Download PDF
Synthesis 2010(9): 1550-1556  
DOI: 10.1055/s-0029-1218695
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Straightforward Diastereoselective Synthesis and Evaluation of Climacostol, A Natural Product with Anticancer Activities

Dennis Fiorinia, Sandra Giulia, Enrico Marcantoni*a, Luana Quassintib, Massimo Bramuccib, Consuelo Amantinic, Giorgio Santonic, Federico Buonannod, Claudio Ortenzi*d
a School of Sciences and Technologies, Section of Chemistry, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy
Fax: +39(0737)402297; e-Mail: enrico.marcantoni@unicam.it;
b School of Pharmacy, Physiology, University of Camerino, via Gentile III da Varano, 62032 Camerino (MC), Italy
c School of Pharmacy, Anatomy Unit, University of Camerino, via Scalzino 3, 62032 Camerino (MC), Italy
d Department of Educational Sciences and Training, University of Macerata, P. le Bertelli 1, 62100 Macerata, Italy
e-Mail: claudio.ortenzi@unimc.it;
Further Information

Publication History

Received 28 December 2009
Publication Date:
09 March 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

On the basis of continued interest in plant-derived natural products as anticancer agents, a shorter and more efficient synthesis of climacostol is reported. This compound showed an anticancer activity better than that of the natural product. The improved potency and selectivity can be due to the absence of traces of the undesired E-isomer present in the natural climacostol. Furthermore, the versatile strategy developed for this simple molecule such as climacostol could aid in the synthesis of other more complex natural products.

Key words

bioorganic chemistry - C-C bond formation - diastereoselectivity - natural products - protecting groups - Wittig reaction

