Abstract
Concise synthetic methods for synthesizing 3-carboranyl thymidine analogues (3CTAs) modified with cyclic and acyclic alcohols have been developed. The synthesis of these potential boron neutron capture therapy (BNCT) agents and their preliminary biological evaluation is described.
This work was supported by the U.S. Department of Energy grant DE-FG02–90ER60972 and grants from the Swedish Research Council. The authors thank Dianne Adams for technical assistance. Presented at the XVI International Roundtable Conference, September 12–16, 2004.
Notes
1 6: 1H NMR (CD3OD) δ: 1.84 (d, 3H, CH3), 2.09–2.12 (m, 2H, H-2′), 3.18 (s, 1H, H-Ccarborane), 3.34–3.36 (m, 1H, CH-OH), 3.51–3.52 (m, 1H, CH-OH), 3.68–3.76 (m, 3H, H-5′ and H-4′), 3.81–3.85 (m, 2H, CH2-N), 4.08–4.17 (m, 1H, CH-OH), 4.30–4.35 (m, 1H, H-3′), 6.22 (t, 1H, H-1′), 7.79 (d, 1H, H-6); 13C NMR (CD3OD) δ: 165.86 (C-4), 152.79 (C-2), 136.55 (C-6), 110.72 (C-5), 88.91 (C-4′), 87.27 (C-1′), 73.11 (C-O), 72.92 (C-O), 72.17 (C-O), 72.04 (C-3′), 62.73 (C-5′), 44.87 (CH2-N), 41.46 (C-2′), 13.21 (CH3); MS (HR-ESI) C16H32B10N2O8Na (M+Na)+ calcd: 513.2987, found 513.3016.
2 14: 1H NMR (CD3OD) δ: 1.44–1.47 (m, 2H, CH2), 1.66–1.70 (m, 2H, CH 2-Ccarborane), 1.88 (d, 3H, CH3), 2.14–2.28 (m, 1H, H-2′), 3.40–3.58 (m, 5H, CH-OH and CH2 -OH), 3.68–3.92 (m, 5H, H-4′, H-5′, and CH2-N), 4.36–4.38 (m, 1H, H-3′), 6.27 (t, 1H, H-1′), 7.81 (d, 1H, H-6); 13C NMR (CD3OD) δ: 165.28 (C-4), 152.20 (C-2), 136.58 (C-6), 110.65 (C-5), 89.11 (C-1′), 87.10 (C-4′), 75.17 (C-O), 72.66 (C-O), 72.41 (C-3′), 72.05 (C-O), 63.74 (CH2-O), 62.73 (C-5′), 41.56 (CH2-N), 41.29 (C-2′), 36.29 (C-Ccarborane), 28.70 (CH2), 13.14 (CH3); MS (HR-ESI) C19H38B10N2O9Na (M+Na)+ calcd: 569.3489, found: 569.3480.
3 17: 1H NMR (CDCl3) δ: 1.47–1.50 (m, 4H, CH2), 1.56–1.58 (m, 2H, CH2), 1.89 (d, 3H, CH3), 1.93–1.98 (m, 2H, CH 2-Ccarborane), 2.29–2.44 (m, 4H, CH 2-Ccarborane and H-2′), 3.78–3.98 (m, 9H, CH-OH, H-5′, H-4′, and CH2-N), 4.58 (m, 1H, H-3′), 4.80 (d, 1H, CH(OH)-O), 6.12 (t, 1H, H-1′), 7.28 (d, 1H, H-6); 13C NMR (CDCl3) δ: 162.35 (C-4), 150.78 (C-2), 135.21 (C-6), 110.78 (C-5), 109.71 (C(OH)-O), 90.17(C-O), 88.06 (C-4′), 87.18 (C-1′), 78.97 (C-O), 71.99 (C-3′), 70.72 (C-O), 62.83 (C-5′), 55.30 (C-O), 41.55 (CH2-N), 40.88 (C-2′), 40.44 (C-Ccarborane), 37.98 (C-Ccarborane), 29.55 (CH2), 27.53 (CH2), 26.78 (CH2), 13.71 (CH3); MS (HR-ESI) C23H44B10N2O10Na (M+Na)+ calcd: 639.3909, found: 639.3904.