PAPER
Synthesis of AZT/d4T Boranophosphates as Anti-HIV Prodrug Candidates
515
OCH2CH2(CH2)13CH3], 0.87 [t, 3 H, OCH2CH2(CH2)13CH3, J = 6.5
3 ), 37.79, 37.52* (T-C-2 ), 36.05, 35.94* (AZT-C-2 ), 11.35, 11.15
Hz], 0.6–0.2 (t, 3 H, BH3).
(5-CH3).
13C NMR (CD3OD, 125 MHz): = 166.60 (C-4), 152.80 (C-2),
138.68, 138.65* (C-6), 135.83, 135.73* (C-2 ), 127.16, 127.09* (C-
3 ), 111.95 (C-5), 90.87, 90.84* (C-1 ), 87.45, 87.39* (d, C-4 ,
3J = 6.3 Hz), 64.67 (C-5 ), 64.13, 63.90* [d, OCH2(CH2)14CH3,
2J = 4.4 Hz), 33.06–23.72 [m, OCH2(CH2)14CH3], 14.46
[OCH2(CH2)14CH3], 12.72, 12.65 (5-Me).
31P NMR (D2O, 81 MHz): = 92.1–95.5 (br).
ESI-MS: m/z = 568.
HRMS (ESI): m/z calcd for C20H28BN7O10P: 568.1728; found:
568.1724.
O-Thymidyl-O -(2 , 3 -didehydro-2 , 3 -dideoxythymidin-5 -yl)
Boranophosphate (9 )
31P NMR (CD3OD, 81 MHz): = 94.2–99.3 (br).
ESI-MS: m/z = 525.
Yield: 57.4%; white solid.
HRMS (ESI): m/z calcd for C26H47BN2OP: 525.3265; found:
525.3261.
1H NMR (D2O, 500 MHz): = 7.69, 7.64* (s, 1 H, H-6), 7.61, 7.55*
(s, 1 H, H-6), 6.26–6.23 (m, 1 H, d4T-H-1 ), 6.50–6.49 (t, 1 H, d4T-
H-2 ), 6.24, 6.21 (d, 1 H, T-H-1 , J = 6.5 Hz), 5.99, 5.98* (s, 1 H,
d4T-H-3 ), 5.11 (s, 1 H, T-H-3 ), 4.87 (s, 1 H, d4T-H-4 ), 4.17–3.72
(m, 5 H, d4T-H-5 , T-H-5 , T-H-4 ), 2.48–2.22 (m, 2 H, T-H-2 ),
1.93, 1.91 (d, 6 H, 2 × C5-CH3).
O-Isopropyl-O -(2 ,3 -didehydro-2 ,3 -dideoxythymidin-5 -yl)
Boranophosphate (4 d)
Yield: 59.6% colorless oil.
1H NMR (CD3OD, 500 MHz): = 7.66 (s, 1 H, H-6,), 6.94, 6.93*
(d, 1 H, H-1 , J = 1.5 Hz), 6.41 (d, 1 H, H-2 , J = 1.8 Hz), 5.88,
5.87* (d, 1 H, H-3 , J = 2.0 Hz), 4.96 (s, 1 H, H-4 ), 4.83–4.42 (m,
1 H, CH), 3.99–3.93 (m, 2 H, H-5 ), 1.94, 1.93* (s, 3 H, CH3-5),
1.22–1.19 [m, 6 H, CH(CH3)2], 0.6–0.2 (q, 3 H, BH3).
13C NMR (D2O, 125 MHz): = 165.87 (2 × C-4), 151.65, 150.94
(2 × C-2), 137.78, 137.64*, 136.84, 136.75* (2 × C-6), 134.02,
133.74* (d4T-C-2 ), 124.96, 124.80* (d4T-C-3 ), 111.00, 110.92*,
110.67, 110.61* (2 × C-5), 89.66 (d4T-C-1 ), 85.55–84.70 (T-C-4 ,
d4T-C-4 , T-C-1 ), 72.35, 72.90* (d4T-C-4 ), 60.46 (T-C-5 ), 37.87,
37.43* (T-C-2 ), 11.42, 11.15 (5-CH3).
