9
1
343.15400; found: 343.15430. H NMR (300 MHz, CDCl3) δ
130.1, 129.8, 128.5, 128.1, 127.8, 117.9, 75.7, 75.2, 72.7, 71.8,
ACCEPTED MANUSCRIPT
8.04 (dd, J = 5.2, 3.3 Hz, 2H), 7.58 (ddd, J = 6.8, 4.0, 1.3 Hz,
1H), 7.44 (dd, J = 10.5, 4.7 Hz, 2H), 7.40 – 7.28 (m, 5H), 5.95
(ddd, J = 17.2, 10.5, 5.2 Hz, 1H), 5.40 (dt, J = 17.3, 1.5 Hz, 1H),
5.27 (dt, J = 10.6, 1.4 Hz, 1H), 4.81 (d, J = 11.4 Hz, 1H), 4.74
(dd, J = 12.1, 3.3 Hz, 1H), 4.64 (d, J = 11.4 Hz, 1H), 4.55 (dd, J =
12.1, 4.8 Hz, 1H), 4.47 (m, 1H), 3.92 (ddd, J = 7.1, 4.7, 3.3 Hz,
1H), 3.71 (td, J = 6.6, 2.5 Hz, 1H), 2.63 (d, J = 6.2 Hz, 1H), 2.39
(d, J = 5.7 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 166.8, 137.5,
137.1, 133.2, 129.7, 128.6, 128.5, 128.1, 128.1, 116.7, 77.8, 72.9,
72.4, 71.3, 63.6. IR (film, cm-1): 3438, 1716, 1601, 1070.
63.8, 25.9, 18.2, -4.2, -4.7. IR (film, cm-1): 2908, 1724, 1633,
1454, 1404, 1261, 1223, 1184, 1110, 1092, 1068, 1030.
4.14. (R)-2-(benzyloxy)-2-((2R,3R)-3-((tert-
butyldimethylsilyl)oxy)-6-oxo-3,6-dihydro-2H-pyran-2-yl)ethyl
benzoate 29
To a stirred solution of 28 (110 mg, 0.215 mmol, 1 eq.) in
toluene (10 mL) was added HG-II (6.5 mg, 10 µmol). The
resulting reaction mixture was allowed to stir at 85°C for 2 h,
before a second portion of HGII (8 mg, 12 µmol) was added to
ensure full conversion after 4 additional hours. The reaction
mixture was then filtered through a pad of celite®/silica (1/1);
which was thoroughly washed with Et2O (2 x 15 mL). The
combined organic fractions were concentrated under reduced
pressure and the brown residue was purified by flash column
chromatography on silica gel (PE/EtOAc 10:1 to 2:1) to yield
lactone 29 (82 mg, 79%) as a colorless oil. [α]D20= -105.7 (c=0.8,
CHCl3). HRMS m/z calcd for C27H35O6Si: 483.21974; found:
4.12. (2R,3R,4R)-2-(benzyloxy)-4-((tert-butyldimethylsilyl)oxy)-
3-hydroxyhex-5-en-1-yl benzoate 27
To a stirred solution of 26 (60 mg, 0.175 mmol, 1 eq.) in
DCM (3 mL) was added subsequently at 0°C, 2,6-lutidine (0.045
mL, 0.386 mmol, 2.2 eq.) and TMSOTf (0.04 mL, 0.175 mmol, 1
eq.). After 30 min, the reaction was quenched by addition of a
saturated aqueous solution of NaHCO3 (20 mL) and DCM (50
mL). After phase separation, the aqueous layer was extracted
with DCM (2 x 20 mL). The combined organic fractions were
dried over MgSO4, filtered and concentrated under reduced
pressure. The resulting residue was further purified by flash
column chromatography on silica gel (PE/EtOAc 20:1 to 15:1) to
yield 27 as a colorless oil (78 mg, 97%). [α]D20= -3.9 (c=3.7,
CHCl3). HRMS m/z calcd for C26H37O5Si: 457.24048; found:
1
483.21986. H NMR (300 MHz, CDCl3) δ 8.09 – 7.97 (m, 2H),
7.56 (tt, J = 7.1, 1.3 Hz, 1H), 7.50 – 7.37 (m, 2H), 7.34 – 7.26 (m,
5H), 7.00 (dd, J = 9.7, 5.8 Hz, 1H), 6.15 (d, J = 9.7 Hz, 1H), 5.14
(dd, J = 12.5, 2.2 Hz, 1H), 4.91 (d, J = 10.7 Hz, 1H), 4.51 (m,
4H), 4.23 (dt, J = 5.3, 2.4 Hz, 1H), 0.90 (s, 9H), 0.10 (s, 3H),
0.08 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 166.3, 162.8, 144.8,
137.7, 133.2, 130.2, 129.8, 128.5, 128.0, 127.8, 123.5, 78.8, 74.5,
71.9, 61.1, 60.2, 25.9, 18.2, -3.2, -4.2. IR (film, cm-1): 2932,
2854, 1724, 1454, 1342, 1315, 1273, 1250, 1111, 1068, 1030.
