Utility of 1-(5′-Acetoxy-4′-Benzoyltetrahydrofuran-2′-yl)-3- Benzyloxymethylthymine for the Synthesis of 5′-Modified Furanoid Nucleoside Analogs

Synlett

Volumn 1996, Issue 4, 1996, Pages 346-348

  Teng, Kelly ^a   Bharadwaj, Ramesh ^a   Cook, P Dan ^a  

^a ISIS PHARMACEUTICALS   (United States)

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Indexed keywords

EID: 0011610373     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1996-5428     Document Type: Article

References (10)

1. A portion of the results described herein was presented at the 15th International Congress of Heterocyclic Chemistry, Taipei, Taiwan, R.O.C., August, 1995.
2. Teng, K.; Cook, P. D. J. Org. Chem. 1994, 59, 278.
3. In consistence with the literature report (Kim, C. U.; Luh, B. Y.; Martin, J. C. J. Org. Chem. 1991, 56, 2642), the numbering system of the tetrahydrofuranyl ring shown in Scheme 1 is used through out this text.
4. Phillion, D. P.; Andrew, S. S. Tetrahedron Lett. 1986, 27, 1477.
5. Selected physical and spectroscopic data for compound 7. For 7a (white solid): mp 84-6 0C. Rf(hexanes/AcOEt 3:1) 0.32. 1H NMR (CDCl3) d 1.99 (s, 3H), 2.35 (ddd, IH, J = 14.8, 8.4, 4.9 Hz, 3'-H3), 2.63 (dd, 1H, J = 14.8, 6.4 Hz, 3'-Hb), 3.57 (t, 2H, J = 5.5 Hz, BrCW2CH2O), 3.99 (dt, 1H, J = 16.4, 5.5 Hz, BrCH2CWHO), 4.10 (dt, IH, J = 16.4, 5.5 Hz, BrCH2CHWO), 4.72 (s, 2H), 5.25 (s, IH, 5'-H), 5.49 (d, IH, J = 4.9 Hz, 4'-H), 5.52 (s, 2H), 6.82 (dd, IH, J = 8.4, 6.4 Hz, 2'-H), 7.27-7.66 (m, 9H), 8.02-8.06 (m, 2H). 13C NMR (CDCl3) d 13.42, 30.26 (Br-C-C-O), 34.73 (3'-C), 68.87 (Br-C-C-O), 70.76, 72.28, 77.48 (4'-C), 86.46 (2'-C), 106.40 (5'-C), 111.63 (5-C), 127.68, 128.34 (6-C), 128.66, 128.96, 129.86, 133.83, 134.94, 138.05, 151.42 (2-C), 163.24 (4-C), 165.65 (benzoyl C=O). Anal Calcd for C26H2TN2O7Br: C, 55.82; H, 4.83; N, 5.01; Br, 14.30. Found: C, 55.78; H, 4.85; N, 4.76; Br, 14.43. For 7e (hydroscopic white foam): Rf(hexanes/AcOEt 1:1) 0.22. 1H NMR (CDCl3) d 1.89 (s, 3H), 2.30 (ddd, IH, J = 13.2, 8.3, 4.6 Hz, 3'-Ha), 2.57 (dd, IH, J = 13.2, 6.5 Hz, 3'-Hb), 3.63-4.01 (m, 8 H), 4.71 (s, 2H), 5.19 (s, IH, 5'-H), 5.36 (d, IH, J = 4.6 Hz, 4'-H), 5.48 (s, 2H), 6.72 (dd, IH, J = 8.3, 6.5 Hz, 2'-H), 7.28-8.01 (m, 13H), 8.02 (dd, 2H, J = 7.8, 1.5 Hz). I3C NMR (CDCl3) d 13.01, 34.87 (3'-C), 36.91, 67.64, 67.78, 69.34, 70.62, 72.05, 73.60 (4'-C), 86.30 (2'-C), 106.16 (5'-C), 111.13 (5-C), 123.08, 127.51, 127.76, 128.21, 128.50, 129.20, 129.70, 131.92, 133.54 (6-C), 134.00, 134.41, 138.08, 151.26 (2-C), 163.07 (4-C), 165.29 (phthalimido C=O), 168.02 (benzoxy C=O). Anal Calcd for C36H35N3O]0-O.? CHCl3: C, 58.51; H, 4.74; N, 5.58. Found: C, 58.78; H, 4.74; N, 5.60. For 7g (colorless syrup): Rf(CH2Cl2/AcOEt 3:1) 0.24. 