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Synthesis 2009(15): 2471-2491  
DOI: 10.1055/s-0029-1216891
REVIEW
© Georg Thieme Verlag Stuttgart ˙ New York

Advances in Synthetic Approaches for the Preparation of Combretastatin-Based Anti-Cancer Agents

Rohit Singh*, Harneet Kaur
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA
Fax: +1(612)6252633; e-Mail: singh109@umn.edu;
Further Information

Publication History

Received 13 March 2009
Publication Date:
10 July 2009 (online)

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Abstract

The natural product combretastatin A-4 (CA4) is a potent anti-cancer agent known for its antimitotic and antiangiogenic properties. The basic structure of CA4 has inspired the design and synthesis of a variety of medicinally active analogues that take advantage of the relatively simple stilbenoid architecture of the molecule. Here, we examine recent advances in the synthesis of various CA4-based analogues. A significant focus is placed on the modifications to the bridging alkene moiety of the stilbene scaffold for conformationally restricting the structure in a bioactive form. An effort is also made to discuss promising ring modifications and replacements, including the incorporation of indazole and oxindole rings, as well as the design and synthesis of amino-substituted analogues.

1 Introduction

2 New Approaches for the Synthesis of CA4

3 Synthetic Approaches for the Preparation of CA4 Analogues

3.1 Modification of the Bridging Moiety

3.2 Modification of the Bridging Moiety via Heterocyclic Functionalities

3.3 Macrocyclic Rings Affording Conformational Restriction to Combretastatin Analogues

4 Amine Substituents on Aryl Rings of Combretastatin Analogues

5 Conclusions

Key words

natural products - drugs - combretastatin - inhibitors - antitumor­ agents - medicinal chemistry

