gem-Difluorocyclopropanes as Key Building Blocks for Novel Biologically Active Molecules

Fluorine in Medicinal Chemistry and Chemical Biology

Volumn , Issue , 2009, Pages 313-334

  Itoh, Toshiyuki ^a  

^a TOTTORI UNIVERSITY   (Japan)

Author keywords

Biologically active gem difluorocyclopropane F2 CBI as duocarmycin analogue; Biologically active gem difluorocyclopropanes; Multidrug resistance (MDR) reversal activity of gem difluorinated compound 5; Strong DNA cleaving property switched on by photoirradiation; Synthesis of gem difluorocyclopropanes; Synthetic methodology for preparing optically active gem difluorocyclopropane building blocks using lipase technology

Indexed keywords

EID: 84889345073     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781444312096.ch12     Document Type: Chapter

References (76)

1. De Meijere, A., Rademacher, P., Lebel, FL, et al. (2003) Cyclopropanes and related rings. Chem. Rev., 103, 931-1448, 1603-1648.
2. Tozer, M. J. and Herpin, T. F. (1996) Methods for the synthesis of gem-difluoromethylene compounds. Tetrahedron, 52, 8619-8683.
3. Wong, H. N. C., Hon, M-Y., Tse, C-H. and Yip, Y-C. (1989) Use of cyclopropanes and their derivatives in organic synthesis. Chem. Rev., 89, 165-198.
4. Welch, J. T. (1987) Tetrahedron report number 221: Advances in the preparation of biologically active organofluorine compounds. Tetrahedron, 43, 3123-3197.
5. Resnati, G. (1993) Synthesis of chiral and bioactive fluoroorganic compounds, Tetrahedron, 49, 9385-9445.
6. Soloshonok, V. A. (ed.) (1999) Enantiocontrolled Synthesis of Fluoroorganic Compounds: Stereochemical Challenges and Biomedicinal Targets, John Wiley & Sons, Ltd, Chichester, UK.
7. Rosen, T. C., Yoshida, S., Kirk, K. L. and Haufe, G. (2004) Fluorinated phenylcyclopropylamines as inhibitors of monoamine oxidases. Chem Bio Chem., 5, 1033-1043.
8. Dolbier, W. R., Jr. and Battiste, M. A. (2003) Structure, synthesis, and chemical reactions of fluorinated cyclopropanes and cyclopropenes, Chem. Rev., 103, 1071-1098.
9. Itoh, T. (2006) Optically active gem-difluorocyclopropanes; synthesis and application for novel molecular materials, current fluoroorganic chemistry, in New Synthetic Directions, Technologies, Materials and Biological Applications, ACS Symposium Series 949, Oxford University Press/American Chemical Society, Washington D.C., Chapter 21, pp. 352-362 and references cited therein.
10. Itoh, T., Mitsukura, K. and Furutani, M. (1998) Efficient synthesis of enantiopure 1,2-bis(hydroxymethyl)-3,3-difluorocyclopropane derivatives through lipase-catalyzed reaction. Chem. Lett., 903-904.
11. Mitsukura, K., Korekiyo, S. and Itoh, T. (1999) Synthesis of optically active bisdifluorocy-clopropanes through a chemo- enzymatic reaction strategy. Tetrahedron Lett., 40, 5739-5742.
12. Itoh, T., Mitsukura, K., Ishida, N. and Uneyama, K. (2000) Synthesis of bis- and oligo-gem difluorocyclopropanes using the olefin metathesis reaction, Org. Lett., 2, 1431-1434.
13. Itoh, T. (2000) Asymmetric synthesis of novel gem-difluorinated compounds using chemo-enzymatic methodology. J. Synth. Org. Chem. Jpn., 58, 316-326.
14. Itoh, T., Ishida, N., Mitsukura, K. and Uneyama, K. (2001) Synthesis of novel bis- and oligo-gem-difluorocyclopropanes. J. Fluorine Chem., 112, 63-69.
15. Itoh, T., Ishida, N., Ohashi, M., et al. (2003) Synthesis of novel liquid crystals which possess gem-difluorocyclopropane moieties, Chem. Lett., 32, 494-495.
16. Itoh, T., Ishida, N., Mitsukura, K., et al. (2004) Synthesis of optically active gem-difluorocyclopropanes through a chemo-enzymatic reaction strategy. J. Fluorine Chem., 125, 775-783.
17. Holan, G., Johnson, W. M., Virgona, C. T. and Walser, R. A. (1986) Synthesis and biological activity of DDT-pyrethroid insecticides. J. Agric. Food Chem., 34, 520-524.
