Y. Wu et al.
(s, 3H), 1.30–1.17 (m, 8H), 1.06–0.97 (m, 1H), 0.94 ppm (d, J=6.3 Hz,
3H); FTIR (film): n˜ =2927, 2855, 1639, 1442, 1187, 1143, 1010 cmÀ1; ESI-
MS: m/z: 352.3 [M+H]+, 374.2 [M+Na]+; elemental analysis: calcd (%)
for C20H33NO4: C 68.34, H 9.46, N 3.99; found: C 68.50, H 9.41, N 3.54.
>1808C (decomp.). [a]D28 = +42.21 (c=1.70 in CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.33 (d, J=8.8 Hz, 2H), 7.30 (brs, 1H), 6.77 (d,
J=8.8 Hz, 2H), 4.20 (d, J=11.3 Hz, 1H), 3.96 (d, J=11.3 Hz, 1H), 3.71
(s, 3H), 2.57 (quint., J=7.1 Hz, 1H), 2.36 (dt, J=14.0, 3.7 Hz, 1H), 1.94–
1.86 (m, 1H), 1.85–1.76 (m, 1H), 1.76–1.68 (m, 1H), 1.63–1.45 (m, 3H),
1.36 (d, J=7.0 Hz, 3H), 1.28–1.13 (m, 6H), 0.97–0.90 (m, 1H), 0.87 ppm
(d, J=6.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=174.2, 156.4, 130.8,
121.8 (2C), 114.0 (2C), 104.2, 86.2, 60.2, 55.4, 53.5, 48.5, 43.4, 37.4, 37.2,
34.8, 26.6, 25.5, 25.3, 19.8, 18.4 ppm; FTIR (film): n˜ =3504, 2949, 2833,
1655, 1451, 1413, 1116, 1033, 1016 cmÀ1; ESI-MS: m/z: 390.2 [M+H]+,
412.2 [M+Na]+; ESI-HRMS: m/z: calcd for C22H31NaO5: 412.20944
[M+Na]+; found: 412.20898.
Compound 57: A white powder; m.p. 1558C (decomp.); [a]2D8 = +83.70
(c=0.27, CHCl3); 1H NMR (300 MHz, CDCl3): d=5.47 (d, J=7.3 Hz,
1H), 4.26 (d, J=11.4 Hz, 1H), 4.22–4.11 (m, 1H), 4.01 (d, J=11.1 Hz,
1H), 2.51–2.36 (m, 2H), 2.04–1.83 (m, 4H), 1.77–1.49 (m, 8H), 1.45–0.99
(m, 12H), 0.95 ppm (d, J=6.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
175.4, 104.1, 86.3, 60.2, 53.5, 50.9, 48.4, 42.6, 37.4, 37.2, 34.8, 33.00, 32.99,
26.4, 25.6, 25.4, 23.7, 23.6, 19.8, 18.4 ppm; FTIR (film): n˜ =3292, 2954,
2925, 2870, 1638, 1552, 1454, 1374, 1208, 1190, 1141, 1090, 1066, 1046,
940, 893, 830 cmÀ1; ESI-MS: m/z: 352.2 [M+H]+, 374.2 [M+Na]+; ESI-
HRMS: m/z: calcd for C20H33N1Na1O4: 374.23018 [M+Na]+; found:
374.23046; elemental analysis: calcd (%) for C20H33NO4: C 68.34, H 9.46,
N 3.99; found: C 68.75, H 9.76, N 4.50.
Compound 52: Amorphous; m.p.>1858C (decomposed); 99.81% pure
(tr (major)=15.51 min) as determined by HPLC analysis on a Diamonsil
C18 column (250ꢃ4.5 mm) eluted with MeOH (containing 0.1% aq.
