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Synthesis 2003(18): 2785-2794  
DOI: 10.1055/s-2003-42454
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 8-Methoxypenciclovir and 8-Methoxyganciclovir through Methyl Triflate, a New Potential Approach to Label Penciclovir and Ganciclovir with Carbon-11

Qi-Huang Zheng*, Ji-Quan Wang, Xiangshu Fei, Gary D. Hutchins
Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L-3 Room 202, Indianapolis, IN 46202-2111, USA
Fax: +1(317)2789711; e-Mail: qzheng@iupui.edu;
Further Information

Publication History

Received 4 August 2003
Publication Date:
23 October 2003 (online)

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Abstract

In an effort to make HSV-tk gene reporter probes 8-FPCV and 8-FGCV labeled with fluorine-18, via the nucleophilic substitution reaction of PCV and GCV quaternized methylamine salt precursors with KF/Kryptofix 2.2.2, a new and unusual reaction through methyl triflate was discovered. Subsequently, new compounds 8-MeOPCV and 8-MeOGCV were synthesized from PCV and GCV in six steps with 12% and 20% overall chemical yield, respectively, and a novel potential approach to label PCV and GCV with carbon-11 has been proposed.

Key words

gene reporter probes - herpes simplex virus thymidine kinase (HSV-tk) - positron emission tomography (PET) - 8-methoxypenciclovir - 8-methoxyganciclovir

