Synlett 2010(13): 1959-1962  
DOI: 10.1055/s-0030-1258503
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Novel Exocyclic Nucleoside Related to Clitocine: A Convergent Synthesis of 3′-Azido-2′,3′-dideoxy Clitocine

Xianghai Guo*a, Can Liub, Lanxi Zhengb, Shende Jiang*b, Jiaxiang Shenb
a Key Laboratory of Systems Bioengineering, Ministry of Education and Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. of China
e-Mail: Guoxh@tju.edu.cn;
b School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. of China
e-Mail: sjiang@tju.edu.cn;
Further Information

Publication History

Received 17 March 2010
Publication Date:
16 July 2010 (online)

Abstract

The synthesis of a new clitocine derivative was achieved through a convergent strategy. A protected 4,6-diamino-5-nitro­pyrimidine was condensed with p-chlorobenzoyl (PCB)-protected methyl 3′-azido-2′,3′-dideoxyribofuranoside, followed by subsequently deprotection to give the desired product.

    References and Notes

  • 1 Kubo I. Kim M. Wood WF. Naoki H. Tetrahedron Lett.  1986,  27:  4277 
  • 2a Moss RJ. Petrie CR. Meyer RB. Dee Nord L. Willis RC. Smith RA. Larson SB. Kini GD. Robins RK. J. Med. Chem.  1988,  31:  786 
  • 2b Kamikawa T. Fujie S. Yamagiwa Y. Kim M. Kawaguchi H.
    J. Chem. Soc., Chem. Commun.  1988,  195 
  • 2c Choi H. Choi BS. Chang JH. Lee KW. Nam DH. Kim YK. Lee JH. Heo T. Shin H. Kim N. Synlett  2005,  1942 
  • 3a Fortin H. Tomasi S. Delcros J. Bansard J. Boustie J. ChemMedChem  2006,  1:  189 
  • 3b Ren G. Zhao YP. Yang L. Fu CX. Cancer Lett.  2008,  262:  190 
  • 3c Shin H. Min C. Clitocine and its Analogues, In Modified Nucleosides   Herdewijn P. Wiley-VCH; Weinheim: 2008.  Chap. 22. p.567 
  • 4a Lee CH. Daanen JF. Jiang M. Yu H. Kohlhaas KL. Alexander K. Jarvis MF. Kowaluk EL. Bhagwat SS. Bioorg. Med. Chem. Lett.  2001,  11:  2419 
  • 4b Varaprasad CV. Habib Q. An H. Hong Z. Nucleosides, Nucleotides Nucleic Acids  2006,  25:  61 
  • 4c Long MC. Parker WB. Biochem. Pharmacol.  2006,  71:  1671 
  • 5 Liu FY, Ren G, Fu CX, and Wu P. inventors; CN  101333236.  ; Chem. Abstr. 2008, 150, 106103
  • 6 Liu FY, Guo TD, Wu SH, Wu P, and Feng GP. inventors; CN  101347442.  ; Chem. Abstr. 2009, 150, 206311
  • 7a Wilde RG, Kennedy PD, Almstead NG, Welch EM, Takasugi JJ, and Friesen WJ. inventors; WO  2004009609.  ; Chem. Abstr. 2004, 140, 128608
  • 7b Wilde RG, Almstead NG, Welch EM, and Beckmann H. inventors; WO  2004009610.  ; Chem. Abstr. 2004, 140, 122839
  • 7c Wilde RG, Almstead NG, Welch EM, and Beckmann H. inventors; US  2006166926.  ; Chem. Abstr. 2006, 145, 167496
  • 8a Eger K. Klünder EM. Schmidt M. J. Med. Chem.  1994,  37:  3057 
  • 8b Franchetti P. Cappellacci L. Abu Sheikha G. Grifantini M. Loi AG. De Montis A. Spiga MG. La Colla P. Nucleosides Nucleotides  1995,  14:  607 
  • 8c Bacchelli C. Condom R. Patino N. Aubertin AM. Nucleosides, Nucleotides Nucleic Acids  2000,  19:  567 
  • 9a Palmer CF. Parry KP. Roberts SM. Tetrahedron Lett.  1990,  31:  279 
  • 9b Baxter AD. Penn CR. Storer R. Weir NG. Woods JM. Nucleosides Nucleotides  1991,  10:  393 
  • 9c Marquez VE. Lim BB. Driscoll JS. Snoek R. Balzarini J. Ikeda S. Andrei G. De Clercq E. J. Heterocycl. Chem.  1993,  30:  1393 
  • 9d Demaison C. Hourioux C. Roingeard P. Agrofoglio LA. Tetrahedron Lett.  1998,  39:  9175 
  • 9e Agrofoglio LA. Demaison C. Toupet L. Tetrahedron  1999,  55:  8075 
  • 10 Varaprasad CV. Habib Q. Li DY. Huang JF. Abt JW. Rong F. Hong Z. An HY. Tetrahedron  2003,  59:  2297 
  • 11 Sharkin YA. Semizarov DG. Viktorova LS. Kukhanova MK. Russ. J. Bioorg. Chem.  2001,  27:  340 
  • 12a Gryaznov SM. Biochem. Biophys. Acta  1999,  1489:  131-140  
  • 12b Eglia M. Gryaznov SM. Cell. Mol. Life Sci.  2000,  57:  1440 
  • 12c Ford LP. Zou Y. Pongracz K. Gryaznov SM. Shay JW. Wright WE. J. Biol. Chem.  2001,  276:  32198 
  • 12d Herbert BS. Pongracz K. Shay JW. G ryaznov SM. Oncogene  2002,  21:  638 
  • 12e Zielinska D. Pongracz K. Gryaznov SM. Tetrahedron Lett.  2006,  47:  4495 
  • 13a Boon WR. Jones WGM. Ramage GR. J. Chem. Soc.  1951,  96 
  • 13b Robins RK. Dille KJ. Willits CH. Christensen BE. J. Am. Chem. Soc.  1953,  75:  263 
  • 14 Hansen P. Pedersen EB. Acta Chem. Scand.  1990,  44:  522 
  • 15 Gold A. Sangaiah R. Nucleosides Nucleotides  1990,  9:  907 
  • 16a Anderson NG. Lust DA. Colapret KA. Simpson JH. Malley MF. Gougoutas JZ. J. Org. Chem.  1996,  61:  7955 
  • 16b Davis AP. Dresen SD. Lawless LJ. Tetrahedron Lett.  1997,  38:  4305 
17

