New Convergent Synthesis of Carbocyclic Nucleoside Analogues

Abstract

Two convergent approaches towards the synthesis of carbocyclic nucleoside analogs will be described. Both approaches start from the stereochemically pure cyclopentenol 8 that has been prepared enantioselectively from an alkylated cyclopentadiene. Using these approaches, carbocyclic analogues of dT, FdU and BVdU have been prepared. Moreover, the conversion into the cycloSal-pronucleotide and the corresponding nucleotide will be presented for one example.

carbocyclic nucleosides - stereoselective synthesis - Mitsunobu reaction - cycloSal-pronucleotides - nucleotides

References

<A NAME="RE09503SS-1A">1a</A> Agrofoglio L. Suhas E. Farese A. Condom R. Challand SR. Earl RA. Guedj R. Tetrahedron  1994,  50:  10611 

<A NAME="RE09503SS-1B">1b</A> Borthwick AD. Biggadike K. Tetrahedron  1992,  48:  571 

<A NAME="RE09503SS-1C">1c</A> Huryn DM. Okabe M. Chem. Rev.  1992,  92:  1745 

<A NAME="RE09503SS-2">2</A> Shealy YF. Clayton JD. J. Pharm. Sci.  1973,  62:  858 

<A NAME="RE09503SS-3">3</A> Yaginuma S. Muto N. Tsujino M. Sudate Y. Hayashi M. Otani M. J. Antibiot.  1981,  34:  359 

<A NAME="RE09503SS-4">4</A> Marquez VE. In Advances in Antiviral Drug Design   2:  De Clercq E. JAI Press; Greenwich: 1996.  p.89 

<A NAME="RE09503SS-5">5</A> Vince R. Hua M. J. Med. Chem.  1990,  33:  17 

<A NAME="RE09503SS-6A">6a</A> Daluge SM. Martin MT. Sickles BR. Livingston DA. Nucleosides, Nucleotides Nucleic Acids  2000,  19:  297 

<A NAME="RE09503SS-6B">6b</A> Crimmins MT. King BW. J. Org. Chem.  1996,  61:  4192 

<A NAME="RE09503SS-6C">6c</A> Kimberlain DW. Coen DM. Biron KK. Cohen JI. Lamb RA. Mckinlay M. Emini EA. Whitley RJ. Antiviral Res.  1995,  26:  369 

<A NAME="RE09503SS-7">7</A> Norbeck DW. Kern E. Hayashi S. Rosenbrook W. Sham H. Herrin T. Plattner JJ. Erickson J. Clement J. Swanson R. Shipkowitz N. Hardy D. Marsh K. Arnett G. Shannon W. Broder S. Mitsuya H. J. Med. Chem.  1990,  33:  1281 

<A NAME="RE09503SS-8">8</A> Bisacchi GS. Chao ST. Bachard C. Daris JP. Innaimo S. Jacobs GA. Kocy O. Lapointe P. Martel A. Merchant Z. Slusarchyk WA. Sundeen JE. Young MG. Colonno R. Zahler R. Bioorg. Med. Chem. Lett.  1997,  7:  127 

<A NAME="RE09503SS-9">9</A> Balzarini J. Baumgartner H. Bodenteich M. De Clercq E. Griengl H. Nucleosides Nucleotides  1989,  8:  855 

<A NAME="RE09503SS-10">10</A> Wyatt PG. Anslow AS. Coomber BA. Cousins RPC. Evans DN. Gilbert VS. Humber DC. Paternoster IL. Sollis SL. Tapolczay DJ. Weingarten GG. Nucleosides Nucleotides  1995,  14:  2039 

<A NAME="RE09503SS-11">11</A> Bricaud H. Herdewijn P. De Clercq E. Biochem. Pharmacol.  1983,  3583 

<A NAME="RE09503SS-12">12</A> Cookson R. Dudfield P. Newton R. Ravenscroft P. Scopes D. Cameron J. Eur. J. Med. Chem. Chim. Ther.  1985,  20:  375 

<A NAME="RE09503SS-13">13</A> Biggadike K. Borthwick AD. Evans D. Exall AM. Kirk BE. Roberts SM. Stephenson L. Youds P. Chem. Soc., Perkin Trans. 1  1988,  549 

<A NAME="RE09503SS-14A">14a</A> Parker D. Chem. Rev.  1991,  91:  1441 

<A NAME="RE09503SS-14B">14b</A> Anderson RC. Shapiro MJ. J. Org. Chem.  1984,  49:  1304 

<A NAME="RE09503SS-15">15</A> Gathergood N. Knudsen KR. Jørgensen KA. J. Org. Chem.  2001,  66:  1014 

<A NAME="RE09503SS-16A">16a</A> Baumgartner H. Marschner C. Pucher R. Griengl H. Tetrahedron Lett.  1991,  32:  611 

