Palladium-Catalyzed Approach to 1,2-Disubstituted Carbocyclic Nucleoside Analogues of 5-Alkynyl and 5-Alkenyl Uracil

Abstract

The preparation of new analogues of 5-alkynyl- and 5-alkenyl-uracil is described. The synthesis involved palladium-catalyzed­ C-C coupling reactions, with the 5-ethynyl, 5-(1-hexynyl), and 5-(2-phenylethynyl) derivatives prepared through a Sonogashira coupling. A Stille coupling reaction was used to obtain the 5-(1-hexynyl) derivative, whilst the (E)-5-(2-bromovinyl) derivative was prepared using the Heck reaction. All the methods were clean and simple to perform.

nucleosides - heterocycles - cross-coupling - palladium

References

<A NAME="RT08606SS-1A">1a</A> Chu CK. Recent Advances in Nucleosides: Chemistry and Chemotherapy   Elsevier; Amsterdan: 2002. 

<A NAME="RT08606SS-1B">1b</A> Simons C. Nucleoside Mimetics: Their Chemistry and Biological Properties   Gordon and Breach Science Publishers; Amsterdam: 2001. 

<A NAME="RT08606SS-1C">1c</A> Agrofoglio L. Challand ST. Acyclic Carbocyclic and l -Nucleosides   Kluwer Academic Publishers; Dordrecht: 1998. 

<A NAME="RT08606SS-2A">2a</A> Bricaud H. Herdewijn P. De Clercq E. Biochem. Pharmacol.  1983,  3583 

<A NAME="RT08606SS-2B">2b</A> Herdewijn P. De Clercq E. Balzarini J. Vanderhaeghe H. J. Med. Chem.  1985,  28:  550 

<A NAME="RT08606SS-3">3</A> Cookson RC. Dudfield PJ. Newton RF. Ravenscroft P. Scopes DIC. Cameron JM. Eur. J. Med. Chem.  1985,  20:  375 

For recent reviews, see:

<A NAME="RT08606SS-4A">4a</A> Jeong LS. Lee JA. Antivir. Chem. Chemother.  2004,  15:  235 

<A NAME="RT08606SS-4B">4b</A> Wang J. Froeyen M. Herdewijn P. In Advances in Antiviral Drug Design   Vol. 4:  De Clercq E. Elsevier; Amsterdan: 2004.  p.119 

<A NAME="RT08606SS-4C">4c</A> Agrofoglio LA. Gillaizeau I. Saito Y. Chem. Rev.  2003,  103:  1875 

<A NAME="RT08606SS-4D">4d</A> Rodriguez JB. Comin MJ. Mini-Rev. Med. Chem.  2003,  3:  95 

<A NAME="RT08606SS-4E">4e</A> Schneller SW. Curr. Top. Med. Chem.  2002,  2:  1087 

<A NAME="RT08606SS-4F">4f</A> Ichikawa E. Kato K. Synthesis  2002,  1 

<A NAME="RT08606SS-5">5</A> Melroy J. Nair V. Curr. Pharm. Des.  2005,  11:  3847 

<A NAME="RT08606SS-6">6</A> Opio CK. Lee WM. Kirkpatrick P. Nat. Rev. Drug Discovery  2005,  4:  535 

<A NAME="RT08606SS-7">7</A> Balzarini J. Baumgartner H. Bodenteich M. De Clercq E. Griengl H. J. Med. Chem.  1989,  32:  1861 

<A NAME="RT08606SS-8">8</A> Besada P. González-Moa MJ. Terán C. Santana L. Uriarte E. Synthesis  2002,  2445 

<A NAME="RT08606SS-9">9</A> González-Moa MJ. Besada P. Teijeira M. Terán C. Uriarte E. Synthesis  2004,  543 

<A NAME="RT08606SS-10">10</A> González-Moa MJ. Terán C. Mosquera R. Tetrahedron  2003,  59:  4901 

<A NAME="RT08606SS-11">11</A> González-Moa MJ. Besada P. Terán C. Santana L. Uriarte E. Viña D. Helv. Chim. Acta  2006,  89:  954 

<A NAME="RT08606SS-12">12</A> Choi Y. Sun G. George C. Nicklaus MC. Kelley JA. Marquez VE. Nucleosides, Nucleotides Nucleic Acids  2003,  22:  2077 

<A NAME="RT08606SS-13">13</A> Manssur TS. Storer R. Curr. Pharm. Des.  1997,  3:  227 

<A NAME="RT08606SS-14A">14a</A> Escuret V. Aucagne V. Joubert N. Durantel D. Rapp KL. Schinazi RF. Zoulimb F. Agrofoglio LA. Bioorg. Med. Chem.  2005,  13:  6015 

