B. O. Okandeji et al. / Bioorg. Med. Chem. 19 (2011) 7679–7689
7687
4.2.4.3. Entry F (Table 1).
Post deprotection flash column
40.3, 33.4, 32.8, 29.8, 29.4, 28.5, 22.5. HRMS: calcd 676.3363 for
C
39H47N3NaO6, observed 676.3355 [M+Na]+.
chromatography conditions: 4:1 (Isopropanol/NH4OH). HPLC con-
ditions 0–35% B over 18 min (tR = 12.5 min). 1H NMR (400 MHz;
CD3OD): d 9.41–9.38 (m, 1H), 8.97 (m, 1H), 8.14 (m, 2H), 7.96–
7.92 (m, 1H), 7.82 (t, J = 7.7, 1H), 7.28–7.26 (m, 4H), 7.16 (m, 1H),
4.64 (m, 1H), 4.13 (q, J = 6.4, 1H), 3.07–3.02 (m, 2H), 2.95–2.86
(m, 1H), 2.84–2.76 (m, 1H), 2.35–2.26 (m, 1H), 2.25–2.15 (m,
1H), 2.10–1.98 (m, 2H), 1.95–1.84 (m, 2H). 13C (100 MHz; CD3OD):
d 171.8, 171.7, 168.9, 168.8, 140.6, 140.5, 133.1, 131.7, 131.6,
131.5, 130.41, 130.39, 130.02, 129.99, 129.2, 129.1, 128.2, 128.1,
125.9, 122.8, 122.64, 122.62, 122.60, 54.5, 54.3, 52.5, 52.1, 38.7,
38.6, 33.4, 33,3, 31.9, 31.8, 28.3, 28.2, 22.9, 22.4. LRMS: calcd
420.24 for C24H30N5O2, observed 420.39 [M+H]+.
4.2.5.3. Compound 3, Figure 3.
Flash Chromatography
conditions: 15:1 (DCM/EtoAc). 1H NMR (400 MHz; CDCl3): d 8.96
(s, 1H), 8.04 (d, J = 0.71, 1H), 7.79–7.75 (m, 3H), 7.46 (t, J = 7.4,
1H), 7.40 (t, J = 7.3, 1H), 7.35–7.29 (m, 3H), 7.24–7.20 (m, 3H),
6.93 (d, J = 8.3, 1H), 6.37 (dd, J = 8.3, 2.0, 1H), 6.30–6.29 (m, 1H),
4.86 (br, 1H), 4.51 (m, 2H), 3.72 (s, 3H), 3.68 (s, 3H), 3.13–3.09
(m, 2H), 2.75–2.63 (m, 2H), 2.53–2.49 (m, 2H), 1.77–1.72 (m,
4H), 1.53–1.49 (m, 2H), 1.45 (s, 9H), 1.39–1.37 (m, 2H). 13C NMR
(100 MHz; CDCl3): d 176.2, 169.1, 160.7, 158.0, 141.0, 135.6,
133.8, 130.4, 128.5, 127.6, 127.5, 126.4, 126.2, 124.8, 120.0,
116.4, 116.3, 104.2, 98.5, 55.3, 55.2, 33.8, 32.8, 29.9, 29.4, 28.4,
26.6, 25.0. HRMS: calcd 690.3519 for C40H49N3NaO6, observed
690.3541 [M+Na]+.
4.2.4.4. Entry G (Table 1).
Post deprotection flash column
chromatography conditions: 4:1 (isopropanol/NH4OH). HPLC con-
ditions 0–40% B over 18 min (rt = 16.5 min). 1H NMR (400 MHz;
CD3OD): d 8.21 (s, 1H), 7.79 (m, 3H), 7.60–7.56 (m, 1H), 7.43 (m,
2H), 7.26 (m, 4H), 7.18 (t, J = 6.9, 1H), 4.58 (dd, J = 8.5, 5.8, 1H),
4.04 (t, J = 6.5, 1H), 3.02 (t, J = 7.6, 2H), 2.86–2.69 (m, 2H), 2.28–
2.19 (m, 1H), 2.18–2.08 (m, 1H), 2.06–1.95 (m, 2H), 1.88–1.80
(m, 2H). 13C (100 MHz; CD3OD): d 170.9, 167.7, 140.7, 135.5,
133.8, 130.9, 128.2, 128.1, 127.2, 127.1, 126.2, 125.9, 124.8,
119.9, 116.8, 54.5, 52.5, 52.5, 38.7, 33.9, 32.0, 28.3, 22.9. HRMS:
calcd 441.2266 for C25H30N4NaO2, observed 441.2280 [M+Na]+.
