Absolute configuration of helminthogermacrene

Article abstract of DOI:10.1016/j.tetasy.2004.03.030

The absolute configuration of the sesquiterpene hydrocarbon helminthogermacrene is established. Helminthogermacrene is an (E,Z)-configurational isomer of germacrene A and thus undergoes similar transformations forming elemenes via Cope rearrangement and yielding bicyclic systems via acid catalyzed reactions. The reaction products are investigated using enantioselective GC and extensive NMR measurements (¹H-; ¹H¹H-COSY; HSQC; HMBC and NOE-experiments). In addition, NMR data of related compounds isolated during the course of this investigation not yet reported in literature are given.

Full text of DOI:10.1016/j.tetasy.2004.03.030

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1631–1635
Absolute configuration of helminthogermacrene
Adewale Martins Adio, Claudia Paul,* Hailemichael Tesso, Petra Kloth
€
and Wilfried A. Konig
Institut f€ur Organische Chemie, Universit€at Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
Received 12 March 2004; accepted 19 March 2004
Available online 16 April 2004
Abstract—The absolute configuration of the sesquiterpene hydrocarbon helminthogermacrene is established. Helminthogermacrene
is an (E,Z)-configurational isomer of germacrene A and thus undergoes similar transformations forming elemenes via Cope rear-
rangement and yielding bicyclic systems via acid catalyzed reactions. The reaction products are investigated using enantioselective
1
GC and extensive NMR measurements (1H–; H1H-COSY; HSQC; HMBC and NOE-experiments). In addition, NMR data of
related compounds isolated during the course of this investigation not yet reported in literature are given.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
enantioselective GC investigations conducted with
authentic standards of (+)-germacrene A 2, (+)- and ())-
b-elemene 3, (+)- and ())-d-selinene 4, isolation of
known ())-a-helmiscapene 54 and 1H–, 1H1H-COSY,
HSQC, HMBC and NOE-experiments with the respec-
tive pure compounds. We also report the NMR data of
germacrene B 6,5 which was isolated during the course
of this work.
The sesquiterpene hydrocarbon helminthogermacrene 1
(Fig. 1) known from the fungus Helminthosporium sat-
ivum1 and the termite Amitermes wheeleri2 was recently
found in the essential oil of the liverwort Scapania
undulata (Hepaticae).3 Contrary to the previously
assumed configuration1;3 it was possible to deduce the
absolute configuration beyond doubt in this work due to
Thermally induced Cope rearrangement has been
observed for the members of the germacrene skeleton
sesquiterpene family.6 It is well known that germacrene
C 77 yields racemic d-elemene 8, germacrene B 6 forms
racemic c-elemene 9 and that (+)-germacrene A 2 is
easily converted into ())-b-elemene 3.8–10 It has been
observed that helminthogermacrene 1 having 1(10),4-
(E,Z)-configuration is less susceptible to Cope rear-
rangement than 2 with 1(10),4-(E,E)- configuration.3;11
In an earlier communication3 we have reported that
Cope rearrangement of (+)-1 yielded more than one
product, namely ())-cis-b-elemene 10, another b-elem-
ene diastereoisomer 11 and b-elemene 3 in an 8:1:0.08
ratio as determined by GC.
14
+ H
10
7
11
1
15
13
(+)-1
12
- H
H
2. Results and discussion
(-)-5
2.1. Absolute configuration of (+)-helminthogermacrene 1
Figure 1. Observed transformations of (+)-helminthogermacrene 1.
Compound (+)-1, isolated from S. undulata undergoes
rearrangement when stored in CDCl3 at 4 ꢁC for more
than 1 week to form a series of sesquiterpene hydro-
carbons with mass 204 as also observed on treatment of
* Corresponding author. Tel.: +49-40-53693947; fax: +49-40-536954-
32; e-mail: claudia.paul2@epost.de
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.030

1632
A. M. Adio et al. / Tetrahedron: Asymmetry 15 (2004) 1631–1635
netic precursor as suggested for termites,16 which also
generate ())-1.