    References

  • 1a Watt JM. Breyer-Brandwijk MG. In The Medicinal and Poisonous Plants of Southern and Eastern Africa   2nd ed.:  E. and S. Livingstone; London: 1962. 
    Google Scholar
  • 1b Gurib FA. Brendler T. In Medicinal and Aromatic Plants of Indian Ocean Islands: Madagascar, Comoros, Seychelles and Mascarenes   Medpharm Scientific Publishers; Stuttgart: 2004. 
    Google Scholar
  • 2 Pettit GR. Cragg GM. Herald DL. Schmidt JM. Lobovanijaya P. Can. J. Chem.  1982,  60:  1374 
    CrossrefGoogle Scholar
  • 3 Pinney KG. Jelinek C. Edvardsen K. Chaplin DJ. Pettit GR. In Anticancer Agents from Natural Products   Cragg GM. Kingston DGI. Newman DJ. CRC/Taylor and Francis; Boca Raton: 2005.  p.23 
    Google Scholar
  • 4a Cushman M. Nagarathnam D. Gopal D. Chakraborty AK. Lin CM. Hamel E. J. Med. Chem.  1991,  34:  2579 
    Google Scholar
  • 4b Sackett DL. Pharm. Ther.  1993,  59:  163 
    Google Scholar
  • 4c Hamel E. Med. Res. Rev.  1996,  16:  207 
    Google Scholar
  • 4d Cirla A. Mann J. Nat. Prod. Rep.  2003,  20:  558 
    Google Scholar
  • 4e Thorpe PE. Clin. Cancer Res.  2004,  10:  415 
    Google Scholar
  • 4f Li Q. Sham HL. Exp. Opin. Ther. Pat.  2002,  12:  1663 
    Google Scholar
  • 4g Nam NH. Curr. Med. Chem.  2003,  10:  1697 
    Google Scholar
  • 4h Pettit GR. Lippert JW. Herald DL. Hamel E. Pettit RK. J. Nat. Prod.  2000,  63:  969 
    Google Scholar
  • 4i Ohsumi K. Nakagawa R. Fukuda Y. Hatanaka T. Morinaga Y. Nihei Y. Ohishi K. Suga Y. Akiyama Y. Tsuji T. J. Med. Chem.  1998,  41:  3022 
    Google Scholar
  • 4j Tron GC. Pirali T. Sorba G. Pagliai F. Busacca S. Genazzani AA. J. Med. Chem.  2006,  49:  3033 
    Google Scholar
  • 5 Lin CM. Singh SB. Chu PS. Dempcy RO. Schmidt JM. Pettit GR. Hamel E. Mol. Pharmacol.  1988,  34:  200 
    Google Scholar
  • 6a Grosios K. Holwell SE. McGown AT. Pettit GR. Bibby MC. Br. J. Cancer  1999,  81:  1318 
    Google Scholar
  • 6b Horsman MR. Murata R. Breidahl T. Nielsen FU. Maxwell RJ. Stodkiled-Jorgensen H. Overgaard J. Adv. Exp. Med. Biol.  2000,  476:  311 
    Google Scholar
  • 6c Siemann DW. Mercer E. Lepler S. Rojiani AM. Int. J. Cancer  2002,  99:  1 
    Google Scholar
  • 6d Galbraith SM. Maxwell RJ. Lodge MA. Tozer GM. Wilson J. Taylor NJ. Stirling JJ. Sena L. Padhani AR. Rustin GJ. J. Clin. Oncol.  2003,  21:  2831 
    Google Scholar
  • For antivascular activity of CA4 at low concentrations, see:
  • 6e Tozer GM. Kanthou C. Parkins CS. Hill SA. Int. J. Exp. Pathol.  2002,  83:  21 
    Google Scholar
  • For examples of vascular-targeting tubulin binding compounds in prodrug form, see:
  • 6f Hadimani MB. Kessler RJ. Kautz JA. Ghatak A. Shirali AR. O’Dell H. Garner CM. Pinney KG. Acta Crystallogr., Sect. C: Cryst. Struct. Commun.  2002,  58:  330 
    Google Scholar
  • 6g Siemann DW. Rojiani AM. Int. J. Radiat. Oncol. Biol. Phys.  2002,  54:  1512 
    Google Scholar
  • 6h Chaplin DJ. Hill SA. Int. J. Radiat. Oncol. Biol. Phys.  2002,  54:  1491 
    Google Scholar
  • 6i Thorpe PE. Chaplin DJ. Blakeley DC. Cancer Res.  2003,  63:  1144 
    Google Scholar
  • For a review on the current status of CA4P, see:
  • 6j Siemann DW. Chaplin DJ. Walicke PA. Expert Opin. Investig. Drugs  2009,  18:  189 
    Google Scholar
  • 7a Rustin GJS. Galbraith SM. Anderson H. Stratford M. Folkes LK. Sena L. Gumbrell L. Price PM. J. Clin. Oncol.  2003,  21:  2815 
    Google Scholar
  • 7b Dowlati A. Robertson K. Cooney M. Petros WP. Stratford M. Jesberger J. Rafie N. Overmoyer B. Makkar V. Stambler B. Taylor A. Waas J. Lewin JS. McCrae KR. Remick SC. Cancer Res.  2002,  62:  3408 
    Google Scholar