The CCDC number of compound 12α is 777653.

18

6-Amino-5-nitro-4-(3′-azido-5′- O - p -chloro-benzoyl-2′,3′-dideoxy-β- d -ribofuranosylamino) Pyrimidine (16)
TMS-protected 4,6-diamino-5-nitropyrimidine 8 (0.86 g, 2.9 mmol) was dissolved in DCE (10 mL). To this solution, methyl 3′-azido-5′-O-p-chlorobenzoyl-2′,3′-dideoxy-β-d-ribofuranoside (13, 0.75 g, 2.4 mmol) and TMSOTf (0.72 mL, 4.0 mmol) were added, the mixture was stirred for 48 h at r.t., and 10% NaHCO3 (15 mL) was added. After 20 min stirring, CH2Cl2 (20 mL) was added to the resulting suspension; the mixture was filtered through Hyflo Super Cel; the organic layer was separated, washed with H2O (10 mL), and dried with Na2SO4. Nucleoside 16 (0.11 g) and recovered sugar 13 (0.27 g) were isolated by silica gel chromatography (elution with EtOAc-PE = 1:2). The yield was 16% based on recovered starting material. A white solid was afforded after recrystallizaion in EtOAc; mp 178-180 ˚C. IR (KBr): ν = 3440, 3332, 2109, 1389, 1344, 1290, 1245 cm. ¹H NMR (500 MHz, DMSO-d 6): δ = 9.57 (1 , d, J NH-H1  = 8.51 Hz, NH), 8.61 (2 H, d, J NH2 = 15.10 Hz, NH2), 8.00 (1 H, s, C2-H), 7.98 (2 H, m, ArH), 7.61 (2 H, m, ArH), 6.32 (1 H, m, C1′-H), 4.56 (1 H, m, C4′-H), 4.36 (3 H, m, C5′-H, C3′-H), 2.62 (1 H, dd, J = 5.69, 12.80 Hz, C2′-H), 2.20 (1 H, m, C2′-H) ppm. ¹³C NMR (500 MHz, DMSO-d 6): δ = 164.66 (C=O), 159.29 (C-2), 158.58 (C-6), 156.02 (C-4), 138.46 (CCl), 131.11 (2 C, Ar), 128.98 (2 C, Ar), 128.17 (CC=O), 112.03 (C-5), 81.11 (C-1′), 80.62 (C-4′), 64.83 (C-5′), 61.68 (C-3′), 36.77 (C-2′) ppm.

19

6-Amino-5-nitro-4-(3′-azido-2′,3′-dideoxy-β- d -ribofuranosylamino) Pyrimidine 6
To a solution of nucleoside 16 (90 mg, 0.2 mmol) in MeOH (10 mL) cooled to 0 ˚C was added 0.1 M NaOMe in MeOH (0.64 mL), and the mixture was stirred at r.t. for 18 h in the argon atmosphere. The reaction mixture was neutralized with Dowex 50 (H+), and the resin was rapidly filtered. After evaporation under vacuum to dry, a light yellow solid product 6 was isolated from the residue by silica gel chromatography, elution with an EtOAc-PE (3:2). The yield was 40 mg (65%). ¹H NMR (500 MHz, DMSO-d 6): δ = 9.39 (1 H, d, J NH-H1  = 8.2 Hz, NH), 8.56 (2 H, br s, NH2), 8.00 (1 H, s, C2-H), 6.22 (1 H, td, J = 6.0 Hz, J NH-H1  = 8.2 Hz, C1′-H), 5.23 (1 H, t, J = 5.0 Hz, OH), 4.33 (1 H, td, J = 4.2 Hz, J H2 α -H3  = 7.0 Hz, C3′-H), 3.88 (1 H, q, J = 3.58, 3.58, 3.60 Hz, C4′-H), 3.51 (2 H, t, J = 4.2 Hz, C5′-H), 2.39 (1 H, ddd, J H2 α -H1  = 6.0 Hz, J H2 α -H3  = 7.0 Hz, J H2 β -H2 α  = 13.0 Hz, C2′-Hα), 2.27 (1 H, ddd, J H2 β -H3  = 4.2 Hz, J H2 β -H1  = 6.0 Hz, J H2 β -H2 α  = 13.0 Hz, C2′-Hβ) ppm. ¹³C NMR (500 MHz, DMSO-d 6): δ = 159.98 (C-2), 159.29 (C-6), 156.49 (C-4), 109.99 (C-5), 84.62 (C-1′), 82.21 (C-4′), 62.14 (C-5′), 62.08 (C-3′), 38.40 (C-2′) ppm.