Synthetic studies on mycolactones: Synthesis of the mycolactone core structure through ring-closing olefin metathesis

Synlett

Volumn , Issue 3, 2007, Pages 415-418

  Feyen, Fabian ^a,b   Jantsch, Andrea ^a   Altmann, Karl Heinz ^a  

^a ETH ZURICH   (Switzerland)

^b CARBOGEN AMCIS AG   (Switzerland)

Author keywords

Buruli; Mycolactone; Natural products; Ring closing olefin metathesis; Stereoselectivity; Total synthesis

Indexed keywords

ALKADIENE; CARBOXYLIC ACID; LACTONE DERIVATIVE; MYCOLACTONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; RING CLOSING METATHESIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 33847349751     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-967943     Document Type: Article

References (33)

1. The term 'mycolactone' usually refers to the naturally occurring mixture of mycolactones A and B, which are geometric isomers at the C4′=C5′ double bond. Although both isomers can be isolated separately, each of them rapidly isomerizes to the mixture of mycolactones A and B.
2. George, K. M.; Chatterjee, D.; Gunawardana, G.; Welty, D.; Hayman, J.; Lee, R.; Small, P. L. Science 1999, 283, 854.
3. Adusumilli, S.; Mve-Obiang, A.; Sparer, T.; Meyers, W.; Hayman, J.; Small, P. L. Cell. Microbiol. 2005, 7, 1295.
4. Coutanceau, E.; Marsollier, L.; Brosch, R.; Perret, E.; Goossens, P.; Tanguy, M.; Cole, S. T.; Small, P. L.; Demangel, C. Cell. Microbiol. 2005, 7, 1187.
5. George, K. M.; Pascopella, L.; Welty, D. M.; Small, P. L. Infect. Immun. 2000, 68, 877.
6. Benowitz, A. B.; Fidanze, S.; Small, P. L.; Kishi, Y. J. Am. Chem. Soc. 2001, 123, 5128.
7. Song, F.; Fidanze, S.; Benowitz, A. B.; Kishi, Y. Org. Lett. 2002, 4, 647.
8. (a) The synthesis and structure confirmation of mycolactone C, which is a ca. 1:1 mixture of 12′-deoxymycolactones A and B is described in: Judd, T. C.; Bischoff, A.; Kishi, Y.; Adusumilli, S.; Small, P. L. C. Org. Lett. 2004, 6, 4901.
9. (b) Mycolactone C is the major metabolite of Australian strains of M. ulcerans and it is 10,000-fold less cytopathic than mycolactones A and B: Mve-Obiang, A.; Lee, R. E.; Portaels, F.; Small, P. L. C. Infect. Immun. 2003, 71, 774.
10. (c) West African strains of M. ulcerans produce mycolactone C only as a minor metabolite.
11. Gurjar, M. K.; Cherian, J. Heterocycles 2001, 55, 1095.
12. Van Summeren, R. P.; Feringa, B. L.; Minnaard, A. J. Org. Biomol. Chem. 2005, 3, 2524.
13. Yin, N.; Wang, G.; Qian, M.; Negishi, E. Angew. Chem. Int. Ed. 2006, 45, 2916;
14. Angew. Chem. 2006, 118, 2982.
15. Leadlay and co-workers have recently reported the isolation and structure elucidation of new mycolactones from a pathogenic strain of M. ulcerans from China (MU98912). In comparison with mycolactones A and B from the African strain MUAgy99, these new mycolactones incorporate an additional methyl group attached to C2′. MU98912 does not produce mycolactones A/B: Hong, H.; Spencer, J. B.; Porter, J. L.; Leadlay, P. F.; Stinear, T. ChemBioChem 2005, 6, 643.
16. Alexander, M. D.; Fontaine, S. D.; La Clair, J. J.; DiPasquale, A. G.; Rheingold, A. L.; Burkart, M. D. Chem. Commun. 2006, 4602.
17. For recent reviews on olefin metathesis cf., e.g.: (a) Grubbs, R. H. Tetrahedron 2004, 60, 7117.
18. (b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
19. (a) Oppolzer, W.; Blagg, J.; Rodriguez, I.; Walther, E. J. Am. Chem. Soc. 1990, 112, 2767.
20. (b) Nguyen, G.; Perlmutter, P.; Rose, M. L.; Vounatsos, F. Org. Lett. 2004, 6, 893.
21. (a) Carreira, E. M.; Du Bois, J. J. Am. Chem. Soc. 1995, 117, 8106.
22. (b) See also: Eis, M. J.; Wrobel, J. E.; Ganem, B. J. Am. Chem. Soc. 1984, 106, 3693.
23. Wang, Y.; Dong, X.; Larock, R. C. J. Org. Chem. 2003, 68, 3090.
24. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7217.
25. Kraus, G. A.; Roth, B. J. Org. Chem. 1980, 45, 4825.
26. White, J. D.; Blakemore, P. R.; Green, N. J.; Hauser, E. B.; Holoboski, M. A.; Keown, L. E.; Nylund Kolz, C. S.; Phillips, B. W. J. Org. Chem. 2002, 67, 7750.
27. Aïssa, C.; Riveiros, R.; Ragot, J.; Fürstner, A. J. Am. Chem. Soc. 2003, 125, 15512.
28. 2)] has been reported by Fürstner and co-workers to produce the syn product in good yield and with excellent selectivity (see ref. 22).
29. Höfle, G.; Steglich, W.; Vorbrüggen, H. Angew. Chem. Int. Ed. Engl. 1978, 17, 569;
30. Angew. Chem. 1978, 90, 602.
31. 2 moiety.
32. Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527.
33. Encouraged by the efficiency and selectivity of ring closure observed with RCM substrate 3, we have also investigated triene 17 as a possible substrate for RCM-mediated formation of the 12-membered ring (Figure 3). However, treatment of this compound with Grubbs' second-generation catalyst did not produce any of the desired 12-membered macrolactone. Instead, and perhaps not too surprisingly, the major product formed in the reaction appears to be cyclohexene 18 (based on MS analysis of the reaction mixture). (Chemical Equation Presented)