Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

Abstract

2-Alkoxy-2-thiono-1,3,2-oxathiaphospholanes are readily transformed into phosphorothioate monoesters of the corresponding alcohols in a one-pot process, involving the reaction with 3-hydroxypropionitrile in the presence of DBU, followed by treatment with aqueous ammonia. In this way a series of nucleoside-3′-O- and 5′-O-phosphorothioates were prepared, as well as phosphorothioate derivatives of selected polyols.

nucleosides - polyols - thiophosphorylation - oxathiaphospholanes - ring-opening condensation

References

<A NAME="RG07202ST-1A">1a</A> Eckstein F. J. Am. Chem. Soc.  1996,  88:  4292 

<A NAME="RG07202ST-1B">1b</A> Eckstein F. Tetrahedron Lett.  1967,  1157 

<A NAME="RG07202ST-1C">1c</A> Eckstein F. J. Am. Chem. Soc.  1970,  92:  4718 

<A NAME="RG07202ST-2">2</A> Murray AW. Atkinson MR. Biochemistry  1968,  7:  4023 

<A NAME="RG07202ST-3">3</A> Tsai M.-D. Chang T.-T. J. Am. Chem. Soc.  1980,  102:  5416 

<A NAME="RG07202ST-4">4</A> Eckstein F. Annu. Rev. Biochem.  1985,  54:  367 

<A NAME="RG07202ST-5A">5a</A> Sheu K.-F. Richard JP. Frey PA. Biochemistry  1979,  18:  5548 

<A NAME="RG07202ST-5B">5b</A> Connolly BA. Romaniuk PJ. Eckstein F. Biochemistry  1982,  21:  1983 

<A NAME="RG07202ST-6A">6a</A> Brody RS. Frey PA. Biochemistry  1981,  20:  1245 

<A NAME="RG07202ST-6B">6b</A> Potter BVL. Eckstein F. J. Biol. Chem.  1984,  259:  14243 

<A NAME="RG07202ST-7">7</A> Chen J.-T. Benkovic SJ. Nucleic Acids Res.  1983,  11:  3737 

<A NAME="RG07202ST-8">8</A> Chladek S. Nagyvary J. J. Am. Chem. Soc.  1972,  94:  2079 

<A NAME="RG07202ST-9">9</A> Cook AF. J. Am. Chem. Soc.  1970,  92:  190 

<A NAME="RG07202ST-10A">10a</A> Ma kiewicz A. Smrt J. Coll. Czech. Chem. Commun.  1973,  38:  2953 

<A NAME="RG07202ST-10B">10b</A> Kresse J. Nagpal KL. Nagyvary J. Uchic JT. Nucleic Acids Res.  1975,  2:  1 

<A NAME="RG07202ST-11A">11a</A> Uhlmann E. Engels J. Tetrahedron Lett.  1986,  27:  1023 

<A NAME="RG07202ST-11B">11b</A> Thuong NT. Chassignol M. Tetrahedron Lett.  1987,  28:  4157 

<A NAME="RG07202ST-11C">11c</A> Francois J.-C. Saison-Behmoaras T. Barbier C. Chassignol M. Thuong NT. Helene C. Proc. Natl. Acad. Sci. U.S.A  1989,  86:  9702 

<A NAME="RG07202ST-12A">12a</A> Horn T. Urdea MS. Tetrahedron Lett.  1986,  27:  4705 

<A NAME="RG07202ST-12B">12b</A> Gryaznov SM. Letsinger RL. Nucleic Acids Res.  1993,  21:  1403 

<A NAME="RG07202ST-12C">12c</A> Xu Y. Kool ET. Nucleic Acids Res.  1998,  26:  3159 

<A NAME="RG07202ST-13">13</A> Baker GR. Billington DC. Gani D. Tetrahedron  1991,  47:  3895 

<A NAME="RG07202ST-14">14</A> Alefelder S. Patel BK. Eckstein F. Nucleic Acids Res.  1998,  26:  4983 

<A NAME="RG07202ST-15">15</A> Szczepanik MB. Desaubry L. Johnson RA. Tetrahedron Lett.  1998,  39:  7455 

<A NAME="RG07202ST-16A">16a</A> Stec WJ. Grajkowski A. Kozio kiewicz M. UznaÒ ski B. Nucleic Acids Res.  1991,  19:  5883 

<A NAME="RG07202ST-16B">16b</A> Stec WJ. Grajkowski A. Karwowski B. KobylaÒ ska A. Kozio kiewicz M. Misiura K. Okruszek A. Wilk A. Guga P. Boczkowska M. J. Am. Chem. Soc.  1995,  117:  12019 

<A NAME="RG07202ST-16C">16c</A> Sierzchaa A., Okruszek A., Stec W. J.; J. Org. Chem.; 1996, 61: 6713

<A NAME="RG07202ST-16D">16d</A> Stec WJ. Karwowski B. Boczkowska M. Guga P. Kozio kiewicz M. Sochacki M. Wieczorek MW. B aszczyk J. J. Am. Chem. Soc.  1998,  120:  7156 

<A NAME="RG07202ST-17">17</A>

A linear gradient 0.05→0.5 M triethylammonium bicarbonate (TEAB) was used as eluent.

<A NAME="RG07202ST-18">18</A>

RP HPLC purification of nucleoside 5′-O- or 3′-O-phosphorothioates was performed portionwise, on a semi-preparative ODS-Hypersil column (C₁₈), with a linear gradient of 0 → 40% acetonitrile in 0.1 M TEAB as eluent (2%/min). Pure products were collected at retention times ranging from 8.3 to 11.1 min.

<A NAME="RG07202ST-19">19</A> Kozio kiewicz M. Gendaszewska E. Maszewska M. Stein CA. Stec WJ. Blood  2001,  98:  995 

<A NAME="RG07202ST-20">20</A> DaCosta CP. Krajewska D. Okruszek A. Stec J W. Sigel H. J. Biol. Inorg. Chem.  2002,  7:  405 

<A NAME="RG07202ST-21">21</A> Guga P. DomaÒ ski K. Stec WJ. Angew. Chem. Int. Ed.  2001,  40:  610 

<A NAME="RG07202ST-22">22</A>

Guga, P.; DomaÒski, K.; unpublished results.

<A NAME="RG07202ST-23">23</A> Baraniak J. Wasilewska E. Korczy Òski D. Stec WJ. Tetrahedron Lett.  1999,  40:  8603 

<A NAME="RG07202ST-24A">24a</A> Ushakova IP. Tuvin MY. Serebrennikova GA. Kol’tsova GN. Vyazova EP. Rosenberg GY. Evstigneeva RP. Bioorg. Khim.  1985,  11:  845 

<A NAME="RG07202ST-24B">24b</A> Chuvilin AN. Serebrennikova GA. Evstigneeva RP. Kol’tsova GN. Vyazova EP. Rosenberg GY. Bioorg. Khim.  1985,  11:  187 

<A NAME="RG07202ST-24C">24c</A> Chuvilin AN. Serebrennikova GA. Evstigneeva RP. Bioorg. Khim.  1990,  16:  1157 

<A NAME="RG07202ST-25">25</A> Varnum JM. Baraniak J. Stec WJ. Brenner C. BMC Chem. Biol.  2001,  1:  1 

<A NAME="RG07202ST-26">26</A> Okruszek A. Olesiak M. Krajewska D. Stec WJ. J.Org.Chem.  1997,  62:  2269