The absolute stereochemistry of a diterpene from Ballota aucheri

Article abstract of DOI:10.1016/S0031-9422(03)00156-0

The semi-synthetic transformation of hispanolone, isolated from Ballota africana, into βp-hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one has established an ent-labdane absolute stereochemistry for a diterpene metabolite originally isolated from B. aucheri.

Full text of DOI:10.1016/S0031-9422(03)00156-0

Phytochemistry 63 (2003) 409–413
www.elsevier.com/locate/phytochem
The absolute stereochemistry of a diterpene from Ballota aucheri
Christopher A. Gray, Douglas E.A. Rivett, Michael T. Davies-Coleman*
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa
Received 7 October 2002; received in revised form 25 February 2003
Abstract
The semi-synthetic transformation of hispanolone, isolated from Ballota africana, into 6b-hydroxy-15,16-epoxylabda-8,13(16),14-
trien-7-one has established an ent-labdane absolute stereochemistry for a diterpene metabolite originally isolated from B. aucheri.
# 2003 Elsevier Science Ltd. All rights reserved.
Keywords: Ballota africana; Ballota aucheri; Lamiaceae; Diterpene; Furanolabdane; Hispanolone; Hispanone; 6b-Hydroxy-15,16-epoxylabda-
8,13(16),14-trien-7-one; 6a-Hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one; 6b-Acetoxy-15,16-epoxylabda-8,13(16),14-trien-7-one; 6a-Acetoxy-
15,16-epoxylabda-8,13(16),14-trien-7-one
1. Introduction
The genus Ballota (Lamiaceae) consists of about 33
species growing mainly in the Mediterranean region and
adjoining Asia Minor (Codd, 1985). Phytochemical
investigations of about a third of these species have
revealed that furanolabdane diterpenes are the pre-
dominant natural products (recently reviewed by Seidel
et al., 1999). The indigenous southern African species,
Ballota africana, is a good source of the furanolabdane,
hispanolone (1), and we have demonstrated that this
compound is a useful starting point for semi-synthetic
transformations (Davies-Coleman and Rivett, 1993).
Recently we have used the dehydrated analogue of 1,
hispanone (2), as a model compound to investigate the
preparation of 6b,7a-hydroxylated labd-8-enes. Inter-
estingly, one of the compounds prepared during this
investigation, 6b-hydroxy-15,16-epoxylabda-8,13(16),14-
trien-7-one (3), is a natural product originally isolated
from B. aucheri by Rustaiyan et al. (1995). However,
although the NMR data of synthetic 3 was compatible
with those reported for the natural product, the sign of
the optical rotation of 3 was opposite to that of the
naturally occurring diterpene. In this paper we report
the synthesis and spectroscopic data for 3, its acetylated
derivative 4 and their C-6 epimers (5 and 6).
*Corresponding author. Tel.: +27-46-603-8264; fax: +27-46-622-
5109.
E-mail address: m.davies-coleman@ru.ac.za (M.T. Davies-Coleman).
0031-9422/03/$ - see front matter # 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0031-9422(03)00156-0

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C.A. Gray et al. / Phytochemistry 63 (2003) 409–413
2. Results and discussion
(Garcia-Alvarez et al., 1981). Once again, the C-6 ste-
reochemistries of the two products were assigned
through analysis of 2D NOESY data and recourse to
their H-5–H-6 coupling constants (J5,6=3.3 and 13.4
Hz, respectively). With the acetate 4 in hand, we then
treated 3 with acetic anhydride in anhydrous pyridine to
yield an oil that was identical to 6b-acetoxy-15,16-
epoxylabda-8,13(16),14-trien-7-one (4) by 1H and 13C
NMR and gave an optical rotation ([a]D=ꢀ53ꢁ) which
was consistent with that obtained for 4 derived from
manganese (III) acetate acetoxylation of hispanone
([a]D=ꢀ61ꢁ).
