9
10.3, 4.4 Hz, 1H, H-3a), 3.41 (dd, J = 10.3, 5.9 Hz, 1H, H-3b),
3.21 (s, 9H, N(CH3)3), 2.28-2.18 (m, 3H, H-6’ and H-2”a), 2.12-
2.03 (m, 1H, H-2”b), 1.76 (s, 3H, H-19’), 1.45 (quint, J = 6.9 Hz,
2H, H-7’), 1.41 (s, 6H, H-17’ and H-18’), 1.37-1.25 (m, 16H),
0.90 (t, J =7.1 Hz, 3H, H-16’); 13C NMR (100 MHz, CD3OD): δ
200.69, 176.59, 171.82, 144.24, 135.70, 77.65, 73.39, 69.36,
68.57, 67.24, 54.00, 52.36 (t, J C-N = 3.8 Hz; with 3 lines at 52.39,
52.36 and 52.32, respectively), 33.08, 30.75, 30.70, 30.54, 30.49,
30.41, 29.84, 29.66, 28.98, 25.09, 23.75, 14.45, 12.60; FT-IR
(film of a solution in CH2Cl2): 3396, 2923, 2854, 1733, 1667,
1628, 1466, 1390, 1364, 1271, 1123, 1043 cm–1. ESI-MS: m/z
528.5 ([M+H]+); ESI-HRMS calcd for C29H54NO7 ([M+H]+):
528.3895, found 528.3897.
24.528, 22.646, 14.081, 12.396; FT-IR (film): 3406, 2924,
ACCEPTED MANUSCRIPT
2854, 1734, 1668, 1626, 1466, 1390, 1273, 1123 cm–1. ESI-MS:
m/z 536.9 ([M+Na]+); ESI-HRMS calcd for C28H51NO7Na
([M+Na]+): 536.3558, found 536.3547.
4.29. Methylation of epi-36 to afford (2R,3’’S)-3
The same procedure given above for methylation of 36 to
afford (2S,3’’S)-3 was employed (except for that epi-36 was used
instead of 36). Yield (a colorless oil, 10 mg, 0.02 mmol): 67%
overall from epi-36. Data for (2R,3’’S)-3: [α]D27+12.2 (c 0.23,
1
MeOH). H NMR (400 MHz, CD3OD): δ 6.42 (dt, J = 1.0, 7.3
Hz, 1H), 4.13 (dd, J = 11.2, 4.9 Hz, 1H), 4.10 (dd, J = 11.2, 5.9
Hz, 1H), 3.90 (quint, J = 5.4 Hz, 1H), 3.77 (dd, J = 11.2, 2.5 Hz,
1H), 3.62 (ddd, J = 9.3, 5.4, 3.9 Hz, 1H), 3.56 (dt, J = 4.4, 9.3
Hz, 1H), 3.45 (dd, J = 10.1, 4.7 Hz, 1H), 3.42 (dd, J = 10.3, 5.9
Hz, 1H), 3.21 (s, 9H), 2.28-2.18 (m, 3H), 2.12-2.02 (m, 1H), 1.76
(s, 3H), 1.45 (quint, J = 6.9 Hz, 2H), 1.41 (s, 6H), 1.37-1.25 (m,
16H), 0.90 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CD3OD): δ
200.70, 176.59, 171.84, 144.23, 135.72, 77.61, 73.25, 69.11,
68.32, 67.18, 53.99, 52.36 (t, J C-N = 3.8 Hz; with 3 lines at 52.40,
52.36 and 52.32, respectively), 33.07, 30.75, 30.70, 30.53, 30.48,
30.41, 29.84, 29.65, 28.92, 25.10, 23.75, 14.44, 12.60; FT-IR
(film of a solution in CH2Cl2): 3396, 2923, 2854, 1733, 1667,
1628, 1466, 1390, 1364, 1271, 1123, 1043 cm–1. ESI-MS: m/z
528.5 ([M+H]+); ESI-HRMS calcd for C29H54NO7 ([M+H]+):
528.3895, found 528.3894.