<A NAME="RE09503SS-16B">16b</A> Bisacchi GS. Chao ST. Bachard C. Daris JP. Innaimo S. Jacobs GA. Kocy O. Lapointe P. Martel A. Merchant Z. Slusarchyk WA. Sundeen JE. Young MG. Colonno R. Zahler R. Bioorg. Med. Chem. Lett.  1997,  7:  127 

<A NAME="RE09503SS-17A">17a</A> Overman LE. Sugai S. J. Org. Chem.  1985,  50:  4154 

<A NAME="RE09503SS-17B">17b</A> Kapeller H. Baumgartner H. Marschner C. Pucher R. Griengl H. Monatsh. Chem.  1997,  128:  953 

<A NAME="RE09503SS-18">18</A> Robins MJ. Wilson JS. Hansske F. J. Am. Chem. Soc.  1983,  105:  4059 

<A NAME="RE09503SS-19">19</A> Rodebaugh R. Debenham JS. Fraser-Reid B. Tetrahedron Lett.  1996,  37:  5477 

<A NAME="RE09503SS-20A">20a</A> Brown HC. Organic Syntheses via Boranes   Wiley; New York: 1974. 

<A NAME="RE09503SS-20B">20b</A> Brown HC. Jadhav PK. Mandal AK. Tetrahedron  1981,  37:  3547 

<A NAME="RE09503SS-20C">20c</A> Brown HC. Ayyangar NR. Zweifel G. J. Org. Chem.  1964,  86:  397 

<A NAME="RE09503SS-20D">20d</A> Brown HC. Knights EF. Scouten CG. J. Am. Chem. Soc.  1974,  96:  7765 

<A NAME="RE09503SS-21A">21a</A> Larock RC. Solvomercuration/Demercuration Reactions in Organic, Synthesis   Springer-Verlag; Berlin: Heidelberg.  1986. p.443 

<A NAME="RE09503SS-21B">21b</A> Larock RC. Angew. Chem.  1978,  90:  28 

<A NAME="RE09503SS-22A">22a</A> Brown HC. Heydkamp WR. Breuer E. Murphy WS. J. Am. Chem. Soc.  1964,  86:  3565 

<A NAME="RE09503SS-22B">22b</A> Rathke MW. Inoue N. Varma KR. Brown HC. J. Am. Chem. Soc.  1966,  88:  2870 

<A NAME="RE09503SS-23">23</A> Mitsunobu O. Synthesis  1981,  1 

<A NAME="RE09503SS-24">24</A> Cruickshank KA. Jiricny J. Reese CB. Tetrahedron Lett.  1984,  25:  681 

<A NAME="RE09503SS-25A">25a</A> Jenny TF. Horlacher J. Previsani N. Benner SA. Helv. Chim. Acta  1992,  75:  1944 

<A NAME="RE09503SS-25B">25b</A> Bonnal C. Chavis C. Lucas M. J. Chem. Soc., Perkin Trans. 1  1994,  1401 

<A NAME="RE09503SS-26A">26a</A> Barrett AGM. Braddock DC. James RA. Procopiou PA. Chem. Commun.  1997,  433 

<A NAME="RE09503SS-26B">26b</A> Barrett AGM. Braddock DC. James RA. Koike N. Procopiou PA. J. Org. Chem.  1998,  63:  6273 

<A NAME="RE09503SS-27">27</A> Meier C. Mini-Rev. Med. Chem.  2002,  2:  219 

<A NAME="RE09503SS-28">28</A> Meier C. Lorey M. De Clercq E. Balzarini J. J. Med. Chem.  1998,  41:  1417 

<A NAME="RE09503SS-29">29</A> Balzarini J. Aquaro S. Knispel T. Rampazzo C. Bianchi V. Perno C.-F. De Clercq E. Meier C. Mol. Pharmacol.  2000,  58:  928 

<A NAME="RE09503SS-30">30</A> Meier C. Knispel T. Marquez VE. Siddiqui MA. De Clercq E. Balzarini J. J. Med. Chem.  1999,  42:  1615 

<A NAME="RE09503SS-31">31</A> Balzarini J. Haller-Meier F. De Clercq E. Meier C. Antiviral Chem. Chemother.  2002,  12:  301 

<A NAME="RE09503SS-32A">32a</A> Meier C. Lomp A. Meerbach A. Wutzler P. J. Med. Chem.  2002,  45:  5157 

<A NAME="RE09503SS-32B">32b</A> Meier C. Habel L. Haller-Meier F. Lomp A. Herderich M. Klöcking R. Meerbach A. Wutzler P. Antiviral Chem. Chemother.  1998,  9:  389 

<A NAME="RE09503SS-33">33</A> Ostermann N. Segura-Pena D. Meier C. Veit T. Monnerjahn C. Konrad M. Lavie A. Biochemistry  2003,  42:  2568 

<A NAME="RE09503SS-34">34</A>

Konrad M., Lavie A.; Mini-Rev. Med. Chem.; 2003, in press

<A NAME="RE09503SS-35">35</A> Balzarini J. J. Pharm. World Sci.  1994,  16:  113