New routes to clavine-type ergot alkaloids. Part 1. First total synthesis of three natural products: (+)-setoclavine, (+)-isosetoclavine, (-)-9,10-dihydroisoseto-clavine, and structure correction of the latter

Article abstract of DOI:10.3987/COM-05-S(T)26

The double bond in ring D of (+)-9,10-didehydro-6-methylergolin-8-one (2) was reduced selectively by catalytic hydrogenation to yield (-)-6-methylergolin-8-one (6). Grignard reaction of 6 has been performed with methylmagnesium iodide to afford two isomers (5 and 7). The main isomer having an 8α-methyl group at C8 with a C/D-trans junction (5; (-)-dihydroisosetoclavine) proved to be identical with the natural product, hence its name and structure should be corrected. As a minor isomer (7) a C/D-cis clavine derivative was also isolated which can be regarded as unnatural (+)-8α-hydroxycostaclavine. (+)-Setoclavine (8) and (+)-isosetoclavine (9) have also been prepared from 2, thus achieving the first total synthesis of these natural products. Detailed structure elecidation of 5-9 has been carried out as well.

Full text of DOI:10.3987/COM-05-S(T)26

HETEROCYCLES, Vol. 67, No. 1, 2006
291
HETEROCYCLES, Vol. 67, No. 1, 2006, pp. 291 - 298. © The Japan Institute of Heterocyclic Chemistry
Received, 5th July, 2005, Accepted, 29th August, 2005, Published online, 30th August, 2005. COM-05-S(T)26
NEW ROUTES TO CLAVINE-TYPE ERGOT ALKALOIDS. PART 1.
FIRST TOTAL SYNTHESIS OF THREE NATURAL PRODUCTS: (+)-
SETOCLAVINE, (+)-ISOSETOCLAVINE, (-)-9,10-DIHYDROISOSETO-
CLAVINE, AND STRUCTURE CORRECTION OF THE LATTER #
István Moldvai,a,* Eszter Temesvári-Major,a Eszter Gács-Baitz,a Mária
Incze,a Gábor Dörnyei,a and Csaba Szántaya,b,*
aChemical Research Center, Institute of Biomolecular Chemistry, Hungarian
b
Academy of Sciences, H-1525 Budapest, POB 17, Hungary; Department for
Organic Chemistry, Research Group for Alkaloid Chemistry of the Hungarian
Academy of Sciences, Budapest University of Technology and Economics,
Gellért tér 4, H-1521 Budapest, Hungary
e-mails: imoldvai@chemres.hu and szantay@mail.bme.hu
#We dedicate this paper to Professor Barry M. Trost on the occasion of his 65th
birthday.
Abstract – The double bond in ring D of (+)-9,10-didehydro-6-methylergolin-8-
one (2) was reduced selectively by catalytic hydrogenation to yield (-)-6-
methylergolin-8-one (6). Grignard reaction of 6 has been performed with
methylmagnesium iodide to afford two isomers (5 and 7). The main isomer
having an 8α-methyl group at C8 with a C/D-trans junction (5; (-)-dihydro-
isosetoclavine) proved to be identical with the natural product, hence its name
and structure should be corrected. As a minor isomer (7) a C/D-cis clavine
derivative was also isolated which can be regarded as unnatural (+)-8α-hydroxy-
costaclavine. (+)-Setoclavine (8) and (+)-isosetoclavine (9) have also been
prepared from 2, thus achieving the first total synthesis of these natural products.
Detailed structure elucidation of 5-9 has been carried out as well.
INTRODUCTION
In our previous publication1 we described the first direct synthesis of (+)-lysergic acid (3, Scheme 1). In
our procedure (+)-9,10-didehydro-6-methylergolin-8-one (2) prepared from 4-bromo-Uhle’s ketone (1)
proved to be the main key intermediate. This optically active key compound (2) with (5R)-configuration
opened the way to elaborate new routes toward further ergot alkaloids.