4.26. Synthesis of epi-37 from (R)-9b and ent-30 via epi-31b
The same procedure given above for synthesis of 37 from (S)-
9b and 30 via 31b was employed (except for that ent-30 was used
instead of 30). Yield (a colorless oil, 260 mg, 0.75 mmol): 31%
from ent-30. Data for epi-37: [α]D26 +5.6 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): δ 5.31 (d, J = 7.3 Hz, 1H), 4.44-4.30 (m,
1H), 3.88-3.82 (m, 1H), 3.74-3.66 (m, 1H), 3.62-3.52 (m, 3H),
3.46-3.36 (m, 2H), 2.18-2.00 (m, 1H), 1.82-1.70 (m, 1H), 1.45 (s,
9H), 1.42 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 172.215,
155.559, 82.141. 79.946, 72.457, 70.597, 67.104, 63.444, 51.288,
32.875, 28.266, 27.945; FT-IR (film): 3390, 2977, 2931, 2870,
1713, 1505, 1393, 1367, 1252, 1155, 1053 cm–1. ESI-MS: m/z
372.5 ([M+Na]+); ESI-HRMS calcd for C16H31NO7Na ([M+Na]+):
372.1993, found 372.1994.
Acknownledgments
4.27. Condensation of acid 29 with alcohol epi-37 to afford epi-
38
This work was supported by the National Natural Science Foundation of
China (21372248, 215732002, 21672244) and the Strategic Priority Research
Program of the Chinese Academy of Sciences (Grant No. XDB20020200).
The same procedure given above for condensation of acid 29
with alcohol 37 to afford 38 was employed (except for that epi-
37 was used instead of 37). Yield (a colorless oil, 100 mg, 0.16
mmol): 34% from epi-37, along with recovered epi-37 (35%).
Supplementary data
Scanned spectra for new compounds, NMR data comparison tables.
References and notes
1
Data for epi-37: [α]D25 +4.2 (c 1.0, CDCl3). H NMR (500 MHz,
CDCl3): δ 6.36 (dt, J = 1.0, 7.3 Hz, 1H), 5.22 (d, J = 7.9 Hz, 1H),
4.39-4.32 (m, 1H), 4.10 (dd, J = 11.5, 5.6 Hz, 1H ), 4.06 (dd, J =
11.2, 5.4 Hz, 1H), 3.95-3.88 (m, 1H), 3.57-3.50 (m, 1H), 3.50-
3.40 (m, 2H), 3.28-3.20 (m, 1H), 2.16 (q, J = 7.3 Hz, 2H), 2.13-
2.05 (m, 1H), 1.84-1.75 (m, 1H), 1.76 (s, 3H), 1.45 (s, 9H), 1.42
(s, 9H), 1.41 (s, 6H), 1.42-1.35 (m, 2H), 1.32-1.20 (m, 16H), 0.86
(t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 199.028,
175.277, 172.142, 155.450,142.674, 134.463, 82.039, 79.822,
72.362, 68.293, 67.265, 65.646, 52.666, 51.288, 32.685, 31.825,
29.549, 29.528, 29.477, 29.323, 29.258, 28.988, 28.463, 28.237,
27.923, 24.518, 22.600, 14.039, 12.311; FT-IR (film): 3435,
2977, 2926, 2855, 1732, 1671, 1504, 1456, 1392, 1367, 1253,
1155, 1056 cm–1; ESI-MS: m/z 665.0 ([M+Na]+); ESI-HRMS
calcd for C35H63NO9Na ([M+Na]+): 664.4395, found 664.4397.
1. Shen, S.; Liu, D.; Proksch, P.; Lin, W. Bioorg. Med. Chem. 2012,
20, 6924-6928.
2. Tsuda, M.; Endo, T.; Watanabe, K.; Fromont, J.; Kubayashi, J. J.
Nat. Prod. 2002, 65, 1670-1671.
