Molecules 2019, 24, 737
7 of 9
4
.6. Synthesis of
4
0
0
0
N -benzoyl-5-cyano-7-(2 ,3 -di-O-acetyl-5 -deoxy-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine (16)
1
0% Pd/C (0.75 g, 0.70 mmol) and Et N (0.94 g, 9.22 mmol) were added to a solution of nucleoside
3
14 (2.50 g, 4.61 mmol) in the mixture of THF (65 mL) and MeOH (35 mL). After stirring at room
temperature for 2.25 h under H atmosphere (1 atm), the reaction mixture was filtered and concentrated
2
to dryness under reduced pressure. The residue was purified by silica gel column chromatography
(
CH Cl /EtOAc = 20:1, v:v) to afford 16 as light yellow solid (1.99 g, 93%). R = 0.3 (CH Cl /EtOAc,
2
2
f
2
2
◦
25
1
V/V = 20:1); m.p. 92–94 C;
H-2, H-6), 8.07 (d, J = 7.5 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.57 (t, J = 7.4 Hz, 2H), 6.40 (d, J = 5.4 Hz,
1
3
α
−
45.80 (c = 0.109, CH Cl ); H-NMR δ 11.50 (s, 1H, NH), 8.88 (s, 2H,
2 2
D
0 0 0 0
H, H-1 ), 5.90 (t, J = 5.6 Hz, 1H, H-2 ), 5.32 (t, J = 5.2 Hz, 1H, H-3 ), 4.32–4.26 (m, 1H, H-4 ), 2.13 (s,
0
13
H, OAc), 2.04 (s, 3H, OAc), 1.44 (d, J = 6.3 Hz, 3H, H-5 ); C-NMR δ 170.0 (C=O, OAc), 169.8 (C=O,
OAc), 167.5 (C=O, Bz), 153.2 (C-2), 152.5 (C-4), 152.1(C-7a), 137.1 (C-6), 133.3, 133.0, 128.9, 128.8, 114.9
0 0 0 0
CN), 111.4 (C-4a), 87.5 (C-5), 86.6 (C-1 ), 78.6 (C-4 ), 74.3 (C-3 ,), 73.2 (C-2 ), 20.8 (OAc), 20.6 (OAc),
1
(
0
8.8 (C-5 ); HRMS: calcd for C H N O [M + H] 464.1565; found 464.1579.
23 22 5 6
+
0
0
4
.7. Synthesis of 5 -deoxytoyocamycin (3) and 5 -deoxysangivamycin (4)
Ammonium hydroxide (45 mL) was added to a solution of 5 (1.80 g, 3.88 mmol) in 1,4-dioxane
◦
(
18 mL). The reaction mixture was sealed and heated to 45 C for 21 h. Then the reaction mixture
was evaporated to dryness under reduced pressure and the residue was purified by silica gel column
chromatography (CH Cl /MeOH 20:1, v:v) to afford compounds
3
(716 mg, 67%) and
4
(274 mg,
2
2
2
4%), respectively.
0
4
.8. 5 -Deoxytoyocamycin (3)
◦
◦
25
R = 0.2 (CH Cl /MeOH, V/V = 20:1); m.p. 190–192 C (literature: 187–188 C [16]);
α
87.88
f
2
2
D
1
(
1
4
1
c = 0.099, DMSO); H-NMR
δ
8.40 (s, 1H, H-8), 8.23 (s, 1H, H-2), 6.90 (s, 2H, NH ), 6.04 (d, J = 4.7 Hz,
H, H-1 ), 5.48 (d, J = 5.6 Hz, 1H, 2 -OH), 5.20 (d, J = 5.3 Hz, 1H, 3 -OH), 4.44–4.37 (m, 1H, H-2 ),
.00–3.91 (m, 1H, H-4 ), 3.91–3.84 (m, 1H, H-3 ), 1.30 (d, J = 6.3 Hz, 3H, CH ); C-NMR
54.1 (C-2), 150.8 (C-4), 132.9 (C-8), 115.8 (CN), 101.7 (C-5), 88.4 (C-1 ), 83.8 (C-7), 80.2 (C-4 ), 75.0 (C-3 ),
2
0
0
0
0
0
0
13
δ
0
157.5 (C-6),
3
0
0
0
+
7
4.2 (C-2 ), 19.4 (CH ); HRMS: calcd for C H N O [M + H] 276.1091; found 276.1099.
3
12 14
5
3
0
4
.9. 5 -Deoxysangivamycin (4)
◦
◦
25
D
R = 0.15 (CH Cl /MeOH, V/V = 10:1); m.p. 257–259 C (literature value 260–262 C [16]);
α
f
2
2
1
−
77.05 (c = 0.122, DMSO); H-NMR
δ
8.09 (s, 2H, H-2, H-8), 7.99 (s, 1H, NH), 7.39 (s, 1H, NH), 6.08 (d,
J = 4.2 Hz, 1H, H-1 ), 5.50 (d, J = 5.5 Hz, 1H, 2 -OH), 5.20 (d, J = 5.7 Hz, 1H, 3 -OH), 4.24–4.19 (m, 1H,
H-2 ), 4.00–3.91 (m, 1H, H-4 ), 3.91–3.84 (m, 1H, H-3 ), 1.32 (d, J = 6.3 Hz, 3H, CH ); C-NMR δ 166.8
0
0
0
0
0
0
13
3
0 0
(
7
C=O), 158.5 (C-6), 153.4 (C-2), 151.4 (C-4), 125.4 (C-8), 111.7 (C-7), 101.3 (C-5), 87.7 (C-1 ), 79.5 (C-4 ),
0 0
5.2 (C-3 ), 74.8 (C-2 ), 19.4 (CH ); HRMS: calcd for C H N O [M + H] 294.1197; found 294.1208.
3 12 16 5 4
+
Author Contributions: Q.X. and H.D. conceived and designed the experiments; X.D., J.T. and C.H. performed the
experiments; C.H. and J.B. analyzed the data; Q.X. and H.D. wrote the paper.
Funding: This research was funded by the National Natural Science Foundation of China (no. 21676131 and
no. 21462019), the Science Foundation of Jiangxi Province (20143ACB20012), and Jiangxi Science & Technology
Normal University (Doctor Startup Fund for Dr. Haixin Ding) for financial support.
Conflicts of Interest: The authors declare no conflict of interest.