Total synthesis of taspine

Journal of Organic Chemistry

Volumn 63, Issue 22, 1998, Pages 8045-8048

  Ross Kelly, T ^a   Xie, Roger L ^a  

^a BOSTON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; TASPINE; UNCLASSIFIED DRUG;

ARTICLE; CYTOTOXICITY; DIMERIZATION; DRUG SYNTHESIS; NONHUMAN; PROMOTER REGION; VIRUS INHIBITION; WOUND HEALING;

EID: 0032582582     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo981099j     Document Type: Article

References (47)

1. (a) Perdue, G. P.; Blomster, R. N.; Blake, D. A.; Farnsworth, N. R. J. Pharm. Sei. 1979, 63,124-126.
2. (b) Vaisberg, A. J.; Milla, M.; del Carmen Planas, M.; Cordova, J. L.; Rosas de Agusti, E.; Ferreyra, R.; del Carmen Mustiga, M.; Carlin, L.; Hammond, G. B. Planta Med. 1989, 55, 140-143.
3. Cai, Y.; Chen, Z. P.; Phillipson, J. D. Phytochemistry 1993,32, 755-760.
4. Pieters, L.; De Bruyne, T.; van Poel, B.; Vingerhoets, R.; Totté, J.; Vanden Berghe, D.; Vlietinck, A. Phytomedicine 1995, 2, 17-22.
5. (a) Persinos, G. J. (Amazon Natural Drug Co.) U.S. Patent 3 694 557, 1972;
6. Chem. Abstr. 1973, 78, 7827.
7. (b) Lewis, W. H.; Stonard,-R. J.; Porras-Reyes, B. H.; Mustoe, T. A. U.S. Patent 5 156 847, 1992;
8. Chem. Abstr. 1992, 117, 245630.
9. Porras-Reyes, B. H.; Lewis, W. H.; Roman, J.; Simchowitz, L.; Mustoe, T. A. Proc. Soc. Exp. Blol. Med. 1993, 203, 18-25.
10. Winter, R. E. K.; Kolodziej, S. A.; Lewis, W. H. U.S. Patent 5 474 782, 1995;
11. Chem. Abstr. 1996, 124, 97769.
12. (a) Itokawa, H.; Ichihara, Y.; Mochizuki, M.; Enomori, T.; Morita, H.; Shirota, O.; Inamatsu, M.; Takeya, K. Chem. Pharm. Bull. 1991, 39, 1041-1042.
13. (b) Pieters, L.; De Bruyne, T.; Claeys, M.; Vlietinck, A.; Calomme, M.; Vanden Berghe, D. J. Nat. Prod. 1993, 56, 899906.
14. Sethi, M. L. Can. J. Pharm. Sei. 1977, 12, 7-9.
15. (a) Platonova, T. F.; Kuzovkov, A. D.; Massagetov, P. S. Zh. Obshch. Khlm. 1953,23, 880-886.
16. (b) Platonova, T. F.; Kuzovkov, A. D. Zh. Obshch. Khim. 1954, 24, 2246-2249.
17. Platonova, T. F.; Kuzovkov, A. D.; Sheinker, Yu. N. Zh. Obshch. Khim. 1956,26, 2651-2656.
18. (a) Shamma, M. The Isoquinoline Alkaloids; Academic Press: New York, 1972; Chapter 15.
19. (b) Cordell, G. A. Introduction to Alkaloids: A Biogenetic Approach; Wiley: New York, 1981; pp 422-423.
20. Strictly speaking, a formal total synthesis of 1 has been achieved. In 1971, Shamma and Moniot (Shamma, M.; Moniot, J. L. J. Chem. Soc. D 1971, 18, 1065-1966)
21. reported the biogenetically patterned conversion of the widespread quaternary aporphine (+)-magnoflorine (i) into taspine (1). For a synthesis of (±) magnoflorine, see: Tomita, M.; Kikkawa, I. J. Pharm. Soc. Jpn. 1957, 77, 195-199.
22. For a report of model studies directed toward the synthesis of 1, see: Scarpati, M. L.; Bianco, A.; Lo Scalzo, R. Synth. Commun. 1991, 21, 849-858.
23. Bodanszky, M. Peptide Chemistry: A Practical Textbook; SpringerVerlag: Berlin, 1988; pp 62-68.
24. (a) van Heerden, F. R.; van Zyl, J. J.; Rail, G. J. H.; Brandt, E. V.; Roux, D. G. Tetrahedron Lett. 1978, 661-662.
25. (b) For related applications, see: Kelly, T. R.; Jagoe, C. T.; Li, Q. J. Am. Chem. Soc. 1989, 111, 4522-4524 and references therein.
26. For a recent review, see: Snieckus, V. Chem. Rev. 1990, 90, 879-933.
27. For a review, see: Jukes, A. E. Adv. Organomet. Chem. 1974, 12, 215-322.
28. Kleiderer, E. C.; Adams, R. J. Am. Chem. Soc. 1933,55,42194225.
29. 3SnCl), were not successful, perhaps because of severe steric hindrance. For a leading reference to successful palladium-catalyzed biaryl couplings from this laboratory, see: Kelly, T. R.; Lee, Y.-J.; Mears, R. J. J. Org. Chem. 1997, 62, 2774-2781.
30. 16 (prepared in situ from the HC1 salt by addition of 1 equiv of BuLi)