The hispanolone used in this study was isolated from
the aerial parts of local specimens of B. africana (0.8%
dry weight) as described by Davies-Coleman and Rivett
(1993). Treatment of 1 with catalytic iodine in refluxing
benzene gave hispanone (2) as pale yellow needles in
87% yield. a0-Oxidation of the a,b-unsaturated ketone 2
was achieved via Vedejs’ oxidation (Vedejs, 1974;
Vedejs et al., 1978), in which the lithium dienolate of
hispanone was treated with two molar equivalents of
oxodiperoxymolybdenumpyridinehexamethylphosphor-
amide (MoOPH) to yield, after semi-preparative HPLC,
6b-hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one (3,
21%), 6a-hydroxy-15,16-epoxylabda-8,13(16),14-trien-
7-one (5, 43%), 6-hydroxy-15,16-epoxylabda-5,8,13(16),14-
tetraen-7-one (7, 5%) and unreacted hispanone (13%).
The structures of 3, 5 and 7 were assigned from their
respective spectroscopic data, and the stereochemistry
at C-6 of 3 and 5 confirmed by the H-5–H-6 coupling
constants (J5,6=3.6 and 13.1 Hz, respectively) and 1D
gradient selected NOESY experiments (Table 1).
Although there was reasonable agreement (except con-
cerning C-20, Table 2) between the NMR, IR and MS
data obtained for 3 and those reported for the natural
product isolated from B. aucheri (Rustaiyan et al.,
1995), there was a discrepancy in their optical rota-
tions. While Rustaiyan et al. (1995) reported an optical
rotation of ꢀ34ꢁ for the natural product, we obtained
optical rotations in the range +17ꢁ to +20ꢁ for our syn-
thetically derived 3. The optical rotation of the 6a-epimer
(5) was +51ꢁ. From these data we conclude that the nat-
ural product from B. aucheri has an ent-labdane absolute
stereochemistry (8) and not a labdane stereochemistry as
originally proposed by Rustaiyan et al. (1995).
3. Experimental
3.1. General
1
The H and 13C NMR spectra were recorded on a
Bruker 400 MHz Avance NMR spectrometer using
CDCl3 as the solvent, referenced at ꢀ 7.25/77.0 ppm.
The HRFABMS data were acquired by Professor Louis
Fourie of the University of Potchefstroom on a Micro-
mass 70-70E spectrometer and the LREI mass spectra
(70 eV) were obtained on a Finnegan-Matt GCQ mass
spectrometer by Mr. Aubrey Sonemann of Rhodes
University. The IR data for all compounds were
obtained from thin films on NaCl discs using a Perkin-
Elmer 2000 FTIR spectrometer. All rotations were
Table 2
13C and 1H NMR data for compound 3a
b
c
Carbon
ꢀC
ꢀH
1
37.5 (t)
18.8 (t)
43.4 (t)
34.2 (s)
53.3 (d)
71.2 (d)
199.4 (s)
128.5 (s)
169.6 (s)
41.1 (s)
30.7 (t)
24.4 (t)
124.5 (s)
110.6 (d)
143.1 (d)
138.7 (d)
11.7 (q)
32.4 (q)
24.0 (q)
22.2 (q)
1.37 (1H, td, 12.6, 3.8) 1.90 (1H, bd, 12.2)
1.60 (1H, m) 1.81 (1H, tt, 13.6, 3.3)
1.23 (1H, td, 13.3, 3.8) 1.44 (1H, bd, 14.3)
2
We also prepared the C-6 diastereomeric a0-acetoxy
enones 4 and 6 (obtained pure in 30 and 57% yield
respectively after semi-preparative HPLC) through
manganese (III) acetate oxidation of 2 (Williams and
Hunter, 1976; Dunlap et al., 1984). Although both 4
and 6 had previously been prepared from 1 via a differ-
ent route by Garcia-Alvarez et al. (1981), only limited
data for the equatorial acetate 6 has been reported
3
4
5
1.57 (1H, d, 3.6)
4.32 (1H, dd, 3.6, 2.6)
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20d
OH
2.51 (2H, m)
2.57 (2H, m)
6.31 (1H, bs)
7.37 (1H, t, 1.6)
7.27 (1H, bs)
1.86 (3H, s)
Table 1
Selected NOE enhancements observed for compounds 3 and 5
1
Irradiated H
NOE correlated protons
1.06 (3H, s)
1.31 (3H, s)
3
5
1.38 (3H, s)
2.25 (1H, d, 2.6)
H-5
H-6
H-6, H3-18
H-5, H3-18, OH
H-5, H-6, H3-19
H3-18, H-320
H3-19
H3-18
H3-19, H3-20, OH
H-5, H3-19, OH
H3-18, H3-20, H-6
H3-19
a
Values in ppm, spectra acquired in CDCl3.