1H NMR (CDCl3) d 1.33 (t, 3H, J = 7.0 Hz), 1.39 (t, 3H, J = 7.0 Hz), 2.03 (s, 3H), 2.36 (ddd, IH, J = 14.8, 8.4, 4.9 Hz, 3'-Ha), 2.63 (dd, IH, J = 14.8, 6.3 Hz, 3'-Hb), 3.84 (dd, H, 2Jgem = 13.3 Hz, 2JP.H = 10.0 Hz, P-CWH-O), 4.02 (dd, H, 2Jgem = 13.3 Hz, 2JP.H = 10.0 Hz, P-CHH-O), 4.18 (qd, 2H, 3JH-H = 7.0 Hz, 3JP.H = 0.8 Hz, CH3CW2-O-P), 4.26 (qd, 2H, 3JH-H = 7.0 Hz, 3JP.H = 0.8 Hz, CH3CW2-O-P), 4.71 (s, 2H), 5.23 (s, IH, 5'-H), 5.52 (s, 2H), 5.53 (d, IH, J = 4.9 Hz, 4'-H), 6.86 (dd, IH, J = 8.4, 6.3 Hz, 2'-H), 7.27-7.66 (m, 9H), 8.02-8.06 (m, 2H). 13C NMR (CDCl3) d 13.15, 16.72 (d, 3JP. C = 5.5 Hz, O-C-Q, 34.67 (3'-C), 61.51 (d, 'JP.C = 135.5 Hz, P-C-O), 63.28 (d, 2Jp-C = 28.9 Hz, O-C-C), 70.93, 72.40, 77.41 (4'-C), 86.71 (2'-C), 107.02 (d, 3JP.C = 12.8 Hz, 5'-C), 112.29 (5-C), 127.84, 128.42, 128.85, 129.09, 129.97, 133.91, 138.21, 151.59 (2-C), 163.34 (4-C), 165.63 (benzoyl C=O). 31P NMR (CDCl3) d 20.45. Anal Calcd for C29H35N2O10POJ CHCl3: C, 55.06; H, 5.53; N, 4.39; P, 4.86. Found: C, 54.95; H, 5.58; N, 4.28; P, 4.65. For 7k (white solid): mp 98-100 0C. RKhexanes/AcOEt 1:1) 0.60. 1H NMR (CDCl3) d 1.50-1.95 (m, 12H), 1.98 (s, 3H), 2.05-2.25 (m, 3H), 2.30 (ddd, IH, J = 14.5, 7.9, 4.5 Hz, 3'-Ha), 2.63 (dd, IH, J = 14.5, 6.5 Hz, 3'-Hb), 4.73 (s, 2H), 5.27 (d, IH, J = 4.5 Hz, 4'-H), 5.52 (s, 2H), 5.61 (s, IH, 5'-H), 6.71 (dd, IH, J = 7.9, 6.5 Hz, 2'-H), 7.20-7.65 (m, 8H), 7.78 (s, IH, 6-H), 8.08 (d, 2H, J = 7.6 Hz). 13C NMR (CDCl3) d 13.37, 30.58, 35.42 (3'-C), 42.66, 45.33, 70.65, 72.20, 75.96, 79.14 (4'-C), 86.31 (2'-C), 99.48 (5'-C), 110.54 (5-C), 127.61, 128.28, 129.25, 129.83, 133.61, 135.36 (6-C), 138.14, 151.37 (2-C), 163.36 (4-C), 165.77 (benzoyl C=O). Anal Calcd for C34H38N2O7-0.4 CHCl3: C, 65.13; H, 6.06; N, 4.42. Found: C, 64.97; H, 6.34; N, 4.30.
6. Kristinsson, H.; Nebel, K.; O'sullivan, A. C.; Struber, F.; Winkler, T.; Yamaguchi, Y. Tetrahedron, 1994, 50, 6825.
7. 3: C, 60.00; H, 5.19; N, 5.19; S, 5.93. Found: C, 59.64; H, 5.13; N, 4.96; S; 6.05.
8. 3: C, 55.28; H, 4.42; N, 13.19. Found: C, 55.38; H, 4.39; N, 13.00.
9. (a) For general alkylation, acylation, sulfonylation of amine, see Larock, R. C. "Comprehensive Organic Transformations" VCH Publishers, Inc.: New York, 1989; p 385.
10. (b) For nucleo-base moieties construction, see Marquez, V. E.; Lim, M.-I. Med. Res. Rev. 1986, 6, 1.