TFA) at a flow rate of 1.0 mLminÀ1 and with detection by an evaporative
light-scattering detector (ELSD); [a]2D8 = +54.72 (c=0.73 in CHCl3);
1H NMR (300 MHz, CDCl3): d=5.68 (brs, 1H; NH), 4.20 (d, J=11.7 Hz,
1H), 3.98 (d, J=11.1 Hz, 1H), 2.72–2.61 (m, 1H), 2.48–2.32 (m, 2H),
2.00–1.78 (m, 2H), 1.68–1.47 (m, 4H), 1.40–1.32 (m, 1H), 1.32–1.11 (m,
8H), 1.05–0.89 (m, 1H), 0.92 (d, J=6.2 Hz, 3H), 0.78–0.70 (m, 2H),
0.49–0.41 ppm (m, 2H); FTIR (film): n˜ =3267, 2950, 2930, 1638, 1542,
1375, 1189 cmÀ1; ESI-MS: m/z: 324.2 [M+H]+, 346.2 [M+Na]+; ESI-
HRMS: m/z: calcd for C18H29NNaO4: 346.19888 [M+Na]+; found:
346.19906.
Compound 53: A colorless oil; 99.66% pure (tr (major)=14.29 min) as
determined by HPLC analysis on
a Diamonsil C18 column (250ꢃ
4.5 mm) eluted with MeOH (containing 0.1% aq. TFA) at a flow rate of
1.0 mLminÀ1 and with detection by an ELSD; [a]2D8 = +79.54 (c=0.26 in
CHCl3); 1H NMR (400 MHz, CDCl3): d=5.96 (brs, 1H; NH), 4.19 (dd,
J=11.6, 1.8 Hz, 1H), 3.95 (d, J=11.3, 1H), 3.65 (t, J=5.0 Hz, 1H), 3.41–
3.27 (m, 2H), 2.54 (brs, 1H; OH), 2.49 (quint., J=7.0 Hz, 1H), 2.36 (dt,
J=14.4, 3.8 Hz, 1H), 1.94–1.86 (m, 1H), 1.84–1.76 (m, 1H), 1.69–1.61 (m,
1H), 1.59–1.45 (m, 4H), 1.39–1.30 (m, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.25
(s, 3H), 1.24–1.10 (m, 2H), 0.95 (dt, J=3.7, 13.1 Hz, 1H), 0.88 ppm (d,
J=6.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=177.3, 104.2, 86.3, 62.6,
60.2, 53.6, 48.4, 42.5, 42.3, 37.4, 37.2, 34.8, 26.5, 25.6, 25.4, 19.8, 18.5 ppm;
FTIR (film): n˜ =3505, 2925, 2873, 1648, 1545, 1455, 1375, 1207, 1189,
1064, 1033, 829 cmÀ1; ESI-MS: m/z: 328.2 [M+H]+, 350.2 [M+Na]+; ele-
mental analysis: calcd (%) for C17H29NO5: C 62.36, H 8.93, N 4.28; found
C 62.80, H 9.40, N 4.48.
Compound 58: A white solid; 96.79% pure (tr (major)=22.00 min) as de-
termined by HPLC analysis on a Kromasil C18 column (150ꢃ4.5 mm)
eluted with MeOH/H2O (10:90 to 100:0) at a flow rate of 1.0 mLminÀ1
with a UV detector set to 243 nm; m.p. 180–1828C; [a]2D6 = +46.37 (c=
1.00 in CHCl3); 1H NMR (400 MHz, CDCl3): d=7.72–7.64 (m, 3H), 7.56
(d, J=8.9 Hz, 2H), 4.24 (dd, J=11.3, 1.6 Hz, 1H), 4.04 (d, J=11.3 Hz,
1H), 2.74 (quint., J=7.0 Hz, 1H), 2.44 (dt, J=14.1, 3.8 Hz, 1H), 2.02–
1.95 (m, 1H), 1.93–1.76 (m, 3H), 1.63–1.54 (m, 3H), 1.44 (d, J=7.1 Hz,
3H), 1.42–1.33 (m, 1H), 1.32 (s, 3H), 1.31–1.25 (m, 1H), 1.02 (dt, J=
12.8, 3.7 Hz, 1H), 0.95 ppm (d, J=6.5 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=174.7, 140.9, 126.6, 126.2 (q, JCÀF =3.7 Hz), 125.9, 125.6, 124.0
(q, JCÀF =271 Hz), 119.5, 104.3, 86.2, 60.2, 53.6, 48.8, 43.4, 37.4, 37.2, 34.8,
26.3, 25.5, 25.3, 19.8, 18.5 ppm; 19F NMR (282 MHz, CDCl3): d=
À62.5 ppm (s, 3F); FTIR (film): n˜ =3301, 2932, 2876, 1666, 1605, 1535,
1410, 1325, 1253, 1166, 1123, 1091, 1068, 1017, 943, 844, 829, 739, 593,
512 cmÀ1; ESI-MS: m/z: 428.2 [M+H]+, 450.3 [M+Na]+; ESI-HRMS:
m/z: calcd for C22H28F3NNaO4: 450.18386 [M+Na]+; found: 450.18465.
