Organic & Biomolecular Chemistry
Paper
w/w).36 1H NMR (400 MHz, CDCl3): δ 5.75 (m, 1H), 4.30 yield). IR (NaCl): ν 2928, 1737, 1712, 1500, 1386, 1207, 1195,
1
(d, J = 12.3 Hz, 1H), 3.92 (d, J = 12.3 Hz, 1H), 3.85 (dd, J = 10.9, 754 cm−1; H NMR (400 MHz, CDCl3): δ 9.58 (d, 4.7 Hz, 1H),
1.8 Hz, 1H), 3.61 (dd, J = 10.7, 8.31 Hz, 1H), 2.14–1.79 7.43 (m, 2H), 7.36 (m, 1H), 7.10 (m, 2H), 5.98 (m, 1H), 4.29 (m,
(complex m, 5H), 1.57–1.35 (complex m, 4H), 1.27–1.06 2H), 3.84 (dd, J = 8.8, 6.0 Hz, 1H), 3.34 (dd, J = 8.8, 6.0 Hz, 1H),
(complex m, 4H), 0.85 (s, 3H), 0.84 (s, 3H), 0.72 (s, 3H); 13C 3.27 (m, 1H), 2.74 (m, 1H), 2.52 (ddd, J = 14.4, 4.8, 1.3 Hz, 1H),
NMR (100 MHz, CDCl3): δ 137.0, 127.1, 67.3, 61.2, 54.5, 49.5, 2.47 (m, 1H), 1.99 (m, 1H), 1.57–1.39 (complex m, 4H), 1.31 (t,
42.1, 39.4, 35.6, 33.3, 33.0, 23.6, 22.0, 18.9, 14.6 (see ESI, Appen- J = 7.1 Hz, 3H), 1.30–1.19 (m, 3H), 1.10 (s, 3H), 0.98 (s, 3H),
dix II† for the 1H and 13C NMR spectra of the isolated product).
0.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 202.5, 176.6, 175.7,
170.2, 137.1, 131.6, 129.4, 129.0, 126.7, 123.5, 67.3, 61.6, 48.5,
45.7, 43.6, 42.1, 41.8, 40.1, 36.8, 33.7, 33.6, 32.7, 22.4, 21.9,
(−)-Drimenol (5)
5% Pd/C (15 mg) was added to a solution of drimendiol (4) 18.4, 17.3, 14.3; MS (EI): 477 (M+), 462, 459, 432, 403, 402, 374,
(180 mg, 0.76 mmol) in EtOH (25 mL). The resulting suspen- 373, 304, 174, 137, 123, 109, 91, 81, 79, 69, 55; HRMS (EI):
sion was maintained under H2 (1 atm) for 1.25 h then filtered calcd for C29H35NO5 477.25152, found 477.25083; [α]2D2 = +72.9
through Celite™ and the solvent was removed on a rotary evap- (c 0.9, CHCl3).
orator. The ensuing residue was purified by flash chromato-
graphy (silica; 0 → 25% EtOAc/hexane) to provide the title
compound as a colourless solid (107 mg, 64% yield).37 1H
(6aS,10aS)-7,7,10a-Trimethyl-5,6,6a,7,8,9,10,10a-
octahydrobenzo[f]phthalazine (8)
NMR (400 MHz, CDCl3): δ 5.54 (m, 1H), 3.85 (dd, J = 11.3, 3.4
Hz, 1H), 3.73 (dd, J = 11.3, 4.9 Hz, 1H), 2.01–1.75 (complex m, Hydrazine hydrate (150 mg, 3.00 mmol) was added to a solu-
8H), 1.64–1.38 (complex m, 4H), 1.29 (br s, 1H), 1.22–1.12 tion of polygodial (2) (52 mg, 0.22 mmol) in EtOH (10 mL).
(complex m, 1H), 1.06 (td, J = 13.2, 3.8 Hz, 1H), 0.89 (s, 3H), The reaction mixture was heated at reflux for 1.5 h then cooled
0.86 (s, 3H), 0.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 133.1, and the mixture was concentrated on a rotary evaporator to
124.1, 61.0, 57.3, 42.2, 39.9, 36.1, 33.4, 33.0, 23.7, 22.1, 22.0, provide the title compound as a colourless solid (51 mg, >99%
18.9, 15.0; [α]2D2 = −12.5 (c 1.0, CHCl3).37
yield). IR (NaCl): ν 2999, 2959, 2947, 2926, 2866, 1559, 1458,
1422, 1383, 1175, 997, 909, 733 cm−1 1H NMR (400 MHz,
CDCl3): δ 8.99 (s, 1H), 8.80 (s, 1H), 2.91 (dd, J = 18.5, 6.7 Hz,
1H), 2.80 (ddd, J = 18.5, 11.1, 7.5 Hz, 1H), 2.34 (d, J = 12.5 Hz,
mg, 1H), 2.00 (dd, J = 13.7, 7.5 Hz, 1H), 1.85–1.62 (complex m, 3H),
;
(E)-Ethyl 3-((1R,4aS,8aS)-1-formyl-5,5,8a-trimethyl-
1,4,4a,5,6,7,8,8a-octahydronaphthalen-2-yl)acrylate (6)
Ethyl
(triphenylphosphoranylidene)acetate
(208
0.60 mmol) was added to a solution of polygodial (2) (101 mg, 1.53 (m, 1H), 1.41 (td, J = 13.0, 4.0 Hz, 1H) 1.30–1.19 (complex
0.43 mmol) in EtOH (15 mL). The reaction was heated to 40 °C m, 5H), 0.97 (s, 3H), 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3):
and after 2.5 h, the mixture was cooled and the solvent was δ 152.3, 149.1, 148.4, 135.7, 49.6, 41.4, 37.1, 36.5, 33.6, 33.2,
removed on a rotary evaporator. The ensuing residue was puri- 27.0, 24.3, 21.6, 18.8, 17.9; MS (EI): 230 (M+), 215, 161, 159,
fied by flash chromatography (silica; 0 → 15% EtOAc/hexane) 147, 145, 133, 119, 108, 91; HRMS (EI): calcd for C15H22N2
to provide the title compound as a colourless oil (102 mg, 79% 230.17830, found 230.17887; [α]2D2 = +16.9 (c 0.7, CHCl3).
