Download PDF
Synthesis 2022; 54(24): 5509-5519
DOI: 10.1055/s-0040-1720042
paper

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

Kazuhiro Haraguchi∗
,
Noyori Hannda
,
Mizuki Wakasugi
,
Madoka Maruyama
,
Hirokazu Ishii
,
Daisuke Nagano
,
Hiroki Kumamoto
Financial support from the Japan Society for the Promotion of Science (KAKENHI No. 24590144 to K.H.) is gratefully acknowledged.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

The unprecedented DAST-mediated (DAST = diethylaminosulfur trifluoride) deoxygenative fluorination of benzoyl-, TBDPS-, and Bn-protected 1-(β-d-4-thioarabinofuranosyl)uracil at the sugar portion was examined. Three kinds of nucleoside (Ns) products were formed: target thiolane Ns, ring-contracted thietane Ns, and anhydro Ns products. The reaction pathway was determined by the electronic effect of the protecting groups at the sugar and base moieties. The benzoylated uracil starting material gave the 2,2′-anhydronucleoside (anhydro Ns) as a major product, whereas the silylated and benzylated starting materials furnished the corresponding fluorinated products, in which the ring-contracted thietanes predominantly formed. The desired thiolane Ns could be obtained as major product by the addition of a pyridine derivative as an additive. Upon reacting N 3-benzoylated 1-(β-d-4-thioarabinofuranosyl)uracil with DAST in the presence of 2,4,6-collidine, the target 2′-deoxy-2′-β-fluoro-4′-thiouracil nucleoside could be obtained in 72% isolated yield along with the corresponding thietane Ns (7%) and anhydro Ns (3%) (thiolane Ns/thietane Ns/anhydro Ns = 10.3:1.00:0.43), with recovery of the starting material (12%). In this study, the first stereoselective synthesis of the β-anomer of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabino-pentofuranosyl)cytosine (4′-thioFAC) has been developed.

Keywords

nucleosides - thiosugars - glycal - fluorination - antineoplastic activity - oligonucleotide therapeutics

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1720042.
  • Supporting Information


