Synthesis of azetidine-type taxanes 1

Tetrahedron Letters

Volumn 37, Issue 18, 1996, Pages 3203-3206

  Fenoglio, Ivana ^a   Nano, Gian Mario ^a   Vander Velde, David G ^b   Appendino, Giovanni ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 DEACETYL 2 DEBENZYLOXY 1 DEOXYBACCATIN IV; TAXANE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0029883913     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00495-9     Document Type: Article

References (24)

1. Part XXV in the series: The Chemistry and Occurrence of Taxane Derivatives. For part XXIV, see reference 9b.
2. Cragg, G. M.; Schepartz, S. A.; Suffness, M.; Grever, M. R. J. Nat. Prod 1993, 56, 1657-1668.
3. Appendino, G. Nat. Prod. Rep. 1995, 12, 349-360.
4. Appendino, G. in Alkaloids: Chemical and Biosynthetic Perspectives Pelletier, S. W. Ed.; Pergamon Press, 1996, (in press).
5. Ettouati, L.; Ahond, A.; Poupat, C.; Potier, P. Tetrahedron 1991, 47, 9823-9838.
6. a) Nicolaou, K. C. et al. Nature 1994, 367, 630-634.
7. b) Holton, R. et al. J. Am. Chem. Soc. 1994, 116, 1599-1600.
8. c) Masters, J. J.; Danishefsky, S. J. et al. Angew. Chem. Int. Ed. Engl. 1995, 34, 1723-1726.
9. Chen, S.-H.; Farina, V. "Paclitaxel (Taxol®) Chemistry and Structure-Activity Relationships" in The Chemistry and Pharmacology of Taxol® andits Derivatives Farina V. Ed.; Elsevier, 1995, pp. 165-253.
10. Vander Velde, D.G.; Georg, G.I.; Grunewald, G. L.; Gunn, C. W.; Mitscher, L.A. J. Am. Chem. Soc. 1993, 115, 11650-11651.
11. a) Reference 7;
12. b) Appendino, G.; Jakupovic, J.; Varese, M.; Bombardelli, E. Tetrahedron Lett. 1996, 727-730.
13. Ettouati, L.; Ahond, A.; Convert, O.; Laurent, D.; Poupat, C.; Potier, P. Bull. Soc. Chim. Fr. 1988, 749-755.
14. Cram, D. J.; Sahyun, M. R. V.; Knox, G. R. J. Am. Chem. Soc. 1962, 84, 1734-1735.
15. Bathini, Y.; Micetich, R. G.; Daneshtalab, M. Synth. Commun. 1994, 24, 1513-1517.
16. Also the 4,20-epoxide was refractory to nucleophilic opening in basic medium (Cf. Holton, R. et al. "Total Synthesis of Paclitaxel from Camphor" in Taxane Anticancer Agents: Basic Science and Current Status Georg, I. G.; Chen, T. T.; Ojima, I.; Vyas, D. M. Ed.; ACS Symposium Series 583, American Chemical Society, Washington D.C., 1995, pp. 288-301). The poor electrophilicity of the primary C-20 carbon in the 4,20-epoxide and 20-tosylate is reminiscent of the poor nucleophilicity of the 19-hydroxyl (Margraff, R. M.; Bezard, D.; Bourzat, J.D.; Commerçon, A. Bioorg. Med. Chem. Lett. 1994, 4, 233-236). The underlying cause is presumably a 1,3-diaxial interaction between C-19 and C-20. This contrasts to the easy opening of the 20(5)-oxetane, which is, however, an anchimerically assisted (4-acetyl) process (7).
17. Also the 4,20-epoxide was refractory to nucleophilic opening in basic medium (Cf. Holton, R. et al. "Total Synthesis of Paclitaxel from Camphor" in Taxane Anticancer Agents: Basic Science and Current Status Georg, I. G.; Chen, T. T.; Ojima, I.; Vyas, D. M. Ed.; ACS Symposium Series 583, American Chemical Society, Washington D.C., 1995, pp. 288-301). The poor electrophilicity of the primary C-20 carbon in the 4,20-epoxide and 20-tosylate is reminiscent of the poor nucleophilicity of the 19-hydroxyl (Margraff, R. M.; Bezard, D.; Bourzat, J.D.; Commerçon, A. Bioorg. Med. Chem. Lett. 1994, 4, 233-236). The underlying cause is presumably a 1,3-diaxial interaction between C-19 and C-20. This contrasts to the easy opening of the 20(5)-oxetane, which is, however, an anchimerically assisted (4-acetyl) process (7).
18. Taber, D. F.; Amedio, J. C. Jr.; Jung, K.-Y. J. Org. Chem. 1987, 52, 5621-5622.
19. 3CN (Cf. Chen, S.-H.; Huang, S.; Wei, J,; Farina, V. Tetrahedron, 1993, 49, 2805-2828.)
20. Leeds, J. P.; Kirst, H. A. Synth. Commun. 1988, 18, 777-782.
21. 3/ether) to give 302 mg 9 (68%) as a white solid.
22. 13C NMR δ 39.2 (d, C-1), 27.5 (t, C-2), 44.2 (d, C-3), 76.6 (s, C-4), 62.8 (d, C-5), 35.9 (t, C-6), 72.9 (d, C-7), 45.4 (s, C-8), 75.6 (d, C-9), 71.6 (d, C-10), 138.2 (s, C-11), 136.5 (s, C-12), 70.0 (d, C-13), 31.8 (t, C-14), 38.8 (s, C-15), 33.7 (q, C-16), 25.7 (q, C-17), 16.3 (q, C-18), 13.0 (q, C-19), 53.2 (t, C-20), 21.4, 21.1, 21.0, 20.8 (q, Ac), 170.4, 170.3, 169.0, 168.9 (s, Ac).
23. Attempts to cyclise 12 with other bases (NaH/cat.TBAI, KOtBu/18-crown-6) afforded mainly the 13-deacetyl derivative of 10. Under these conditions, the N-Cbz derivative (i) of 9 gave the 4,20 cyclic carbamate (ii). formula represented
24. 13C NMR δ 39.2 (d, C-1), 27.5 (t, C-2), 42.5 (d, C-3), 72.6 (s, C-4), 67.1 (d, C-5), 33.2 (t, C-6), 72.1 (d, C-7), 45.0 (s, C-8), 75.2 (d, C-9), 72.9 (d, C-10), 136.9 (s, C-11), 136.9 (s, C-12), 68.1 (d, C-13), 33.5 (t, C-14), 38.4 (s, C-15), 35.0 (q, C-16), 25.4 (q, C-17), 17.1 (q, C-18), 13.2 (q, C-19), 56.7 (t, C-20), 21.3, 21.1, 20.8, 19.8, (q, Ac), 171.5, 170.3, 170.1, 169.4 (s, Ac).