type: Article

References (42)

1. Reviews: (a) Gellert, E. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W., Ed.; John Wiley & Sons: New York, New York, 1987; Vol. 5, p 55.
2. (b) Suffness, M.; Cordell, G. A. The Alkaloids; Brossi, A., Ed.; Academic Press, Orlando, FL, 1985; Vol. 25, p 156
3. (c) Bick, R. C.; Sinchai, W. In The Alkaloids; Rodrigo, R. G. A., Ed.; Academic Press: New York, 1981; Vol. 19, p 193.
4. (d) Govindachari, T. R.; Viswanathan, N. Heterocycles 1978, 11, 587.
5. (e) Govindachari, T. R. In The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New York, 1967; Vol. 9, p 517.
6. Detailed discussion: Suffness, M.; Cordell, G. A. In The Alkaloids; Brossi, A., Ed.; Academic Press: Orlando, FL, 1985; Vol. 25, ch. 1, pp 3-355.
7. Duan, J.; Yu, L. Zhongcaoyao 1991, 22, 316
8. (Chem. Abstr. 1992, 116, 386u).
9. The literature cited in ref 2 contains extensive discussion of earlier syntheses of these alkaloids. More recent reports containing new strategic ideas: (a) Khatri, N. A.; Schmitthenner, H. F.; Shringarpure, J.; Weinreb, S. M. J. Am. Chem. Soc. 1981, 103, 6387.
10. (b) Cragg, J. E.; Hedges, S. H.; Herbert, R. B. Tetrahedron Lett. 1981, 22, 2127.
11. (c) Bremmer, M. I.; Khatri, N. A.; Weinreb, S. M. J. Org. Chem. 1983, 48, 3661.
12. (d) Iwao, M.; Mahalanabis, K. K.; Watanabe, M.; de Silva, S. O.; Snieckus, V. Tetrahedron 1983, 39, 1955.
13. (e) Iida, H.; Watanabe, Y.; Tanaka, M.; Kibayashi, C. J. Org. Chem. 1984, 49, 2412.
14. (f) Iwasa, K.; Kamigauchi, M.; Takao, N. J. Nat. Prod. 1988, 51, 172.
15. (g) Grieco, P. A.; Parker, D. T. J. Org. Chem. 1988, 53, 3325.
16. (h) Ihara, M.; Takino, Y.; Tomotake, M.; Fukumoto, K. J. Chem. Soc., Perkin Trans. 1 1990, 2287.
17. (i) Snieckus, V. Chem. Rev. 1990, 90, 879.
18. j) Snieckus, V. Pure Appl. Chem. 1990, 62, 2047.
19. (k) Comins, D. L.; Morgan, L. A. Tetrahedron Lett. 1991, 32, 5919.
20. (1) Yerxa, B. R.; Yang, K.; Moore, H. W. Tetrahedron 1994, 50, 6173.
21. Pearson, W. H.; Walavalkar, R. Tetrahedron 1994, 50, 12293. This last work contains an extensive bibliography of synthetic activity in the phenanthroizidine area.
22. Cf. Ciufolini, M. A.; Shen, Y.-C.; Bishop, M. J. J. Am. Chem. Soc. 1995, 117, 12460, and references cited therein. See also ref 10.
23. The term "cycloaddition" is used throughout this paper only to describe the gross outcome of reactions between α,β-unsaturated carbonyl compounds and vinyl ethers. No mechanistic inferences should be drawn from such usage, particularly with respect to concertedeness or other intimate electronic details of the reactions.
24. Because the reaction proceeds with inverse demand, the major frontier orbital interaction is assumed to be the one between the HOMO of the electron-rich ether and the LUMO of the electron-deficient enone.
25. Calculations were carried out with the Hyperchem package (version 4.0) available from Hypercube, Inc., Ontario, Canada.
26. This may reflect the fact that in structure 20 the enone system is essentially planar, though the dihedral angle between the vicinal carbonyl groups is approximately 129°; therefore, excellent conjugations exists throughout the π network involved in the cycloaddition. By contrast, significant out-of-plane distortion of aryl, olefin, and carbonyl groups is apparent in the MM+ structure of 22: conjugation is thus likely to be disrupted. Indeed, the LUMO energy of 22 is identical to that of 21, indicating that the activation provided by the second carbonyl is barely sufficient to counterbalance the presence of two electron-releasing OMe groups on the phenyl ring.
27. Ciufolini, M. A.; Bishop, M. J. J. Chem. Soc., Chem. Commun. 1993, 1463.
28. Ciufolini, M. A. In Advances in Heterocyclic Natural Product Synthesis; Pearson. W. H., Ed.; JAI Press: Greenwich, CT, 1996; Vol. 3, ch. 1, pp 1-55. See also ref 10.
29. Cf., e.g., Danishefsky, S.; Cain, P. J. Am. Chem. Soc. 1975, 97, 5282.
30. Discussion: Jones, J. K. N. In Chemistry of Carbon Coumpounds; Rodd, E. H., Ed.; Elsevier: Amsterdam, The Netherlands, 1952; Vol. I, Part B, Ch. 19; see especially p 1238.
31. We thank Dr. Larry Alemany, of this department, for valuable assistance with the NOE measurements.
32. The abnormal products displayed the same chromatographic mobility as the major pyridines under a variety of conditions, rendering their isolation quite arduous, but they were found to undergo benzoate cleavage at a considerably slower rate than "normal" pyridines 30a,b, probably for steric reasons, and were thus separated from the major product at the stage of alcohols 31.
33. Bishop, M. J. Unpublished results from these laboratories.
34. Liepa, A. J.; Summons, R. E. J. Chem. Soc., Chem. Commun. 1977, 826.
35. Cragg, J. E.; Herbert, R. B. J. Chem. Soc., Perkin Trans, 1 1992, 2487.
36. It was not possible to compare the spectra of our synthetic final products with spectra of authentic natural materials. However, all of these alkaloids have been synthesized several times, and physical and spectral data obtained by us were in complete agreement with those reported by previous workers. As further detailed in ref 22, controversy exists regarding the melting point (but not the spectral properties) of (±)-tylophorine, literature values for which span almost 30 °C.
37. (a) Ciufolini, M. A.; Byrne, N. E. J. Am. Chem. Soc. 1991, 113, 8016 (cystodytins).
38. (b) Bishop, M. J.; Ciufolini, M. A. J. Am. Chem. Soc. 1992, 114, 10081 (dercitins and kuanoniamines).
39. (c) Ciufolini, M. A.; Shen, Y.-C. Tetrahedron Lett. 1995, 36, 4709 (diplamine and shermilamine), as well as refs 5, 10 (lavendamycin methyl ester), and 11.
40. 2, MeOH was dried over 4 Å mol sieves. All other reagents and solvents were used as received.
41. Discord exists in the literature regarding the melting point of (±)-1, e.g.: 292-294 °C (ref 4k); 287 °C (ref 4m); 273 °C (ref 17); 263-265 °C (ref 4f).
42. Govindachari, T. R.; Ragade, I. S.; Viswanathan, N. J. Chem. Soc. 1962, 1356.