13C NMR (CD3OD, 125 MHz):
166.60 (C4), 152.81 (C2),
139.16, 138.66* (C6), 135.93, 135.81* (C2 ), 127.06, 126.96*
(C3 ), 111.89 (C5), 90.92, 90.88* (C1 ), 87.48, 87.41* (d, C4 ,
31P NMR (D2O, 81MHz): = 91.3–96.6 (br).
ESI-MS (ESI): m/z = 525.
2
3J = 8.4 Hz), 68.13, 67.67 (CH, J = 4.0 Hz), 64.69, 63.92 (C5 ,
2J = 5.0 Hz), 24.68, 24.52* (CH3), 12.70, 12.63* (5-Me).
31P NMR (CD3OD, 81 MHz): = 95.1–102.3 (br).
ESI-MS: m/z = 343.
HRMS: m/z calcd for C20H27BN4O10P: 525.1558; found: 525.1561.
Acknowledgment
HRMS (ESI): m/z calcd for C13H21BN2O6P: 343.1230; found:
343.1235.
The authors would like to thank the financial supports from the Ex-
cellent Dissertation Foundation by the Chinese Ministry of Educa-
tion (No. 200222).
O-Cyclohexyl-O -(2 ,3 -didehydro-2 , 3 -dideoxythymidin-5 -yl)
Boranophosphate (4 e)
Yield: 64.7%; colorless oil.
References
1H NMR (CD3OD, 500 MHz): = 7.68, 7.64* (d, 1 H, H-6, J = 1
Hz), 6.94, 6.93* (m, 1 H, H-1 ,), 6.41 (m, 1 H, H-2 ), 5.87 (d, 1 H,
H-3 , J = 2.5 Hz), 4.95 (s, 1 H, H-4 ), 4.17–4.04 (m, 2 H , H-5 ),
3.97–3.93 (m, 1 H, CH), 1.89–1.14 [m, 13 H, CH3-5, (CH2)5], 0.6–
0.2 (q, 3 H, BH3).
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13C NMR (CDCl3, 125 MHz): = 166.65 (C4), 152.86 (C2), 138.81,
138.73* (C6), 135.96, 135.85* (C2 ), 127.02, 126.95* (C3 ), 111.93
(C5), 90.92, 90.88* (C1 ), 87.50, 87.45* (C4 ), 73.50, 72.90* (CH,
2
2J = 4.1 Hz), 64.74, 63.72* (C 5 , J = 5.3 Hz), 35.30–20.90 (5 C,
CH2), 12.82, 12.67* (5-Me).
31P NMR (CD3OD, 81 MHz): = 94.2–98.7 (br).
ESI-MS: m/z = 383.
HRMS (ESI): m/z calcd for C16H25BN2O6P: 383.1543; found:
383.1549.
O-Thymidyl-O -(3 -azido-3 -deoxythymidin-5 -yl) Boranophos-
phate (9)
Yield: 55.9%; white solid.
1H NMR (D2O, 500 MHz): = 7.73, 7.69* (d, 2 H, 2 × H-6), 6.26–
6.23 (m, 2 H, 2 × H-1 ), 4.92 (s, 1 H, T-H-3 ), 4.49 (s, 1 H, AZT-H-
3 ), 4.16 (t, 4 H, 2 × AZT-H-5 , 2 × T-H-5 ), 3.88–3.81 (m, 2 H,
2 × H-4 ), 2.56–2.50 (m, 4 H, 2 × H-2 ), 1.95, 1.90 (d, 6 H, 2 × C5-
CH3).
13C NMR (D2O, 125 MHz): = 165.76, 165.68 (2 × C-4), 150.95
(2 × C-2), 136.82, 136.73 (2 × C-6), 110.96, 110.89 (2 × C-5),
85.42–84.23 (T-C-4 , 2 × C-1 ), 82.58 (AZT-C-4 ), 72.54 (T-C-3 ),
71.96, 71.93* (AZT-C-5 ), 61.99 (T-C-5 ), 59.77, 59.67* (AZT-C-
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Synthesis 2004, No. 4, 509–516 © Thieme Stuttgart · New York