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A Stereoselective Asymmetric Synthesis of Antibiotic (-)-Fumagillol Using Claisen Rearrangement and Intramolecular Ester Enolate Alkylation as Key Steps

Kim Deukjoon    (College of Pharmacy, Seoul National University   ); Ahn Soon Kil    (New Drug Research Laboratories, Chong Kun Dang Research Institute Cheonan   ); Bae Hoon    (Department of Chemistry and Biochemistry, Florida State University   ); Kim Hak Sung    (Wonkwang University, College of Pharmacy  );
  • 초록

    (-)-Fumagillol (1), a hydrolysis product of fumagillin, has been synthesized by several group from commercially available 1,2:5,6-di-O-isopropylidene- ${\alpha}$ -D-allofuranose in a highly stereoselective manner. Chiral centers on C5 and C6 came from D-allofuranose and the asymmetric center on C4 was accomplished by 1,3-chirality transfer using the Claisen rearrangement on a chiral allyl alcohol. Chirality, which is necessary on an epoxide consisting of the spiro-ring system, was diastereoselectively constructed by the well-known reaction, intramolecular ester enolate alkylation (IEEA), which showed that this reaction can be applied to the alpha-alkoxy ester system. The epoxide on the side chain was regioselectively introduced by the difference between the number of substituents on the vinyl groups. This accomplishment proved that IEEA can be a useful tool for the synthesis of complex molecules.


  • 주제어

    Fumagillol .   Fumagillin .   Total synthesis .   Stereoselective .   1,3-Chirality transfer.  

  • 참고문헌 (34)