100 MHz; multiplicity by DEPT.
400 MHz; integrals, multiplicity and coupling constants (Hz) in
H3-18
H3-19
H3-20
OH
b
c
parentheses.
d
H-6
H-6, H3-18
Lit. (Rustaiyan et al., 1995); ꢀC 18.6 (q), ꢀH 1.42 (s).

C.A. Gray et al. / Phytochemistry 63 (2003) 409–413
411
ꢁ
ꢁ
recorded on a Perkin-Elmer 141 polarimeter as CHCl3
solns. Melting points were determined using a Reichert
hot-stage microscope and are uncorrected. Reactions
with exclusion of moisture were performed in flame-
dried glassware under N2. Immediately prior to their use
in dry reactions, Et2O, THF and C6H6 were distilled
from sodium metal/benzophenone ketyl. Pyridine was
distilled at reduced pressure from KOH and stored over
4 A molecular sieves under nitrogen. General laboratory
solvents were distilled from glass before use. The oxo-
was stirred at ꢀ78 C for 12 h, warmed to 0 C over 30
min and immediately quenched with satd. aq. Na2SO3
ꢁ
(5.0 ml). After stirring for a further 30 min at 0 C, the
mixture was warmed to RT, H2O (5.0 ml) added and the
aqueous and organic phases separated. The aqueous
fraction was extracted with Et2O (3ꢂ5 ml) and the
combined organic phases washed with 0.5 M HCl (10
ml), 5% NaHCO3 (5 ml) and H2O (5 ml). Drying
(MgSO4), removal of solvent in vacuo and passage of
the resulting brown oil (456 mg) through a column of
silica in hexane–EtOAc (4:1) yielded a mixture of pro-
ducts as a pale yellow oil (264 mg). Semi-preparative
normal phase HPLC of the mixture in 9:1 hexane–
EtOAc yielded (in order of elution) 6-hydroxy-15,16-
epoxylabda-5,8,13(16),14-tetraen-7-one (7, 16 mg, 0.05
mmol, 5%) as a colourless oil, 6a-hydroxy-15,16-
epoxylabda-8,13(16),14-trien-7-one (5, 137 mg, 0.43
mmol, 43%) as a white crystalline solid, hispanone (2,
40 mg, 0.13 mg, 13%) as a yellow crystalline solid and
6b-hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one (3,
65 mg, 0.21 mmol, 21%) as a white crystalline solid.
.
.
diperoxymolybdenum pyridine hexamethyl - phosphor-
amide (MoOPH) used was prepared and stored as
described by Vedejs et al. (1978). Reactions were mon-
itored by analytical thin layer chromatography on DC-
Plastikfolien Kieselgel 60 F254 plates visualised under
UV light (254 nm) and developed by spraying with 10%
H2SO4 in MeOH followed by heating. Open column
chromatography was performed using Kieselgel 60 (70–
230 mesh) silica gel and flash chromatography was per-
formed using Kieselgel 60 (230–400 mesh) silica gel.
Normal phase semi-preparative HPLC separations were
performed on a Whatman Magnum 9 Partisil 10 column
(9.5ꢂ500 mm) with an eluent flow rate of 4 mlminꢀ1
and a Waters R401 refractive index detector.