  • 8 Lee JC. Harrison D. Timasheff SN. J. Biol. Chem.  1975,  24:  9276 
    Google Scholar
  • 9 Dustin P. Microtubules   2nd ed.:  Springer-Verlag; Berlin: 1984. 
    Google Scholar
  • 10 Jordan MA. Wilson L. Nat. Rev. Cancer  2004,  4:  253 
    CrossrefPubMedGoogle Scholar
  • 11a Hamel E. Pharm. Ther.  1992,  55:  31 
    Google Scholar
  • 11b Shih C. Teicher BA. Curr. Pharm. Des.  2001,  7:  1259 
    Google Scholar
  • 11c Gupta S. Bhattacharya B. Mol. Cell. Biochem.  2003,  253:  41 
    Google Scholar
  • 12 Atalay C. Deliloglu GI. Irkkan C. Gunduz U. Tumour Biol.  2006,  27:  309 
    CrossrefGoogle Scholar
  • 13 Chaudhary A. Pandeya SN. Kumar P. Sharma PP. Gupta S. Soni N. Verma KK. Bhardwaj G. Mini Rev. Med. Chem.  2007,  7:  1186 ; and references therein
    CrossrefGoogle Scholar
  • For the synthesis of (-)-combretastatin, see:
  • 14a Pettit GR. Singh SB. Cragg GM. J. Org. Chem.  1985,  50:  3404 
    Google Scholar
  • For the synthesis of combretastatin-A1 and combretastatin-B1, see:
  • 14b Pettit GR. Singh SB. Niven ML. Hamel E. Schmidt JM. J. Nat. Prod.  1987,  50:  119 
    Google Scholar
  • For the synthesis of combretastatin-A2, combretastatin-A3 and combretastatin-B2, see:
  • 14c Pettit GR. Singh SB. Can. J. Chem.  1987,  65:  2390 
    Google Scholar
  • For a previous report on the synthesis of (±)-combretastatin, see:
  • 14d Annapurna GS. Deshpande VH. Synth. Commun.  1983,  13:  1075 
    Google Scholar
  • 15 Pettit GR. Singh SB. Boyd MR. Hamel E. Pettit RK. Schmidt JM. Hogan F. J. Med. Chem.  1995,  38:  1666 
    CrossrefGoogle Scholar
  • 16 Harrowven DC. Guy IL. Howell M. Packam G. Synlett  2006,  2977 
    Article in Thieme ConnectGoogle Scholar
  • 17a Dunne EC. Coyne J. Crowley PB. Gilheany DG. Tetrahedron Lett.  2002,  43:  2449 
    Google Scholar
  • 17b See also: Hwang J.-J. Lin R.-L. Shieh R.-L. Jwo J.-J. J. Mol. Catal. A: Chem.  1999,  142:  125 
    Google Scholar
  • 17c Sinhababu AK. Borchardt RT. J. Org. Chem.  1983,  48:  2356 
    Google Scholar
  • 18 Robinson JE. Taylor RJK. Chem. Commun.  2007,  1617 
    CrossrefGoogle Scholar
  • 19 Chan T.-L. Fong S. Li Y. Man T.-O. Poon C.-D. J. Chem. Soc., Chem. Commun.  1994,  1771 
    Google Scholar
  • 20 Yang G. Franck RW. Byun H.-S. Bittman R. Samadder P. Arthur G. Org. Lett.  1999,  1:  2149 
    CrossrefGoogle Scholar
  • 21 Meyers CY. Malte AM. Matthews WS. J. Am. Chem. Soc.  1969,  91:  7510 
    CrossrefGoogle Scholar
  • 22 Giraud A. Provot O. Hamze A. Brion J.-D. Alami M. Tetrahedron Lett.  2008,  49:  1107 
    CrossrefGoogle Scholar
  • 23a Hamze A. Provot O. Brion J.-D. Alami M. Synthesis  2007,  2025 
    Google Scholar
  • 23b Hamze A. Provot O. Alami M. Brion J.-D. Org. Lett.  2005,  7:  5625 
    Google Scholar
  • 24a Lindlar H. Helv. Chim. Acta  1952,  35:  446 
    Google Scholar
  • 24b Lindlar H. Dubuis R. Org. Synth.  1973,  5:  880 
    Google Scholar
  • 25a Bujard M. Ferri F. Alami M. Tetrahedron Lett.  1998,  39:  4243 
    Google Scholar
  • 25b Liron F. Le Garrec P. Alami M. Synlett  1999,  246 
    Google Scholar
  • 25c Alami M. Liron F. Gervais M. Peyrat J.-F. Brion J.-D. Angew. Chem. Int. Ed.  2002,  41:  1578 
    Google Scholar
  • 25d Liron F. Gervais M. Peyrat J.-F. Alami M. Brion J.-D. Tetrahedron Lett.  2003,  44:  2789 
    Google Scholar
  • 25e Hamze A. Provot O. Brion J.-D. Alami M. J. Org. Chem.  2007,  72:  3868 
    Google Scholar
  • 26 Zou Y. Xiao C.-F. Zhong R.-Q. Wei W. Huang W.-M. He S.-J. J. Chem. Res.  2008,  354 
    CrossrefGoogle Scholar
  • 27 Camacho-Davila AA. Synth. Commun.  2008,  3823 
    CrossrefGoogle Scholar
  • 28 Pettit GR. Cragg GM. Singh SB. J. Nat. Prod.  1987,  56:  386 
