JOURNAL OF CHEMICAL RESEARCH 2007 345
Coupling of the bromide 14 with 3-furyllithium: To a cooled
solution of the 3-bromofuran (0.163 g, 0. mmol) in dry THF
(3 ml) at –78°C, was added n-butyllithium (0.6 ml, 1.6M in hexane).
The resulting brown solution was stirred for 10 min. at –78°C and
then a solution of bromide 14 (0.121 g, 0.51 mmol) in THF (2 ml)
was added dropwise. After this mixture had been stirred for 2 h at
–78°C, excess H2O was added at room temperature with additional
stirring for 30 min. The product was extracted with ether, dried and
the solvent was evaporated under reduced pressure and the product
was chromatographed over silica gel. Elution with 5% diethyl ether
in hexane afforded furanolabdane 15 (0.192 g, 93%) as a colourless
oil; [a]D + 23 (c 2.0, CHCl3), lit.12 [a]D –22 (c 0.14, CHCl3);
IR (KBr) nmax 3050, 1635, 1495, 870 cm -1; HRMS m/z 286.2290
(M+, C20H30O requires 286.2299); EIMS m/z 286 (31), 271 (9), 191
(27), 137 (80), 95 (100), 67 (18); 1H NMR (CDCl3, 300 MHz) 0.67,
0.78, 0.85 (3H each, s, CH3), 2.23 (1H, m, H-12), 2.39 (1H, m, H-7),
2.54 (1H, m, H-17), 4.55 (1H, bs, H-17), 4.84 (1H, bs, H-17), 6.25
(1H, bs, H-14), 7.18 (1H, bs, H-16), and 7.33 (1H, t, H-15); 13C NMR
(CDCl3, 75.45 MHz) d 14.47 (C-20), 19.36 (C-11), 21.70 (C-19),
23.59 (C-12), 24.05 (C-2), 24.42 (C-6), 33.55 (C-4), 33.55 (C-18),
38.30 (C-7), 38.98 (C-1), 39.56 (C- 10), 42.10 (C-3), 55.42 (C-5),
56.05 (C-9), 106.23 (C-17), 110.94 (C-14), 125.59 (C-13), 138.62
(C-16), 142.58 (C-15) and 148.51 (C-8).
Experimental
Melting points were measured with a Kofler hot-stage apparatus and
are uncorrected. NMR spectra were recorded with a Bruker Avance-
300 and Avance-500 spectrometers. IR spectra were recorded using
a Nicolet Magna 560 FT–IR spectrometer. High-resolution mass
spectra (HRMS) were obtained on a JEOL JMS-AX505WA mass
spectrometer. The intensity of each peak in the mass spectrum relative
to the base peak is reported in parentheses. Optical rotations were
obtained for CHCl3 solutions on a Perkin-Elmer 341 polarimeter,
and their concentrations are expressed in g/100 ml. Manool resin was
purchased from Westchem Industries, Ltd and purified to obtain (+)-
Manool, [a]24 + 28 (c 1.5, CHCl3). THF, ether, DME and benzene
D
were freshly distilled from Na-benzophenone before use. All other
solvents and reagents were obtained from commercal suppliers and
used without further purification. Merck silica gel (70–230 mesh
ASTM) was used for column chromatography. TLC was performed
on Analtech silica gel 60 G254 and the spots were observed either by
exposure to iodine or by UV light. All organic extracts were dried
over Na2SO4 and evaporated under reduced pressure below 60°C.