Moreover the co-occurrence of ())-a-ylangene 84 and
(+)-a-amorphene 9 in the essential oil of S. undulata is in
agreement with the proposed absolute configuration.
H
6
(-)-3
H
2.2. Investigation of Cope rearrangement of helmintho-
germacrene 1
7
(-)-10
In addition, the interconversion of (+)-1 to its Cope
products was further investigated. For comparison (+)-
germacrene A 2, isolated from a diethyl ether extract of
Solidago canadensis, was injected under identical con-
ditions (injection port temperature of 200 ꢁC) as (+)-
helminthogermacrene 1. A minor isomer 12 eluting
shortly before the main product ())-b-elemene 3 from
the GC column is a second Cope product of (+)-ger-
macrene A 2 as it increases with increasing amount of
rearranged germacrene A and is also an elemene as re-
vealed by GC–MS. Interestingly, diastereomers with a
mass spectrum very similar to b-elemene were observed
from fresh costus roots8 and thermal isomerization of
(E,E)-hedycaryol 19.17
H
H
11
12
(-)-15
(-)-16
OH
The 95:5 mixture of two Cope products from germac-
1
rene A was isolated and investigated by H NMR to
19
yield a single set of b-elemene signals probably due to
the low concentration of the minor constituent in the
mixture. The mixture was hydrogenated to confirm that
one more product was generated apart from the pure b-
elemene 3. Coinjection of the two Cope rearrangement
products from 1 and 2 on two parallel columns with
nonpolar dimethylpolysiloxane CPSil-5 and the more
polar CPSil-19 stationary phases, respectively, reveals
that 12 is not identical to cis-b-elemene 10 but probably
is the enantiomer of 11. Thus, this observation may be
similar to the thermal isomerization of bicyclogermac-
rene18 and 19.17 Coinjections on enantioselective GC
show separation of 11 and 12 and hence support the
finding that they are of opposite absolute configuration
(Fig. 2).
1 with BF3 in diethyl ether or upon interaction with
acidic ion exchange resin amberlyst 15, respectively. The
isolation of the major unknown compound common to
all three treatments resulted in a product with 1H NMR,
13C NMR (CDCl3) and MS data totally consistent with
a-helmiscapene 5, earlier isolated from S. undulata4 and
synthesized12–14 with known absolute configuration. The
specific rotation of isolated 5 was negative as earlier
reported.4 The MS of 5 is very similar to that of its
10-epimer a-selinene 13. The formation of 5 from 1 can
be rationalized as demonstrated in Figure 1.
The comparison of hydrogenation products from ())-a-
helmiscapene 5 with the hydrogenated products of
compounds of known absolute configuration like (+)-a-
selinene 13, (+)-b-selinene 14 and ())-selina-5,11-diene
15, one of the dehydrated products of ())-maalian-5-ol15
(13C NMR data are reported for the first time) by
enantioselective GC again confirmed the absolute con-
figuration of ())-5, which is characterized by b-orien-
tation of the angular methyl substituent at C-10 and the
H-5 and H-7 protons and thus should be (5R,7S,10R).
From this it can be concluded that the absolute config-
uration of the precursor (+)-helminthogermacrene 1
should also have (7S)-configuration (b-orientation of
the H-7 proton).
Further investigation of the products obtained from
rearrangement of 1 by enantioselective GC on a modi-
fied c-cyclodextrin phase (cf. Fig. 2) suggests that the
third product formed is a racemic mixture of b-elemene
3. The other conceivable possibility that there are epi-
mers formed accidentally coeluting with the respective
b-elemenes is highly unlikely as such epimers should be
resolved as well.