    Google Scholar
  • 29 Ravelli RBG. Gigant B. Curmi PA. Jourdain I. Lachkar S. Sobel A. Knossow M. Nature  2004,  428:  198 
    CrossrefGoogle Scholar
  • For examples of bridge modified tubulin polymerization inhibitors, see:
  • 30a Synthesis of phenstatin: Pettit GR. Toki B. Herald DL. Verdier-Pinard P. Boyd MR. Hamel E. Pettit RK. J. Med. Chem.  1998,  41:  1688 
    Google Scholar
  • 30b Synthesis of hydroxy-phenstatin: Pettit GR. Grealish MP. Herald DL. Boyd MR. Hamel E. Pettit RK. J. Med. Chem.  2000,  43:  2731 
    Google Scholar
  • 31 Gurjar MK. Wakharkar RD. Singh AT. Jaggi M. Borate HB. Shinde PD. Verma R. Rajendran P. Dutt S. Singh G. Sanna VK. Singh MK. Srivastava SK. Mahajan VA. Jadhav VH. Dutta K. Krishnan K. Chaudhary A. Agarwal SK. Mukherjee R. Burman AC. J. Med. Chem.  2007,  50:  1744 
    CrossrefGoogle Scholar
  • 32 Gurjar MK, Wakharkar RD, Desiraju GR, Nangia A, Yadav JS, Burman AC, Mukherjee R, Borate HB, Chandrasekhar S, Jaggi M, Singh AT, Kapoor KK, Sarkhel S, and Sairam KVVM. inventors; US Pat. Appl. Publ. US  2003229146. 
  • 33 Trost BM. Pinkerton AB. J. Org. Chem.  2001,  66:  7714 
    CrossrefGoogle Scholar
  • 34 Kerr DJ. Hamel E. Jung MK. Flynn BL. Bioorg. Med. Chem.  2007,  15:  3290 
    CrossrefGoogle Scholar
  • 35 Kerr DJ. Metje C. Flynn BL. Chem. Commun.  2003,  1380 
    CrossrefGoogle Scholar
  • 36 Sriram M. Hall JJ. Grohman NC. Strecker TE. Wooton T. Franken A. Trawick ML. Pinney KG. Bioorg. Med. Chem.  2008,  16:  8161 
    CrossrefGoogle Scholar
  • 37 Hu L. Li Z.-R. Li Y. Qu J. Ling Y.-H. Jiang J.-D. Boykin DW. J. Med. Chem.  2006,  49:  6273 
    CrossrefGoogle Scholar
  • 38 Mitsumori S. Tsuri T. Honma T. Hiramatsu Y. Okada T. Hashizume H. Inagaki M. Arimura A. Yasui K. Asanuma F. Kishino J. Ohtani M. J. Med. Chem.  2003,  46:  2436 
    CrossrefGoogle Scholar
  • 39 Mousset C. Giraud A. Provot O. Hamze A. Bignon J. Liu J.-M. Thoret S. Dubois J. Brion J.-D. Alami M. Bioorg. Med. Chem. Lett.  2008,  18:  3266 
    CrossrefPubMedGoogle Scholar
  • 40 Giraud A. Provot O. Peyrat J.-F. Alami M. Brion J.-D. Tetrahedron  2006,  62:  7667 
    CrossrefGoogle Scholar
  • 41 Sun L. Vasilevich NI. Fuselier JA. Hocart SJ. Coy DH. Bioorg. Med. Chem. Lett.  2004,  14:  2041 
    CrossrefGoogle Scholar
  • 42 Kaffy J. Monneret C. Mailliet P. Commercon A. Pontinkis R. Tetrahedron Lett.  2004,  45:  3359 
    CrossrefGoogle Scholar
  • 43 Wang L. Woods KW. Li Q. Barr KJ. McCroskey RW. Hannick SM. Gherke L. Credo RB. Hui Y.-H. Marsh K. Warner RJ. Lee Y. Zielenski-Mozng N. Frost D. Rosenberg S.-H. Sham HL. J. Med. Chem.  2002,  45:  1697 
    CrossrefGoogle Scholar
  • 44 LeBlanc R. Dickson J. Brown T. Stewart M. Pati H. VanDerveer D. Arman H. Harris J. Pennington W. Holt H. Lee M. Bioorg. Med. Chem.  2005,  13:  6025 
    CrossrefGoogle Scholar
  • 45 Flynn BL. Flynn GP. Hamel E. Jung MK. Bioorg. Med. Chem. Lett.  2001,  11:  2341 
    CrossrefGoogle Scholar
  • 46 Pinney KG. Bounds AD. Dingeman KM. Mocharla VP. Pettit GR. Bai R. Hamel E. Bioorg. Med. Chem. Lett.  1999,  9:  1081 
    CrossrefGoogle Scholar
  • 47 Kim Y. Nam N.-H. You Y.-J. Ahn B.-Z. Bioorg. Med. Chem. Lett.  2002,  12:  719 
    CrossrefGoogle Scholar
  • 48 Zhang Q. Peng Y. Wang XI. Keenan SM. Arora S. Welsh WJ. J. Med. Chem.  2007,  50:  749 
    CrossrefPubMedGoogle Scholar
  • 49 Curphey TJ. J. Org. Chem.  2002,  67:  6467 
    Google Scholar
  • 51 Nguyen TL. McGrath C. Hermone AR. Burnett JC. Zaharevitz DW. Day BW. Wipf P. Hamel E. Gussio RA. J. Med. Chem.  2005,  48:  6107 
    CrossrefGoogle Scholar