18. Wegner, P., Joppien, H., Hoemberger, G. and Koehn, A. (1989) European Patent Application, EP 318425 A1; CAN111:169387.
19. Pfister, J. R., Makra, F., Muehldorf, A. V., et al. (1995) Methanodibenzosuberylpiperazines as potent multidrug resistance reversal agents. Bioorg. Med. Chem. Lett., 5, 2473-2476.
20. Barnett, C. J., Huff, B., Kobierski, M. E., et al. (2004) Stereochemistry of C-6 nucleophilic displacements on 1,1-difluorocyclopropyldibenzosuberanyl substrates. An improved synthesis of multidrug resistance modulator LY335979 trihydrochloride. J. Org. Chem., 69, 7653-7660.
21. Boger, D. L. and Jenkins, T. J. (1996) Synthesis, X-ray structure, and properties of fluorocyclo-propane analogs of the Duocarmycins incorporating the 9,9-difluoro-1,2,9,9a-tetrahydrocyclop ropa[c]benzo[e]indol-4-one (F2CBI) alkylation subunit. J. Am. Chem. Soc., 118, 8860-8870.
22. Taguchi, T., Kurishita, M., Shibuya, A. and Aso, K. (1997) Preparation of methylene-gem-difluorocyclopropanes and its reactivity as Michael acceptor. Tetrahedron, 53, 9497-9508.
23. Haufe, G., Rosen, T. C., Meyer, O. G. J., et al. (2002) Synthesis, reactions and structural features of monofluorinated cyclopropanecarboxylates. J. Fluorine Chem., 114, 189-198.
24. For a review, see: Fedoryski, M. (2003) Syntheses of gem- dihalocyclopropanes and their use in organic synthesis. Chem. Rev., 103, 1099-1132.
25. Baker, G. B., Urichuk, L. J., McKenna, K. F. and Kennedy, S. H. (1999) Metabolism of monoamine oxidase inhibitors. Cell. Mol. Neurobiol., 19, 411-126.
26. Koizumi, N., Takegawa, S., Mieda, M. and Shibata, K. (1996) Antiandrogen. IV. C-17 Spiro 2-oxasteroids. Chem. Pharm. Bull., 44, 2162-2164.
27. Yang, Z-Q., Geng, X., Solit, D., et al. (2004) New efficient synthesis of resorcinylic macrolides via ynolides: Establishment of cycloproparadicicol as synthetically feasible preclinical anticancer agent based on Hsp90 as the target. J. Am. Chem. Soc., 126, 7881-7889.
28. Taguchi, T., Shibuya, A., Sasaki, H., et al. (1994) Asymmetric synthesis of difluorocyclopropanes. Tetrahedron Asymmetry, 5, 1423-1426.
29. Shibuya, A., Kurishita, M., Ago, C. and Taguchi, T. (1996) Ahighly diastereoselective synthesis of trans-3,4-(difluoromethano)glutamic acid. Tetrahedron, 52, 271-278.
30. Shibuya, A., Sato, A. and Taguchi, T. (1998) Preparation of difluoro analogs of CCGs and their pharmacological evaluations. Bioorg. Med. Chem. Lett., 8, 1979-1984.
31. Saitoh, T., Ishida, M. and Shinozaki, A. (1998) Potentiation by DL-CC-aminopimelate of the inhibitory action of a novel mGluR agonist (L- F2CCG-I) on monosynaptic excitation in the rat spinal cord. Br. J. Pharmacol., 123, 771-779.
32. Ishida, M. and Shinozaki, H. (1999) Inhibition of uptake and release of a novel mGluR agonist (L-F2CCG-I) by anion transport blockers in the rat spinal cord. Neuropharmacology, 38, 1531-1541.
33. Taguchi, T., Kurishita, M., Shibuya, A. and Aso, K. (1997) Preparation of methylene-gem-difluorocyclopropanes and its reactivity as Michael acceptor. Tetrahedron, 53, 9497-9508.
34. Taguchi, T., Kurishita, M. and Shibuya, A. (1999) Preparation of F2MCPGs via selenoxide elimination. J. Fluorine Chem., 97, 157-159.
35. Shibuya, A., Okada, M., Nakamura, Y., et al. (1999) Preparation of methylenedifluorocyclopropanes via cyclopropyl anion promoted ß-elimination. Tetrahedron, 55, 10325-10340.
36. Lai, M-T., Liu, L-D. and Liu, H-W. (1991) Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A. J. Am. Chem. Soc., 113, 7388-7397.
37. Li, D., Guo, Z. and Liu, H.-W. (1996) Mechanistic studies of the inactivation of crotonase by (methylenecyclopropyl)formyl- CoA. J. Am. Chem. Soc., 118, 275-276.
