N. Winssinger et al.
3.49 (s, 3H), 3.48 (s, 3H), 3.18 (dd, J=7.0, 2.2 Hz, 1H), 3.03 (td, J=5.6,
2.2 Hz, 1H), 2.32 (s, 3H), 2.00 (ddd, J=14.5, 5.9, 5.9 Hz, 1H), 1.90 (ddd,
J=14.5, 5.4, 5.4 Hz, 1H), 1.45 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3, 258C): d = 167.4, 158.6, 155.2, 137.7, 135.3, 119.2, 118.6, 110.6,
101.0, 94.6, 94.2, 69.2, 57.9, 56.9, 56.1, 56.0, 38.1, 19.9, 19.6; IR (film):
n˜max =2933, 1724, 1607, 1452, 1320, 1268, 1214, 1268, 1148, 1095, 1051,
1025, 926 cmꢀ1; HRMS (ESI-TOF): m/z: calcd for C19H26O7Na: 389.1571,
Compound 53: A 2 mm solution of compound 49a (100 mg, 0.18 mmol)
in anhydrous toluene was heated at 1208C and treated with 5% mol of
Grubbs catalyst, 2nd generation (8 mg, 0.009 mmol). The reaction mix-
ture was stirred for 10 min at that temperature and quenched quickly by
cooling down to ꢀ788C. The reaction mixture was then filtered through a
pad of silica gel, washed with CH2Cl2 and concentrated under reduced
pressure. Purification by flash chromatography (silica gel, 0–25%
EtOAc/hexane gradient) afforded compound 53 (89 mg, 94%) as a mix-
ture of diastereoisomers (epimers and mixture of cis/trans olefin 1:1). By
preparative TLC (silica gel, 50% EtOAc/hexane), it was possible to sepa-
rate the two epimers: Rf =0.10 (silica gel, EtOAc/hexane 1:3); less polar
found 389.1601 [M+Na+]. (ꢀ)-(2R,4S,5R): [a]2D0
=
ꢀ15.3 (c 0.51,
CHCl3).
Compound 49a: A solution of compound 48a (366 mg, 1.0 mmol) in an-
hydrous THF (1 mL) was treated at ꢀ788C with freshly made LDA
(3.8 mL, 2.0 mmol). After 5 min stirring, a solution of compound 12
(251 mg, 1.0 mmol) in THF (0.7 mL) was added dropwise. The resulting
mixture was then stirred for 5 min at ꢀ788C and quenched by addition
of a solution of saturated NH4Claq. Upon warming to room temperature,
the reaction was diluted with EtOAc, washed several times with saturat-
ed NH4Claq, brine and dried over MgSO4. Concentration under reduced
pressure, followed by flash chromatography (silica gel, 0–10% EtOAc/cy-
clohexane gradient) afforded compound 49a (450 mg, 81%) as a mixture
of diastereoisomers. Rf =0.35 (silica gel, hexane/EtOAc 3:1); 1H NMR
(400 MHz, CDCl3, 258C): d=7.40–7.35 (m, 4H), 7.33–7.30 (m, 6H), 6.69
(d, J=2.2 Hz, 2H), 6.57 (d, J=2.2 Hz, 2H), 5.83–5.77 (m, 2H), 5.63–5.44
(m, 4H), 5.35–5.26 (m, 4H), 5.16 (s, 4H), 5.14 (s, 4H), 5.18–5.08 (m, 4H),
4.10 (d, J=16.1 Hz, 1H), 4.07 (d, J=16.6 Hz, 1H), 4.02 (d, J=16.5 Hz,
1H), 3.97 (d, J=16.1 Hz, 1H), 3.85–3.77 (m, 2H), 3.48 (s, 6H), 3.46 (s,
6H), 3.13 (dd, J=7.3, 2.2 Hz, 2H), 3.08–3.04 (m, 2H), 2.66–2.55 (m, 2H),
2.47–2.39 (m, 2H), 1.96–1.92 (m, 4H), 1.41 (d, J=6.4 Hz, 6H).