  • 52 Odlo K. Hentzen J. Chabert JFD. Ducki S. Gani OABSM. Sylte I. Skrede M. Florenes VA. Hansen TV. Bioorg. Med. Chem.  2008,  16:  4829 
    CrossrefGoogle Scholar
  • 53 Colvin EW. Hamill BJ. J. Chem. Soc., Chem. Commun.  1973,  151 
    CrossrefGoogle Scholar
  • 54 Huisgen R. Szeimies G. Mobius L. Chem. Ber.  1967,  100:  2494 
    CrossrefGoogle Scholar
  • 55 Johnson M. Younglove B. Lee L. LeBlanc R. Holt H. Hills P. Mackay H. Brown T. Mooberry SL. Lee M. Bioorg. Med. Chem. Lett.  2007,  17:  5897 
    CrossrefGoogle Scholar
  • 56 Ducki S. Forrest R. Hadfield JH. Kendall A. Lawrence NJ. McGown AT. Rennison D. Bioorg. Med. Chem. Lett.  1998,  8:  1051 
    CrossrefGoogle Scholar
  • 57a Sun L. Tran N. Tang F. App H. Hirth P. McMahon G. Tang C. J. Med. Chem.  1998,  41:  2588 
    Google Scholar
  • 57b Sun L. Tran N. Liang C. Tang F. Rice A. Schreck R. Waltz K. Shawver LK. McMahon G. Tang C. J. Med. Chem.  1999,  42:  5120 
    Google Scholar
  • 58 Pandit B. Sun Y. Chen P. Sackett DL. Hu Z. Rich W. Li C. Lewis A. Schaefer K. Li P.-K. Bioorg. Med. Chem.  2006,  14:  6492 
    CrossrefGoogle Scholar
  • 59 Li P.-K. Xiao Z. Hu Z. Pandit B. Sun Y. Sackett DL. Werbovetz K. Lewis A. Johnsamuel J. Bioorg. Med. Chem. Lett.  2005,  15:  5382 
    CrossrefGoogle Scholar
  • 60 Quallich G. Morrissey P. Synthesis  1993,  51 
    Article in Thieme ConnectGoogle Scholar
  • 61 Arthuis M. Pontikis R. Florent J.-C. Tetrahedron Lett.  2007,  48:  6397 
    CrossrefGoogle Scholar
  • 62 Kaffy J. Pontikis R. Florent J.-C. Monneret C. Org. Biomol. Chem.  2005,  5:  2657 
    Google Scholar
  • 63a Cheung WS. Patch RJ. Player MR. J. Org. Chem.  2005,  70:  3741 
    Google Scholar
  • 63b Yanada R. Obika S. Inokuma T. Yanada K. Yamashita M. Ohta S. Takemoto Y. J. Org. Chem.  2005,  70:  6972 
    Google Scholar
  • 64 Couty S. Liégault B. Meyer C. Cossy J. Org. Lett.  2004,  6:  2511 
    CrossrefPubMedGoogle Scholar
  • 65a Oh CH. Lim YM. Tetrahedron Lett.  2003,  44:  267 
    Google Scholar
  • 65b Min S.-H. Pang S.-J. Cho C.-G. Tetrahedron Lett.  2003,  44:  4439 
    Google Scholar
  • 66 Burns B. Grigg R. Sridharan V. Stevenson P. Sukirthalingam S. Worakun T. Tetrahedron Lett.  1989,  30:  1135 
    CrossrefGoogle Scholar
  • 67 Yanada R. Obika S. Kobayashi Y. Inokuma T. Oyama M. Yanada K. Takemoto Y. Adv. Synth. Catal.  2005,  347:  1632 
    CrossrefGoogle Scholar
  • 68 Brunton SA. Jones K. J. Chem. Soc., Perkin Trans. 1  2000,  763 
    CrossrefGoogle Scholar
  • 69 Duan J.-X. Cai X. Meng F. Lan L. Hart C. Matteucci M. J. Med. Chem.  2007,  50:  1001 
    CrossrefGoogle Scholar
  • 70 Provot O. Giraud A. Peyrat J. Alami M. Brion J. Tetrahedron Lett.  2005,  49:  8547 
    Google Scholar
  • 71 Idiya GF. Nataliya AZ. Tetrahedron Lett.  2005,  29:  5453 
    Google Scholar
  • 72 Wu M. Sun Q. Yang C. Chen D. Ding J. Chen Y. Lin L. Xie Y. Bioorg. Med. Chem. Lett.  2007,  17:  869 
    CrossrefGoogle Scholar
  • 73 Napolitano E. Ramacciotti A. Gazz. Chim. Ital.  1989,  119:  19 
    Google Scholar
  • 74 Tong YG. Zhang XW. Geng MY. Yue JM. Xin XL. Fang T. Xu S. Tong LJ. Li MH. Zhang C. Li WH. Lin LP. Ding J. Mol. Pharmacol.  2006,  69:  1226 
    CrossrefGoogle Scholar
  • 75 Lee L. Davis R. Vanderham J. Hills P. Mackay H. Brown T. Mooberry SL. Lee M. Eur. J. Med. Chem.  2008,  43:  2011 
    CrossrefGoogle Scholar
  • 76 For the synthesis and a limited cytotoxicity study of chalcones, see: Dickson J. Flores L. Stewart M. Holt HL. LeBlanc R. Lee M. J. Chem. Educ.  2006,  83:  934 
    CrossrefGoogle Scholar
  • 77 Rappl C. Barbier P. Bourgarel-Rey V. Gregoire C. Gilli R. Carre M. Combes S. Finet J.-P. Peyrot V. Biochemistry  2006,  45:  9210 
    CrossrefGoogle Scholar