2.3. Investigation of germacrene A 2 transformations
Diethyl ether extracts of the aerial parts of S. canadensis
concentrated under reduced pressure below 40 ꢁC were
fractionated by silica gel column chromatography
without prolonged contact to minimize decomposition
of sensitive constituents. The fraction that eluted with
100% n-pentane (yellow solution) was repeatedly sub-
mitted to preparative TLC using n-pentane as the
In addition, the observation that under BF3 treatment a
ratio of 5:1 in favour of the (+)-enantiomer of d-selinene
4 is formed3 underlines the asymmetric induction during
the formation of the bicyclic systems. Thus, this may
result in the formation of various eudesmanes of all
possible conformations by the cyclization of the bioge-

A. M. Adio et al. / Tetrahedron: Asymmetry 15 (2004) 1631–1635
1633
known constituents in trace amounts adding up to 4%
(Fig. 3).
Interestingly, the germacrene A 2 analyzed by GC at
120 ꢁC injection port temperature resulted in only a very
small amount of ‘normal’ ())-b-elemene 3 (ca. 5%), a
broadened germacrene A 2 peak (ca. 81%), which was
preceded by a ‘hump’ in the baseline containing 13
(0.2%), 14 (0.3%) and 17 (0.08%).
When the diethyl ether extract of S. canadensis was
exposed to silica gel at room temperature for 24 h it
formed a well known compound ())-selin-11-en-4-ol 18
(23%), (18 had been reported as a major constituent of
the essential oil of Conocephalum conicum)20 in addition
to reported compounds 13, 14 and 17,21 indicating that
germacrene A 2 rearranges to these bicyclic systems in
an analogous fashion as helminthogermacrene 1 does.
The proposed biosynthetic pathway for the formation of
18 is shown in Figure 3. This observation has never been
reported before for compound 2, even though it has
been reported that germacrenes B 6 and C 7 gave similar
oxygenated products when subjected to acid rearrange-
ment reactions.22–24 Moreover, similar acid induced
rearrangement reaction products of germacrene B 6
were obtained, which include selina-4(15),7(11)-diene,
selina-3,7(11)-diene and eudesm-7(11)-en-4a-ol as re-
ported,22–24 but we noticed that this occurred rather
slowly with very low yield as compared to 2 under the
same conditions. This suggests that 6 is much more
stable than 2 when treated with silica gel under the same
conditions. Even though 2 proved to be much more
stable than reported in literature with silica gel if the
experiment is run within a very short period of time.
2.4. Investigation of germacrene B 6
The NMR data of the known naturally occurring 6 were
recorded in C6D6 in which all the methyl and the me-
thine signals are well resolved. The H NMR spectrum
Figure 2. Comparison of the elemenes from (+)-1 (a) ( )-(3) (b) and
co-injection (c) on cyclodextrin chiral phase 2,6-Me-3-Pe-c-CD at
100 ꢁC isothermal.
1
showed signals of four methyl singlets at d 1.47 (3H, br
s, H-14), 1.48 (3H, br s, H-15), 1.63 (3H, s, H-12/13) and
1.67 (3H, s, H-12/13). The vinylic protons at d 4.76 (1H,
br d, J ¼ 12 Hz) and 4.65–4.72 (1H, br s) are assigned to
developing solvent at )25 ꢁC to give (+)-germacrene A 2
(Rf 0.40), germacrene B 6 (Rf 0.45), both enantiomers of
germacrene D 1619 (Rf 0.61), and a single band [con-
taining ())-a-selinene (41%) 13, (+)-b-selinene 14 (45%)
and (+)-selina-4,11-diene 17 (12%)] (Rf 0.74) and other
1
H-1 and H-5, respectively. Only the H NMR in CDCl3
1
of 65 and the H NMR and 13C NMR of the (E,Z)-
isomer of 6 have been reported before.25
+H
+ H2O
- H
H
HO
H
(-)-18
(+)-2
- H
H
H
(-)-13
(+)-14
(+)-17
Figure 3. Observed transformations of (+)-germacrene A 2.

