Total synthesis of (+)-condylocarpine, (+)-isocondylocarpine, and (+)-tubotaiwine

Organic Letters

Volumn 13, Issue 1, 2011, Pages 138-141

  Martin, Connor L ^a   Nakamura, Seiichi ^a,b   Otte, Ralf ^a,c   Overman, Larry E ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NAGOYA CITY UNIVERSITY   (Japan)

^c BOSTON CONSULTING GROUP   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; CONDYLOCARPINE; INDOLE ALKALOID; ISOCONDYLOCARPINE;

ARTICLE; CHEMICAL STRUCTURE; STEREOISOMERISM; SYNTHESIS; TUBOTAIWINE;

ALKALOIDS; INDOLE ALKALOIDS; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 78650861141     PISSN: 15237060     EISSN: 15237052     Source Type: Journal    
DOI: 10.1021/ol102709s     Document Type: Article

References (52)

1. The Alkaloids; Cordell, G. A., Ed.; Academic Press: New York, 1996; Vol. 48, Chapter 4.
2. Alvarez, M.; Joule, J. A. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: New York, 2001; Vol. 57, Chapter 4.
3. Martin, C. L.; Overman, L. E.; Rohde, J. M. J. Am. Chem. Soc. 2008, 130, 7568-7569
4. Martin, C. L.; Overman, L. E.; Rohde, J. M. J. Am. Chem. Soc. 2010, 132, 4894-4906
5. For representative examples of syntheses of the hexahydro-1,5-methano-1 H -azocino[4,3- b ]indole ring system, see
6. Jackson, A.; Joule, J. A. Chem. Commun. 1967, 459-460 Full paper: Jackson, A.; Wilson, N. D. V.; Gaskell, A. J.; Joule, J. A. J. Chem. Soc. C 1969, 19, 2738-2747
7. Büchi, G.; Gould, S. J.; Näf, F. J. Am. Chem. Soc. 1971, 93, 2492-2501
8. Grierson, D. S.; Harris, M.; Husson, H.-P. Tetrahedron 1983, 39, 3683-3694
9. Magnus, P.; Sear, N. L.; Kim, C. S.; Vicker, N. J. Org. Chem. 1992, 57, 70-78
10. Gràcia, J.; Casamitjana, N.; Bonjoch, J.; Bosch, J. J. Org. Chem. 1994, 59, 3939-3951
11. Micouin, L.; Diez, A.; Castells, J.; López, D.; Rubiralta, M.; Quirion, J.-C.; Husson, H.-P. Tetrahedron Lett. 1995, 36, 1693-1696
12. Blechert, S.; Knier, R.; Schroers, H.; Wirth, T. Synthesis 1995, 592-604
13. Saito, M.; Kawamura, M.; Hiroya, K.; Ogasawara, K. Chem. Commun. 1997, 765-766
14. Amat, M.; Hadida, S.; Pshenichnyi, G.; Bosch, J. J. Org. Chem. 1997, 62, 3158-3175
15. Ergün, Y.; Patir, S.; Okay, G. J. Heterocycl. Chem. 2002, 39, 315-317
16. Jiricek, J.; Blechert, S. J. Am. Chem. Soc. 2004, 126, 3534-3538
17. Ishikura, M.; Takahashi, N.; Takahashi, H.; Yanada, K. Heterocycles 2005, 66, 45-50
18. Uludag, N.; Hökelek, T.; Patir, S. J. Heterocycl. Chem. 2006, 43, 585-591
19. Bennasar, M.-L.; Roca, T.; García-Díaz, D. J. Org. Chem. 2008, 73, 9033-9039
20. Ketones 7a and 7b are available in racemic form in four steps from dimethyl or di- tert -butyl malonate in 24% and 33% overall yield, respectively. (2)
21. For review of this group of alkaloids, see: Lounasmaa, M.; Somersalo, P. The Condylocarpine Group of Indole Alkaloids. In Progress in the Chemistry of Natural Products; Herz, W.; Grisebach, H.; Kirby, G. W.; Tamm, Ch., Eds.; Springer-Verlag/Wien: New York, 1986; Vol. 50, pp 27 - 56. For the recent isolation of isocondylocarpine, see: Wu, Y.; Kitajima, M.; Kogure, N.; Wang, Y.; Zhang, R.; Takayama, H. J. Nat. Med. 2009, 63, 283-289
22. For total syntheses of (±)-condylocarpine, see
23. Harley-Mason, J. Pure Appl. Chem. 1975, 41, 167-174
24. Kuehne, M. E.; Brook, C. S.; Frasier, D. A.; Xu, F. J. Org. Chem. 1995, 60, 1864-1867 For studies on the synthesis of condylocarpine, see: Lounasmaa, M.; Somersalo, P. Tetrahedron 1986, 42, 1501-1509 For total syntheses of (±)-tubotaiwine, see: Dadson, B. A.; Harley-Mason, J. J. Chem. Soc. D 1969, 665b
