Please cite this article in press as: Banuelos-Sanchez et al., Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian
TLC diethyl ether/hexane (5:1); preparative TLC diethyl ether/hexane (1:1). White solid (24 mg, 16%). mp: 147-149ꢁC; ½aꢂD28 -20.9 (C
0.7, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.84 (s, 1H), 7.67 (s, 1H), 6.02 (dd, J = 6.1, J = 3.0 Hz, 1H), 4.50 – 4.41 (m, 1H), 3.71 (dd, J =
11.0, J = 4.1 Hz, 1H), 3.64 (dd, J = 11.0, J = 4.0 Hz, 1H), 2.61 – 2.49 (m, 1H), 2.06 – 1.96 (m, 3H), 0.91 (s, 9H), 0.08 (s, 6H); 13C NMR
(125 MHz, CDCl3) d 159.1, 149.5, 139.1, 96.3, 88.7, 82.4, 65.3, 33.2, 26.0, 25.6, 18.4, -5.21, -5.26; HRMS (m/z): [M - H]- calcd. for
C15H24N2O4SiBr, 403.0689; found 403.0679.
1-[5’-O-(tert-butyldimethylsilyl)-2’,3’-dideoxy-b-D-ribofuranosyl]-5-bromouracil (GBS-124-P2).
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TLC diethyl ether/hexane (5:1); preparative TLC diethyl ether/hexane (1:1). White solid (32 mg, 21%). mp: 153-155ꢁC; ½aꢂD -3.5
1
(C 1.8, CHCl3); H NMR (500 MHz, CDCl3) d 9.44 (s, 1H), 8.17 (s, 1H), 6.02 (dd, J = 6.4, J = 4.3 Hz, 1H), 4.21 – 4.15 (m, 1H), 4.03
(dd, J = 11.6, J = 2.3 Hz, 1H), 3.70 (dd, J = 11.6, J = 2.7 Hz, 1H), 2.44 – 2.36 (m, 1H), 2.08 – 1.91 (m, 3H), 0.93 (s, 9H), 0.13
(s, 6H); 13C NMR (125 MHz, CDCl3) d 159.4, 149.9, 139.8, 96.4, 87.0, 81.9, 64.4, 33.3, 26.2, 25.0, 18.7, -5.07, -5.09; HRMS (m/z):
[M + Na]+ calcd. for C15H25N2O4NaSiBr, 427.0665; found 427.0671.
2’,3’-dideoxy-a-D-5-bromouridine (GBS-128).
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Obtained as a colorless syrup (13 mg, quant.) from GBS-124-P1 (18 mg, 0.044 mmol). TLC dichloromethane/methanol (9:1). ½aꢂD
-15.8 (C 1, MeOH); 1H NMR (500 MHz, CDCl3) d 9.07 (s, 1H), 7.67 (s, 1H), 6.07 (dd, J = 6.1, J = 4.4 Hz, 1H), 4.54 – 4.48 (m, 1H), 3.79 (dd,
J = 12.0, J = 3.2 Hz, 1H), 3.60 (dd, J = 12.0, J = 5.6 Hz, 1H), 2.62 – 2.51 (m, 1H), 2.14 – 2.01 (m, 2H), 2.00 – 1.90 (m, 1H), 1.70 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 159.2, 149.6, 139.1, 96.7, 88.2, 82.3, 64.7, 33.1, 25.7; HRMS (m/z): [M + H]+ calcd. for C9H11N2O4Br,
312.9800; found 312.9785.
2’,3’-dideoxy-b-D-5-bromouridine (GBS-197). 2’,3’-dideoxy-b-D-5-bromouridine (GBS-197) has been previously synthesized
Obtained as a colorless syrup (12 mg, quant.) from GBS-124-P2 (17 mg, 0.044 mmol). TLC dichloromethane/methanol (9:1). mp:
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182-184ꢁC (Furukawa et al., 1970); ½aꢂD +25.6 (C 0.7, MeOH); 1H NMR (600 MHz, CD3OD) d 8.64 (s, 1H), 6.00 (dd, J = 6.7, J = 2.9 Hz,
1H), 4.19 – 4.14 (m, 1H), 3.93 (dd, J = 12.3, J = 2.8 Hz, 1H), 3.68 (dd, J = 12.2, J = 3.2 Hz, 1H), 2.44 – 2.36 (m, 1H), 2.15 – 2.09 (m, 1H),
2.02 – 1.92 (m, 2H); 13C NMR (150 MHz, CD3OD) d 161.8, 151.6, 142.4, 96.2, 88.3, 84.0, 63.0, 34.0, 25.2; HRMS (m/z): [M - H]- calcd.
for C9H10N2O4Br, 288.9824; found 288.9823.
1-[5’-O-(tert-butyldimethylsilyl)-2’,3’-dideoxy-a-D-ribofuranosyl]-5-fluorouracil (GBS-135-P1).
TLC diethyl ether/hexane (5:1); preparative TLC diethyl ether/hexane (1:1). White solid (19 mg, 15%). mp: 106-108ꢁC (Lin et al.,
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1
1994); ½aꢂD -43.3 (C 1, CHCl3); H NMR (500 MHz, CDCl3) d 9.53 (s, 1H), 7.42 (d, J = 6.1 Hz, 1H), 6.04 – 6.01 (m, 1H), 4.48 – 4.36
(m, 1H), 3.69 (dd, J = 11.0, J = 4.2 Hz, 1H), 3.63 (dd, J = 11.0, J = 4.1 Hz, 1H), 2.59 – 2.48 (m, 1H), 2.04 – 1.93 (m, 3H), 0.90
(s, 9H), 0.07 (s, 6H) (Lin et al., 1994); 13C NMR (125 MHz, CDCl3) d 157.2 (d, J = 26.6 Hz), 148.9, 140.5 (d, J = 236.9 Hz), 123.8
(d, J = 33.7 Hz), 88.2, 82.3, 65.3, 32.9, 26.0, 25.7, 18.4, -5.23, -5.29; HRMS (m/z)=: [M + Na]+ calcd. for C15H25N2O4NaFSi,
367.1465; found 367.1450.
e7 Cell Chemical Biology 26, 1–15.e1–e14, August 15, 2019