38. Pechacek, J. T., Bargar, T. M., Sabol, M. R. (1997) Inhibition of nematode induced root damage by derivatives of methylenecyclopropane acetic acid. Bioorg. Med. Chem. Lett., 7, 2665-2668.
39. Kirihara, M., Takuwa, T., Kawasaki, M., et al. (1999) Synthesis of (+)-(R)-1-amino-2,2-difluorocyclopropane-1-carboxylic acid through lipase-catalyzed asymmetric acetylation. Chem. Lett., 405-406.
40. Kirihara, M., Kawasaki, M., Takuwa, T., et al. (2003) Efficient synthesis of (R)- and (S)-1-amino-2,2-difluorocyclopropanecarboxylic acid via lipase-catalyzed desymmetrization of prochiral precursors. Tetrahedron Asymmetry, 14, 1753-1761.
41. Song, Y., Yoshida, S., Fröhlich, R., et al. (2005) Fluorinated phenylcyclopropylamines. Part 4: Effects of aryl substituents and stereochemistry on the inhibition of monoamine oxidases by 1- aryl-2-fluoro-cyclopropylamines. Bioorg. Med. Chem., 13, 2489-2499.
42. Roe, R., Kallapur, V., Linderman, R. J. and Viviani, F. (2005) Organic synthesis and bioassay of novel inhibitors of JH III epoxide hydrolase activity from fifth stadium cabbage loopers, Trichoplusia ni. Pestic. Biochem. Physiol., 83, 140-154.
43. Itoh, T. (2005) Optically active gem-difluorocyclopropanes; synthesis and application for novel molecular materials, in Fluorine-Containing Synthons, ACS Symposium Series 911, Oxford University Press/American Chemical Society, Washington D.C., Chapter 25, pp. 430-439.
44. Ninomiya, K., Tanimoto, K., Ishida, N., et al. (2006) Synthesis of novel gem-difluorinatedcyclopropane hybrids: applications for DNA cleavage agents switched by photo irradiation. J. Fluorine Chem., 127, 651-656.
45. Csuk, R. and Eversmann, L. (1998) Synthesis of difluorocyclopropyl carbocyclic homo-nucleosides. Tetrahedron, 54, 6445-6459.
46. Csuk, R. and Thiede, G. (1999) Preparation of novel difluorocyclopropane nucleosides. Tetrahedron, 55, 739-750.
47. Csuk, R. and Eversmann, L. (2003) Synthesis of trans-configurated spacered nucleoside analogues comprising a difluorocyclopropane moiety. Z. Naturforsch., B: Chem. Sci., 58, 997-1004.
48. Csuk, R. and Thiede, G. (2003) Synthesis of spacered nucleoside analogues comprising a difluorocycloprop-nae moiety. Z. Naturforsch., B: Chem. Sci., 58, 853-860.
49. Csuk, R. and Eversmann, L. (2003) Synthese flexibler difluorieter cyclopropanoider nucleosidanaloga. Z. Naturforsch., B: Chem. Sci., 58, 1176-1186.
50. Wang, R., Ksebati, M. B., Corbett, T. H., et al. (2001) Methylene-gem-difluorocyclopropane analogues of nucleosides: Synthesis, cyclopropene-methylenecyclopropane rearrangement, and biological activity. J. Med. Chem., 44, 4019-4022.
51. Nowak, I. and Robins, M. J. (2006) Addition of difluorocarbene to 4),5'-unsaturated nucleosides: Synthesis and deoxygenation reactions of difluorospirocyclopropane nucleosides. J. Org. Chem., 71, 8876-8883.
52. Nowak, I., Cannon, J. F. and Robins, M. J. (2007) Addition of difluorocarbene to 3)4'.unsaturated nucleosides: Synthesis of 2Ψdeoxy analogues with a 2- oxabicyclo[3.1.0]hexane framework. J. Org. Chem., 72, 532-537.
53. Nowak, I. and Robins, M. J. (2007) Synthesis of 3'-deoxynucleosides with 2-oxabicyclo[3.1.0]hexane sugar moieties: Addition of difluorocarbene to a 3',4'-unsaturated uridine derivative and 1,2-dihydrofurans derived from D- and L-xylose. J. Org. Chem., 72, 3319-3325.
54. Kobayashi, Y., Taguchi, T., Morikawa, T., et al. (1980) Ring opening reaction of gem-difluorocyclopropyl ketones with nucleophiles. Tetrahedron Lett., 21, 1047-1050 and references cited therein.
55. Tian, F., Kruger, V., Bautista, O., et al. (2000) A novel and highly efficient synthesis of gem-difluorocyclopropanes. Org. Lett., 2, 563-564.
56. Burton, D. J. and Naae, D. G. (1973) Bromodifluoromethylphosphonium salts. Convenient source of difluorocarbene. J. Am. Chem. Soc., 95, 8467-8468.
