A novel and general route to diverse A-ring aromatic trichothecanes via cyclobutanes

Tetrahedron

Volumn 52, Issue 31, 1996, Pages 10363-10374

  Nemoto, Hideo ^a   Miyata, Junji ^a   Fukumoto, Keiichiro ^a  

^a TOHOKU UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

SESQUITERPENE; TRICHOTHECANE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY; TECHNIQUE;

EID: 0030605916     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4020(96)00549-2     Document Type: Article

References (48)

1. 1. (a) Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring Compounds Vol. II, Terpenes: Academic Press, New York, 1972, p 114.
2. (b) Terpenoids and Steroids; The Chemical Society, London, Vol. 1-12.
3. (c) Grove, J. F. Nat. Prod. Rep. 1988, 187-209.
4. (d) ApSimon, J. W.; Blackwell, B. A.; Blais, L.; Fielder, D. A.; Greenhalgh, R.; Kasitu, G.; Miller, J. D.; Savard, M. Pure Appl. Chem. 1990, 62, 1339-1346.
5. 2. (a) Bamburg, J. R. Clin. Toxicol. 1972, 5, 495-515.
6. (b) Tamm, C. Fortschr. Chem. Org. Naturst. 1974, 31, 63-117.
7. (c) Purchase, I. F. H. Ed., Mycotoxins; American Elsevier, New York, 1974.
8. (d) Kupchan, S. M.; Jarvis, B. B.; Dailey Jr., R. G.; Bright, W.; Bryan, R. F.; Shizuri, Y. J. Am. Chem. Soc. 1976, 98, 7092-7093.
9. (e) Ueno, Y. Trichothecanes-Chemical, Biological and Toxicological Aspects, Developments in Food Science 4, American Elsevier, New York, 1983.
10. 3. Doyle, T. W.; Bradner, W. T. In Anticancer Agents Based on Natural Product Models; Cassady, J. M.; Douros, J. D., Eds.; Academic, New York, 1980, p 43.
11. 4. (a) McDougal, P. G.; Schmuff, N. R. In Progress in the Chemistry of Organic Natural Products; Herz, W.; Grisebach, H.; Kirby, G. W.; Tamm, Ch., Eds.; Springer-Verlag, New York, 1985. Vol. 47, p 153.
12. (b) Heathcock, C. H.; Graham, S. L.; Pirrung, M. C.; Plavac, F.; White, C. T. In The Total Synthesis of Natural Products; ApSimon, J. W., Ed.; John Wiley & Sons, Inc., New York, 1983, Vol. 5, p 238.
13. (c) Boeckman, R. H.; Goldstein, M. ibid. 1988, Vol. 7, p 116.
14. (d) Schlessinger, R. H.; Nugent, R. A. J. Am. Chem. Soc. 1982, 104, 1116-1118.
15. (e) Trost, B.M.; McDougal, P. G. ibid. 1982, 104, 6110-6112.
16. (f), Kraus, G. A.; Roth, B.; Frazier, K.; Shimagaki, M. ibid. 1982, 104, 1114-1116.
17. (g) Rousch, W. R.; D'Ambra, T. E. ibid. 1983, 105, 1058-1060.
18. (h) Brooks, D. W.; Grothaus, P. G.; Mazdiyasni, H. ibid. 1983, 105, 4472-4473.
19. (i) Gilbert, J. C.; Selliah, R. D. Tetrahedron Lett. 1992, 33, 6259-6262.
20. (j) idem J. Org. Chem. 1993, 58, 6255-6265 and references cited therein.
21. 5. (a) Nemoto, H.; Ishibashi, H.; Fukumoto, K. Heterocycles, 1992, 33, 549-552.
22. (b) Nemoto, H.; Ishibashi, H.; Nagamochi, M.; Fukumoto, K. J. Org. Chem. 1992, 57, 1707-1712.
23. (c) Nemoto, H.; Nagamochi, M.; Fukumoto, K. J. Chem. Soc., Chem. Commun. 1992, 1695-1697.
24. (d) Nemoto, H.; Nagamochi, M.; Fukumoto, K. J. Chem. Soc., Perkin Trans. 1 1993, 2329-2332.
25. (e) Nemoto, H.; Tanabe, T.; Nagamochi, M.; Fukumoto, K. Heterocycles 1993, 35, 707-710.
26. (f) Nemoto, H.; Shiraki, M.; Nagamochi, M.; Fukumoto, K. Tetrahedron Lett. 1993, 34, 4939-4942.
27. (g) Nemoto, H.; Shiraki, M.; Fukumoto, K. Synlett. 1994, 599-600.
28. (h) Nemoto, H.; Shiraki, M.; Fukumoto, K. Tetrahedron 1994, 50, 10391-10396.
29. (i) Nemoto, H.; Tanabe, T.; Fukumoto, K. Tetrahedron Lett. 1994, 35, 6499-6502.
30. (j) Nemoto, H.; Nagamochi, M.; Ishibashi, H.; Fukumoto, K. J. Org. Chem. 1994, 59, 74-79.
31. (k) Nemoto, H.; Tanabe, T.; Fukumoto, K. ibid. 1995, 60, 6785-6790.
32. (l) Nemoto, H.; Shiraki, M.; Fukumoto, K. Tetrahedron Lett. 1995, 36, 8799-8802.