Publication History

Received: 21 May 2022

Accepted after revision: 11 August 2022

Article published online:
23 September 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Huryn DM, Okabe M. Chem. Rev. 1992; 92: 1745
    Crossref
  • 2 Nucleosides and Nucleotides as Antitumor and Antiviral Agents. Chu CK, Baker DC. Plenum Press; New York: 1993
    Google Scholar
  • 3 Franchetti P, Grifantini M. Curr. Med. Chem. 1999; 6: 599
    CrossrefPubMed
  • 4 Ichikawa E, Kato K. Curr. Med. Chem. 2001; 8: 385
    CrossrefPubMed
  • 5 Nucleoside Mimetics: Their Chemistry and Biological Properties. Simons C. Gordon and Breach Science Publishers; ­Amsterdam: 2001
    Google Scholar
  • 6 Ichikawa E, Kato K. Synthesis 2002; 1
  • 7 Recent Advances in Nucleosides: Chemistry and Chemotherapy. Chu CK. Elsevier; Amsterdam: 2002
    Google Scholar
  • 8 Antiviral Nucleosides: Chemical Synthesis and Chemotherapy. Chu CK. Elsevier; Amsterdam: 2003
    Google Scholar
  • 9 Nucleoside Triphosphates and their Analogs: Chemistry, Biotechnology, and Biological Applications. Vaghefi M. Tayler & Francis; Boca Raton: 2005
    Google Scholar
  • 10 Lawton P. Expert. Opin. Ther. Pat. 2005; 15: 987
    Crossref
  • 11 Richardson SK, Howell AR, Taboada R. Org. Prep. Proced. Int. 2006; 38: 101
    Crossref
  • 12 Deoxynucleoside Analogs in Cancer Therapy. Peters GJ. Humana Press; New Jersey: 2006
    Google Scholar
  • 13 Modified Nucleosides in Biochemistry, Biotechnology and ­Medicine. Herdewijn P. Wiley-VCH; Weinheim: 2008
    Google Scholar
  • 14 Romeo G, Chiacchio U, Corsaro A, Merino P. Chem. Rev. 2010; 110: 3337
    CrossrefPubMed
  • 15 Antiviral Drug Design. De Clercq E. Wiley-VCH; Weinheim: 2011
    Google Scholar
  • 16 Calenbergh SV, Pochet S, Munier-Lehman H. Curr. Top. Med. Chem. 2012; 12: 694
    CrossrefPubMed
  • 17 Chemical Synthesis of Nucleoside Analogues. Merino P. John Wiley & Sons; Hoboken: 2013
    Google Scholar
  • 18 De Clercq E. Med. Res. Rev. 2013; 33: 1215
    CrossrefPubMed
  • 19 Jordheim LP, Durantel D, Zoulim F, Dumontet C. Nat. Rev. Drug Discov. 2013; 12: 447
    CrossrefPubMed
  • 20 De Clercq E, Li G. Clin. Microbiol. Rev. 2016; 29: 695
    CrossrefPubMed
  • 21 Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF. Chem. Rev. 2016; 116: 14379
    CrossrefPubMed
  • 22 Yokoyama M. Synthesis 2000; 1637
    Article in Thieme Connect
  • 23 Gunaga P, Moon H.-R, Choi W.-J, Shin D.-H, Park JG, Jeong LS. Curr. Med. Chem. 2004; 11: 2585
    CrossrefPubMed
  • 24 Mulamoottil VA, Majik MS, Chandra G, Jeong LS. Chemical Synthesis of Nucleoside Analogues. Merino P. John Wiley & Sons; Hoboken: 2013: 655
    CrossrefGoogle Scholar
  • 25 Rodrigues L, Tilve SG, Majik MS. Eur. J. Med. Chem. 2021; 224: 113659
    CrossrefPubMed
  • 26 Haraguchi K, Kumamoto H, Tanaka H. Curr. Med. Chem. 2022; 29: 3684
    CrossrefPubMed
    • 27a Yoshimura Y, Saitoh K, Ashida N, Sakata S. Bioorg. Med. Chem. Lett. 1994; 4: 721
      Crossref
    • 27b Yoshimura Y, Kitano K, Satoh H, Watanabe M, Miura S, Sakata S, Sasaki T, Matsuda A. J. Org. Chem. 1996; 61: 822
      Crossref
    • 27c Yoshimura Y, Kitano K, Yamada K, Sakata S, Miura S, Ashida N, Machida H, Matsuda A. Nucleic Acids Symp. Ser. 1997; 37: 43
    • 27d Yoshimura Y, Watanabe M, Saitoh H, Ashida N, Ijichi K, Sakata S, Machida H, Matsuda A. J. Med. Chem. 1997; 40: 2177
      CrossrefPubMed
    • 27e Yoshimura Y, Kitano K, Yamada K, Satoh H, Watanabe M, Miura S, Sakata S, Sasaki T, Matsuda A. J. Org. Chem. 1997; 62: 3140
      CrossrefPubMed
    • 27f Yoshimura Y, Endo M, Kitano K, Yamada K, Sakata S, Miura S, Machida H. Nucleosides Nucleotides 1999; 18: 815
      CrossrefPubMed
    • 27g Yoshimura Y, Endo M, Sakata S. ­Tetrahedron Lett. 1999; 40: 1937
      Crossref
    • 27h Yoshimura Y, Endo M, Miura S, Sakata S. J. Org. Chem. 1999; 64: 7912
      Crossref
    • 27i Yoshimura Y, Kitano K, Yamada K, Sakata S, Miura S, Ashida N, Machida H. Bioorg. Med. Chem. 2000; 8: 1545
      CrossrefPubMed
  • 28 Watts JK, Choubdar N, Sadalapure K, Robert F, Wahba AS, Pelletier J, Mario Pinto B, Damha MJ. Nucleic Acids Res. 2007; 35: 1441
    CrossrefPubMed
  • 29 Haraguchi K, Kumamoto H, Konno K, Yagi H, Tatano Y, Odanaka Y, Matsubayashi S, Snoeck R, Andrei G. ­Tetrahedron 2019; 75: 4542
    Crossref
  • 30 Jeong LS, Nicklaus MC, George C, Marquez VE. ­Tetrahedron Lett. 1994; 35: 7569
    CrossrefPubMed
  • 31 Haraguchi K, Takahashi H, Shiina N, Horii C, Yoshimura Y, Nishikawa A, Sasakura E, Nakamura KT, Tanaka H. J. Org. Chem. 2002; 67: 5919
    CrossrefPubMed
  • 32 Miller JA, Pugh AW, Ullah GM. Nucleosides, Nucleotides Nucleic Acids 2000; 19: 1475
    CrossrefPubMed
  • 33 Jeong LS, Tosh DK, Choi WJ, Lee SK, Kang Y.-J, Choi S, Lee JH, Lee H, Lee HW, Kim HK. J. Med. Chem. 2009; 52: 5303
    CrossrefPubMed
  • 34 Watts JK, Sadalapure K, Choubdar N, Pinto BM, Damha MJ. J. Org. Chem. 2006; 71: 921
    CrossrefPubMed