31. 17
32. 18 2-(dimethylamino)-JV-methoxy-N-methylacetamide
33. 1,2-dibromoethane (the Li in 12 is replaced by Br)
34. 19
35. For a review of synthetic applications of /Mialo amines in medicinal chemistry, see: Miocque, M.; Duclos, J. P. Chim. Ther. 1969, 4, 363.
36. Pearson, W. H.; Lian, B. W.; Bergmeier, S. C. In Comprehensive Heterocyclic Chemistry, II: A Review of the Literature 1982-1995; Katritzky, A. R., Rees, C. \V., Scriven, E. F. V., Editors-in-Chief; Padwa, A., Vol. Ed.; Pergamon Press: New York, 1996; Vol. 1A, pp 1-60.
37. (a) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981,22,38153818. For a review, see:
38. (b) Sibi, M. P. Org. Prep. Proce'd. Int. 1993, 25, 17-40.
39. Lipshutz, B. H.; Kozlowski, J. A.; Wilhelm, R. S. J. Org. Chem. 1984,49, 3943-3949.
40. Coupling reactions between iodide iii and allyltributyltin under various conditions only gave iv in low yields (<10%).
41. For a review, see: Hutchins, R. O.; Hutchins, M. K. In Comprehensive Organic Synthesis: Selectivity, Strategy & Efficiency in Modern Organic Chemistry; Trost, B. M., Fleming, I., Eds.; Pergamon': New York, 1991; Vol. 8, Chapter 1.2.
42. (a) Gribble, G. W.; Ferguson, D. C. J. Chem. Soc., Chem. Commun. 1975, 535-536.
43. For related applications, see: (b) AbdelMagid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849-3862 and references therein.
44. Most papers reporting the isolation of natural taspine2"'5"'26 state it to be optically inactive, but one publication13 reports an [a]24o of +7.6 (c 0.64, pyridine), a value that has been repeated in the secondary literature (Dictionary of Natural Products; Chapman & Hall: London, 1994; p 5338). In our view, a compound with the structure of 1 should not be capable of optical activity under ordinary circumstances. In support ofthat view, AMI calculations using version 5.0 of Spartan (Wavefunction, Inc., Irvine, CA) indicate that the two carbocyclic rings in 1 are within 1 of coplanarity. We measured the [a]24D of a sample of natural taspine obtained from Croton lechlerilb generously provided by Dr. G. B. Hammond. In our measurement, we found an [a]24D of +0.9 (c 0.64, pyridine, heat to dissolve), but that value corresponds to a meter reading of only 0.006 on a Perkin-Elmer 241 polarimeter using a 1 dm cell (the meter reading fluctuated from 0.002 to 0.011; a control measurement using pure pyridine under the same conditions gave a less fluctuating meter reading of -0.001 to . 0.002). While the !H NMR spectrum of the natural taspine provided by Dr. Hammond indicated the compound to be pure, we believe the optical rotation observed for taspine is due to contamination by a small amount of a highly optically active impurity. For whatever negative evidence is worth, as expected, we were unable to "resolve" synthetic (= racemic or achiral) taspine using the chiral NMR shift reagents europium tris[3-[(heptafluoropropyl)hydroxymethylene]-(+)-camphorate] (Aldrich catalog no. 16,474-7) and europium trisβ-[(trifluoromethyl)hydroxvmethylene]-(-)-camphorate] (Aldrich catalog no. 29,6597).
45. For most general experimental procedures, see: Kelly, T. R.; Lang, F. J. Org. Chem. 1996, 61, 4623-4633. 1,2-Dichloroethane was distilled from calcium hydride. Neutral alumina (activated, Brockmann I, ~150 mesh) was purchased from Aldrich (catalog no. 19,997-4). For reactions monitored by alumina analytical TLC, neutral aluminum oxide plates were used. Ozone was generated using an OSMONICS OREC V5-O ozone generator (Phoenix Operations, Phoenix, AZ) and bubbled into the reaction mixture.
46. 13C NMR spectra of compounds 13-15 were not recorded.
47. Talapatra, B.; Chaudhuri, P. K.; Talapatra, S. K. Phytochemistry 1982, 21, 747-750.