3.3.1. 6-Hydroxy-15,16-epoxylabda-5,8,13(16),14-
tetraen-7-one (7)
Pale yellow oil; [a]2D5 ꢀ41ꢁ (c 0.88, CHCl3); IR ꢁmax
3.2. Dehydration of hispanolone (1)
3367 (br), 2927, 1624, 1600, 1455, 1384, 1029, 872, 772
1
cmꢀ1; H NMR (CDCl3, 400 MHz) ꢀ 7.38 (1H, br s,
Hispanolone (1, 1.00 g, 3.14 mmol) was dissolved in
dry C6H6 (100 ml) and 0.1 M I2 in dry C6H6 (1.60 ml,
0.16 mmol, 0.05 eq) added. The resulting pink soln was
refluxed under anhydrous conditions (6 h) after which
the benzene was removed in vacuo and the residue taken
up in Et2O (40 ml). The Et2O soln was washed with 5%
Na2S2O3 (3ꢂ25 ml) and H2O (25 ml), dried (MgSO4) and
concentrated to give a brown oil (1.07 g). The crude
product was purified by column chromatography on
silica gel in hexane–EtOAc (19:1) to give hispanone (2,
0.82 g, 2.73 mmol, 87%) as pale yellow needles and his-
panolone (1, 91 mg, 0.29 mmol, 9%) as a colourless oil.
H-15), 7.28 (1H, br s, H-16), 6.32 (1H, br s, H-14), 2.66
(1H, m, H-11a), 2.57 (2H, m, H2-12), 2.53 (1H, m,
H-11b), 2.05 (1H, m, H-1a), 1.98 (3H, s, H3-17), 1.89
(1H, m, H-3a), 1.83 (1H, m, H-2a), 1.72 (1H, m, H-2b),
1.41 (1H, m, H-3b), 1.39 (3H, s, H3-18), 1.38 (6H, s, H3-
19 and H3-20) ppm; 13C NMR (CDCl3, 100 MHz) ꢀ
181.7 (s, C-7), 165.8 (s, C-9), 143.1 (s, C-6 and d, C-15),
140.5 (s, C-5), 138.7 (d, C-16), 127.4 (s, C-8), 124.4 (s, C-
13), 110.5 (d, C-14), 43.9 (s, C-10), 37.3 (t, C-3), 35.7 (s,
C-4), 31.5 (t, C-11), 29.4 (t, C-1), 28.1 (q, C-18), 28.0 (q,
C-20), 27.6 (q, C-19), 23.8 (t, C-12), 17.2 (t, C-2), 11.6
(q, C-17) ppm; EIMS m/z (rel. int.) 314 [M+] (76), 299
(69), 281 (72), 267 (14), 245 (19), 233 (23), 215 (100), 205
(58), 177 (39); HRFABMS m/z 315.1960 (calc. for
C20H27O3 [(M+H)+], 315.1960).
3.2.1. Hispanone (2)
ꢁ
Fine white needles (from MeOH); mp 60–61 C, lit.
58–60 ꢁC (Garcia-Alvarez et al., 1981); [a]2D4+41ꢁ (c 3.94,
CHCl3), lit. +39.7ꢁ (Garcia-Alvarez et al., 1981); IR, 1H
NMR, 13C NMR and EIMS consistent with literature
values (Garcia-Alvarez et al., 1981); HRFABMS m/z
301.2167 (calc. for C20H29O2 [(M+H)+], 301.2168).
