Synthesis and antimicrobial evaluation of 6-azauracil non-nucleosides
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CH2), 7.29–7.36 (m, 5H, Harom), 9.81 (s, 1H, NH) ppm; 13C
NMR (CDCl3, 125 MHz): ꢂ ¼ 10.32 (CH3), 23.22 (CH2),
72.02 (CH2), 79.03 (CH2), 127.69, 127.89, 128.37, 137.38
(Carom), 148.04 (C-5), 149.07 (C-2), 156.21 (C-4) ppm; MS
(EI): m=z (%) ¼ 261 (Mþ, 11), 244 (3), 232 (6), 181 (4), 155
(47), 147 (16), 107 (31), 91 (100).
rated under reduced pressure. The residue was chromato-
graphed on silica gel column with CHCl3 to afford the
desired non-nucleosides 8a–8g.
1-Allyloxymethyl-5-phenyl-6-azauracil (8a, C13H13N3O3)
1
White solid; yield 0.174 g (67%); mp 101–102ꢁC; H NMR
(CDCl3, 500 MHz): ꢂ ¼ 4.26 (d, J ¼ 5.5Hz, 2H, CH2), 5.24 (d,
J ¼ 10.5 Hz, 1H, CH(Z)¼), 5.35 (d, J ¼ 17.0Hz, 1H, CH(E)¼),
5.48 (s, 2H, CH2), 5.90–5.98 (m, 1H, ¼CH–), 7.28–7.47,
8.03–8.05 (2ꢀm, 5H, Harom), 10.14 (s, 1H, NH) ppm; 13C
NMR (CDCl3, 125 MHz): ꢂ ¼ 71.04 (CH2), 79.26 (CH2),
117.98 (CH2¼), 128.38, 128.40, 130.47, 131.08 (Carom),
133.38 (¼CH–), 142.44 (C-5), 148.89 (C-2), 155.99 (C-4)
ppm; MS (EI): m=z (%) ¼ 259 (Mþ, 14), 228 (5), 202 (28),
190 (21), 175 (4), 160 (6), 131 (43), 115 (17), 104 (100).
1-Benzyloxymethyl-5-phenyl-6-azauracil (5f, C17H15N3O3)
1
White solid; yield 0.195 g (63%); mp 124–125ꢁC; H NMR
(CDCl3, 500 MHz): ꢂ ¼ 4.80 (s, 2H, CH2), 5.53 (s, 2H, CH2),
7.28–8.05 (m, 10H, Harom), 9.92 (s, 1H, NH) ppm; 13C NMR
(CDCl3, 125 MHz): ꢂ ¼ 72.20 (CH2), 79.51 (CH2), 127.02,
127.76, 127.96, 128.36, 128.41, 130.45, 131.12, 137.27
(Carom), 142.40 (C-5), 148.71 (C-2), 155.74 (C-4) ppm; MS
(EI): m=z (%) ¼ 309 (Mþ, 11), 203 (78), 176 (16), 160 (6),
147 (53), 131 (24), 118 (12), 104 (72), 91 (100).
5-Methyl-1-(2-methylallyloxymethyl)-6-azauracil
(8b, C9H13N3O3)
5-Benzyl-1-benzyloxymethyl-6-azauracil (5g, C18H17N3O3)
White solid; yield 0.165 g (51%); mp 73–74ꢁC; 1H NMR
(CDCl3, 500 MHz): ꢂ ¼ 3.94 (s, 2H, CH2), 4.71 (s, 2H, CH2),
5.40 (s, 2H, CH2), 7.30–7.38 (m, 10H, Harom), 9.69 (s, 1H,
NH) ppm; 13C NMR (CDCl3, 125 MHz): ꢂ ¼ 35.89 (CH2),
71.99 (CH2), 78.97 (CH2), 127.07, 127.74, 127.90, 128.37,
128.63, 129.35, 135.73, 137.23 (Carom), 146.01 (C-5),
146.89 (C-2), 155.94 (C-4) ppm; MS (EI): m=z (%) ¼ 323
(Mþ, 13), 232 (10), 217 (65), 204 (7), 161 (43), 131 (19),
118 (7), 91 (100).
White solid; yield 0.118 g (56%); mp 71–72ꢁC; 1H NMR
(CDCl3, 500 MHz): ꢂ ¼ 1.74 (s, 3H, CH3), 2.26 (s, 3H, CH3),
4.08 (s, 2H, CH2), 4.91, 5.00 (2ꢀs, 2H, CH2¼), 5.32 (s, 2H,
CH2), 10.23 (s, 1H, NH) ppm; 13C NMR (CDCl3, 125 MHz):
ꢂ ¼ 16.17 (CH3), 19.32 (CH3), 73.82 (CH2), 78.70 (CH2),
112.80 (CH2¼), 141.20 (C-5), 144.43 (¼C(Me)–), 149.31
(C-2), 156.76 (C-4) ppm; MS (EI): m=z (%) ¼ 211 (Mþ,
15), 196 (8), 141 (9), 127 (5), 112 (6), 85 (11), 70 (29), 42
(100).