33. 6. (a) Nemoto, H.; Hakamata, H.; Nagamochi, M.; Fukumoto, K. Heterocycles 1994, 39, 467-470.
34. (b) Nemoto, H.; Miyata, J.; Hakamata, H.; Fukumoto, K. Tetrahedron Lett. 1995, 36, 1055-1058.
35. (c) Nemoto, H.; Miyata, J.; Hakamata, H.; Nagamochi, M.; Fukumoto, K. Tetrahedron 1995, 51, 5511-5522.
36. 7. Anderson, W. K.; Lee, G. E. J. Med. Chem. 1980, 23, 96-97.
37. 8. Weber, H. W. Fr. 1, 511, 331 (Chem. Abstr. 1969, 70, 77767 h).
38. 8. Weber, H. W. Fr. 1, 511, 331 (Chem. Abstr. 1969, 70, 77767 h).
39. 9. Stafford, J. A.; McMurry, J. E. Tetrahedron Lett. 1988, 29, 2531-2534.
40. 1H NMR integration of methyl signals (1.35 ppm for 15 and 1.46 ppm for 16). These isomers could not be separated and used as a mixture (Figure 1).
41. 11. THis type of transformtion has been developed by us and others, see 5j and references cited therein.
42. 1H NMR (300 MHz) studies as follows. Namely, the definite NOE enhancement between methyl (Ha) (1.56 ppm, s) and allylic 1hydrogen (Hb) (4.66-4.76 ppm, m) of 25 confirmed these two groups to (Equation Presented) be cis. On the other hand, no such enhancement between methyl (Ha) (1.44 ppm, s) and allylic hydrogen (Hb) (4.54-4.64 ppm, m) of 26 showed these two groups to be trans (Figure 2). Since the next cyclization process giving 31 seems to proceed via allylic cation, the both diastereomers 25 and 26 might be used for this reaction. 25 : R = MOM 26 : R = MOM 27 : R = SEM 28 : R = SEM
43. 14 of the compound 33 in which the epoxidation took place in the completely stereoselective manner to give the compound 34 with the syn relationship between the methylene hydrogens of the epoxide ring and the aromatic ring. This stereochemical outcome was explained by the effective size of the π system making the aromatic region of 33 to be more encumbered one. This stereochemical assignment was also supported by the somewhat large difference of the chemical shifts between the two hydrogens Ha (2.91 ppm, d, J = 4.2 Hz) and Hb (3.11 ppm, d, J = 4.2 Hz) of the epoxide 2 due to the deshielding effect of the phenoxy group and this seemed not to be the case for the isomeric epoxide 35. This was also confirmed afterward by the identification with the sample obtained via the diol 32 (Figure 3).
44. 14. Goldsmith, D. J.; John, T. K.; Kwong, C. D.; Painter III, G. R. J. Org. Chem. 1980, 45, 3989-3993.
45. 1H NMR integration of methyl signals (1.34 ppm for 17 and 1.44 ppm for 18) (see Figure 1).
46. 1H NMR (300 MHz) studies as follows. The difinite NOE enhancement between methyl (Ha) (1.52 ppm, s) and allylic hydrogen (Hb) (4.67-4.78 ppm, m) of 27 showed these two groups to be cis. On the other hand, no such enhancement between methyl (Ha) (1.43 ppm, s) and allylic hydrogen (Hb) (4.55-4.66 ppm, m) of 28 confirmed these two groups to be trans. These two isomers were separated at this stage and used separately for further elaboration (see Figure 2).
47. 1H NMR (500 MHz) studies of the corresponding acetonide 36 as follows. The signals of the methylene hydrogens Ha and Hb were observed at 3.68 ppm (d, J = 9.2 Hz) and 4.20 ppm (d, J = 9.2 Hz) respectively with large difference (0.52 ppm) of chemical shifts which could be due to the deshielding effect of phenoxy group. On the other hand, the two methyl groups of acetonide were observed at 1.46 ppm with the same chemical shift. This showed the aromatic ring and the methylene group of dioxolane ring to be syn relationship. This could not be the case for the isomeric acetonide 37 (Figure 4).
48. 18. All compounds reported in this paper are racemic. For convenience, only one enantiomer is shown.