57. Bessard, Y., Müller, U. and Schlosser, M. (1990) gem-Difluorocyclopropanes: an improved method for their preparation. Tetrahedron, 46, 5213-5221.
58. Birmingham, J. M., Seyferth, D. and Wilkinson, G. (1954) A new preparation of bis-cyclopentadienyl-metal compounds. J. Am. Chem. Soc., 76, 4179-4179.
59. Seyferth, D. and Hopper, S. P. (1972) Halomethyl metal compounds. LX. Phenyl(trifluoromethyl)mercury. Useful difluorocarbene transfer agent. J. Org. Chem., 37, 4070-4075.
60. Seyferth, D., Hopper, S. P. and Murphy, G. J. (1972) Halomethyl-metal compounds : LVII. A convenient synthesis of aryl (trifluoromethyl)mercury compounds. J. Organomet. Chem., 46, 201-209.
61. Seyferth, D., Dertouzos, H., Suzuki, R. and Mui, J. Y. P. (1967) Halomethyl-metal compounds. XIII. Preparation of gem-difluorocyclopropanes by iodide ion-induced CF2 transfer from trimethyl (trifluoromethyl)tin. J. Org. Chem., 32, 2980-2984.
62. Miyazawa, K., Yufit, D. S., Howard, J. A. K. and de Meijere, A. (2000) Cyclopropyl building blocks for organic synthesis, 60. Synthesis and properties of optically active dispiro[2.0.2.1]heptane derivatives as novel ferroelectric liquid crystalline compounds. Eur. J. Org. Chem., 2000, 4109-4117.
63. Da Ros, T., Spalluto G., Boutorine, A. S., et al. (2001) DNA-photocleavage agents. Curr Pharm Des., 7, 1781-1821.
64. Armitage, B. (1998) Photocleavage of nucleic acids. Chem. Rev., 98, 1171-1200.
65. Ly, D., Kan, Y., Armitage, B. and Schuster, G. B. (1996) Cleavage of DNA by irradiation of substituted anthraquinones: Intercalation promotes electron transfer and efficient reaction at GG steps. J. Am. Chem. Soc., 118, 8747-8748.
66. Gasper, S. M., Armitage, B., Shi, X., et al. (1998) Three-dimensional structure and reactivity of a photochemical cleavage agent bound to DNA. J. Am. Chem. Soc., 120, 12402-12409.
67. Kumar, C. V., Punzalan, E. H. A. and Tan, W. B. (2000) Adenine-thymine base pair recognition by an anthryl probe from the DNA minor groove. Tetrahedron, 56, 7027-7040.
68. Toshima, K., Takano, R., Maeda, Y., et al. (1999) 2-Phenylquinoline-carbohydrate hybrids: Molecular design, chemical synthesis, and evaluation of a new family of light-activatable DNA-cleaving agents. Angew. Chem. Int. Ed., 38, 3733-3735.
69. Toshima, K., Maeda, Y., Ouchi, H., et al. (2000) Carbohydrate-modulated DNA photocleavage: design, synthesis, and evaluation of novel glycosyl anthraquinones. Bioorg. Med. Chem. Lett., 10, 2163-2165.
70. Toshima, K., Takai, S., Maeda, Y., et al. (2000) Chemical synthesis and DNA photo-cleavage of the intercalator-carbohydrate hybrid moiety of the neocarzinostatin chromo-phore. Angew. Chem. Int. Ed. 39, 3656-3658.
71. Toshima, K., Takano, R., Ozawa, T. and Matsumura, S. (2002) Molecular design and evaluation of quinoxaline-carbohydrate hybrids as novel and efficient photo-induced GG-selective DNA cleaving agents. Chem. Commun., 212-213.
72. Tian, F., Bartberger, M. D. and Dolbier, W. R., Jr. (1999) Density functional theory calculations of the effect of fluorine substitution on the kinetics of cyclopropylcarbinyl radical ring openings. J. Org. Chem., 64, 540-545.
73. Helissey, P., Bailly, C., Vishwakarma, J. N., et al. (1996) DNAminor groove cleaving agents: synthesis, binding and strand cleaving properties of anthraquinone- oligopyrrolecarboxamide hybrids. Anticancer Drug Des., 11, 527-551.
74. Amishiro, N., Nagamura, S., Murakata, C., et al. (2000) Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups. Bioorg. Med. Chem., 8, 381-391. 37.
75. Scholl, M., Ding, S., Lee, C. W. and Grubbs, R. H. (1999) Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands. Org. Lett., 1, 953-956.
76. Ulman, M. and Grubbs, R. H. (1996) Ruthenium carbene-based olefin metathesis initiators: Catalyst decomposition and longevity. J. Org. Chem., 64, 7202-7207.