Compound 54: A colorless oil; 98.64% pure (tr (major)=21.30 min) as
determined by HPLC analysis on a Kromasil C18 column (150ꢃ4.5 mm)
eluted with MeOH/H2O (10:90 to 100:0) at a flow rate of 1.0 mLminÀ1
with a UV detector set to 243 nm; [a]2D8 = +64.30 (c=1.10 in CHCl3);
1H NMR (300 MHz, CDCl3): d=7.51 (d, J=8.2 Hz, 2H), 7.47 (brs, 1H),
7.30 (t, J=7.6 Hz, 2H), 7.09 (t, J=7.4 Hz, 1H), 4.26 (d, J=10.9 Hz, 1H),
4.03 (d, J=11.4 Hz, 1H), 2.66 (quint., J=7.0 Hz, 1H), 2.43 (dt, J=3.8,
14.0 Hz, 1H), 2.01–1.75 (m, 4H), 1.70–1.50 (m, 3H), 1.43 (d, J=7.1 Hz,
3H), 1.36–1.27 (m, 2H), 1.31 (s, 3H), 1.07–0.96 (m, 1H), 0.94 ppm (d, J=
6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=174.4, 137.8, 128.9, 124.2,
119,9, 104.2, 86.2, 60.2, 53.5, 48.4, 43.7, 37.4, 37.2, 34.7, 26.6, 25.5, 25.3,
19.8, 18.4 ppm; FTIR (film): n˜ =3301, 2927, 2873, 1659, 1598, 1543, 1500,
1441, 1375, 1178, 943, 755, 692 cmÀ1; ESI-MS: m/z: 360.3 [M+H]+, 382.3
[M+Na]+; EI-HRMS: m/z: calcd for C21H30NO4: 360.21693 [M+H]+;
found: 360.21817.
Coupling of acid 33 with alcohol 30 to afford ester 59: A solution of acid
33 (100 mg, 0.352 mmol), DMAP (8.6 mg, 0.0704 mmol), and EDCI
(135 mg, 0.704 mmol) in dry CH2Cl2 (3 mL) was stirred at ambient tem-
perature for 30 min before alcohol 30 (190 mg, 0.704 mmol) was added.