4.2.5.4. Compound 4, Figure 3.
Flash Chromatography
conditions: 20:1 (DCM/EtOAc)—48% yield. 1H NMR (400 MHz;
CDCl3): d 8.55 (s, 1H), 7.97 (d, J = 0.51, 1H), 7.78–7.73 (m, 3H),
7.46 (t, J = 7.3, 1H), 7.40 (t, J = 7.32, 1H), 7.33 (t, J = 7.3, 2H), 7.27
(dd, J = 2.4, 1.9, 1H), 7.23 (t, J = 6.4, 3H), 6.91 (d, J = 8.1, 1H), 6.39
(dd, J = 8.2, 2.0, 1H), 6.26 (d, J = 1.8, 1H), 4.65 (br, 1H), 4.41 (m,
2H), 4.23 (m, 2H), 3.71 (s, 3H), 3.67 (s, 3H), 2.72 (m, 2H), 2.60
(m, 1H), 2.25–2.18 (m, 1H), 1.50 (s, 9H). 13C NMR (100 MHz;
CDCl3): d 171.4, 168.6, 161.2, 158.4, 140.9, 135.3, 133.8, 130.5,
128.6, 128.4, 127.6, 127.5, 126.4, 126.3, 124.8, 120.0, 116.5,
115.0, 104.5, 98.7, 79.8, 55.4, 53.5, 43.0, 32.7, 29.2, 28.4. HRMS:
calcd 634.2893 for C36H41N3NaO6, observed 634.2875 [M+Na]+.
4.2.4.5. Entry H (Table 1).
Post deprotection flash column
chromatography conditions: 4:1 (isopropanol/NH4OH). HPLC con-
ditions 0–40% B over 18 min (tR = 16.5 min). 1H NMR (400 MHz;
CD3OD): d 8.15 (s, 1H), 7.84–7.76 (m, 3H), 7.54 (dd, J = 8.8, 2.2,
1H), 7.48–7.39 (m, 2H), 7.30–7.23 (m, 4H), 7.20–7.16 (m, 1H),
4.62 (dd, J = 9.0, 5.1, 1H), 4.07 (t, J = 6.3, 1H), 3.03–2.96 (m, 2H),
2.90–2.84 (m, 1H), 2.80–2.73 (m, 1H), 2.26–2.19 (m, 1H), 2.17–
2.11 (m, 1H), 2.03–1.98 (m, 2H), 1.90–1.80 (m, 2H). 13C
(100 MHz; CD3OD): d 171.2, 168.4, 140.7, 135.4, 133.7, 130.9,
130.4, 130.2, 128.3, 128.2, 128.0, 127.3, 127.1, 126.2, 125.9,
124.9, 120.0, 117.0, 54.3, 52.2, 38.7, 34.0, 31.9, 28.2, 22.4. HRMS:
calcd 441.2266 for C25H30N4NaO2, observed 441.2271 [M+Na]+.
4.2.5.5. Compound 5, Figure 3.
Flash Chromatography
conditions: 15:1 (DCM/EtOAc)—22% yield. 1H NMR (400 MHz;
