Synthesis 2011(15): 2483-2489  
DOI: 10.1055/s-0030-1260090
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

N 6-Acetyl-2′,3′,5′-tri-O-acetyladenosine; A Convenient, ‘Missed Out’ Substrate for Regioselective N6-Alkylations

Vitali I. Tararov, Svetlana V. Kolyachkina, Cyril S. Alexeev, Sergey N. Mikhailov*
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, Moscow 119991, Russian Federation
Fax: +7(499)1351405; e-Mail: smikh@eimb.ru;
Further Information

Publication History

Received 15 April 2011
Publication Date:
28 June 2011 (online)

Abstract

A simple and efficient route to N 6-acetyl-2′,3′,5′-tri-O-acetyladenosine (1) was developed based on selective N-deacetylation of pentaacetylated adenosine 2 with methanol at room temperature in the presence of imidazole. Preparative synthesis of 1 was elaborated utilizing a crude mixture of 2 and 1 which is produced by reaction of adenosine with acetic anhydride in pyridine at elevated temperatures. The total yield of 1 was 80-85% starting with adenosine. It was shown that 1 is a convenient substrate for selective N6-alkylations. The study revealed the same regioselectivity in base-promoted reactions of 1 with activated alkyl halides and Mitsunobu reactions of 1 with alcohols. A series of N 6-alkyladenosines 5a-f were prepared. Cytokinins 6b,d,e were prepared by enzymatic transformation of parent nucleoside derivatives 5b,d,e using a combination of nucleoside phosphorylase and alkaline phosphatase.

    References

  • 1a Kamada-Nobusada T. Sakakibara H. Phytochemistry  2009,  70:  444 
  • 1b Sakakibara H. Plant Hormones: Biosynthesis, Signal Transduction, Action   Davies PJ. Springer; Dordrecht: 2010.  p.95-114  
  • 2 McCullough JL. Kelly KM. Ann. N. Y. Acad. Sci.  2006,  1067:  323 
  • 3a Laezza C. Notarnicola M. Caruso MG. Messa C. Macchia M. Bertini S. Minutolo F. Portella G. Fiorentino L. Stingo S. Bifulco M. FASEB J.  2006,  20:  412 
  • 3b Vollera J. Zatloukal M. Lenobel R. Dolezal K. Béreša T. Kryštof V. Spíchal L. Niemann P. Dzubák P. Hajdúch M. Strnad M. Phytochemistry  2010,  71:  1350 
  • 4 Rozenski J. Crain PF. McCloskey JA. Nucleic Acids Res.  1999,  27:  196 
  • 5a Jones JW. Robins RK. J. Am. Chem. Soc.  1963,  85:  193 
  • 5b Robins MJ. Trips EM. Biochemistry  1973,  12:  2179 
  • 5c Timofeev EN. Mikhailov SN. Zuev AN. Efimtseva EV. Herdewijn P. Somers RL. Lemaitre MM. Helv. Chim. Acta  2007,  90:  928 
  • 5d Ottria R. Casati S. Manzocchi A. Baldoli E. Mariotti M. Maier JAM. Ciuffreda P. Bioorg. Med. Chem.  2010,  18:  4249 
  • 6a Vorbrüggen H. Krolikiewicz K. Justus Liebigs Ann. Chem.  1976,  745 
  • 6b Wan Z.-K. Binnun E. Wilson DP. Lee J. Org. Lett.  2005,  7:  5877 
  • 6c Wan Z.-K. Wacharasindhu S. Binnun E. Mansour T. Org. Lett.  2006,  8:  2425 
  • 7a Fleysher MC. Hakala MT. Bloch A. Hall RH.
    J. Med. Chem.  1968,  11:  717 
  • 7b Fleysher MC. Bloch A. Hakala MT. Nichol CA. J. Med. Chem.  1969,  12:  1056 
  • 7c Fleysher MC. J. Med. Chem.  1972,  15:  187 
  • 7d Dole˛al K. Popa I. Hauserová E. Spíchal L. Chakrabarty K. Novák O. Kryštof V. Voller J. Holub J. Strnad M. Bioorg. Med. Chem.  2007,  15:  3737 
  • 7e Ottria R. Casati S. Baldoli E. Maier JAM. Ciuffreda P. Bioorg. Med. Chem.  2010,  18:  8396 
  • 8 Lescrinier E. Pannecouque C. Rozenski J. van Aerschot A. Kerremans L. Herdewijn P. Nucleosides Nucleotides  1996,  1863 
  • 9 Aritomo K. Wada T. Sekine M. J. Chem. Soc., Perkin Trans. 1  1995,  1837 
  • 10a Car . Petrović V. Tomić S. J. Carbohydr. Chem.  2006,  25:  713 
  • 10b Nowak I. Conda-Sheridan M. Robins MJ. J. Org. Chem.  2005,  70:  7455 
  • 11 For a review on the Mitsunobu reaction, see: Kumara Swamy KC. Bhuvan Kumar NN. Balaraman E. Pavan Kumar KVP. Chem. Rev.  2009,  109:  2551 
  • 12 Seebach D. Beck AK. Studer A. In Modern Synthetic Methods   Ernst B. Leumann C. Verlag Helvetica Chimica Acta; Basel: 1995.  p.27 
  • 13a Mikhailov SN. Blaton N. Rozenski J. Balzarini J. De Clercq E. Herdewijn P. Nucleosides Nucleotides  1996,  15:  867 
  • 13b Efimtseva EV. Mikhailov SN. Fomicheva MV. Meshkov SV. Rodionov MS. Khomutov AR. De Clercq E. Bioorg. Khim.  1998,  24:  16 
  • 13c Holý A. Günter J. Dvořáková H. Masojídková M. Andrei G. Snoeck R. Balzarini J. De Clercq E. J. Med. Chem.  1999,  42:  2064 
  • 13d Enkvist E. Raidaru G. Uri A. Patel R. Redick C. Boyer JL. Subbi J. Tammiste I. Nucleosides Nucleotides  2006,  25:  141 
  • 14a Casati S. Manzocchi A. Ottria R. Ciuffreda P. Magn. Reson. Chem.  2010,  48:  745 
  • 14b Vícha J. Maloň M. Veselá P. Humpa O. Strnad M. Marek R. Magn. Reson. Chem.  2010,  48:  318 
  • 15 Esipov RS. Gurevich AI. Chuvikovsky DV. Chupova LA. Muravyova TI. Miroshnikov AI. Protein Expr. Purif.  2002,  24:  56 
  • 16 Mikhailopulo IA. Curr. Org. Chem.  2007,  11:  317 
  • 17 Gottlieb HE. Kotlyar V. Nudelman A. J. Org. Chem.  1997,  62:  7512 
  • 18 Lin X. Robins MJ. Org. Lett.  2000,  2:  3497 
  • 19 Fleysher MH. Bernaki RG. Bullard GA. J. Med. Chem.  1980,  23:  1448 
  • 20 Hampton A. Biesele JJ. Moore AE. Brown GB.
    J. Am. Chem. Soc.  1956,  78:  5695 
  • 21 Martin DMG. Reese CB. J. Chem. Soc. C  1968,  1731 
  • 22 Leonard NJ. Henderson TR. J. Am. Chem. Soc.  1975,  97:  4990 
  • 23 Whitehead CW. Traverso JJ. J. Am. Chem. Soc.  1960,  82:  3971