  • 78 Bailly C. Bal C. Barbier P. Combes S. Finet J.-P. Hildebrand M.-P. Peyrot V. Wattez N. J. Med. Chem.  2003,  46:  5437 
    CrossrefGoogle Scholar
  • 79 Combes S. Finet J.-P. Siri D. J. Chem. Soc., Perkin Trans. 1  2002,  38 
    CrossrefGoogle Scholar
  • 80a Ishiyama T. Abe S. Miyaura N. Suzuki A. Chem. Lett.  1992,  691 
    Google Scholar
  • 80b Miyaura N. Ishiyama T. Sasaki H. Ishikawa M. Satoh M. Suzuki A. J. Am. Chem. Soc.  1989,  111:  314 
    Google Scholar
  • 80c Miyaura N. Yanagi T. Suzuki A. Synth. Commun.  1981,  11:  513 
    Google Scholar
  • 80d Miyaura N. Yamada K. Suzuki A. Tetrahedron Lett.  1979,  36:  3437 
    Google Scholar
  • 80e Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Google Scholar
  • 80f Miyaura N. Top. Curr. Chem.  2002,  219:  11 
    Google Scholar
  • 80g Suzuki A. J. Organomet. Chem.  1999,  576:  147 
    Google Scholar
  • 80h Hassan J. Sevignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 
    Google Scholar
  • 81a Walker SD. Barder TE. Martinelli JR. Buchwald SL. Angew. Chem. Int. Ed.  2004,  43:  1871 
    Google Scholar
  • 81b Zhou J. Fu GC. J. Am. Chem. Soc.  2004,  126:  1340 
    Google Scholar
  • 81c Brenstrum T. Gerristma DA. Adjabeng GM. Frampton CS. Britten J. Rabertson AJ. McNulty J. Capretta A. J. Org. Chem.  2004,  69:  7635 
    Google Scholar
  • 81d Arensten K. Caddick S. Cloke FGN. Herring AP. Hitchcock PB. Tetrahedron Lett.  2004,  45:  3511 
    Google Scholar
  • 81e Gstottmayr CWK. Bohm VPW. Herdtweck E. Grosche M. Herrmann WA. Angew. Chem. Int. Ed.  2002,  41:  1363 
    Google Scholar
  • 81f Navarro O. Kaur H. Poppet B. Mahjoor P. Nolan SP. J. Org. Chem.  2004,  69:  3173 
    Google Scholar
  • 81g Singh R. Viciu MS. Kramareva N. Navarro O. Nolan SP. Org. Lett.  2005,  7:  1829 
    Google Scholar
  • 82a Boland GM. Donnelly DMX. Finet J.-P. Rea MD. J. Chem. Soc., Perkin Trans. 1  1996,  2591 
    Google Scholar
  • 82b Donnelly DMX. Finet J.-P. Guiry PJ. Rea MD. Synth. Commun.  1999,  29:  2719 
    Google Scholar
  • 83 Ganina OG. Daras E. Bourgarel-Rey V. Peyrot V. Andresyuk AN. Finet J.-P. Federov AY. Beletskaya I. Combes S. Bioorg. Med. Chem.  2008,  16:  8806 
    CrossrefGoogle Scholar
  • 84a Pettit GR. Singh SB. Niven ML. J. Am. Chem. Soc.  1988,  110:  8539 
    Google Scholar
  • 84b Singh SB. Pettit GR. J. Org. Chem.  1990,  55:  2797 
    Google Scholar
  • 85 Mateo C. Lopez V. Medarde M. Pelaez R. Chem. Eur. J.  2007,  13:  7246 
    CrossrefGoogle Scholar
  • 86 Maya ABS. Pérez-Melero C. Mateo C. Alonso D. Fernández JL. Gajate C. Mollinedo F. Peláez R. Caballero E. Medarde M. J. Med. Chem.  2005,  48:  556 
    CrossrefGoogle Scholar
  • 87a Mitsunobu O. Synthesis  1981,  1 
    Google Scholar
  • 87b Hughes DL. Org. React.  1992,  42:  335 
    Google Scholar
  • 87c Hughes DL. Org. Prep. Proced. Int.  1996,  28:  127 
    Google Scholar
  • 88 McMurry JE. Chem. Rev.  1989,  89:  1513 
    CrossrefGoogle Scholar
  • 89 Mateo C. Pérez-Melero C. Peláez R. Medarde M. J. Org. Chem.  2005,  70:  6544 
    Google Scholar
  • 90 Mateo C. Alvarez R. Perez-Melero C. Pelaez R. Medarde M. Bioorg. Med. Chem. Lett.  2007,  17:  6316 
    CrossrefGoogle Scholar
  • 91 Pettit GR. Rhodes MR. Herald DL. Hamel E. Schmidt JM. Pettit RK. J. Med. Chem.  2005,  48:  4087 
    CrossrefGoogle Scholar
  • 92a Monk KA. Siles R. Hadimani MB. Mugabe BE. Ackley JF. Studerus SW. Edvardsen K. Trawick ML. Garner CM. Rhodes MR. Pettit GR. Pinney KG. Bioorg. Med. Chem.  2006,  14:  3231 
    Google Scholar
  • For earlier reports on the synthesis of 3′-amino combretastatin tubulin polymerization inhibitors, see:
  • 92b