yield). IR (NaCl): ν 2928, 1713, 1627, 1368, 1311, 1712,
1040 cm−1; H NMR (400 MHz, CDCl3): δ 9.46 (d, J = 4.8 Hz,
1H), 7.30 (d, J = 16.3 Hz, 1H), 6.49 (m, 1H), 5.48 (d, J = 16.3 Hz,
1
(+)-Euryfuran (10)
1H), 4.15 (q, 7.2 Hz, 2H), 2.81 (s, 1H), 2.31 (m, 1H), 2.20 (m, NaBH4 (27 mg, 0.71 mmol) was added to a solution of poly-
1H), 1.83 (m, 1H), 1.56–1.42 (complex m, 3 H), 1.38–1.13 godial (2) (83 mg, 0.35 mmol) in EtOH (20 mL) at 0 °C. After
(complex m, 6H), 0.99 (s, 3H), 0.93 (s, 3H), 0.89 (2, 3H); 13C 0.33 h H2O (30 mL) was added and the resulting mixture was
NMR (100 MHz, CDCl3): δ 205.4, 167.1, 146.4, 141.5, 130.5, extracted with CH2Cl2 (3 × 30 mL) to provide a pale-yellow oil
116.7, 62.9, 60.5, 48.8, 41.8, 40.3, 37.5, 33.3, 33.2; MS (EI): 304 (74 mg). This residue was subjected to flash chromatography
(M+), 275, 259, 231, 229, 215, 103, 180, 166, 145, 123, 109, 95, (silica; 0 → 30% EtOAc/hexane over 10 min) to afford lactol 9
91, 81, 69, 55; HRMS (EI): calcd for C19H28O3 304.2038, found (21 mg) which still contained impurities. HCl (2 M, 2 drops)
304.2030; [α]2D2 = −7.6 (c 1.1, CHCl3).
was then added to a solution of lactol 9 in CH2Cl2 (5 mL). After
18 h, the solvent was removed on a rotary evaporator and the
ensuing residue was purified by flash chromatography (silica;
hexane) to provide the title compound as a pale-yellow oil
(10 mg, 0.046 mmol, 13% yield over two steps).38 1H NMR
(3aR,4S,6R,6aS,10aS,11aS,11bR)-Ethyl 6-formyl-6a,10,10-
trimethyl-1,3-dioxo-2-phenyl-2,3,3a,4,6,6a,7,8,9,10,10a,11,11a,11b-
tetradecahydro-1H-naphtho[2,3-e]isoindole-4-carboxylate (7)
N-Phenylmaleimide (13.7 mg, 0.079 mmol) was added to a (400 MHz, CDCl3): δ 7.08 (d, J = 1.5 Hz, 1H), 7.05 (q, J = 1.5 Hz,
solution of diene 6 (22 mg, 0.072 mmol) in toluene (10 mL) 1H), 2.77 (dd, J = 16.4, 6.4 Hz, 1H), 2.50 (dddd, J = 16.4, 12.0,
and the resulting solution was then heated at reflux. After 7.4, 1.8 Hz, 1H), 1.97 (m, 1H), 1.81 (dd, J = 13.5, 7.4 Hz, 1H),
18 h, the reaction mixture was cooled and the solvent was 1.74–1.44 (complex m, 5H), 1.30–1.24 (complex m, 2H), 1.21
removed on a rotary evaporator. The ensuing residue was then (s, 3H), 0.94 (s, 3H), 0.91 (s, 3H); 13C NMR (100 MHz, CDCl3):
purified by flash chromatography (silica; 30% EtOAc/hexane) δ 137.6, 137.1, 120.1, 51.7, 42.2, 39.6, 34.0, 33.7, 33.3, 25.1,
to provide the title compound as a light-yellow oil (19 mg, 55% 21.7, 20.6, 19.24, 19.18; [α]2D2 = +17.0 (c 0.2, CHCl3).38
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