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9H). 13C NMR (CD3OD) d 173.8, 173.6, 170.8, 161.1,
157.9, 155.3, 143.0, 141.6, 134.2, 133.8, 133.3, 130.7,
128.8, 127.0, 125.1, 123.5, 119.4, 118.6, 116.2, 80.6,
63.1, 59.5, 42.8, 35.8, 35.6, 32.1, 28.8, 27.2, 23.4, 6.7,
6.5. HRMS calcd for C37H43N5O8ClS (MꢁH+)
752.2521, found: 752.2505. RP-HPLC purity (column
1: 98.1%, column 2: 98.7%). Phg D-isomer 40b: 1H
NMR (CD3OD) d 8.39 (ddd, J = 0.96, 2.1, 8.4 Hz,
1H), 7.87–7.79 (m, 2H), 7.6 (m, 1H), 7.56 (m, 2H),
7.51 (s, 1H), 7.32 (m, 2H), 5.75 (ddd, J = 8.7, 10.3,
17.1 Hz, 1H), 5.30 (dd, J = 2.0, 17.1 Hz, 1H), 5.24 (s,
1H), 5.13 (dd, J = 2.0, 10.5 Hz, 1H), 3.98 (s, 1H), 2.98
(m, 1H), 2.22 (m, 1H), 1.85 (m, 1H), 1.45 (s, 9H),
1.33–1.18 (m, 3H), 1.15–1.04 (m, 2H), 1.00 (s, 9H). 13C
NMR (CD3OD) d 174.7, 174.4, 170.8, 161.1, 158.1,
155.3, 143.0, 141.6, 134.2, 133.3, 130.8, 128.8, 127.0,
125.1, 123.5, 119.4, 118.6, 116.2, 106.2, 80.9, 63.5,
60.0, 42.6, 36.1, 35.5, 32.0, 28.9, 27.0, 23.5, 6.7, 6.6.
HRMS calcd for C37H45N5O8 ClS (M+H+) 754.2677,
found: 754.2689. RP-HPLC purity (column 1: 98.6%,
column 2: 99.0%).
(dd, J = 2.0, 17.1 Hz, 1H), 5.18 (s, 1H), 5.12 (dd,
J = 2.0, 10.3 Hz, 1H), 3.99 (s, 1H), 2.94 (m, 1H), 2.16
(m, 1H), 1.85 (dd, J = 5.4, 8.2 Hz, 1H), 1.44 (s, 9H),
1.23 (m, 3H), 1.08 (m, 2H), 1.03 (s, 9H). 13C NMR
(CD3OD) d 173.8, 173.5, 170.7, 164.3, 157.9, 155.5,
149.8, 143.6, 134.2, 133.4, 130.8, 122.7, 119.9, 118.6,
111.0, 80.6, 63.1, 59.4, 42.8, 35.8, 35.5, 32.1, 28.7, 27.1,
23.3, 6.7, 6.5. HRMS calcd for C33H41N5O8SCl
(MꢁH+) 702.2364, found: 702.2360. RP-HPLC purity
(column 1: 96.1%, column 2: 97.7%).
5.48. Compound 43
Compound 43 was prepared according to method B
using the hydrochloride salt of deprotected 32
(0.162 mmol), Boc-Tle-OH (0.075 g, 0.324 mmol),
HATU (0.148g, 0.389 mmol), DIEA (0.244 mL,
1.426 mmol), and DMF (2.0 mL). Purification by RP-
HPLC (ACE 5 Phenyl S/N-A15161 column, MeCN/
H2O gradient with 0.1% TFA) gave 43 (0.070 g, 64%)
as a white solid, after freeze-drying. 1H NMR (CD3OD)
d 8.14 (ddd, J = 0.88, 2.0, 5.1 Hz, 1H), 7.86 (ddd,
J = 2.0, 7.3, 8.3 Hz, 1H), 7.50 (m, 2H), 7.15 (m, 3H),
6.99 (m, 1H), 5.70 (ddd, J = 8.8, 10.4, 17.1 Hz, 1H),
5.28 (dd, J = 2.1, 17.1 Hz, 1H), 5.17 (s, 1H), 5.12 (dd,
J = 2.1, 10.3 Hz, 1H), 3.99 (s, 1H), 2.94 (m, 1H), 2.15
(m, 1H), 1.83 (dd, J = 5.4, 8.1 Hz, 1H), 1.44 (s, 9H),
1.21 (m, 3H), 1.07 (m, 2H), 1.02 (s, 9H). 13C NMR
(CD3OD) d 173.8, 173.5, 170.7, 164.6, 157.8, 156.0,
148.0, 142.1, 134.2, 133.2, 130.9, 122.3, 120.5, 118.6,
113.2, 80.6, 63.1, 59.4, 42.8, 35.8, 35.6, 32.1, 28.7, 27.2,
23.2, 6.7, 6.5. HRMS calcd for C33H44N5O8S (M+H+)
670.2911, found: 670.2914. RP-HPLC purity (column
2: 99.1%, column 3: 99.2%).