    Ref. 4i.

    Google Scholar
  • 92c Pinney KG. Mejia MP. Villalobos VM. Rosenquist BE. Pettit GR. Verdier-Pinard P. Hamel E. Bioorg. Med. Chem.  2000,  8:  2417 
    Google Scholar
  • 93 Chang J.-Y. Yang M.-F. Chang C.-Y. Chn C.-M. Kuo C.-C. Liou J.-P. J. Med. Chem.  1996,  49:  6412 
    Google Scholar
  • 94 Siles R. Ackley JF. Hadimani MB. Hall JJ. Mugabe BE. Guddneppanavar R. Monk KA. Chapuis J.-C. Pettit GR. Chaplin DJ. Edvardsen K. Trawick ML. Garner CM. Pinney KG. J. Nat. Prod.  2008,  71:  313 
    CrossrefGoogle Scholar
  • 95 Gal’bershtam MA. Budarina ZN. Zh. Org. Khim.  1969,  5:  953 
    Google Scholar
  • 96 Simonsen JL. Rau MG. J. Chem. Soc., Dalton Trans.  1917,  220:  236 
    Google Scholar
  • 97 Monk K. Siles R. Pinney KG. Garner CM. Tetrahedron Lett.  2003,  44:  3759 
    CrossrefGoogle Scholar
  • 98 Chaplin DJ, Garner CM, Kane RR, Pinney KG, Prezioso JA, and Edvardsen K. inventors; United States Patent US  6919324B2. 
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The conformation from the X-ray crystal structure was utilized in molecular dynamics simulations by docking it into the colchicines binding site of tubulin by Zhang et al.48