1634
A. M. Adio et al. / Tetrahedron: Asymmetry 15 (2004) 1631–1635
3. Experimental
molybdatophosphoric acid (20% w/v) reagent was used
as spray reagent. The TLC plate was developed twice in
n-pentane at )25 ꢁC and immediately extracted with
diethyl ether.
3.1. General experimental procedures
3.1.1. GC–MS. Electron impact (70 eV) GC–MS was
carried out with a Hewlett Packard HP 5890 gas chro-
matograph coupled to a VG Analytical 70–250S mass
spectrometer. All compounds were identified by com-
parison of their mass spectra and gas chromatographic
retention indices with a spectral library established
under identical experimental conditions.26;27
3.2. Isolation of reference compounds
3.2.1. Isolation of ())-a-helmiscapene 5.
(a) From the reaction mixture: A solution of ca. 1 mg of
(+)-1 in n-hexane (1.5 mL) was mixed with acidic ion
exchange resin Amberlyst 15 and kept at room tem-
perature for 2 h. After (+)-1 had completely disap-
peared (GC control) the solution was filtered and
the catalyst was washed with n-hexane. The solution
was shaken with a saturated aqueous solution of
NaHCO3 (3 mL). The organic layer was partitioned
and dried over Na2SO4, the solvent was evaporated
and 5 was isolated using preparative GC.
3.1.2. NMR-spectroscopy. NMR measurements were
carried out with a Bruker WM 400 (400 MHz) or a
Bruker WM 500 (500 MHz) instrument in C6D6 using
TMS as internal standard if not otherwise stated.
3.1.3. Gas chromatography. Orion Micromat 412 double
column instrument with 25 m fused silica capillaries with
polysiloxane CPSil-5 and polysiloxane CPSil-19
(Chrompack); Carlo Erba Fractovap 2150 or 4160 gas
chromatographs with 25 m fused silica capillaries
with octakis(2,6-di-O-methyl-3-O-pentyl)-c-cyclodextrin,28
heptakis(2,6-di-O-methyl-3-O-pentyl)-b-cyclodextrin28 or
heptakis(6-O-tert-butyldimethylsilyl-2,3-di-O-methyl)-b-
cyclodextrin29 in OV 1701 (50%, w/w), split injection;
split ratio approx. 1:30; FID; carrier gas 0.5 bar H2;
injector and detector temperatures were 200, and 250 ꢁC,
respectively.
(b) From Radula perrottettii (liverwort): An indepen-
dent isolation and structure elucidation of ())-5
recently isolated from the essential oil obtained by
hydrodistillation of the liverwort R. perrottettii col-
lected in Tokushima, Japan, in October 2003,31 and
spectral comparisons confirm complete identity.
3.2.2. Isolation of (+)-germacrene A 2. The macerated
air-dried aerial parts of S. canadensis, collected in
Hamburg, Germany in September 2003, was extracted
for 3 days at room temperature with diethyl ether. The
concentrated crude extract obtained below 40 ꢁC by
evaporation of the solvent was fractionated using flash
silica gel column chromatography. The 100% n-pentane
fraction was then subjected to repeated TLC at )25 ꢁC,
and n-pentane as the developing solvent.
3.1.4. Preparative GC. Modified Varian 1400 and 2800
instruments, equipped with stainless steel columns
(1.85 m · 4.3 mm) with 10% polydimethylsiloxane SE-30
on Chromosorb W-HP or with 2.5% octakis(2,6-di-O-
methyl-3-O-pentyl)-c-cyclodextrin28 in OV-1701 (50%,
w/w) on Chromosorb G-HP or with 6% heptakis(6-O-
tert-butyldimethylsilyl-2,3-di-O-methyl)-b-cyclodextrin29
in SE-52 (50%, w/w) on Chromosorb W-HP; FID;
helium as carrier gas at a flow rate of 240 mL/min;
injector and detector temperatures were 200 and 250 ꢁC,
respectively.30
3.2.3. Isolation of germacrene B 6. Compound 6 was
isolated simultaneously with 2 by using the same
method since both are present in the same fraction.
