J. CHEM. RESEARCH (S), 1997 29
Table 2 13C NMR data for some aromadendrane derivatives, determined in CDCl3 at 125
MHz
Compound
Carbon
2
3
4
5
6
7
9
10
C-1
39.6
28.3
19.3
26.7
20.1
44.6
75.3
57.0
26.1
34.6
36.3
16.0
15.8
28.6
20.2
39.9
27.9
19.7
34.2
66.9
54.4
73.4
55.8
26.0
34.3
36.5
15.4
15.7
28.4
20.9
39.9
27.6
38.7
24.9
26.3
23.5
19.7
44.1
75.2
56.5
25.9
34.5
36.3
15.9
11.5
73.1
20.1
39.3
24.6
27.1
20.7
27.7
79.2
78.1
53.3
25.2
34.8
36.4
15.9
11.6
73.1
13.4
38.1
28.6
19.5
26.5
19.6
37.5
76.3
55.5
25.9
34.6
36.2
15.7
15.7
28.3
61.4
38.4
27.8
19.9
33.8
66.2
47.6
74.5
54.3
25.7
34.4
36.3
15.4
15.5.
28.3
62.1
37.2
24.9
26.5
23.4
19.2
37.2
76.1
55.1
25.7
34.6
36.2
15.7
11.5
73.0
61.3
C-2
C-3
20.0
C-4
31.2
C-5
69.8
C-6
51.6
C-7
73.4
C-8
55.7
C-9
25.8
C-10
C-11
C-12
C-13
C-14
C-15
Ac
34.3
36.4
15.5
15.7
28.1
20.6
21.5/170.1
7a,15-dihydroxyaromadendrane (7) (900 mg) which crystallized
from ethyl acetate as needles, mp 112 °C (Found: C, 75.7; H, 10.8.
C15H26O2 requires C, 75.6; H, 10.9%), vmax/cmꢀ1 3348; dH 0.56 (1 H,
t, J 9.3 Hz, H-2), 0.63 (1 H, m, H-4), 0.89 (3 H, d, J 7.1 Hz, H-12),
0.94 and 1.01 (each 3 H, s, H-13 and H-14), 3.62 (2 H, s, H-15).
Preparation of Globulol (2).—The diol 7 (500 mg) in dry pyridine
(10 cm3) was treated with fresh toluene-p-sulfonyl chloride (1 g) at
room temperature overnight. The solution was poured into dilute
hydrochloric acid and the product recovered in ethyl acetate and
chromatographed on silica to give the 15-toluene-p-sulfonate 8
which crystallized from petrol as cubes, mp 93–94 °C (Found: C,
67.5; H, 8.3. C22H32O4S requires C, 67.3; H, 8.2%); vmax/cmꢀ1 3559,
1598, 1178; dH 0.53 (2 H, m, H-2 and H-4), 0.84 (3 H, s), 0.97 (3 H,
s) (H-13 and H-14), 0.86 (3 H, d, J 7 Hz, H-12), 2.44 (3 H, s,
Ar-M4e), 4.06 (2 H, s, H-15), 7.30 and 7.78 (each 2 H, d, J 8 Hz,
Ar-H). The toluene-p-sulfonate (450 mg) in dry tetrahydrofuran
(10 cm3) was treated with lithium aluminium hydride (400 mg)
under reflux for 3 h. The solution was cautiously treated with moist
ethyl acetate, acidified with dilute hydrochloric acid and the
product recovered in ethyl acetate. The extract was dried over
sodium sulfate and the solvent evaporated. The residue was chro-
matographed on silica to give globulol (160 mg), mp 78–80 °C,
identified by its 1H and 13C NMR spectra and by comparison with
an authentic sample. On one occasion the epoxide 11 was obtained
as an oil from the chromatography of the toluene-p-sulfonate
(Found: m/z (e.i) 200.184. C15H24O requires Mr, 220.183); m/z 220
(5%), 205 (15), 189 (25), 187 (10), 177 (65), 159 (25), 147 (50); dH
0.59 (1 H, t, J 9.3 Hz, H-2), 0.63 (1 H, t, J 9.3 Hz, of d, J 6.0 Hz,
H-4), 0.92 (3 H, d, J 7.1 Hz, H-12), 1.00 and 1.03 (each 3 H, s, H-13
and H-14), 2.43 (1 H, dd, J 4.4 and 1 Hz), 2.67 (1 H, dd, J 4.4 and
2.2 Hz) (each H-15).
Experimental
1H and 13C NMR spectra were determined at 500 and 125 MHz
respectively. IR spectra were determined as nujol mulls. Silica gel
for chromatography was Merck 9385. Petrol refers to the fraction
of bp 60–80 °C. Extracts were dried over sodium sulfate. Mucor
plumbeus was grown in shake flasks (100 cm3 medium per 250 cm3
conical flask) on a medium comprising (per dm3) glucose (20 g),
peptone (5 g), yeast extract (3 g) and potassium dihydrogen phos-
phate (5 g) and the pH was adjusted to 5.6.