3.3.2. 6ꢂ-Hydroxy-15,16-epoxylabda-8,13(16),14-trien-
7-one (5)
25
ꢁ
White crystalline solid; mp 95–96 C; [a]D +51ꢁ (c
4.29, CHCl3); IR ꢁmax 3437 (br), 2924, 2855, 1660, 1464,
1345, 1315, 1118, 874, 775 cmꢀ1; 1H NMR (CDCl3, 400
MHz) ꢀ 7.37 (1H, t, J=1.6 Hz, H-15), 7.26 (1H, s, H-
16), 6.29 (1H, d, J=0.8 Hz, H-14), 4.38 (1H, dd,
J=13.1, 2.0 Hz, H-6), 2.54 (2H, m, H2-12), 2.52 (1H, m,
H-11a), 2.44 (1H, m, H-11b), 1.95 (1H, br d, J=12.4
Hz, H-1a), 1.85 (3H, s, H3-17), 1.69 (1H, d, J=13.1 Hz,
H-5), 1.68 (1H, m, H-2a), 1.57 (1H, m, H-2b), 1.46 (1H,
br d, J=13.6 Hz, H-3a), 1.39 (1H, m, H-1b), 1.26 (1H,
m, H-3b), 1.25 (3H, s, H3-20), 1.17 (6H, s, H3-18 and
3.3. Vedejs’ oxidation of hispanone (2)
Hispanone (2, 300 mg, 1.0 mmol) in THF (5.0 ml) was
added dropwise via a cannula to LDA (2.0 M, 1.00 ml,
ꢁ
2.0 mmol, 2 eq) in THF (5.0 ml) at ꢀ78 C. The result-
ꢁ
ing soln was stirred (ꢀ78 C, 1 h) before MoOPH (870
mg, 2.0 mmol, 2 eq) was added in a single portion using
a solids addition tube. The deep red reaction mixture

412
C.A. Gray et al. / Phytochemistry 63 (2003) 409–413
H3-19) ppm; 13C NMR (CDCl3, 100 MHz) ꢀ 201.7 (s, C-
7), 168.9 (s, C-9), 143.1 (d, C-15), 138.7 (d, C-16), 127.4
(s, C-8), 124.3 (s, C-13), 110.5 (d, C-14), 73.3 (d, C-6),
56.7 (d, C-5), 42.8 (t, C-3), 42.5 (s, C-10), 36.7 (t, C-1),
35.8 (q, C-18), 34.0 (s, C-4), 30.6 (t, C-11), 24.0 (t, C-12),
22.0 (q, C-19), 19.4 (q, C-20), 18.6 (t, C-2), 11.6 (q, C-17)
ppm; EIMS m/z (rel. int.) 316 [M+] (5), 301 (100), 283
(45), 255 (16), 229 (11), 192 (10), 175 (12), 161 (29), 135
(12), 91 (17); HRFABMS m/z 317.2117 (calc. for
C20H29O3 [(M+H)+], 317.2117).
(1H, d, J=13.4 Hz, H-6), 2.55 (2H, m, H2-12), 2.49 (1H,
m, H-11a), 2.44 (1H, m, H-11b), 2.19 (3H, s, 6-OAc),
2.04 (1H, d, J=13.2 Hz, H-5), 1.99 (1H, br d, J=11.6
Hz, H-1a), 1.76 (3H, s, H3-17), 1.68 (1H, tt, J=13.6, 3.2
Hz, H-2a), 1.60 (1H, m, H-2b), 1.45 (1H, br d, J=13.3
Hz, H-3a), 1.42 (1H, td, J=12.9, 3.7 Hz, H-1b), 1.29
(1H, td, J=13.6, 4.1 Hz, H-3b), 1.28 (3H, s, H3-20), 1.05
(3H, s, H3-18), 1.01 (3H, s, H3-19) ppm; 13C NMR
(CDCl3, 100 MHz) ꢀ 194.6 (s, C-7), 170.4 (s, 6-OAc),
166.9 (s, C-9), 143.1 (d, C-15), 138.7 (d, C-16), 128.9 (s,
C-8), 124.2 (s, C-13), 110.5 (d, C-14), 74.7 (d, C-6), 53.8
(d, C-5), 42.7 (t, C-3), 42.6 (s, C-10), 36.5 (t, C-1), 35.6
(q, C-18), 33.5 (s, C-4), 30.4 (t, C-11), 24.1 (t, C-12), 21.9
(q, C-19), 21.3 (q, 6-OAc), 19.9 (q, C-20), 18.5 (t, C-2),
11.6 (q, C-17) ppm; EIMS m/z (rel. int.) 358 [M+] (4),
343 (25), 298 (62), 283 (84), 265 (45), 255 (100), 203 (57),
189 (78), 175 (41), 161 (91); HRFABMS m/z 359.2222
(calc. for C22H31O4 [(M+H)+], 359.2222).