3.2.4. Characterization of ())-a-helmiscapene 5. Colour-
less oil; RICPSIL5 ¼ 1451; sense of optical rotation
(CDCl3): ()); 1H NMR (500 MHz, CDCl3): 0.87 (3H, s),
1.36–1.42 (2H, m), 1.66 (3H, br s), 1.71 (3H, s), 1.81–
1.90 (4H, m), 2.00–2.09 (2H, m), 4.66 (1H, s), 4.68 (1H,
s), 5.24 (1H, br s); 13C NMR (125.7 MHz, C6D6): 21.2,
23.1, 23.7, 26.7, 27.4, 27.8, 29.3, 35.3, 41.4, 46.4, 48.0,
109.0, 119.8, 137.1, 150.7; MS (EI, 70 eV), m=z (rel int.):
204 [Mþ] (38), 189 (59), 175 (9), 161 (32), 147 (19), 133
(28), 121 (27), 119 (30), 107 (75), 105 (56), 93 (82), 91
(68), 81 (48), 79 (47), 77 (45), 67 (38), 55 (47), 53 (48), 41
(100).
3.1.5. Polarimetry . Measurements were performed with
a polarimeter 341 (Perkin–Elmer) at 589 nm at 20 ꢁC.
Due to very small amounts of isolated compounds only
the sign of optical rotation is given to avoid inaccura-
cies.
3.1.6. Reactions. Hydrogenation reactions were per-
formed by bubbling hydrogen gas through a stirred
solution of ca. 1 mg of sample in 1 mL n-hexane and
0.5 mg Pd/C at room temp for 1 h. The reaction mixture
was filtered and the reaction products were analyzed by
GC–MS and by GC on several capillary columns with
cyclodextrin derivatives.
3.2.5. Characterization of (+)-germacrene A 2. Isolated
from S. canadensis as colourless oil; RICPSIL5 ¼ 1501;
RfðpentaneÞ ¼ 0.40; sense of optical rotation (benzene): (+);
1H NMR (500 MHz, C6D6): d 1.31 (3H, br s, H-14), 1.44
(3H, br s, H-15), 1.48–1.55 (1H, m, H-8a), 1.67 (3H, s,
H-12), 1.67–1.73 (1H, m, H-8b), 1.76–2.36 (9H, br m, H-
2ab, 3ab, 6ab, 7, 9ab), 4.68 (1H, s, H-13a), 4.51 (1H, br
3.1.7. Thin layer chromatography. Thin layer chroma-
tography was effected using aluminium supported plates
of silica 60 F254 (Merck). An ethanolic solution of

A. M. Adio et al. / Tetrahedron: Asymmetry 15 (2004) 1631–1635
1635
2. Scheffrahn, R. H.; Sims, J. J.; Lee, R. K.; Rust, M. K.
J. Nat. Prod. 1986, 49, 699–701.
€
3. Adio, A. M.; Paul, C.; Kloth, P.; Konig, W. A.
Phytochemistry 2004, 65, 199–206.
4. Andersen, N. H.; Bissonette, P.; Liu, C.-B.; Shunk, B.;
Ohta, Y.; Tseng, C.-L. W.; Moore, A.; Huneck, S.
Phytochemistry 1977, 16, 1731–1751.