5.46. Compound 41
Compound 30 (0.060 g, 0.09 mmol) was dissolved in 4
M HCl in EtOAc (2 mL) and stirred for 3 h at room
temperature, after which the solvent was removed in
vacuo. With the exception of this deviation from proto-
col, 41 was prepared according to method B using the
hydrochloride of the deprotected 30, Boc-Tle-OH
(0.042 g, 0.18 mmol), HATU (0.082 g, 0.22 mmol),
DIEA (0.15 mL, 0.88 mmol), and DMF (0.8 mL). Puri-
fication by RP-HPLC (ACE 5 Phenyl S/N-A15161 col-
umn, MeCN/H2O gradient with 0.1% TFA) gave 41
1
(0.006 g, 8%) as a white solid, after freeze-drying. H
NMR (CD3OD, 500 MHz) d 8.67 (m, 2H), 8.51 (dm,
1H), 8.45 (m, 1H), 8.35 (m, 2H), 8.12 (d, J = 8.2 Hz,
1H), 7.93 (m, 1H), 7.85 (m, 1H), 7.62 (m, 2H), 7.41
(m, 2H), 5.71 (m, 1H), 5.29 (dd, J = 1.9, 17.1 Hz, 1H),
5.27 (s, 1H), 5.15 (dd, J = 1.9, 10.3 Hz, 1H), 4.02 (s,
1H), 2.95 (m, 1H), 2.2 (m, 1H), 1.88 (dd, J = 5.5,
8.2 Hz, 1H), 1.45 (s, 9H), 1.27–1.17 (m, 3H), 1.11–1.01
(m, 2H), 1.05 (s, 9H). 13C NMR (CD3OD, 100 MHz)
d 174.1, 173.6, 170.6, 161.6, 158.0, 155.4, 153.0, 146.4,
143.6, 140.3, 134.1, 133.9, 133.2, 130.7, 130.5, 129.1,
125.2, 123.6, 123.4, 121.6, 118.8, 117.4, 80.7, 63.3,
59.4, 43.0, 35.7, 35.5, 32.1, 28.8, 27.2, 22.3, 6.7, 6.6.
HRMS calcd for C42H47N6O8S (MꢁH+) 795.3176,
found: 795.3193. RP-HPLC purity (column 1: 96.4%,
column 2: 98.0%).
5.49. Compounds 44a and 44b
Compound 44 was prepared according to method B
using the hydrochloride salt of deprotected 33
(0.154 mmol), Boc-Tle-OH (0.071 g, 0.308 mmol),
HATU (0.141 mg, 0.370 mmol), DIEA (0.205 mL,
1.202 mmol), and DMF (1.5 mL). Purification by RP-
HPLC (Zorbax SB-C8 column, MeCN/H2O gradient
with 0.1% TFA) gave the Phg L-isomer 44a (0.017 g,
19%) and Phg D-isomer 44b (0.017g, 19%) as white sol-
ids after freeze-drying. Phg L-isomer 44a 1H NMR
(CD3OD) d 7.27 (m, 2H), 6.84 (m, 2H), 5.60 (m, 1H),
5.19 (dd, J = 2.0, 17.2 Hz, 1H), 5.02 (dd, J = 2.0,
10.4 Hz, 1H), 4.98 (s, 1H), 3.88 (s, 1H), 3.70 (s, 3H),
2.84 (m, 1H), 2.02 (m, 1H), 1.74 (dd, J = 5.4, 8.1 Hz,
1H), 1.35 (s, 9H), 1.15 (m, 3H), 1.06 (m, 2H), 0.93 (s,
9H). 13C NMR (CD3OD) d 174.2, 173.4, 170.8, 161.6,
157.9, 134.2, 130.5, 128.6, 118.5, 115.3, 80.6, 63.1,
59.4, 55.8, 42.7, 35.8, 35.6, 32.0, 28.7, 27.2, 23.3, 6.7,
6.5. HRMS calcd for C29H43N4O8S (M+H+) 607.2802,
found: 607.2789. RP-HPLC purity (column 1: 95.0%,
column 2: 97.9%). Phg D-isomer 44b 1H NMR (CD3OD)
d 7.34 (m, 2H), 6.94 (m, 2H), 5.75 (ddd, J = 17.2, 10.4,
8.7 Hz, 1H), 5.28 (dd, J = 17.2, 2.0 Hz, 1H), 5.11 (dd,
J = 10.4, 2.0 Hz, 1H), 5.06 (s, 1H), 3.95 (s, 1H), 3.80
(s, 3H), 2.96 (m, 1H), 2.15 (m, 1H), 1.80 (dd, J = 8.3,
5.2 Hz, 1H), 1.44 (s, 9H), 1.26 (m, 2H), 1.08 (m, 2H),
0.96 (s, 9H). 13C NMR (CD3OD) d 174.7, 174.6,
5.47. Compound 42
Compound 42 was prepared according to method B
using the hydrochloride salt of deprotected 31
(0.139 mmol), Boc-Tle-OH (0.064 g, 0.278 mmol),
HATU (0.127 g, 0.334 mmol), DIEA (0.209 mL,
1.224 mmol), and DMF (1.5 mL). Purification by RP-
HPLC (ACE 5 Phenyl S/N-A15161 column, MeCN/
H2O gradient with 0.1% TFA) gave 42 (0.063 g, 61%)
as a white solid, after freeze-drying. 1H NMR (CD3OD)
d 9.1 (s, 1H), 7.79 (dd, J = 7.6, 8.2 Hz, 1H), 7.51 (m,
2H), 7.14 (m, 3H), 6.91 (m, 1H), 5.71 (m, 1H), 5.28