1
epimer: H NMR (400 MHz, CDCl3, 258C): d = 7.43 (d, J=7.0 Hz, 2H),
7.35–7.26 (m, 3H), 6.73 (d, J=2.4 Hz, 1H), 6.19 (d, J=2.1 Hz, 1H), 5.88–
5.81 (m, 1H), 5.53–5.46 (m, 1H), 5.17–5.13 (m, 1H), 5.15 (d, J=2.4 Hz,
2H), 5.07 (d, J=1.2 Hz, 2H), 4.23 (d, J=18.7 Hz, 1H), 4.00–3.93 (m,
1H), 3.91 (d, J=18.7 Hz, 1H), 3.50 (s, 3H), 3.48 (s, 3H), 3.25 (bd, J=
4.1 Hz, 1H), 2.82–2.77 (m, 1H), 2.57–2.47 (m, 2H), 2.40–2.34 (m, 2H),
1.38 (d, J=6.2 Hz, 3H); more polar epimer: 1H NMR (400 MHz, CDCl3,
258C): d = 7.57–7.54 (m, 2H), 7.40–7.35 (m, 3H), 6.73 (d, J=2.0 Hz,
1H), 6.35 (d, J=2.0 Hz, 1H), 5.80–5.71 (m, 1H), 5.25–5.13 (m, 5H), 5.01
(dd, J=15.5, 8.9 Hz, 1H), 3.98 (d, J=19.3 Hz, 1H), 3.81 (dd, J=12.1,
3.6 Hz, 1H), 3.64 (d, J=19.3 Hz, 1H), 3.52 (s, 3H), 3.48 (s, 3H), 3.25 (dd,
J=8.8, 2.3 Hz, 1H), 2.79–2.76 (m, 1H), 2.65–2.50 (m, 2H), 2.44–2.29 (m,
2H), 1.37 (d, J=6.2 Hz, 3H).
Compound 52: Neat sulfuryl chloride (7.5 mL, 0.09 mmol) was added to a
cooled (08C) solution of compound 51a (13 mg, 0.03 mmol) in Et2O
(1 mL). The reaction was stirred for 1.5 h at 08C and then diluted with
CH2Cl2 (5 mL). The mixture was washed several times with saturated
NH4Claq (8 mL) and dried over MgSO4. Removal of the solvents under
reduced pressure, followed by flash chromatography (silica gel, 0–33%
EtOAc/cyclohexane), afforded compound 52 (10 mg, 68%). Rf =0.25
(silica gel, EtOAc/cyclohexane 1:1); 1H NMR (400 MHz, CDCl3, 258C):
d = 7.18 (dd, J=16.2, 11.2 Hz, 1H), 7.04 (s, 1H), 6.26 (dd, J=10.9,
10.9 Hz, 1H), 6.10 (d, J=16.4 Hz, 1H), 5.81 (dd, J=10.2, 10.2 Hz, 1H),
5.47 (m, 1H), 5.35–5.12 (m, 5H), 4.11 (d, J=15.8 Hz, 1H), 3.92 (d, J=
15.8 Hz, 1H), 3.55 (s, 3H), 3.53 (s, 3H), 3.55–3.48 (m, 1H), 2.08–2.04 (m,
2H), 1.57 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3, 258C): d =
196.3, 166.7, 159.3, 156.0, 140.8, 137.9, 134.7, 133.2, 131.2, 117.8, 102.0,
95.2, 94.6, 71.9, 69.7, 60.4, 56.7, 56.4, 45.1, 21.0, 18.8, (1Cquat. is not visi-
ble); IR (film): n˜max =3075, 2930, 1685, 1647, 1618, 1571, 1439, 1235, 1147,
Compound 50a: A solution of compound 49a (333 mg, 0.6 mmol) in hexa-
fluoroisopropanol (3 mL) was treated with hydrogen peroxide (35% so-
lution in water, 117 mL, 1.2 mmol) and stirred for 3 h at room tempera-
ture. The reaction mixture was diluted in EtOAc, washed with a saturat-