    References

  • 1 Culver KW. Blaese RM. Trends Genet.  1994,  10:  174 
    CrossrefGoogle Scholar
  • 2 Culver KW. Ram Z. Wallbridge S. Ishii H. Oldfield EH. Blaese RM. Science  1992,  256:  1550 
    CrossrefGoogle Scholar
  • 3 Dranoff G. J. Clin. Oncol.  1998,  16:  2548 
    CrossrefGoogle Scholar
  • 4 Huber BE. Richard CA. Krenitski TA. Proc. Natl. Acad. Sci. U.S.A.  1991,  88:  8039 
    CrossrefGoogle Scholar
  • 5 Moolten FL. Wells JM. J. Natl. Cancer Inst.  1990,  82:  297 
    CrossrefGoogle Scholar
  • 6 Moolten FL. Wells JM. Heyman RA. Evans RM. Hum. Gene Ther.  1990,  1:  125 
    CrossrefGoogle Scholar
  • 7 Vile RG. Hart IR. Cancer Res.  1993,  53:  3860 
    Google Scholar
  • 8 Tjuvajev JG. Chen SH. Joshi A. Joshi R. Guo ZS. Balatoni J. Ballon D. Koutcher J. Finn R. Woo SL. Blasberg RG. Cancer Res.  1999,  59:  5186 
    Google Scholar
  • 9 Blasberg R. Tjuvajev JG. Quart. J. Nucl. Med.  1999,  43:  163 
    Google Scholar
  • 10 Weissleder R. Mahmood U. Radiology  2001,  219:  316 
    CrossrefGoogle Scholar
  • 11 Alauddin MM. Conti PS. Nucl. Med. Biol.  1998,  25:  175 
    CrossrefGoogle Scholar
  • 12 Alauddin MM. Conti PS. Mazza SM. Hamzeh FM. Lever JR. Nucl. Med. Biol.  1996,  23:  787 
    CrossrefGoogle Scholar
  • 13 Alauddin MM. Shahinian A. Gordon EM. Bading JR. Conti PS. J. Nucl. Med.  2001,  42:  1682 
    Google Scholar
  • 14 Alauddin MM. Shahinian A. Kundu RK. Gordon EM. Conti PS. Nucl. Med. Biol.  1999,  26:  371 
    CrossrefGoogle Scholar
  • 15 Brust P. Haubner R. Friedrich A. Scheunemann M. Anton M. Koufaki ON. Hauses M. Noll S. Noll B. Haberkorn U. Schackert G. Schackert HK. Avril N. Johannsen B. Eur. J. Nucl. Med.  2001,  28:  721 
    CrossrefGoogle Scholar
  • 16 de Vries EF. van Waarde A. Harmsen MC. Mulder NH. Vaalburg W. Hospers GA. Nucl. Med. Biol.  2000,  27:  113 
    CrossrefGoogle Scholar
  • 17 Gambhir SS. Barrio JR. Herschman HR. Phelps ME. Nucl. Med. Biol.  1999,  26:  481 
    CrossrefGoogle Scholar
  • 18 Gambhir SS. Barrio JR. Phelps ME. Iyer M. Namavari M. Satyamurthy N. Wu L. Green LA. Bauer E. MacLaren DC. Nguyen K. Berk AJ. Cherry SR. Herschman HR. Proc. Natl. Acad. Sci. U.S.A.  1999,  96:  2333 
    CrossrefGoogle Scholar
  • 19 Gambhir SS. Bauer E. Black ME. Liang Q. Kokoris MS. Barrio JR. Iyer M. Namavari M. Phelps ME. Herschman HR. Proc. Natl. Acad. Sci. U.S.A.  2000,  97:  2785 
    CrossrefGoogle Scholar
  • 20 Hakimelahi GH. Khalafi-Nezhad A. Helv. Chim. Acta  1989,  72:  1495 
    CrossrefGoogle Scholar
  • 21 Harnden MR. Jarvest RL. Bacon TH. Boyd MR. J. Med. Chem.  1987,  30:  1636 
    CrossrefGoogle Scholar
  • 22 Hospers GA. Calogero A. van Waarde A. Doze P. Vaalburg W. Mulder NH. de Vries EF. Cancer Res.  2000,  60:  1488 
    Google Scholar
  • 23 Hustinx R. Shiue CY. Alavi A. McDonald D. Shiue GG. Zhuang H. Lanuti M. Lambright E. Karp JS. Eck SL. Eur. J. Nucl. Med.  2001,  28:  5 
    CrossrefGoogle Scholar
  • 24 Inubushi M. Wu JC. Gambhir SS. Sundaresan G. Satyamurthy N. Namavari M. Yee S. Barrio JR. Stout D. Chatziioannou AF. Wu L. Schelbert HR. Circulation  2003,  107:  326 
    CrossrefGoogle Scholar
  • 25 Iyer M. Barrio JR. Namavari M. Bauer E. Satyamurthy N. Nguyen K. Toyokuni T. Phelps ME. Herschman HR. Gambhir SS. J. Nucl. Med.  2001,  42:  96 
    Google Scholar