Incubation of 7a-Hydroxyaromadendrane (2).—(a) The substrate
(1 g) in ethanol (10 cm3) was evenly distributed over 45 shake flasks
of 1 day old cultures of M. plumbeus. After a further 6 days, the
broth was filtered and extracted with ethyl acetate. The extract was
dried and the solvent evaporated to give an oily residue (1.35 g)
which was chromatographed on silica. Elution with petrol–ethyl
acetate (1:1) gave 7a,14-hydroxyaromadendrane (5) (620 mg)
identified by its 1H NMR spectrum.6 Further elution gave
5a,7a-dihydroxyaromadendrane (3) (10mg) as an oil, dH 0.68 (2 H,
m, H-2 and H-4), 0.91 (3 H, J 7.0 Hz, H-12), 1.09 (6 H, s, H-13,
H-14), 1.18 (3 H, s, H-15), 3.42 (1 H, m, H-5); m/z 238 (Mǹ,
C15H26O2) (1%), 220 (5), 205 (71), 202 (13), 187 (10), 177 (21), 161
(15), 159 (15). The sample was acetylated with acetic anhydride in
pyridine to give the 5a-monoacetate (4) as an oil, dH 0.71 (1 H, t, J
10 Hz), 0.83 (1 H, t, J 10 Hz) (H-2 and H-4), 0.92 (3 H, d, J 7 Hz,
H-12), 1.10 (6 H, s, H-13, H-14), 1.20 (3 H, s, H-15), 2.04 (3 H, s,
OAc), 4.52 (1 H, dt, J 2.8 and 9.4 Hz, H-5); m/z 220 (Mꢀ60)
(10%), 205 (8), 202 (21), 187 (18), 177 (32), 162 (24). Further
elution with ethyl acetate gave 6b,7a,14-trihydroxyaromadendrane
(6) (15 mg) as a gum, dH 0.69 (1 H, t, J 10 Hz), 0.84 (1 H, m) (H-2
and H-4), 0.93 (3 H, d, J 7 Hz, H-12), 1.08 and 1.12 (3 H, each, s,
H-13 and H-15), 3.30 and 3.35 (each 1 H, d, J 10.8 Hz, H-14), 3.49
(1 H, dd, J 1.8 and 11.2 Hz, H-6); m/z 239 Mꢀ15) (1%), 236 (2),
221 (3), 218 (5), 205 (4), 193 (11), 175 (30).
(b) Under similar conditions aromadendr-7(15)-ene (1) (1 g)
gave the starting material (700 mg) and 7a,14,15-trihydroxyaroma-
dendrane (10) (40 mg), identified by its H NMR spectrum.
Received, 30th August 1996; Accepted, 11th October 1996
Paper E/6/05991K
1
(c) Under similar conditions 7a,15-dihydroxyaromadendrane (7)
(950 mg) gave 7a,14,15-trihydroxyaromadendrane (10) (620 mg), mp
129–130 °C (Found: C, 70.3; H, 10.3. C15H26O3 requires C, 70.8; H,
10.3%); vmax/cmꢀ1 3583; dH 0.60 (1 H, dd, J 9.6 and 10.5 Hz, H-2),
0.72 [1 H, t, (9.6 Hz) of d (6.4 Hz), 4-H], 0.84 (3 H, d, J 7.1 Hz,
H-12), 1.00 (3 H, s, H-13), 3.20 and 3.31 (each 1 H, d, J 11 Hz,
H-14), 3.49 and 3.54 (each 1 H, d, J 11.3 Hz, H-15). This compound
was identical to the major metabolite (500 mg) obtained from the
incubation of 7a,15-dihydroxyaromadendrane (1.3 g) with C. aphi-
dicola for 7 days as described previously.6 Further elution gave
5a,7a,15-trihydroxyaromadendrane (9) (6 mg) as a gum, dH 0.69
(2 H, m, H-2 and H-4), 0.91 (3 H, d, J 7.1 Hz, H-12), 1.08 and 1.09
(each 3 H, s, H-13 and H-14), 3.44 (1 H, m, H-5), 3.63 (2 H, s,
H-15); m/z 239 (Mꢀ15) (3%), 236 (3), 223 (10), 221 (5), 218 (9),
205 (38), 187 (19).
7a,15-Dihydroxyaromadendrane (7).—Aromadendrene (950 mg)
in tert-butyl alcohol (30 cm3) and water (30 cm3) was treated with a
mixture of potassium hexacyanoferrate(III) (4.5 g), potassium
carbonate (1.9 g) and osmium tetroxide (30 mg) for 24 h at room
temperature. Aqueous sodium thiosulfate (20 cm3, 10%) was
added and the mixture was stirred for 3 h. The product was
recovered in ethyl acetate and chromatographed on silica to give
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