<A NAME="RT08606SS-14B">14b</A> Amblard F. Aucagne V. Guenot P. Schinazi RF. Agrofoglio LA. Bioorg. Med. Chem.  2005,  13:  1239 

<A NAME="RT08606SS-15A">15a</A> McGuigan C. Yarnold CJ. Jones G. Velázquez S. Barucki H. Brancale A. Andrei G. Snoeck R. De Clercq E. Balzarini J. J. Med. Chem.  1999,  42:  4479 

<A NAME="RT08606SS-15B">15b</A> Angell A. McGuigan C. Sevillano GL. Snoeck R. Andrei G. De Clercq E. Balzarini J. Bioorg. Med. Chem. Lett.  2004,  14:  2397 

<A NAME="RT08606SS-15C">15c</A> Kifli N. De Clercq E. Balzarini J. Simons C. Bioorg. Med. Chem.  2004,  12:  4245 

<A NAME="RT08606SS-15D">15d</A> Mansour T. Evans CA. Charron M. Korba BE. Bioorg. Med. Chem. Lett.  1997,  7:  303 

<A NAME="RT08606SS-16A">16a</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  4467 

<A NAME="RT08606SS-16B">16b</A> Sonogashira K. In Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; New York: 1998.  Chap. 5.

<A NAME="RT08606SS-16C">16c</A> Sonogashira KJ. J. Organomet. Chem.  2002,  653:  46 

<A NAME="RT08606SS-17A">17a</A> Stille JK. Angew. Chem., Int. Ed. Engl.  1986,  25:  508 

<A NAME="RT08606SS-17B">17b</A> Casado AL. Espinet P. J. Am. Chem. Soc.  1998,  120:  8978 

<A NAME="RT08606SS-17C">17c</A> Farina V. Hauck SI. Synlett  1991,  157 

<A NAME="RT08606SS-18A">18a</A> Mizoroki T. Mori K. Ozaki A. Bull. Chem. Soc. Jpn.  1971,  44:  581 

<A NAME="RT08606SS-18B">18b</A> Heck RF. Nolley JP. J. Org. Chem.  1972,  37:  2320 

<A NAME="RT08606SS-19A">19a</A> Robins MJ. Barr PJ. Tetrahedron Lett.  1981,  22:  421 

<A NAME="RT08606SS-19B">19b</A> Robins MJ. Barr PJ. J. Org. Chem.  1983,  48:  1854 

<A NAME="RT08606SS-19C">19c</A> Robins MJ. Vinayak RS. Wood SG. Tetrahedron Lett.  1990,  31:  3731 

<A NAME="RT08606SS-20A">20a</A> Brancale A. McGuigan C. Andrei G. Snoeck R. De Clercq E. Balzarini J. Bioorg. Med. Chem. Lett.  2000,  10:  1215 

<A NAME="RT08606SS-20B">20b</A> McGuigan C. Barucki H. Blewett S. Carangio A. Erichsen JT. Andrei G. Snoeck R. De Clercq E. Balzarini J. J. Med. Chem.  2000,  43:  4993 

<A NAME="RT08606SS-20C">20c</A> McGuigan C. Yarnold CJ. Jones G. Velázquez S. Barucki H. Brancale A. Andrei G. Snoeck R. De Clercq E. Balzarini J. J. Med. Chem.  1999,  42:  4479 

<A NAME="RT08606SS-21">21</A> Herdewijn P. Kerremans L. Wigerinck P. Vanderdriessche F. Van Aerschot A. Tetrahedron Lett.  1991,  32:  4397 

<A NAME="RT08606SS-22">22</A> Moloney MG. Pinhey JT. Roche EG. J. Chem. Soc., Perkin Trans. 1  1989,  333 

<A NAME="RT08606SS-23A">23a</A> Farina V. Hauck SI. Synlett  1991,  157 

<A NAME="RT08606SS-23B">23b</A> Farina V. Krishnan B. J. Am. Chem. Soc.  1991,  113:  9585 

<A NAME="RT08606SS-24">24</A> (a) Herdewijn P. De Clercq E. Balzarini J. Vanderhaeghe H. J. Med. Chem.  1985,  28:  550 

<A NAME="RT08606SS-24">24</A> (b) Balzarini J. Baumgartner H. Bodenteich M. De Clercq E. Griengl H. J. Med. Chem.  1989,  32:  1861 

<A NAME="RT08606SS-24">24</A> (c) Hronowski LJJ. Szarek WA. J. Chem. Soc., Chem. Commun.  1990,  1547 

<A NAME="RT08606SS-24">24</A> (d) Ichikawa E. Yamamura S. Kato K. Bioorg. Med. Chem. Lett.  1999,  1113