  • 26 Martin JC. McGee DPC. Jeffrey GA. Hobbs DW. Smee DF. Mattews TR. Verheyden JPH. J. Med. Chem.  1986,  29:  1384 
    CrossrefGoogle Scholar
  • 27 Ogilvie KK. Cheriyan UO. Radatus BK. Can. J. Chem.  1982,  60:  3005 
    CrossrefGoogle Scholar
  • 28 Pantuck AJ. Berger F. Zisman A. Nguyen D. Tso CL. Matherly J. Gambhir SS. Belldegrun AS. J. Urol.  2002,  168:  1193 
    CrossrefGoogle Scholar
  • 29 Shiue GG. Shiue CY. Lee RL. MacDonald D. Hustinx R. Eck SL. Alavi AA. Nucl. Med. Biol.  2001,  28:  875 
    CrossrefGoogle Scholar
  • 30 Tjuvajev JG. Doubrovin M. Akhurst T. Cai S. Balatoni J. Alauddin MM. Finn R. Bornmann W. Thaler H. Conti PS. Blasberg RG. J. Nucl. Med.  2002,  43:  1072 
    Google Scholar
  • 31 Wu JC. Inubushi M. Sundaresan G. Schelbert HR. Gambhir SS. Circulation  2002,  106:  180 
    CrossrefGoogle Scholar
  • 32 Yaghoubi S. Barrio JR. Dahlbom M. Iyer M. Namavari M. Satyamurthy N. Goldman R. Herschman HR. Phelps ME. Gambhir SS. J. Nucl. Med.  2001,  42:  1225 
    Google Scholar
  • 33 Yaghoubi SS. Wu L. Liang Q. Toyokuni T. Barrio JR. Namavari M. Satyamurthy N. Phelps ME. Herschman HR. Gambhir SS. Gene Ther.  2001,  8:  1072 
    CrossrefGoogle Scholar
  • 34 Wang J.-Q. Zheng Q.-H. Fei X. Mock BH. Hutchins GD. Bioorg. Med. Chem. Lett.  2003,  13: 3933
    Google Scholar
  • 35 Zheng Q.-H. Wang J.-Q. Fei X. Liu X. Gardner TA. Kao C. Raikwar SP. Glick-Wilson BE. Sullivan ML. Mock BH. Hutchins GD. J. Labelled Compd. Radiopharm.  2003,  46:  S221 
    CrossrefGoogle Scholar
  • 36 Zheng Q.-H. Wang J.-Q. Liu X. Fei X. Mock BH. Glick-Wilson BE. Sullivan ML. Raikwar SP. Gardner TA. Kao C. Hutchins GD. J. Labelled Compd. Radiopharm.  2003,  46:  S112 
    Google Scholar
  • 37 Namavari M. Barrio JR. Toyokuni T. Gambhir SS. Cherry SR. Herschman HR. Phelps ME. Satyamurthy N. Nucl. Med. Biol.  2000,  27:  157 
    CrossrefGoogle Scholar
  • 38 Ishii K. Ann. Nucl. Med.  2002,  16:  515 
    CrossrefGoogle Scholar
  • 39 Ashton WT, and Tolman RL. inventors; Eur. Pat. Appl. EP  193454. 
  • 40 Maki Y. Makino T. Hirota K. Sako M. Heterocycles  1993,  35:  325 
    CrossrefGoogle Scholar
  • 41 Field AK. Davies ME. DeWitt C. Perry HC. Liou R. Germershausen J. Karkas JD. Ashton WT. Johnston DBR. Tolman RT. Proc. Natl. Acad. Sci. U.S.A.  1983,  80:  4139 
    CrossrefGoogle Scholar
  • 42 Lin T.-S. Cheng J.-C. Ishiguro K. Sartorelli AC. J. Med. Chem.  1985,  28:  1194 
    CrossrefGoogle Scholar
  • 43 Robins MJ. Hatfield PW. Balzarini J. Clercq ED. J. Med. Chem.  1984,  27:  1486 
    CrossrefGoogle Scholar
  • 44 Jalilian AR. Tabatabai SA. Shafiee A. Afarideh H. Najafi R. Bineshmarvasti M. J. Labelled Compd. Radiopharm.  2000,  43:  545 
    CrossrefGoogle Scholar
  • 45 Mock BH. Mulholland GK. Vavrek MT. Nucl. Med. Biol.  1999,  26:  467 
    CrossrefGoogle Scholar
  • 46 Zheng Q.-H. Liu X. Fei X. Wang J.-Q. Ohannesian DW. Erickson LC. Stone KL. Hutchins GD. Nucl. Med. Biol.  2003,  30:  405 
    CrossrefGoogle Scholar
  • 47 Zheng Q.-H. Fei X. Liu X. Wang J.-Q. Sun HB. Mock BH. Stone KL. Martinez TD. Miller KD. Sledge GW. Hutchins GD. Nucl. Med. Biol.  2002,  29:  761 
    CrossrefGoogle Scholar
  • 48 Zheng Q.-H. Stone KL. Mock BH. Miller KD. Fei X. Liu X. Wang J.-Q. Glick-Wilson BE. Sledge GW. Hutchins GD. Nucl. Med. Biol.  2002,  29:  803 
    CrossrefGoogle Scholar