3. Martín, J.; Crespo, G.; González-Menéndez, V.; Pérez-Moreno,
G.; Sánchez-Carrasco, P.; Pérez-Victoria, I.; Ruiz-Pérez, L.;
González-Pacanowska, D.; Vincente, F.; Genilloud, O.; Bills, G.
F.; Reyes, F. J. Nat. Prod. 2014, 77, 2118-2123.
4. (a) Xu, J.; Yadan, J. C. J. Org. Chem. 1995, 60, 6296-6310. (b)
Song, H.; Leninger, M.; Lee, N.; Liu, P. Org. Lett. 2013, 15, 4854-
4957. (c) Lutete, P.; Jardine, A. Org. Biomol. Chem. 2015, 13,
1415-1419.
5. Gao, H.; Kelly, M.; Hamann, M. T. Tetrahedron 1999, 55, 9717-
972.
6. Borreli, F.; Campagnuolo, C.; Capasso, R.; Fattorusso, E.;
Taglialatela-Scafati, O. Eur. J. Org. Chem. 2004, 3227-3232.
7. Fu, P.; MacMillan, J. B. Org. Lett. 2015, 17, 3046-3049.
8. Because 9 tends to cyclize (occurred even during recording the 1H
and 13C NMR), chromatography should be avoided, cf. also: (a)
Reginato, G.; Mordini, A.; Valacchi, M.; Grandini, E. J. Org.
Chem. 1999, 64, 9211-9216. (b) Kawazoe, Y.; Tanaka, Y.; Omura,
S.; Uemura, D. Tetrahedron Lett. 2014, 55, 4445-4447. (c)
Ragains, J. R.; Winkler, J. D. Org. Lett. 2006, 8, 4437-4440.
9. Wang, F.; He, W.-B.; Wang, J.-H.; Yan, X.-S.; Zhan, Y.; Ma, Y.-
Y.; Ye, L.-C.; Yang, R.; Cai, F.; Li, Z.; Jiang, Y.-B. Chem.
Commun. 2011, 47, 11784-11786.
10. Direct methylation with MeI or reductive methylation with
HCHO/NaBH(OAc)3 did not give any (R)-13.
11. Khonde, P. L.; Jardine, A. Org. Biomol. Chem. 2015, 12, 1415-
1419.
12. In the main text of ref 1 it was mentioned that “135.5 (C-3, C-5)
indicated a symmetrically substituted phenyl ring”. The scanned
4.28. Conversion of epi-38 into epi-36 via epi-39
The same procedure given above for conversion of 38 into 36
via 39 was employed (except for that epi-38 was used instead of
38). Yield (a colorless oil, 18 mg, 0.04 mmol): 60% overall from
25
1
epi-38. Data for epi-36: [α]D +11.7 (c 1.0, CHCl3). H NMR
(500 MHz, CDCl3): δ 6.35 (t, J = 6.8 Hz, 1H), 4.09 (dd, J = 11.0,
5.7 Hz, 1H), 4.03 (dd, J = 11.0, 6.1 Hz, 1H ), 3.88 (quint, J = 4.9
Hz, 1H), 3.85-3.77 (m, 1H), 3.68-3.62 (m, 1H), 3.62-3.55 (m,
1H), 3.42-3.35 (m, 2H), 2.89 (s, 6H), 2.16 (q, J = 5.4 Hz, 2H),
2.13-2.03 (m, 2H), 1.75 (s, 3H), 1.40 (s, 6H), 1.39-1.34 (m, 2H),
1.34-1.20 (m, 16H), 0.87 (t, J = 6.9 Hz, 3H); 13C NMR (125
MHz, CDCl3): δ 199.167, 175.131, 170.806, 142.711, 134.449,
72.319, 68.768, 67.660, 67.516, 65.566, 52.721, 41.538, 31.872,
29.596, 29.573, 29.528, 29.369, 29.300, 29.035, 28.526, 27.532,