    References

  • 1a Hengtrakul P. Mathias M. Lorenz K. J. Nutr. Biochem.  1991,  2:  20 
    Google Scholar
  • 1b Arisawa M. Ohmura K. Kobayashi A. Morita N. Chem. Pharm. Bull.  1989,  37:  2431 
    Google Scholar
  • 1c Marumo S. Hattori H. Katayama M. Agric. Biol. Chem.  1985,  49:  1521 
    Google Scholar
  • 2 Kozubek A. Tyman JHP. Chem. Rev.  1999,  99:  1 
    CrossrefPubMedGoogle Scholar
  • 3a Parikka K. Rowland IR. Welch RW. Wähälä K.
    J. Agric. Food Chem.  2006,  54:  1646 
    Google Scholar
  • 3b Winata A. Lorenz K. J. Food Process Preserv.  1996,  20:  417 
    Google Scholar
  • 3c Shobha SV. Ramadoss CS. Ravindranath B. J. Nat. Prod.  1994,  57:  1755 
    Google Scholar
  • 4a Kociubinska A. Godlewska M. Stasiuk M. Kozubek A. Peczynska-Czoch W. Opolski A. Kaczmarek L. Gubernator J. Cell. Mol. Biol. Lett.  2002,  7:  289 
    Google Scholar
  • 4b Barrow RA. Capon RJ. Aust. J. Chem.  1991,  44:  1393 
    Google Scholar
  • 5 Generally the E-derivative is less cytotoxic than its Z-stereoisomer, see: Cushman M. Nagarathanam D. Gopal D. Chakraborti AK. Lin CM. Hamel E. J. Med. Chem.  1991,  34:  2579 
    CrossrefGoogle Scholar
  • 6 Miyake A. Buonanno F. Saltalamacchia P. Masaki ME. Iio H. Eur. J. Protistol.  2003,  39:  25 
    CrossrefGoogle Scholar
  • 7a Buonanno F. Ital. J. Zool.  2005,  72:  293 
    Google Scholar
  • 7b Buonanno F. Quassinti L. Bramucci M. Amantini C. Lucciarini R. Santoni G. Iio H. Ortenzi C. Chem. Biol. Interact.  2008,  176:  151 
    Google Scholar
  • 8 Hoveyda AH. Evans DA. Fu GC. Chem. Rev.  1993,  93:  1307 
    CrossrefGoogle Scholar
  • 9 Rein C. Demel P. Outten RA. Netscher T. Breit B. Angew. Chem. Int. Ed.  2007,  46:  8670 
    CrossrefGoogle Scholar
  • 10a Masaki ME. Hiro S. Usiki Y. Harumoto T. Terazima MN. Buonanno F. Miyake A. Iio H. Tetrahedron  2004,  60:  7041 
    Google Scholar
  • 10b Abe Y. Mori K. Biosci. Biotechnol. Biochem.  2001,  65:  2110 
    Google Scholar
  • 10c Masaki ME. Harumoto T. Terazima MN. Miyake A. Usuki Y. Iio H. Tetrahedron Lett.  1999,  40:  8227 
    Google Scholar
  • 10d Trivedi SV. Subbaraman AS. Chattopadhyay S. Mamdapur VR. Molecules  1999,  4:  245 
    Google Scholar
  • 11a Bartoli G. Bosco M. Giuli S. Giuliani A. Lucarelli L. Marcantoni E. Sambri L. Torregiani E. J. Org. Chem.  2005,  70:  1941 
    Google Scholar
  • 11b Bartoli G. Bosco M. Dalpozzo R. Giuliani A. Marcantoni E. Mecozzi T. Sambri L. Torregiani E. J. Org. Chem.  2002,  67:  9111 
    Google Scholar
  • 11c Bartoli G. Bellucci MC. Bosco M. Marcantoni E. Massaccesi M. Petrini M. Sambri L. J. Org. Chem.  2000,  65:  4553 
    Google Scholar
  • 11d Bartoli G. Bosco M. Marcantoni E. Sambri L. Torregiani E. Synlett  1998,  209 
    Google Scholar
  • 11e Bartoli G. Bosco M. Dalpozzo R. De Nino A. Marcantoni E. Sambri L. J. Org. Chem.  1998,  63:  3745 
    Google Scholar
  • 11f Giovannini R. Marcantoni E. Petrini M. J. Org. Chem.  1995,  60:  5706 
    Google Scholar
  • 11g Ballini R. Marcantoni E. Petrini M. J. Org. Chem.  1992,  57:  1316 
    Google Scholar
  • 12 Ballini R. Bosica G. Marcantoni E. Tetrahedron  1996,  52:  10705 
    CrossrefGoogle Scholar
  • 13 Aïssa C. Eur. J. Org. Chem.  2009,  1831 ; and references cited therein
    CrossrefGoogle Scholar
  • 14 Lanni TB. Greene KL. Kolz CN. Para KS. Visnick T. Mobley JL. Dudley DT. Baginski TJ. Liimatta MB. Bioorg. Med. Chem. Lett.  2007,  17:  756 
    CrossrefGoogle Scholar