5-Ethyl-1-(2-methylallyloxymethyl)-6-azauracil
Bis(2-cyclohexylethoxy)methane (7f, C17H32O2)
(8c, C10H15N3O3)
Colorless viscous oil; yield 0.122g (54%); H NMR (CDCl3,
2-Cyclohexylethanol (6f, 12.8 g, 0.1 mol), 8.79 g (dibro-
momethane 0.0505 mol), and 1.74 g (tetrabutylammonium
bromide 0.00535 mol) were added to 5.66 g (potassium hy-
droxide 0.101 mol) in 30 cm3 anhydrous benzene, and the
suspension was heated under reflux for 5 h. After cooling,
(50 cm3) H2O were added and the resulting solution was
extracted with 3ꢀ50 cm3 ether. The ether phase was dried
with anhydrous MgSO4 and evaporated under reduced pres-
sure to afford 7f as a colorless oil in 55% (7.4g) yield. As
determined from NMR, the desired 7f was contaminated with
the starting material 6f in a 5:2 ratio. The product was used
1
500 MHz): ꢂ ¼ 1.20 (t, J ¼ 7.5 Hz, 3H, CH3), 1.74 (s, 3H,
CH3), 2.65 (q, J ¼ 7.5 Hz, 2H, CH2), 4.09 (s, 2H, CH2),
4.92, 5.01 (2ꢀs, 2H, CH2¼), 5.34 (s, 2H, CH2), 10.17 (s,
1H, NH) ppm; 13C NMR (CDCl3, 125 MHz): ꢂ ¼ 10.31
(CH3), 19.32 (CH3), 23.20 (CH2), 73.86 (CH2), 78.74 (CH2),
112.79 (CH2¼), 141.27 (C-5), 148.06 (¼C(Me)–), 149.22 (C-
2), 156.46 (C-4) ppm; MS (EI): m=z (%) ¼ 225 (Mþ, 24), 196
(5), 155 (13), 154 (61), 141 (16), 112 (4), 85 (7), 70 (19), 56
(100).
1
for further synthesis without purification. H NMR (CDCl3,
500 MHz): ꢂ ¼ 0.90–1.69 (m, 26H, Hhexyl, 2ꢀCH2), 3.59 (t,
J ¼ 6.5 Hz, 4H, 2ꢀCH2), 4.66 (s, 2H, CH2) ppm; 13C NMR
(CDCl3, 125MHz): ꢂ ¼ 26.17, 26.59, 33.38, 34.58 (Chexyl),
37.17 (CH2), 65.70 (CH2), 95.23 (CH2) ppm.
1-(2-Methylallyloxymethyl)-5-phenyl-6-azauracil
(8d, C14H15N3O3)
White solid; yield 0.19 g (70%); mp 125–126ꢁC; H NMR
1
(CDCl3, 500 MHz): ꢂ ¼ 1.77 (s, 3H, CH3), 4.17 (s, 2H, CH2),
4.96, 5.05 (2ꢀs, 2H, CH2¼), 5.47 (s, 2H, CH2), 7.45–7.50,
8.04–8.06 (2ꢀm, 5H, Harom), 10.13 (s, 1H, NH) ppm; 13C
NMR (CDCl3, 125 MHz): ꢂ ¼ 19.38 (CH3), 74.03 (CH2),
79.25 (CH2), 113.00 (CH2¼), 128.38, 128.39, 130.44, 131.12
(Carom), 141.21 (C-5), 142.37 (¼C(Me)–), 148.85 (C-2),
155.98 (C-4) ppm; MS (EI): m=z (%) ¼ 273 (Mþ, 14), 245
(4), 202 (73), 190 (16), 171 (3), 131 (58), 111 (13), 104 (75),
53 (100).
General procedure for preparation of 1-allyloxymethyl-6-
azauracils 8a–8g
Compound 4a–4d (1mmol) was stirred in 15 cm3 anhydrous
CH3CN under nitrogen and 0.87 cm3 (BSA 3.5 mmol) were
added. After a clear solution was obtained (10 min), the reac-
tion mixture was cooled to ꢃ50ꢁC and 0.18cm3 (TMS triflate
1 mmol) were added followed by dropwise addition of 2 mmol
7a–7c appropriate acetal. The mixture was stirred at room
temperature for 4 h. The reaction was quenched with 5 cm3
sat aq NaHCO3 solution and evaporated under reduced pres-
sure. The residue was extracted with 3ꢀ50cm3 ether, the
combined organic fractions were dried (MgSO4), and evapo-
5-Benzyl-1-(2-methylallyloxymethyl)-6-azauracil
(8e, C15H17N3O3)
White solid; yield 0.158 g (55%); mp 76–77ꢁC; 1H NMR
(CDCl3, 500 MHz): ꢂ ¼ 1.73 (s, 3H, CH3), 3.95 (s, 2H,