3.3.3. 6ꢃ-Hydroxy-15,16-epoxylabda-8,13(16),14-trien-
7-one (3)
26
ꢁ
White crystalline solid; mp 99–100 C; [a]D +17ꢁ (c
1.01, CHCl3), lit. ꢀ34ꢁ (Rustaiyan et al., 1995); IR ꢁmax
3402 (br), 2930, 2856, 1651, 1604, 1470, 1385, 1026, 874,
782 cmꢀ1; 1H and 13C NMR see Table 2; EIMS m/z (rel.
int.) 316 [M+] (10), 314 (15), 301 (63), 283 (46), 255
(29), 203 (68), 192 (100), 175 (47), 161 (94), 151 (53);
HRFABMS m/z 317.2117 (calc. for C20 H29O3
[(M+H)+], 317.2117).
3.4.2. 6ꢃ-Acetoxy-14,15-epoxylabda-8,13(16),14-trien-
7-one (4)
Colourless oil; [a]2D6 ꢀ61ꢁ (c 1.04, CHCl3); IR ꢁmax
2932, 2863, 1747, 1668, 1606, 1471, 1370, 1230, 1027,
874, 600 cmꢀ1; 1H NMR (CDCl3, 400 MHz) ꢀ 7.37 (1H,
t, J=1.6 Hz, H-15), 7.27 (1H, br s, H-16), 6.31 (1H, d,
J=0.8 Hz, H-14), 5.79 (1H, d, J=3.3 Hz, H-6), 2.58
(2H, m, H2-12), 2.53 (1H, m, H-11a), 2.50 (1H, m,
H-11b), 2.06 (3H, s, 6-OAc), 1.96 (1H, br d, J=12.5 Hz,
H-1a), 1.85 (3H, s, H3-17), 1.77 (1H, tt, J=13.8, 3.3 Hz,
H-2a), 1.76 (1H, d, J=3.3 Hz, H-5), 1.62 (1H, dt,
J=14.1, 3.5 Hz, H-2b), 1.46 (1H, dd, J=13.2, 1.2 Hz,
H-3a), 1.42 (3H, s, H3-20), 1.37 (1H, td, J=13.1, 3.8 Hz,
H-1b), 1.24 (1H, td, J=13.4, 3.8 Hz, H-3b), 1.05 (3H, s,
H3-18), 1.04 (3H, s, H3-19) ppm; 13C NMR (CDCl3, 100
MHz) ꢀ 193.5 (s, C-7), 169.6 (s, 6-OAc), 168.5 (s, C-9),
143.1 (d, C-15), 138.7 (d, C-16), 129.3 (s, C-8), 124.4 (s,
C-13), 110.5 (d, C-14), 70.2 (d, C-6), 53.0 (d, C-5), 43.6
(t, C-3), 41.1 (s, C-10), 37.6 (t, C-1), 33.8 (s, C-4), 32.5
(q, C-18), 30.7 (t, C-11), 24.3 (t, C-12), 23.0 (q, C-19),
21.8 (q, C-20), 21.4 (q, 6-OAc), 18.6 (t, C-2), 11.7 (q, C-
17) ppm; EIMS m/z (rel. int.) 358 [M+] (2), 298 (58),
283 (63), 265 (36), 255 (100), 234 (46), 203 (68), 192 (88),
161 (95), 81(21); HRFABMS m/z 359.2222 (calcd for
C22H31O4 [(M+H)+], 359.2222).
3.4. ꢂ0-Acetoxylation of hispanone (2)
Hispanone (2, 499 mg, 1.66 mmol) was dissolved in
dry C6H6 (50 ml), dry Mn(OAc)3 (2.50 g; dried over
ꢁ
P2O5 at 70 C and 0.5 mmHg for 6 h immediately prior
to use) added and the resulting brown suspension
heated under reflux with exclusion of moisture for 72 h.