1
457.24006. H NMR (300 MHz, CDCl3) δ 8.05 (d, J = 7.2 Hz,
2H), 7.61 – 7.52 (t, J=7.8 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.37
– 7.23 (m, 5H), 5.96 (ddd, J = 17.4, 10.3, 7.2 Hz, 1H), 5.28 (d, J
= 17.2 Hz, 1H), 5.19 (d, J = 10.4 Hz, 1H), 4.91 (dd, J = 12.1, 2.5
Hz, 1H), 4.82 (d, J = 11.2 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H),
4.51 (dd, J = 12.2, 4.7 Hz, 1H), 4.46 (m, 1H), 3.74 (ddd, J = 7.3,
4.5, 2.5 Hz, 1H), 3.64 (td, J = 7.6, 2.6 Hz, 1H), 2.64 (d, J = 8.0
Hz, 1H), 0.91 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 166.6, 138.6, 138.2, 133.1, 130.3, 129.8, 128.5,
128.5, 127.9, 116.9, 77.7, 74.0, 73.1, 72.1, 63.5, 26.0, 18.3, -3.6,
-4.7. IR (film, cm-1): 3491, 2928, 2854, 1720, 1647, 1454, 1389,
1273, 1258, 1219, 1099, 1057, 1026, 1003.
4.15. (-)-cleistenolide 11
To a stirred solution of 29 (350 mg, 0.725 mmol, 1 eq.) in
acetic anhydride (2 mL) was added FeCl3 (40 mg, 0.247 mmol,
0.34 eq.). The resulting mixture was left stirring at r.t. for 30 min.
DCM (60 mL) and a saturated aqueous solution of NaHCO3 (200
mL) were then added. After phase separation, the red turbid
aqueous layer was extracted with EtOAc (2 x 100 mL). The
combined organic layers were dried over MgSO4, filtered and
concentrated under reduced pressure. The crude residue was
purified by flash column chromatography on silica gel
(PE/EtOAc 10:1 to 1:1) to yield (-)-cleistenolide 11 (230 mg,
88%) as white crystals. Mp=130°C. [α]D20= -144.3 (c=3.85,
CHCl3). HRMS m/z calcd for C18H19O8: 363.10744; found:
4.13. (2R,3R,4R)-3-(acryloyloxy)-2-(benzyloxy)-4-((tert-
butyldimethylsilyl)oxy) hex-5-en-1-yl benzoate 28
To a stirred solution of acrylic acid (0.66 mL, 9.64 mmol, 1.1
eq.) in toluene (80 mL) was added sequentially triethylamine
(7.33 mL, 52.6 mmol, 6 eq.) and 2,4,6-trichlorobenzoyl chloride
(1.5 mL, 9.64 mmol, 1.1 eq.) which resulted in a white
precipitate. After 1 h, alcohol 27 (4.0 g, 8.76 mmol, 1 eq.) and
DMAP (0.53 g, 4.38 mmol, 0.5 eq.) in toluene (20 mL) were
added. After 2 h, the reaction mixture was poured onto a
saturated aqueous solution of NaHCO3 (100 mL) and Et2O (50
mL). After phase separation, the aqueous layer was extracted
