Synthesis of 3′-Deoxy-3′-difluoromethyluridine and 2′-Deoxy-2′-difluoromethyluridine

Stéphane Marcotte; Baudoin Gérard; Xavier Pannecoucke; Christian Feasson; Jean-Charles Quirion

doi:10.1055/s-2001-13419

PAPER

Synthesis of 3′-Deoxy-3′-difluoromethyluridine and 2′-Deoxy-2′-difluoromethyluridine

Stéphane Marcotte, Baudoin Gérard, Xavier Pannecoucke, Christian Feasson, Jean-Charles Quirion*
Laboratoire d’Hétérochimie Organique associé au CNRS, IRCOF, INSA et Université de Rouen, Rue Tesnière, 76821 Mont Saint-Aignan cedex, France
Fax: +33(2)35522959; e-Mail: quirion@ircof.insa-rouen.fr;

Abstract

Alle Artikel dieser Rubrik

Abstract

The synthesis of 3’-deoxy-3’-difluoromethyluridine (9) and 2’-deoxy-2’-difluoromethyluridine (7β) by hydrogenation of the corresponding difluoromethylene derivatives is described. A second synthesis of the latter has been performed. Starting from thymidine, a two-step procedure affords the benzylated furanoid glycal 12. Addition of dibromodifluoromethane gives the α-2’-deoxy-2’-bromodifluoromethylarabinose (13). This compound allowed an access to α- or β -2’-deoxy-2’-difluoromethyluridine via a S_N2 type reaction on a α-halodeoxyarabinose species.

Keywords

addition reactions - fluorine - nucleosides - carbohydrates

Volltext

Referenzen

References

<A NAME="RZ11900SS-1">1</A> Su TL. Watanabe KA. Schinazi RF. Fox JJ. J. Med. Chem. 1986, 151

<A NAME="RZ11900SS-2">2</A> Ojima I. McCarthy JR. Welch JT. Biomedical Frontiers of Fluorine Chemistry, ACS Symposium Series 639 ACS; Washington DC: 1996.

<A NAME="RZ11900SS-3">3</A> Herpin TF. Motherwell WB. Weibel JM. Chem. Commun. 1997, 924

<A NAME="RZ11900SS-4A">4a</A> Dunkel M. Reither V. Ebel-Will S. Ludwig J. Nucleotides and Nucleosides 1995, 799

<A NAME="RZ11900SS-4B">4b</A> Bamford MJ. Coe PL. Walker RT. J. Med. Chem. 1990, 2488

<A NAME="RZ11900SS-4C">4c</A> Houlton JS. Motherwell WB. Ross BC. Tozer MJ. Williams DJ. Slawin AMZ. Tetrahedron 1993, 8087

<A NAME="RZ11900SS-4D">4d</A> McCarthy JR. Jarvi ET. Matthews DP. Edwards ML. Prakash NJ. Bowlin TL. Mehdi S. Sunkara PS. Bey P. J. Am. Chem. Soc. 1989, 1127

<A NAME="RZ11900SS-5A">5a</A> York JL. J. Org. Chem. 1981, 2171

<A NAME="RZ11900SS-5B">5b</A> Marquez CK. Tseng CKH. Mitsuya H. Aoki S. Kelley JA. Ford HJr. Roth JS. Broder S. Johns DG. Driscoll JS. J. Med. Chem. 1990, 978

<A NAME="RZ11900SS-5C">5c</A> Coderre JA. Santi DV. Matsuda A. Watanabe KA. Fox JJ. J. Med. Chem. 1983, 1149

<A NAME="RZ11900SS-6">6</A> Serafinowski PJ. Barnes CL. Tetrahedron 1996, 7929

<A NAME="RZ11900SS-7A">7a</A> Miethchen R. Hein M. Reinke H. Eur. J. Org. Chem. 1998, 919

<A NAME="RZ11900SS-7B">7b</A> See also: Wu FH. Huang BN. Lu L. Huang WY. J. Fluor. Chem. 1996, 91

<A NAME="RZ11900SS-8A">8a</A> Abramski W. Chmielewski M. J. Carbohydr. Chem. 1994, 125

<A NAME="RZ11900SS-8B">8b</A> Ireland RP. Thaisrivongs S. Vanier N. Wilcox CS. J. Org. Chem. 1980, 48

<A NAME="RZ11900SS-9">9</A> Kassou M. Castillon S. Tetrahedron Lett. 1994, 5513

<A NAME="RZ11900SS-10">10</A> Cameron MA. Cush SB. Hammer RP. J. Org. Chem. 1997, 9065

<A NAME="RZ11900SS-11A">11a</A> Howell HG. Broduehrer PR. Brundidge SP. Benigni DA. Sapino C. J. Org. Chem. 1988, 85

<A NAME="RZ11900SS-11B">11b</A> See also: Hubbard AJ. Jones AS. Walker RT. Nucleic Acid Res. 1984, 6827