The heterogeneous reaction mixture was then cooled
and the fine brown precipitate dissolved by vigorous
stirring with 10% aqueous Na2S2O5 (30 ml) for 30 min.
Conc. HCl (3.0 ml) was added (to give a 0.9 M HCl soln
in the aqueous phase) and the mixture stirred for a fur-
ther 10 min. The organic and aqueous phases were then
separated, the aqueous phase thoroughly washed with
EtOAc (4ꢂ25 ml) and the combined organic phases
washed with 5% NaHCO3 (10 ml) and H2O (10 ml).
Drying with MgSO4 and evaporation of the solvent
gave a yellow oil (636 mg) that was purified by silica gel
column chromatography (7:3 hexane/EtOAc) to yield a
1
2:1 mixture (by H NMR spectroscopy) of 6a- and 6b-
acetoxy-14,15-epoxylabda-8,13(16),14-trien-7-one
(6
and 4) as a pale yellow oil (529 mg, 1.48 mmol, 89%).
Normal phase semi-preparative HPLC of a portion (501
mg) of the diastereomeric mixture in hexane-EtOAc
(9:1) afforded the pure acetoxy enones 6 (323 mg) and 4
(169 mg) as colourless oils.
3.5. Acetylation of 6ꢃ-hydroxy-14,15-epoxylabda-
8,13(16),14-trien-7-one (3)
Compound 3 (15 mg) was dissolved in pyridine (0.5
ml) and Ac2O (0.5 ml) and stirred at room temperature
over-night before MeOH (1 ml) was added and the
resulting soln. concentrated in vacuo to give a yellow oil
(22 mg). The reaction product was passed through a
small column of silica gel in hexane–EtOAc (7:3) to
yield a colourless oil (16 mg, [a]2D7 ꢀ53ꢁ) that was iden-
tical to keto-ester 4 in all respects.
3.4.1. 6ꢂ-Acetoxy-14,15-epoxylabda-8,13(16),14-trien-
7-one (6)
Colourless oil; [a]2D5 +50ꢁ (c 1.00, CHCl3), lit. +38ꢁ
(Garcia-Alvarez et al., 1981); IR ꢁmax 2932, 2872, 1747,
1674, 1614, 1470, 1373, 1235, 1025, 874 cmꢀ1; 1H NMR
(CDCl3, 400 MHz) ꢀ 7.36 (1H, t, J=1.6 Hz, H-15), 7.26
(1H, br s, H-16), 6.29 (1H, d, J=0.8 Hz, H-14), 5.64

C.A. Gray et al. / Phytochemistry 63 (2003) 409–413
413
Dunlap, N.K., Sabol, M.R., Watt, D.S., 1984. Oxidation of enones to
a0-acetoxyenones using manganese triacetate. Tetrahedron Letters
25, 5839–5842.
Acknowledgements
Rhodes University, the South African National
Research Foundation (NRF) and the Department of
Environmental Affairs and Tourism are thanked for
their financial support. The award of a Rhodes Uni-
versity post-graduate scholarship to C.A.G. is gratefully
acknowledged.
Garcia-Alvarez, M.C., Perez-Sirvent, L., Rodriguez, B., 1981. Trans-
formaciones de hispanolona. I. Sintesis parcial del diterpenoide fur-
anolabdanico galeopsina. Anales de Quimica (Serie C) 77, 316–319.
Rustaiyan, A., Mosslemin-Kupaii, M.H., Papastergiou, F., Jakupovic,
J., 1995. Persianone, a dimeric diterpene from Ballota aucheri. Phy-
tochemistry 40, 875–879.
Seidel, V., Bailleul, F., Tillequin, F., 1999. Terpenoids and phenolics
in the genus Ballota L. (Lamiaceae). Recent Research Developments
in Phytochemistry 3, 27–40.
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