Reduction of peroxide 10 with lithium aluminium hydride: To a
suspension of LiAlH4 (37.43 mg, 0.98 mmol) in dry THF (5 ml) was
added dropwise peroxide 10 (0.250 g, 0.82 mmol) in THF (4 ml) at
0°C. This mixture was refluxed for 2 h. then water was added and
the product was extracted with ether. The solvent was evaporated
under reduced pressure and the product was chromatographed over
silica gel. Elution with 50% ether in hexane afforded diol 11 (0.241 g,
96%) as white crystals (hexane): m.p. 119–120°C; [a]D + 40 (c 1.0,
CHCl3), lit.12 [a]D –42 (c 0.39, CHCl3); IR(KBr) nmax 3602, 3079,
1642, and 900 cm-1; HRMS m/z 306.2558 (M+, C20H34O2 requires
306.2560); EIMS m/z 306 (5), 288 (20), 205 (75), 177 (65), 137 (100),
98 (86); 1H NMR (CDCl3, 300 MHz) d 0.65, 0.77, 0.84 (3H each, s,
CH3), 4.15 (1H, d, J = 12.9 Hz, H-16), 4.17 (1H, d, J = 12.9 Hz, H-
16), 4.18 (2H, bd, H-15), 4.49 (1H, bs, H-17), 4.80 (1H, bt, H-17),
and 5.57 (1H, bt, J = 6.9 Hz, H-14); 13C NMR (CDCl3, 75.45 MHz)
d 14.47 (C-20), 19.34 (C-11), 21.69 (C-19), 22.09 (C-2), 24.41
(C-6), 33.58 (C-4), 33.58 (C-18), 34.63 (C-12), 38.31 (C-7), 39.06
(C-1), 39.67 (C-10), 42.11 (C-3), 55.48 (C-5), 56.39 (C-9), 58.50
(C-16), 60.80 (C-15), 106.29 (C-17), 126.05 (C-14), 144.47 (C-13)
and 148.56 (C-8);
Photooxygenation of labdafuran 15
Method A: A solution of labdafuran 15 (0.105 g; 0.37 mmol) in THF
(10 ml), containing Rose Bengal (1 mg), was irradiated at 0°C with
an external 150 W halogen–tungsten lamp for 2 h during which time
oxygen was bubbled through the reaction mixture. The solvent was
evaporated under reduced pressure and the residue chromatographed
over silica gel. Elution with 15% ethyl acetate in hexane afforded a
mixture of compounds 1a and 8, as a colourless oil as evidenced by
the NMR spectrum. Crystallisation from hexane gave pure compound
8 (25 mg, 21%): m.p. 89–91°C; [a]D + 48 (c 0.7, CHCl3), lit.8 [a]D
–100 (c 0.43, CHCl3); IR (KBr) nmax 3364, 3015, 1645, 1762 cm-1;
HRMS m/z 318.1970 (M+, C20H30O3 requires 318.2193); EIMS m/z
1
318 (20), (23), 300 (15), 204 (19), 177 (25), 137 (100), 95 (37); H
NMR (CDCl3, 300 MHz) 0.67, 0.78, 0.85 (3H each, s, CH3), 1.31
(1H, m, H-6), 1.72 (1H, m, H-6), 1.93 (1H, m, H-7), 2.37 (1H, m, H-
7), 4.45 (1H, bs, H-17), 4.84 (1H, bs, H-17), 5.83 (1H, s, H-14), 5.95
(1H, bs, H-16); 13C NMR (CDCl3, 75.45 MHz) d 14.41 (C-20), 19.31
(C-11), 20.82 (C-2), 21.69 (C-19), 24.39 (C-6), 26.76 (C-12), 33.57
(C-4), 33.57 (C-18), 38.20 (C-7), 39.14 (C-10), 39.78 (C-1), 42.04
(C-3), 55.49 (C-5), 56.33 (C-9), 99.02 (C-16), 106.51 (C-17), 117.14
(C-14), 147.91 (C-8), 170.41 (C-13), 171.57 (C-15).
Oxidation of diol 11 with tetra-n-propylammonium perruthenate:
Diol 11 (0.110 g, 0.36 mmol) was dissolved in dichloromethane
(3 ml) containing both 4Å molecular sieves (0.200 g) and
N-methylmorpholine N-oxide (63.27 mg, 0.54 mmol). After stirring
themixturefor10min, tetra-n-propylammoniumperruthenate(6.3mg,
0.018 mmol) was added and the reaction was followed by TLC until
complete. After usual work-up, the crude product (0.105 g) was
obtained. The NMR spectrum indicated that it consisted of a mixture
of lactones 5 and 12. Further purification over silica gel failed.
Oxidation of diol 11 with silver carbonate-celite: To a suspension
of silver carbonate-celite (37.43 mg, 0.98 mmol) in dry benzene (3 ml)
was added diol 11 (0.100 g, 0.32 mmol) in benzene (2 ml) at room
temperature. The reaction mixture was filtered through silica gel
and the filtrate was evaporated. The resulting crude product was
chromatographed over silica gel. Elution with 50% ether in hexane
afforded lactone 5 (95 mg, 96%), which after recrystallisation from
hexane showed: m.p. 76–78°C; [a]D24 + 39 (c 1.4, CHCl3), lit.4,11 [a]D
+ 41 (c 1.2, CHCl3); IR(KBr) nmax 1775, 1740, 1640 and 1630 cm-1;
HRMS m/z 302.2258 (M+, C20H30O2 requires 302.2255); EIMS
m/z 302 (10), 287 (15), 206 (34), 137 (71), 109 (100), 98 (92);
1H NMR (CDCl3, 300 MHz) 0.67, 0.78, 0.85 (3H each, s, CH3), 4.42
(1H, br s, H-17), 4.66 (1H, dd, J = 17.3 and 1.7, H-16), 4.72 (1H, dd,
J = 17.3 and 1.7, H-16), 4.84 (1H, br s, H-17), 5.81 (1H, t, J = 1.6,
H-14); 13C NMR (CDCl3, 75.45 MHz) d 14.36, 19.24, 21.20, 21.63,
24.32, 27.45, 33.51, 33.51, 38.14, 39.09, 39.70, 41.93, 55.42, 56.06,
73.08, 106.37, 115.07, 147.84, 171.06 and 174.17.