with Et2O (2 x 40 mL). The combined organic fractions were
dried over MgSO4, filtered and concentrated under reduced
pressure. The brown residue was further purified by flash column
chromatography on silica gel (PE/EtOAc 15:1) to yield 28 as a
colorless oil (3.85 g, 86%). [α]D20= +46.9 (c=2.5, CHCl3). HRMS
m/z calcd for C29H39O6Si: 511.25104; found: 511.25195. 1H
NMR (300 MHz, CDCl3) δ 8.03 (dt, J = 7, 1.5 Hz, 2H), 7.57 (tt, J
= 7.4, 1.3 Hz, 1H), 7.45 (tt, J = 7.5, 1.4 Hz, 2H), 7.37 – 7.24 (m,
5H), 6.45 (dd, J = 17.3, 1.5 Hz, 1H), 6.17 (dd, J = 17.3, 10.4 Hz,
1H), 5.88 (ddd, J = 17.3, 10.3, 6.6 Hz, 1H), 5.86 (dd, J = 10.3, 1.5
Hz, 1H), 5.39 (dd, J = 6.4, 4.0 Hz, 1H), 5.35 (td, J =17.3, 1.3 Hz,
1H), 5.23 (dt, J = 10.4, 1.2 Hz, 1H), 4.71 (d, J = 11.6 Hz, 1H),
4.70 (dd, J = 12.0, 3.1 Hz, 1H), 4.64 (d, J = 11.6 Hz, 1H), 4.41
(dt, J = 6.5, 1.3 Hz, 1H), 4.37 (dd, J = 12.1, 7.0 Hz, 1H), 4.03 (q,
J = 3.5 Hz, 1H), 0.90 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ 166.5, 165.3, 137.9, 136.9, 133.2, 131.4,
1
363.10745. H NMR (300 MHz, CDCl3) δ 8.02 (d, J = 7.1 Hz,
2H), 7.58 (tt, J = 7.4, 1.3 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.00
(dd, J = 9.7, 6.1 Hz, 1H), 6.29 (d, J = 9.7 Hz, 1H), 5.51 (ddd, J =
9.6, 4.4, 2.4 Hz, 1H), 5.42 (dd, J = 6.1, 2.7 Hz, 1H), 4.93 (dd, J =
12.5, 2.4 Hz, 1H), 4.80 (dd, J = 9.6, 2.7 Hz, 1H), 4.53 (dd, J =
12.5, 4.5 Hz, 1H), 2.09 (s, 3H), 2.04 (s, 3H). 13C NMR (125
MHz, CDCl3) δ 170.1, 169.6, 166.1, 161.3, 139.9, 133.4, 129.8,
129.7, 128.7, 125.5, 75.6, 67.8, 62.1, 59.9, 20.8, 20.6. IR (film,
cm-1): 2993, 2966, 1728, 1639, 1443, 1373, 1277, 1215, 1180,
1153, 1072, 1022, 1003.
Acknowledgments
P.K. thanks F.R.I.A (Fonds pour la formation à la recherche
dans l’industrie et dans l’agriculture) for a fellowship. G.C.C.
thanks UCL (Université catholique de Louvain) for financial
support. We thank Fabio Lucaccioni for valuable technical
support and Cécile Le Duff and Alain Jancart for NMR support.
References and notes
1. a) Isolation: Sehgal SN, Baker H, Vézina C. J. Antibiot. 1975, 28:727. b)
Immunosuppressive effects: Martel RR, Klicius J, Galet S, Can. J.
Physiol. Pharmacol. 1977, 55:48.