  • 15 Murakami T. Furusawa K. Synthesis  2002,  479 
    Article in Thieme ConnectGoogle Scholar
  • 16 The Z-stereochemistry was assigned on the basis of the ¹³C chemical shifts of the allylic methylene carbons, see: Porta A. Re S. Zanoni G. Vidari G. Tetrahedron  2007,  63:  3989 ; and confirmed by spectroscopic correlation with compound 2
    CrossrefGoogle Scholar
  • 17 Hayami J. Ono N. Kaji A. Tetrahedron Lett.  1968,  1385 
    CrossrefGoogle Scholar
  • 18a Bartoli G. Giovannini R. G iuliani A. Marcantoni E. Massaccesi M. Melchiorre P. Paoletti M. Sambri L. Eur. J. Org. Chem.  2006,  1476 
    Google Scholar
  • 18b Bartoli G. Bellucci MC. Bosco M. Cappa A. Marcantoni E. Sambri L. Torregiani E. J. Org. Chem.  1999,  64:  5696 
    Google Scholar
  • 19a Kocienski PJ. Protecting Groups   Georg Thieme Verlag; Stuttgart: 2005.  p.285-308  
    Google Scholar
  • 19b Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   Wiley-Interscience; New York: 1999.  p.23-148  
    Google Scholar
  • 20 Although this reagent itself is only mildly carcinogenic, it is usually contaminated with small amounts of bis(chloromethyl) ether, which is strongly carcinogenic. For this reason the literature contains a variety of methods to reduce laboratory hazards, see: Berliner M. Belecki K. Org. Synth.  2007,  84:  102 ; and references cited therein
    Google Scholar
  • 21 Kitamura Y, Nara S, Nakagawa H, Nakatsu R, Soga S, Kajita J, Shiotsu Y, and Kanda Y. inventors; Patent EP 1 704  856.  ; Chem. Abstr. 2005, 143,146661
  • 22 Dickschat JS. Helmuke E. Schultz S.  Chemistry & Biodiversity  2005,  2:  318 
    Google Scholar
  • 23 Hermann C. Pais GCG. Geyer A. Kühnert SM. Maier ME. Tetrahedron  2000,  56:  8461 
    CrossrefGoogle Scholar
  • 24 Boger DL. Brunette SR. Garbaccio RM. J. Org. Chem.  2001,  66:  5163 
    CrossrefGoogle Scholar
  • 25 Ireland RE. Varney MD. J. Org. Chem.  1986,  51:  635 
    CrossrefGoogle Scholar
  • 26 Lee AS.-Y. Hu T.-J. Chu S.-F. Tetrahedron  2001,  57:  2121 
    CrossrefGoogle Scholar
  • 27 Monti H. Leandri G. Klas-Ringuet M. Corriol C. Synth. Commun.  1983,  13:  1021 
    CrossrefGoogle Scholar
  • 28 Chan K.-F. Zhao Y. Chow LMC. Chan TH. Tetrahedron  2005,  61:  4149 
    CrossrefGoogle Scholar
  • 29a Lélias-Vanderperre A. Chambran J.-C. Espinosa E. Terrier P. Leize-Wagner E. Org. Lett.  2007,  9:  2961 
    Google Scholar
  • 29b Kunnagaiu N. Matsunaga S. Kinoshita T. Harada S. Okada S. Sakamoto S. Yamaguchi K. Shibosaki MJ.
    J. Am. Chem. Soc.  2003,  125:  2169 
    Google Scholar
  • 30 Yan B. Shi R. Zhang B. Kishirsagar T. J. Comb. Chem.  2007,  9:  684 
    CrossrefGoogle Scholar
  • 31 Ross AB. Aman P. Andersson R. Kamal-Eldin A.
    J. Chromatogr., A  2004,  1054:  157 
    CrossrefGoogle Scholar
  • 32 Crouch RC. McFayden RB. Daluge SM. Martin GE. Magn. Reson. Chem.  1990,  28:  792 
    CrossrefGoogle Scholar
  • 33 Van Aller RM. Clark LR. Pessoney GF. van Rogers AA. Lipids  1983,  18:  617 
    CrossrefGoogle Scholar
  • 34 Suzuki Y. Esumi Y. Uramoto M. Kono YA. Biosci. Biotechnol. Biochem.  1997,  61:  480 
    CrossrefGoogle Scholar
  • 35 Zarnowski R. Suzuki Y. Esumi Y. Pieter SJ. Phytochemistry  2000,  55 :  975 
    Google Scholar
  • 36 Knodler M. Berardini N. Kanmerer DR. Carle R. Schieber A. Rapid Commun. Mass Spectrom.  2007,  21:  945 
    CrossrefGoogle Scholar
  • 37 Page M. Bejaoui N. Cinq-Mars B. Lemieux P. Int. J. Immunopharm.  1988,  785 
    CrossrefGoogle Scholar