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K. M. Bonger et al. / Bioorg. Med. Chem. 15 (2007) 4841–4856
4.20. Compound 22c
6H,
J = 7.2 Hz).
HRMS
m/z
calcd
for
C72H70N20O6F4+H+: 1387.57961, obsd 1387.59127.
Yield after RP-HPLC purification: 22.3 mg (23.4 lmol,
47%). LC/MS analysis: tR 7.25 min (linear gradient 10–
90% B in 13.5 min; m/z: 838.4 [M+H+]). 1H NMR
(500 MHz, DMSO-d6): d 9.13 (t, 1H, J = 5.2 Hz), 9.01
(s, 1H), 8.84 (s, 1H), 8.63 (br s, 1H), 8.05 (s, 1H),
7.55 (dd, 4H, J1 = 20.9 Hz, J2 = 8.7 Hz), 7.50–7.41 (m,
6H), 7.16 (t, 2H, J = 8.2 Hz), 6.33 (br s, 1H), 5.70 (s,
2H), 5.15–5.11 (m, 1H), 4.82–4.76 (m, 1H), 4.71–4.63
(m, 1H), 4.61–4.47 (m, 2H), 4.55 (t, 2H, J = 5.1 Hz),
4.40–4.37 (m, 1H), 3.83 (t, 2H, J = 5.2 Hz,), 3.55–3.52
(m, 6H), 3.35 (t, 2H, J = 5.0 Hz), 3.11 (q, 2H,
J = 7.1 Hz), 2.46 (s, 3H), 1.05 (t, 3H, J = 7.2 Hz).
HRMS m/z calcd for C41H45N13O5F2+H+: 838.37074,
obsd 838.36890.
4.24. Compound 25b
Yield after RP-HPLC purification: 29.8 mg (18.0 lmol,
36%). LC/MS analysis: tR 7.02 min (linear gradient
10–90%B in 13.5 min; m/z: 1431.8 [M+H+]). H NMR
1
(500 MHz, DMSO-d6): d 9.12 (s, 2H), 9.02 (s, 2H),
8.78 (s, 2H), 8.62 (br s, 2H), 7.95 (s, 2H), 7.53 (dd,
8H, J1 = 19.5 Hz, J2 = 6.7 Hz), 7.49–7.40 (m, 12H),
7.15 (t, 4H, J = 8.2 Hz), 6.34 (br s, 2H), 5.69 (s, 4H),
5.13–5.10 (m, 2H), 4.79–4.70 (m, 2H), 4.68–4.64 (m,
2H), 4.57–4.46 (m, 8H), 4.40–4.36 (m, 2H), 3.83–3.77
(m, 4H), 3.11 (q, 4H, J = 7.2 Hz), 2.46 (s, 6H), 1.05 (t,
6H, J = 7.2 Hz). HRMS m/z calcd for C74H74N20O7F4+
H+: 1431.60582, obsd 1431.61762.
4.21. Compound 22d
4.25. Compound 25c
Yield after RP-HPLC purification: 15.8 mg (15.8 lmol,
32%). LC/MS analysis: tR 5.75 min (linear gradient
Yield after RP-HPLC purification: 11.1 mg (6.5 lmol,
13%). LC/MS analysis: tR 7.20 min (linear gradient
1
10–90%B in 13.5 min; m/z: 882.4 [M+H+]). H NMR
1
(500 MHz, DMSO-d6): d 9.13 (t, 1H, J = 5.2 Hz), 9.02
(s, 1H), 8.83 (s, 1H), 8.62 (br s, 1H), 8.05 (s, 1H), 7.55
(dd, 4H, J1 = 21.8 Hz, J2 = 8.7 Hz), 7.50–7.41 (m, 6H),
7.16 (t, 2H, J = 8.2 Hz), 6.33 (br s, 1H,), 5.70 (s, 2H),
5.15–5.11 (m, 1H), 4.82–4.76 (m, 1H), 4.69 (dd, 2H,
J1 = 15.1 Hz, J2 = 5.8 Hz), 4.62–4.52 (m, 2H), 4.55 (t,
2H, J = 5.2 Hz), 4.40–4.37 (m, 1H), 3.83 (t, 2H,
J = 5.2 Hz), 3.55–3.52 (m, 10H), 3.36 (t, 2H,
J = 5.0 Hz), 3.11 (q, 2H, J = 6.9 Hz), 2.46 (s, 3H), 1.06
(t, 3H, J = 7.2 Hz). HRMS m/z calcd for
C43H49N13O6F2+H+: 882.39696, obsd 882.39498.
10–90%B in 13.5 min; m/z: 1475.8 [M+H+]). H NMR
(500 MHz, DMSO-d6): d 9.14 (t, 2H, J = 5.3 Hz), 9.02
(s, 2H), 8.76 (s, 2H), 8.67–8.58 (m, 2H), 8.05 (s, 2H),
7.59–7.42 (m, 20H), 7.17 (t, 4H, J = 8.2 Hz), 6.38–6.42
(m, 2H), 5.70 (s, 4H), 5.13 (d, 2H, J = 13.5 Hz), 4.82–
4.78 (m, 2H), 4.71–4.58 (ddd, 4H, J1 = 5.1 Hz,
J2 = 15.1 Hz, J3 = 42.5 Hz), 4.54–4.46 (m, 6H), 4.49–
4.37 (m, 2H), 3.80 (t, 4H, J = 5.1 Hz), 3.52 (s, 4H),
3.14–3.10 (m, 4H), 2.48–2.46 (m, 6H), 1.07 (t, 6H,
J = 7.2 Hz). HRMS m/z calcd for C76H78N20O8F4+H+:
1475.63204, obsd 1475.64714.