ed aqueous solution of NaHCO3/Na2S2O3 (10:1, 11 mL), dried over
MgSO4 and concentrated under reduced pressure. The crude mixture was
then dissolved in toluene (5 mL) and stirred for 1 h at 808C. Concentra-
tion under reduced pressure, followed by flash chromatography (silica
gel, 0–50% EtOAc/cyclohexane gradient) afforded compound 50a
(249 mg, 92%). Rf =0.20 (silica gel, hexane/EtOAc 3:1); 1H NMR
(400 MHz, CDCl3, 258C): d = 7.22 (dd, J=15.6, 10.7 Hz, 1H), 6.80 (d,
J=2.2 Hz, 1H), 6.56 (d, J=2.2 Hz, 1H), 6.51–6.41 (m, 1H), 6.27 (d, J=
15.6 Hz, 1H), 5.69 (d, J=17.2 Hz, 1H), 5.63–5.55 (m, 2H), 5.48 (dd, J=
17.2, 1.6 Hz, 1H), 5.34–5.26 (m, 2H), 5.17 (s, 4H), 3.94 (m, 2H), 3.49 (s,
3H), 3.48 (s, 3H), 3.14 (dd, J=7.5, 2.1 Hz, 1H), 3.04 (td, J=5.9, 2.1 Hz,
1H), 1.99–1.87 (m, 2H), 1.41 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3, 258C): d = 196.3, 167.0, 159.1, 156.2, 143.2, 135.4, 135.2, 135.1,
129.2, 126.7, 119.3, 118.5, 111.4, 102.5, 94.8, 94.3, 69.5, 58.1, 56.9, 56.3,
56.2, 45.9, 38.1, 19.9; HRMS (ESI-TOF): m/z: calcd for C24H30O8Na:
469.1833, found 469.1952 [M+Na+].
1112, 1080, 1017, 942 cmꢀ1
; HRMS (ESI-TOF): m/z: calcd for
C22H26Cl2O8: 510.9994, found 511.0002 [M+Na+].
Pochonin C (8): A solution of compound 52 (10 mg, 0.02 mmol) in diox-
ane (5 mL) was treated at 08C with HClconc (125 mL, to reach a 2.5% so-
lution). The reaction was then allowed to warm up to room temperature
and stirred for 1 h. The resulting solution was filtered on a pad of silica
gel and washed several times with Et2O. The solvents were removed
under reduced pressure and preparative TLC (silica gel, 50% EtOAc/cy-
clohexane) provided synthetic pochonin C (8) (6.3 mg, 74%). Synthetic
pochonin C was found to have identical 1H NMR as natural pochonin C
(see Supporting Information). Rf =0.11 (silica gel, EtOAc/cyclohexane
1:3); 1H NMR (400 MHz, CDCl3, 258C): d = 9.28 (s, 1H), 8.59 (s, 1H),
7.11 (dd, J=14.7, 12.3 Hz, 1H), 6.66 (s, 1H), 6.31 (t, J=10.4 Hz, 1H),
6.10 (d, J=16.1 Hz, 1H), 5.91 (m, 1H), 5.78 (t, J=9.9 Hz, 1H), 5.22 (d,
J=15.8 Hz, 1H), 4.92 (t, J=9.1 Hz, 1H), 3.96 (d, J=15.8 Hz, 1H), 3.95
(m, 1H), 2.48 (dd, J=15.8, 10.7 Hz, 1H), 2.13 (m, 1H), 1.54 (d, J=
6.4 Hz, 3H); 1H NMR (400 MHz, [D6]DMSO, 258C): d = 10.58 (s, 1H),
10.13 (s, 1H), 7.12 (dd, J=16.1, 11.3 Hz, 1H), 6.56 (s, 1H), 6.27 (t, J=