CDCl3): d 8.71 (d, J = 0.31, 1H), 8.00 (d, J = 1.7, 1H), 7.76 (t, J = 8.7,
3H), 7.46 (m, 1H), 7.40 (m, 1H), 7.34 (t, J = 7.3, 2H), 7.26–7.21 (m,
3H), 6.90 (d, J = 8.4, 1H), 6.38 (dd, J = 8.3, 2.4, 1H), 6.26 (d, J = 2.3,
1H), 4.70 (br, 1H), 4.46 (s, 2H), 3.71 (s, 3H), 3.65 (s, 3H), 3.54–
3.50 (m, 2H), 2.81–2.77 (m, 2H), 2.74–2.69 (m, 2H), 2.54 (m, 1H),
2.21 (m, 1H), 1.45 (s, 9H). 13C NMR (100 MHz; CDCl3): d 174.5,
169.0, 161.0, 158.3, 156.0, 141.0, 135.5, 133.8, 130.4, 130.0,
128.65, 128.57, 128.48, 127.6, 127.5, 126.4, 126.2, 124.8, 119.9,
116.4, 115.7, 104.4, 98.6, 79.3, 55.3, 55.3, 36.5, 34.4, 32.7, 29.3,
4.2.5. Spectral data for compounds in Figures 3–6
4.2.5.1. Compound 1, Figure 3.
Flash Chromatography
conditions: 8:1 (DCM/EtOAc)—49% yield. 1H NMR (400 MHz;
CDCl3): d 7.89 (s, 1H), 7.77–7.72 (m, 3H), 7.47–7.31 (m, 5H),
7.27–7.23 (m, 4H), 7.07–7.05 (m, 1H), 6.41–6.39 (m, 1H), 6.16–
6.10 (m, 1H), 5.53–5.41 (m, 1H), 5.06–5.01 (m, 1H), 4.67–4.49
(m, 2H), 3.77 (d, J = 7.7, 3H), 3.61 (m, 3H), 3.18–3.13 (m, 2H),
2.77–2.67 (m, 2H), 2.42–2.38 (m, 2H), 1.80–1.78 (m, 1H), 1.67–
1.58 (m, 3H), 1.48–1.43 (m, 18H). 13C NMR (100 MHz; CDCl3): d
155.7, 141.0, 135.5, 133.80, 133.77, 130.4, 128.71, 128.66,
128.55, 128.51, 127.58, 127.47, 126.35, 126.31, 126.27, 124.7,
120.00, 119,97, 116.6, 116.3, 104.6, 104.4, 98.5, 79.9, 55.4, 55.3,
51.3, 40.3, 32.7, 32.6, 31.2, 30.8, 28.43, 28.39, 28.36, 28.32, 26.0.
HRMS: calcd 791.3996 for C44H56N4NaO8, observed 791.3981
[M+Na]+.
28.5. HRMS: calcd 648.3050 for
C
37H43N3NaO6, observed
648.3062 [M+Na]+.
4.2.5.6. Compound 6, Figure 4.
Flash Chromatography
conditions: 10:1 (DCM/EtOAc)—10% yield. 1H NMR (400 MHz;
CDCl3): d 9.11 (m, 1H), 8.43 (d, J = 15.2, 1H), 7.87–7.79 (m, 4H),
7.49–7.40 (m, 2H), 7.32 (m, 2H), 7.26–7.21 (m, 3H), 5.43 (m, 1H),
4.30–4.14 (m, 1H), 3.22–3.19 (m, 2H), 2.85–2.73 (m, 2H), 2.42–
2.31 (m, 2H), 2.01–1.81 (m, 2H), 1.68–1.63 (m, 2H), 1.51–1.42
(m, 18H). 13C NMR (100 MHz; CDCl3): d 172.5, 171.0, 168.3,
168.0, 157.1, 156.34, 156.28, 156.18, 140.8, 140.7, 135.4, 135.2,
133.80, 133.75, 130.82, 130.78, 128.60, 128.56, 128.41, 128.35,
127.8, 127.7, 127.5, 126.34, 126.29, 126.22, 126.19, 125.9, 125.0,
124.99, 120.7, 120.2, 117.4, 117.1, 80.9, 80.8, 79.5, 74.8, 74.2,
62.2, 54.4, 54.2, 40.0, 39.8, 34.3, 33.4, 32.1, 31.5, 31.4, 28.2, 28.2,
28.0, 26.72, 26.66. HRMS: calcd 642.3155 for C35H45N3NaO7, ob-
served 674.3218 [M+Na]+.
4.2.5.2. Compound 2, Figure 3.
Flash Chromatography condi-
tions: 7:1 (DCM/EtOAc)—38% yield. 1H NMR (400 MHz; CDCl3): d
8.93 (s, 1H), 8.04 (s, 1H), 7.77 (m, 3H), 7.46 (t, J = 8.02, 1H), 7.40
(t, J = 7.5, 1H), 7.35–7.30 (m, 3H), 7.22 (m, 3H), 6.93 (d, J = 8.3,
1H), 6.38 (dd, J = 8.4, 2.3, 1H), 6.30 (d, J = 2.2, 1H), 4.85 (br, 1H),
4.51 (q, J = 13.7, 2H), 3.72 (s, 3H), 3.68 (s, 3H), 3.18–3.11 (m, 2H),
2.76–2.65 (m, 2H), 2.54 (t, J = 7.3, 2H), 2.16–2.12 (m, 1H), 1.85
(m, 1H), 1.77 (m, 2H), 1.55 (m, 2H), 1.45 (s, 9H). 13C NMR
(100 MHz; CDCl3): d 175.9, 169.1, 160.8, 158.0, 156.0, 141.0,
135.6, 133.8, 130.5, 129.1, 128.53, 128.51, 127.6, 127.5, 126.4,
126.2, 124.8, 120.0, 116.34, 116.32, 104.2, 98.6, 79.1, 55.3, 55.2,
4.2.5.7. Compound 7, Figure 4.
Flash Chromatography condi-
tions: 7:1 (DCM/EtOAc)—18% yield.
HRMS: calcd 655.3472 for C36H48N4NaO6, observed 655.3480
[M+Na]+.
4.2.5.8. Compound 8, Figure 5.
Flash Chromatography condi-
tions: 8:1 (DCM/EtOAc)—39% yield. 1H NMR (400 MHz; CDCl3): d