The mixture was then stirred at the same temperature for 17 h, at which
time TLC analysis indicated completion of the reaction. EtOAc (3 mL)
was added, followed by H2O (2 mL). The mixture was then extracted
with Et2O (2ꢃ30 mL). The combined organic layers were washed with
brine and dried over anhydrous Na2SO4. The solvent was removed by
rotary evaporation and the residue was subjected to chromatography
(PE/EtOAc, 20:1) on silica gel to give ester 59 as a white solid (172 mg,
0.329 mmol, 94% from 33). M.p. 110–1118C; [a]2D8 = +88.72 (c=2.00 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=4.31 (dd, J=6.2, 1.5 Hz, 1H),
4.27 (dd, J=5.8, 1.4 Hz, 1H), 4.02–3.92 (m, 3H), 3.76–3.66 (m, 1H),
2.90–2.79 (m, 1H), 2.45–2.29 (m, 3H), 1.99–1.88 (m, 2H), 1.88–1.76 (m,
2H), 1.71–1.45 (m, 7H), 1.44–1.32 (m, 2H), 1.32–1.06 (m, 14H), 1.04 (d,
J=6.7 Hz, 3H), 1.05–0.94 (m, 2H), 0.92 ppm (d, J=6.2 Hz, 6H);
13C NMR (75 MHz, CDCl3): d=175.9, 104.09, 104.06, 86.8, 86.1, 67.6,
60.5, 60.3, 53.6, 53.4, 49.1, 48.5, 40.7, 37.2, 37.1, 34.9, 34.6, 30.6, 26.4, 25.4,
25.39, 25.34, 23.9, 19.78, 19.75, 19.2, 18.1 ppm; FTIR (film): n˜ =2933,
2873, 1731, 1455, 1374, 1207, 1196, 1170, 1146, 1088, 1048, 830 cmÀ1; ESI-
MS: m/z: 537.4 [M+H]+, 554.4 [M+NH4]+, 559.4 [M+Na]+; elemental
analysis: calcd (%) for C32H50O10·H2O: C 64.96, H 9.09; found: C 65.07,
H 8.65.
Compound 55: A pale-yellow solid; 97.68% pure (tr (major)=21.08 min)
as determined by HPLC analysis on a Kromasil C18 column (150ꢃ
4.5 mm) eluted with MeOH/H2O (10:90 to 100:0) at a flow rate of
1.0 mLminÀ1 with a UV detector set to 291 nm; m.p. 171–1738C; [a]2D9
=
+72.83 (c=0.65 in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.92–7.83
(m, 3H), 7.76–7.66 (m, 2H), 7.57–7.42 (m, 3H), 4.40 (d, J=11.3 Hz, 1H),
4.07 (d, J=11.6 Hz, 1H), 2.93 (quint, J=7.2 Hz, 1H), 2.46 (dt, J=14.3,
3.5 Hz, 1H), 2.04–1.83 (m, 3H), 1.74–1.57 (m, 2H), 1.54 (d, J=7.1 Hz,
3H), 1.47–1.24 (m, 7H), 1.08–0.98 (m, 1H), 0.95 ppm (d, J=6.3 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=175.1, 134.0, 132.0, 128.5, 127.5, 126.1,
125.86, 125.83, 125.4, 121.5, 120.8, 104.1, 86.2, 60.2, 53.4, 48.4, 37.3, 37.2,
34.7, 26.4, 25.5, 25.3, 19.7, 18.5 ppm; FTIR (film): n˜ =3245, 2929, 2875,
1655, 1536, 1504, 1376, 1345, 1280, 1252, 1206, 1184, 1171, 1142, 1090,
1046, 944, 911, 830, 798, 774, 734 cmÀ1; ESI-MS: m/z: 410.3 [M+H]+,
432.2 [M+Na]+; ESI-HRMS: m/z: calcd for C25H31NNaO4: 432.21453
[M+Na]+; found: 432.21408.
Compound 56:
A yellow/brown solid; 96.88% pure (tr (major)=
5.81 min) as determined by HPLC analysis on a Kromasil C18 column
(150ꢃ4.5 mm) eluted with MeOH/H2O (80:20, containing 0.1% TFA) at
a flow rate of 1.0 mLminÀ1 with a UV detector set to 214 nm; m.p.
Coupling of acid 33 with ethylene glycol to afford esters 60 and 61: A sol-
ution of acid 33 (100 mg, 0.352 mmol), DMAP (8.6 mg, 0.0704 mmol),
and EDCI (135 mg, 0.704 mmol) in dry CH2Cl2 (3 mL) was stirred at am-
7616
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 7605 – 7619