10.8 Hz, 1H), 6.04 (d, J=16.1 Hz, 1H), 5.78 (t, J=10.8 Hz, 1H), 5.46 (d,
J=5.4 Hz, 1H), 5.28 (m, 1H), 5.10 (dd, J=9.9, 4.8 Hz, 1H), 4.05 (d, J=
16.1 Hz, 1H), 3.99 (m, 1H), 3.60 (d, J=16.1 Hz, 1H), 1.87 (m, 2H), 1.37
(d, J=6.2 Hz, 3H); 1H NMR (400 MHz, CD3OD, 258C): d = 7.28 (dd,
J=16.0, 11.1 Hz, 1H, H8), 6.53 (s, 1H, H15), 6.25 (dd, J=10.7, 10.7 Hz,
1H, H7), 6.02 (d, J=16.6 Hz, 1H, H9), 5.82 (dd, J=10.7, 10.7 Hz, 1H,
H6), 5.47–5.43 (m, 1H, H2), 5.20 (dd, J=9.7, 5.9 Hz, 1H, H5), 4.27 (d, J=
16.1 Hz, 1H, H11), 4.03–4.00 (m, 1H, H4), 3.73 (d, J=16.1 Hz, 1H, H11),
2.11 (dd, J=14.0, 6.9 Hz, 1H, H3), 2.00–1.92 (m, 1H, H3), 1.48 (d, J=
Compound 51a: A 2 mm solution of compound 50a (150 mg, 0.34 mmol)
in anhydrous toluene was heated at reflux and treated with 5% mol of
Grubbs catalyst, 2nd generation (14 mg, 0.017 mmol). The reaction mix-
ture was stirred for 10 min at that temperature and quenched by cooling
it down to ꢀ788C. The reaction mixture was then filtered through a pad
of silica gel, washed with CH2CL2 and concentrated under reduced pres-
sure. Purification by flash chromatography (silica gel, 0–25% EtOAc/cy-
clohexane gradient) afforded 51a (122 mg, 87%). Rf =0.19 (silica gel,
EtOAc/cyclohexane 1:3); 1H NMR (400 MHz, CDCl3, 258C): d = 7.68
(dd, J=16.1, 11.3 Hz, 1H), 6.75 (d, J=2.1 Hz, 1H), 6.59 (d, J=2.1 Hz,
1H), 6.26 (dd, J=11.3, 11.2 Hz, 1H), 6.05 (d, J=16.1 Hz, 1H), 5.84 (dd,
J=10.8, 4.4 Hz, 1H), 5.42–5.33 (m, 1H), 5.21–5.17 (m, 2H), 5.14 (s, 2H),
3.97 (d, J=14.0 Hz, 1H), 3.86 (d, J=13.4 Hz, 1H), 3.57 (m, 1H), 3.48 (s,
3H), 3.47 (s, 3H), 3.13–3.10 (ddd, J=7.5, 3.7, 2.2 Hz, 1H), 2.47 (dt, J=
14.5, 4.8 Hz, 1H), 1.73 (ddd, J=15.0, 7.5, 3.2 Hz, 1H), 1.59 (d, J=6.4 Hz,
3H); 13C NMR (100 MHz, CDCl3, 258C): d = 197.9, 166.8, 159.2, 156.0,
140.2, 136.6, 134.5, 131.8, 130.2, 117.8, 108.7, 102.1, 94.6, 94.3, 69.8, 56.3,
55.8, 54.9, 42.4, 37.1, 29.7, 18.9; IR (film): n˜max =2923, 2849, 1719, 1664,
1602, 1461, 1286, 1149, 1027, 920 cmꢀ1; HRMS (ESI-TOF): m/z: calcd for
C22H26O8Na: 441.1520, found 441.1595 [M+Na+]. (ꢀ)-(2R,4S,5R): [a]2D0
ꢀ50.0 (c 0.11, CHCl3).
=
6.4 Hz, 3H, H1); 13C NMR (100 MHz, [D6]DMSO, 258C): d
166.5, 155.5, 139.1, 137.0, 133.2, 132.1, 129.9, 115.1, 112.2, 102.9, 71.1,
= 197.0,
4948
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 4935 – 4952