25. Kuehne, M. E.; Frasier, D. A.; Spitzer, T. D. J. Org. Chem. 1991, 56, 2696-2700
26. Gracia, J.; Bonjoch, J.; Casamitjana, N.; Amat, M.; Bosch, J. J. Chem. Soc., Chem. Commun. 1991, 614-615
27. Gracia, J.; Casamitjana, N.; Bonjoch, J.; Bosch, J. J. Org. Chem. 1994, 59, 3939-3951
28. Amat, M.; Hadida, S.; Pshenichnyi, G.; Bosch, J. J. Org. Chem. 1997, 62, 3158-3175 For studies on the synthesis of tubotaiwine, see: Legseir, B.; Henin, J.; Massiot, G.; Vercauteren, J. Tetrahedron Lett. 1987, 28, 3573-3576
29. Lavilla, R.; Gotsens, T.; Rodriguez, S.; Bosch, J. Tetrahedron 1992, 48, 6445-6454
30. Precursor (±)- 7b was recovered in 25% yield.
31. 1H NMR analysis of these crude intermediates showed no significant impurities, which we indicate in Scheme 1 as a crude yield of >90%.
32. To our knowledge, the first unambiguous example of such fragmentation promoted by acid was described by Husson: Besselièvre, R.; Husson, H.-P. Tetrahedron 1983, 37 (Supplement 1) 241-246
33. 1,3 interactions with the Boc substituent.
34. 3 at room temperature for 2 h yielded a mixture of i (48%) and ii (36%). (b) In neat TFA, decarboxylative aromatization of 16 (X = O, R = t -Bu) apparently occurs rapidly leading to the eventual formation of carbazole acid 11.
35. For a concise discussion of the effect of adjacent C-C and C-O π-bonds on nucleophilic substitution reactions, see: Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry; University Science: Sausalito, CA, 2006; pp 653 - 655.
36. 2 resulting in hydride addition from the Re face.
37. Bates, G. S.; Ramaswamy, S. Can. J. Chem. 1983, 61, 2466-2475
38. Trost, B. M.; Murayama, E. J. Am. Chem. Soc. 1981, 103, 6529-6530
39. The relative configuration of 19, and that of the secondary alcohol in precursors 17 and 18, was secured on the basis of X-ray crystallographic analysis of silyl ether derivative (±)- iii, which was prepared in an analogous fashion to 19. Crystallographic data for (±)- iii were deposited at the Cambridge Crystallographic Data Centre: CCDC 799190.
40. The use of 5-exo thionium ion cyclizations to form this ring of indole alkaloids is a well-established tactic in indole alkaloid synthesis, see
41. Gallagher, T.; Magnus, P.; Huffman, J. C. J. Am. Chem. Soc. 1983, 105, 4750-4757
42. Amat, M.; Linares, A.; Bosch, J. J. Org. Chem. 1990, 55, 6299-1312
43. Amat, M.; Bosch, J. J. Org. Chem. 1992, 57, 5792-5796
44. 1H NMR singlet corresponding to the methyl thioether group at 1.81 ppm and LRMS analysis). This inconsequential side product likely arose by hydrolysis of DMTSF by adventitious water to give methanethiol, which underwent thiol exchange by way of the reactive thionium ion prior to cyclization.
45. It was advantageous to use THF as the solvent instead of methanol or ethanol, as byproducts arising from reduction of the vinylogous carbamate were suppressed in THF.
46. Albright, J. D.; Goldman, L. J. Am. Chem. Soc. 1965, 87, 4214-4216
47. Crystallographic data for a racemic sample of intermediate 20 were deposited at the Cambridge Crystallographic Data Centre: CCDC 799189.
48. Condylocarpine (2a) and isocondylocarpine (2b) equilibrate to a 2:1 mixture of 2a: 2b when heated for 4 h at reflux in toluene or when exposed for 24 h at room temperature to acetic acid in chloroform. (6b)
49. Schumann, D.; Schmid, H. Helv. Chim. Acta 1963, 46, 1996-2003
50. 3). (5b)
51. Stauffacher, D. Helv. Chim. Acta 1961, 44, 2006-2015
52. Pinar, M.; Renner, U.; Hesse, M.; Schmid, H. Helv. Chim. Acta 1972, 55, 2972-2974