4.22. Compound 22e
4.26. Compound 25d
Yield after RP-HPLC purification: 18.6 mg (17.9 lmol,
36%). LC/MS analysis: tR 7.24 min (linear gradient
Yield after RP-HPLC purification: 14.1 mg (8.1 lmol,
16%). LC/MS analysis: tR 7.25 min (linear gradient
1
1
10–90%B in 13.5 min; m/z: 926.2 [M+H+]). H NMR
10–90%B in 13.5 min; m/z: 1519.7 [M+H+]). H NMR
(500 MHz, DMSO-d6): d 9.13 (t, 1H, J = 5.2 Hz), 9.02
(s, 1H), 8.83 (s, 1H), 8.61 (br s, 1H), 8.07 (s, 1H), 7.55
(dd, 4H, J1 = 17.8 Hz, J2 = 8.7 Hz), 7.50–7.41 (m, 6H),
7.16 (t, 2H, J = 8.2 Hz), 6.33 (br s, 1H), 5.70 (s, 2H),
5.15–5.11 (m, 1H), 4.82–4.76 (m, 1H), 4.69 (dd, 2H,
J1 = 15.1 Hz, J2 = 5.8 Hz), 4.62–4.52 (m, 2H), 4.55 (t,
2H, J = 5.2 Hz), 4.40–4.37 (m, 1H,), 3.82 (t, 2H,
J = 5.2 Hz), 3.55–3.52 (m, 14H), 3.36 (t, 2H,
J = 5.0 Hz), 3.11 (q, 2H, J = 7.1 Hz), 2.46 (s, 3H), 1.05
(t, 3H, J = 7.2 Hz). HRMS m/z calcd for
C45H53N13O7F2+H+: 926.42317, obsd 926.41971.
(500 MHz, DMSO-d6): d 9.12 (br s, 2H), 9.00 (s, 2H),
8.82 (s, 2H), 8.67–8.58 (br s, 2H), 8.05 (s, 2H), 7.55
(dd, 8H, J1 = 20.0 Hz, J2 = 8.8 Hz), 7.50–7.38 (m,
12H), 7.17 (t, 4H, J = 8.2 Hz), 6.37 (br s, 2H), 5.69 (s,
4H), 5.13–5.11 (m, 2H), 4.81–4.78 (m, 2H), 4.71–4.61
(m, 2H), 4.59–4.42 (m, 8H), 4.40–4.34 (m, 2H), 3.81 (t,
4H, J = 5.4 Hz), 3.52–3.47 (m, 4H), 3.56–3.49 (m, 4H),
3.16–3.09 (m, 4H), 2.48 (br s, 6H), 1.05 (t, 6H,
J = 7.2 Hz). HRMS m/z calcd for C78H82N20O9F4+H+:
1519.65825, obsd 1519.66753.
4.27. Compound 25e
4.23. Compound 25a
Yield after RP-HPLC purification: 13.8 mg (7.7 lmol,
15%). LC/MS analysis: tR 7.27 min (linear gradient
Yield after RP-HPLC purification: 25.7 mg (15.9 lmol,
32%). LC/MS analysis: tR 6.87 min (linear gradient
1
10–90%B in 13.5 min; m/z: 1563.9 [M+H+]). H NMR
1
10–90%B in 13.5 min; m/z: 1387.6 [M+H+]). H NMR
(500 MHz, DMSO-d6): d 9.12 (br s, 2H), 9.01 (s, 2H),
8.79 (s, 2H), 8.65–8.57 (br s, 2H), 8.05 (s, 2H), 7.55
(dd, 8H, J1 = 21.9 Hz, J2 = 8.7 Hz), 7.50–7.38 (m,
12H), 7.16 (t, 4H, J = 8.2 Hz), 6.34 (br s, 2H), 5.69 (s,
4H), 5.13–5.08 (m, 2H), 4.81–4.75 (m, 2H), 4.71–4.64
(m, 2H), 4.59–4.42 (m, 8H), 4.40–4.36 (m, 2H), 3.81 (t,
4H, J = 5.5 Hz), 3.57–3.43 (m, 12H), 3.14–3.09 (m,
4H), 2.46 (br s, 6H), 1.05 (t, 6H, J = 7.2 Hz). HRMS
(500 MHz, DMSO-d6): d 9.11 (t, 2H, J = 5.3 Hz), 8.99
(s, 2H), 8.71 (s, 2H), 8.59 (br s, 2H), 8.02 (s, 2H), 7.54
(dd, 8H, J1 = 23.7 Hz, J2 = 8.7 Hz), 7.49–7.40 (m,
12H), 7.16 (t, 4H, J = 8.2 Hz), 6.25 (t, 2H, J = 5.2 Hz),
5.69 (s, 4H), 5.13–5.10 (m, 2H), 4.92 (s, 4H), 4.79–4.70
(m, 2H), 4.68–4.59 (m, 2H), 4.57–4.50 (m, 4H), 4.40–
4.36 (m, 2H), 3.14–3.09 (m, 4H), 2.46 (s, 6H), 1.05 (t,