Chromatography of the mother-liquor of compound 1a over silica
gel with 15% ethlyl acetate in hexane afforded pure coronarin C 1a
(37.6 mg, 32%) as an oil; [a]D + 30 (c 0,6; CHCl3), lit.3 [a]D + 34.9
(c 0.13, CHCl3); IR (KBr) nmax 3426, 3015, 1643, 1763 cm-1; HRMS
m/z 318.2284 (M+, C20H30O3 requires 318.2193); EIMS m/z 318
1
(20), 303 (21), 177 (23), 137 (100), 95 (37); H NMR (CDCl3, 300
MHz) 0.65, 0.77, 0.84 (3H each, s, CH3), 4.51 (1H, bs, H-17), 4.83
(1H, bs, H-17), 6.08 (1H, bs, H-15), 6.81 (1H, d, J = 1.5 Hz, H-14);
13C NMR (CDCl3, 75.45 MHz) d 14.41 (C-20), 19.32 (C-2), 21.47
(C-12), 21.69 (C-19), 24.38 (C-6), 24.48 (C-11), 33.56 (C-4), 33.56
(C-18), 38.21 (C-7), 39.11 (C-1), 39.70 (C-10), 42.08 (C-3), 55.49
(C-5), 56.45 (C-9), 97.08 (C-15), 106.56 (C-17), 139.02 (C-13),
142.85 (C-14), 147.97 (C-8).
Method B: A solution of labdafuran 15 (0.1 g, 0.35 mmol) in
CH2Cl2 (10 ml), containing meso-tetraphenylporphin (1 mg) and
diisopropylamin (10 eq), was irradiated at –78°C with an external
150 W halogen–tungsten lamp for 2 h during which time oxygen
was bubbled through the reaction mixture. The solution was warmed
to 23°C, and saturated aqueous oxalic acd (3 ml) was added.
After 30 min of vigorous stirring, water (15 ml) and CH2Cl2–methanol
(3:1, 50 ml) were added to the colourless mixture, and the aqueous
portion was extracted with CH2Cl2–methanol (3:1, 2 ¥ 50 ml).
The solvent was evaporated under reduced pressure and the
residue was chromatographed over silica gel. Crystallisation from
hexane gave pure compound 8 (60.1 mg, 54%) as white crystals.
Chromatography of the mother-liquor of compound 1a over silica
gel with 15% ethlyl acetate in hexane afforded pure compound 1a
(5 mg, 5%).
Bromination of alcohol 13: To a solution of alcohol 13 (0.2 g,
0.84 mmol) in THF (6 ml) was added PPh3 (0.88 g, 3.36 mmol) and
CBr4 (0.83 g, 2.50 mmol) and the whole was stirred for 20 min at
room temperature. The reaction mixture was diluted with brine and
extracted with ether. The solvent was evaporated under reduced
pressure and the product was chromatographed over silica gel. Elution
with hexane afforded bromide 14 (0.21 g, 83%) as a colourless oil;
HRMS m/z 298.1299 (M+, C16H27Br requires 298.1296); H NMR
1
Photooxygenation of labdafuran 17: A solution of labdafuran 17
(72 mg, 0.23 mmol) in THF (10 ml), containing Rose Bengal (1 mg),
was irradiated at 0°C with an external 150 W halogen–tungsten lamp
for 3 h during which time oxygen was bubbled through the reaction
mixture. The solvent was evaporated under reduced pressure and
the residue chromatographed over silica gel. Elution with 30% ethyl
(CDCl3, 300 MHz) 0.67, 0.78, 0.86 (3H each, s, CH3), 2.38 (1H, ddd,
J = 13, 4, 2), 3.25 (1H, ddd, J = 8.6, 8, 7, H-12), 3.51 (1H, ddd,
J = 8.6, 8, 4, H-12), 4.45 (1H, br s, H-17), 4.82 (1H, br s, H-17); 13
C
NMR (CDCl3, 75.45 MHz) d 14.81, 19.4, 21.8, 24.42, 28.06, 33.61,
33.61, 33.75, 38.22, 39.10, 39.64, 42.11, 55.33, 55.42, 106.20 and
147.71.
PAPER: 07/4675