    1. Hutchings, M., Moffat, D., and Simpkins, N. S., A concise synthesis of fumagillol. Synlett., 5, 661-663. (2001) 
    2. Iversen, T. and Bundle, D. R., Benzyl trichloroacetimidate, a versatile reagent for acid-catalyzed benzylation of hydroxygroups. J. Chem. Soc., Chem. Commun., 23, 1240-1243, (1981) 
    3. Killough, J. J., Magill, G. B., and Smith, R. C. The treatment of amebiasis with fumagillin. Science, 115, 71-72 (1952) 
    4. Kim, D., Ahn, S. K., Bae, H., Choi, W. J., and Kim, H. S., An asymmetric total synthesis of (-)-fumagillol. Tetrahedron Lett., 38(25), 4437-4440 (1997) 
    5. McCowen M. C., Callender, M. E., and Lawlis, J. F. Jr., Fumagillin (H-3), a new antibiotic with amebicidal properties. Science, 113, 202-203 (1951) 
    6. Mitsunobu, O., The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis, 1, 1-28 (1981) 
    7. Taber, D. F., Christos, T. E., Rheingold, A. L., and Guzei, I. A., Synthesis of (-)-Fumagillin. J. Am. Chem. Soc., 121, 5589- 5590 (1999) 
    8. Tarbell, D. S., Carman R. M., Chapman, D. D., Cremer, S. E., Cross, A. D., Huffman, K. R., Kunstmann, M., McCorkindale, N. J., McNally, J. G. Jr., Rosowsky, A., Varino, F. H. L., and West, R. L. The chemistry of fumagillin. J. Am. Chem. Soc., 83, 3096-3113 (1961) 
    9. Kallmerten, J. and Gould, T. J., Enolate Claisen rearrangement of glycolate esters. Tetrahedron Lett., 24, 5177-5180 (1983) 
    10. Griffith, E. C., Su, Z., Turk, B. E., Chen, S., Charng, Y, -H., Wu, Z., Biemann, K., and Liu, J. O., Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin. Chem. Biol., 4(6), 461-471 (1997) 
    11. Hanson, T. E. and Eble F. R., An antiphage agent isolated from Aspergillus sp. J. Bact., 58, 527-529 (1949) 
    12. Bedel, O., Haudrechy, A., and LangloisY., A stereoselective formal synthesis of (-)-fumagillol. Eur. J. Org. Chem., 3813- 2819 (2004) 
    13. Ingber, D. E., Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy. Seminars in cancer biology., 3, 57-63 (1992) 
    14. Sin, N., Meng, L., Wang, M. Q. W., Wen, J. J., Bornmann, W.G., and Crews, C. M., The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc. Natl. Acad. Sci. USA, 94, 6099-6103 (1997) 
    15. Corey, E. J. and Snider, B. B. Total synthesis of (${\pm}$)-fumagillin. J. Am. Chem. Soc., 94(7), 2549-2550 (1972) 
    16. Roush, W. R., Ando, K., Powers, D. B., Halterman, R. I., and Palkowitz, A. D., Enantioselective synthesis using diisopropyl tartrate-modified (E)- and (Z)-crotylboronates: reactions with achiral aldehydes. Tetrahedron Lett., 29, 5579-5582 (1988) 
    17. Katznelson, H. and Jamieson, C. A., Control of nosema disease of honeybees with fumagillin. Science, 115, 70-71 (1952) 
    18. Gurjar, M. K., Patil, V. J., and Pawar, S. M. Synthesis of (1R,5R)-2,6-dioxabicyclo [3.3.0]octan-3-one from D-glucose. Carbohyd. Res., 165(2), 313-317 (1987) 
    19. Sato, T., Tajima, K., and Fujisawa, T., Diastereoselective synthesis of erythro- and threo-2-hydroxy-3-methyl-4- pentenoic acids by the ester enolate Claisen rearrangement of 2-butenyl 2-hydroxyacetate. Tetrahedron Lett., 24(7), 729- 730 (1983) 
    20. Burke, S. D., Fobare, W. F., and Pacofsky, G. J., Chelation control of enolate geometry. Acyclic diastereoselection via the enolate Claisen rearrangement. J. Org. Chem., 48(26), 5221-5228 (1983) 
    21. Eustache, J. and van de Weghe, The ring-Closing metathesis approach to fumagillol, Strategies and Tactics in Organic Synthesis, Elsevier, Londen, 4, 247-267 (2004) 
    22. Vosburg, D. A., Weiler, S., and Sorensen, E. J., A concise synthesis of fumagillol. Angew. Chem. Int. Ed., 38, 971-974 (1999) 
    23. Ingber, D., Fujita, T., Kishimoto, S., Sudo, K., Kanamaru, T., Brem, H., and Folkman, J., Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature, 345, 555-557 (1990) 
    24. Kim, D., Min, J., Ahn, S. K., Lee, H. W., Choi, N. S., and Moon, S. K., 5-Demethoxyfumagillol, a potent angiogenesis inhibitor isolated from Aspergillus Fumagatus. Chem. Pharm. Bull., 52, 447-450 (2003) 
    25. Vosburg, D. A., Weiler, S., and Sorensen, E. J., Concise stereocontrolled routes to fumagillol, fumagillin, and TNP- 470. Chirality, 15, 156-166 (2003) 
    26. Folkman, J. and Ingber, D., Inhibition of angiogenesis. Seminars in cancer biology. 3, 89-96 (1992) 
    27. Zhang, P., Nicholson, D. E., Bujnicke, J. M., Su, X., Brendle, J. J., Ferdig, M., Kyle, D. E., Milhous, W. K., and Chiang, P. K., Angiogenesis inhibitors specific for methionine aminopeptidase 2 as drugs for malaria and leishmaniasis. J. Biomed. Sci., 9, 34-40 (2002) 
    28. Haga, M., Takano, M., and Tejima, S., 3-O-Methyl-D-allose and a facile route to 2- and 3-O-methyl-D-riboses. Carbohyd. Res., 21(3), 440-446 (1972) 
    29. Boiteau, J. G., Van de Weghe, P., and Eustache, J., A new, ring closing metathesis-based synthesis of (-)-fumagillol. Org. Lett., 3, 2737-2740 (2001) 
    30. Roush, W. R., Waltz, A. E., and Hong, L. K., Diastereo- and enantioselective aldehyde addition reactions of 2-allyl-1,3,2- dioxaborolane-4,5-dicarboxylic esters, a useful class of tartrate ester modified allylboronates. J. Am. Chem. Soc., 107, 8186 -8190 (1985) 
    31. Han, C. K., Ahn, S. K., Choi, N. S., Hong, R. K., Moon, S. K., Chun, H. S., Lee, S. J., Kim, J. W., Hong, C. I., Kim, D., Yoon, J. H., and No, K. T., Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2. Bioorg. Med. Chem. Lett., 10(1), 39-43 (2000) 
    32. Steglich, W. and Neises, B., 4-Dialkylaminopyridines as acylation catalysts. 5. Simple method for the esterification of carboxylic acids. Angew. Chem., 90, 556-557 (1978) 
    33. Fardis, M., Pyun, H. J., Tario, J., Jin, H., Kim, C. U., Ruckman, J., Lin, Y., Greean, L, and Hicke, B., Design, synthesis and evaluation of a series of novel fumagillin analogues. Bioorg. Med. Chem., 11, 5051-5058 (2003) 
    34. Tarbell, D. S., Carman, R. M., Chapman, D. D., Huffman, K. R., and McCorkindale, N. J., Structure of fumagillin. J. Am. Chem. Soc., 82, 1005-1007 (1960) 

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