5. Brown, E. D.; Solomon, M. D.; Sutherland, J. K.; Torre,
A. J. Chem. Soc., Chem. Commun. 1967, 111–112.
6. Takeda, K. Tetrahedron Lett. 1974, 30, 1525–1534.
7. Morikawa, K.; Hirose, Y. Tetrahedron Lett. 1969, 22,
1799–1801.
d, 10.2 Hz, H-5), 4.79 (1H, s, H-13b), 4.71–4.75 (1H, m,
H-1); 13C NMR (125.7 MHz, C6D6): d 16.6 (q, C-14),
17.0 (q, C-15), 20.6 (q, C-12), 26.8 (t, C-2 or C-3), 34.3
(t, C-8), 35.1 (t, C-6), 40.2 (t, C-3 or C-2), 42.3 (t, C-9),
52.1 (d, C-7), 108.1 (t, C-13), 126.9 (d, C-1), 128.8 (s, C-
4), 131.9 (d, C-5), 137.7 (s, C-10), 153.1 (s, C-11); MS
(EI, 70 eV), m=z (rel int.): 204 [Mþ] (10), 189 (25), 175
(8), 161 (28), 147 (32), 133 (25), 121 (42), 107 (59), 93
(84), 81 (82), 68 (100), 53 (57), 41 (82).
8. de Kraker, J.-W.; Franssen, M. C. R.; de Groot, A.;
Shibata, T.; Bouwmeester, H. J. Phytochemistry 2001, 58,
481–487.
9. Weinheimer, A. J.; Youngblood, W. W.; Washecheck, P.
H.; Karns, T. K. B.; Ciereszko, L. S. Tetrahedron Lett.
1970, 7, 497–500.
10. Nishino, C.; Bowers, W. S.; Montgomery, M. e.; Nault, L.
R.; Nielson, M. W. J. Chem. Ecol. 1977, 3, 349–357.
ꢀ
11. McMurry, J. E.; Kocovsky, P. Tetrahedron Lett. 1985, 26,
2171–2172.
12. Caine, D.; Stanhope, B. Tetrahedron 1987, 43, 5545–5555.
13. Schinzer, D.; Fesserner, K.; Ruppelt, M. Liebigs Ann.
Chem. 1992, 139–143.
14. Baker, R.; Evans, D. A.; McDowell, P. G. Tetrahedron
Lett. 1978, 42, 4073–4076.
15. Matsuo, A.; Nozaki, H.; Kataoka, H.; Nakayama, M.;
Hayashi, S. Experientia. 1979, 35, 1279–1280.
16. Naya, Y.; Prestwich, G. D.; Spanton, S. G. Tetrahedron
Lett. 1982, 23, 3047–3050.
3.2.6. Characterization of germacrene B 6. Colourless oil;
RICPSIL5 ¼ 1555; RfðpentaneÞ ¼ 0.45; 1H NMR (500 MHz,
C6D6): d 1.46 (3H, s, H-14/15), 1.48 (3H, s, H-15/14),
1.63 (3H, s, H-12/13), 1.67 (3H, s, H-13/12), 1.93–2.27
(9H, m, H-2ab, 3ab, 9ab, 8ab, 6a), 2.53 (1H, br s, H-6b),
4.67 (1H, br s, H-1/5), 4.76 (1H, br d, J ¼ 12.0 Hz, H-5/
1); 13C NMR (125.7 MHz, C6D6): 16.7 (q, C-14/15), 16.7
(q, C-15/14), 20.6 (q, C-12/13), 20.7 (q, C-13/12), 26.5 (t,
C-2), 32.8 (t, C-6), 39.3 (t, C-3/C-8), 39.5 (t, C-3/C-8),
41.3 (t, C-9), 126.3 (s, C-7/11), 126.9 (d, C-5/1), 128.3 (d,
C-1/5), 131.6 (s, C-10/4), 133.9 (s, C-11/7), 136.8 (s, C-4/
10); MS (EI, 70 eV), m=z (rel int.): 204 [Mþ] (28), 189
(20), 175 (5), 161 (31), 147 (19), 133 (27), 121 (100),
107 (53), 105 (51), 93 (69), 81 (47), 67 (55), 53 (48), 41
(85).
3.2.7. ())-Selina-5,11-diene 15. Colourless oil;
RICPSIL5 ¼ 1447; sense of optical rotation (benzene): ());
1H NMR (500 MHz, C6D6): d 1.14 (3H, s), 1.14–1.21
(2H, m), 1.17 (3H, d, J ¼ 7.6 Hz), 1.32–1.38 (1H, m),
1.45–1.55 (5H, m), 1.70 (3H, s), 1.71–1.80 (1H, m), 1.81–
1.88 (1H, m), 2.45–2.51 (1H, m), 2.60 (1H, t, J ¼ 5.4 Hz),
4.88 (1H, br s), 4.94 (1H, br s), 5.34 (1H, d, J ¼ 4.1 Hz);
13C NMR (125.7 MHz, C6D6): d 18.2 (t), 22.5 (q), 23.1
(q), 23.2 (t), 27.2 (q), 34.2 (t), 35.1 (s), 38.0 (t), 39.1 (d),
42.4 (d), 42.6 (t), 112.0 (t), 124.1 (d), 148.1 (s), 148.5 (s);
MS (EI, 70 eV), m=z (rel int.): 204 [Mþ] (40), 189 (42),
161 (37), 147 (39), 133 (46), 121 (38), 108 (100), 107 (62),
105 (52), 93 (62), 81 (48), 67 (22), 55 (38), 41 (49).
17. Kodama, M.; Yokoo, S.; Matsuki, Y. Tetrahedron Lett.
1979, 26, 2171–2172.
18. Nishimura, K.; Horibe, I.; Tori, K. Tetrahedron 1973, 29,
271–274.
€
€
19. Bulow, N.; Konig, W. A. Phytochemistry 2000, 55, 141–
168.
20. Melching, S.; Konig, W. A. Phytochemistry 1999, 51, 517–
€
523.
21. de Kraker, J.-W.; Franssen, M. C. R.; de Groot, A.;
€
Konig, W. A.; Bouwmeester, H. Plant Physiol. Biochem.
1998, 117, 1381–1392.
22. Kitagawa, I.; Kobayashi, M.; Cui, Z.; Kiyota, Y.; Ohnishi,
M. Chem. Pharm. Bull. 1986, 34, 4590–4596.
23. Allen, F. H.; Rogers, D. J. Chem. Soc., Chem. Commun.
1967, 588–590.
24. de Pascual Teresa, J.; Barrero, A. F.; Caballero, M. C. An.
Quim. 1978, 74, 519–521.
25. Minnaard, A. J.; Wijnberg, J. B. P. A.; de Groot, A.
J. Org. Chem. 1997, 62, 7336–7345.
Acknowledgements
€
26. Joulain, D.; Konig, W. A. The Atlas of Spectral Data of
Sesquiterpene Hydrocarbons; E.B.: Hamburg, 1998.
The financial support of DAAD (scholarship for AMA
and HT) and of the Fonds der Chemischen Industrie is
gratefully acknowledged. We also thank Dr. V. Sinn-
well, University of Hamburg, for his advise in obtaining
NMR spectra and A. Meiners and M. Preuße for GC–
MS measurements.
€
27. Hochmuth, D. H.; Joulain, D.; Konig, W. A. MassFinder
3.1, software and data bank, University of Hamburg,
2003. (www.massfinder.com).
€
28. Konig, W. A.; Gehrcke, B.; Icheln, D.; Evers, P.;
€
Donnecke, J.; Wang, W. J. High Res. Chromatogr. 1992,
15, 367–372.
29. Dietrich, A.; Maas, B.; Messer, W.; Bruche, G.; Karll, V.;
Kaunzinger, A.; Mosandl, A. J. High Res. Chromatogr.
1992, 15, 590–593.
References and notes
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30. Hardt, I. H.; Konig, W. A. J. Chromatogr. A 1994, 666,
1. Winter, R. E. K.; Dorn, F.; Arigoni, D. J. Org. Chem.
1980, 45, 4786–4789.
611–615.
31. Tesso, H.; Konig, W. A. Unpublished results.
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