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HETEROCYCLES, Vol. 67, No. 1, 2006
CO2H
O
8
9
7
O
H
N
H
10
11
Br
N
Me
Me
5
4
HN
HN
HN
1
1
2
3
Scheme 1
Ergot alkaloids have attracted the attention of synthetic chemists for decades. Certainly the pivotal
representatives of this class have been 3 and its amide derivatives, peptide-type ergot alkaloids, as they
possess a very wide spectrum of biological activity. However other members, clavine-type ergot
alkaloids, have also played an important role in natural product chemistry. On the other hand, several
therapeutically important compounds can be formally regarded as derivatives of clavine alkaloids.2 Thus,
continued research into this field is driven by both chemical and biological interest.3
RESULTS AND DISCUSSION
From saprophytic cultures of Claviceps paspali Stevens et Hall a C8-disubstituted (OH, Me groups)
tetracyclic clavine-type ergot alkaloid was isolated by Sandoz researchers in 1973,4 which was named (-)-
dihydrosetoclavine with formula (4) (Scheme 2). Later, Natsume’s group elaborated two total syntheses5,6
of (±)-4 and its C8-epimer [(±)-5]. In the second alternative route6 tetracyclic ketone [(±)-6],7 prepared
from their commonly used tricyclic nitrovinyl derivative, was allowed to react with methyllithium to
yield (±)-4 and (±)-5. The Japanese group regarded 4 as the racemic form of the natural product.
Unfortunately, the NMR spectral instrumentation at that time was not sophisticated enough to provide
unambiguous stereochemical assignments.
The optically active 2, synthesized by us, seemed to be suitable for preparing the natural product. The
first step of our recent synthesis was to reduce the C9-C10 double bond by catalytic hydrogenation
(H2/10% Pd-C, MeOH, rt, 50% yield) to afford the optically active ketone (6). The α-position of C10-H
and hence the trans junction of rings C and D followed were verified by NMR spectral measurements.
Specifically, the proton-proton coupling values of C10-H with the C5-H and C-9Hax protons (9.1 and 12.8
Hz, respectively) reflect the trans arrangement of these protons. In the second step ketone (6) was
allowed to react with methylmagnesium iodide in a Grignard reaction to afford two isomers (5, yield:
22%; 7, yield: 9%) after separation of the components by column chromatography; 5 and 7 showed the
same molecular weight (M+=256) as determined from the MS spectra. The structure elucidation of 5 and
7 by high-resolution NMR spectral techniques gave surprising results in both cases (see: below). It is
worth mentioning here that the natural product isolated by the Sandoz group4 is a laevo rotatory (-)

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293
compound. By comparison with the optical rotations of our synthetic 5 ([α]D = - 48o) with the isolated
compound from natural sources ([α]D = - 51 ± 5o) we had to assume to obtain the natural material in the
Grignard reaction. After a detailed structure elucidation by NMR spectral measurements, the obtained
results unambiguously proved that the natural product should be characterized with formula (5) and
named as (-)-dihydroisosetoclavine instead of the published structure (4) which should be called (-)-
dihydrosetoclavine.
O
Me
OH
N
HO
Me
N
HO
Me
N
MeMgI
Et2O
+benzene
D
H
H
H
H
H
H
H
N
H
Me
Me
Me
A
C
Me
o
(60 C, 1 h)
+
B
HN
HN
HN
HN
5
6
7
4
H2/10% Pd(C)
MeOH, rt
(50%)
HO
Me
N
Me
OH
H
H
N
Me
Me
MeLi
+
2
HN
HN
8
9
Scheme 2
The dextro rotating (+) minor isomer (7) showed a curious feature, the cis junction of ring C and D.
[Compound (7) has been prepared racemic form earlier by Natsume’s group6 from a C/D-cis ketone
derivative and can be regarded as 8α-hydroxycostaclavine]. To explain the intriguing epimerization that
leads to C/D-cis ring junction from a trans compound (6), requires further investigation. Preliminary
epimerization of either the C5 or the C10 chiral centers could result in C/D-cis ketone, before the
Grignard reaction of the keto function.
Ketone (2) was allowed to react with methyllithium, as described by Italian researchers8 to yield (+)-
setoclavine (8)9 and (+)-isosetoclavine (9).10 As this reaction sequence was performed earlier only with
semisynthetic ketone (2) obtained from natural sources, our approach represents the first total syntheses
of these two natural products. The stereochemistry, mainly the configuration at C8 of 8 and 9 has been
reinvestigated by NMR spectral techniques; the data and thus the structures were in good accordance with
the published ones.
In the proton spectrum of 8 the assignment of the steric orientation of the C7-H protons was obtained
from the NOE enhancement observed on the C7-Hβ proton (2.47 ppm) upon irradiation of the C5-H

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HETEROCYCLES, Vol. 67, No. 1, 2006
proton. The subsequent irradiation of the C8-Me protons gave NOE on the same, C7-Hβ proton. For 9 a
similar experiment assigned the resonance at 2.51 ppm to the C7-Hβ proton. Irradiation of the C8-OH
resonance (4.36 ppm) resulted in a noteworthy NOE on the proton signal of this proton. In addition, the
C8-Me protons gave an NOE with the C7-Hα proton (2.78 ppm), which determined the stereochemistry at
C8 as depicted in Scheme 2.
It is well documented that ring D of lysergic acid derivatives can be characterized by two dominant
conformers11 and the situation is expected to be similar in the case of 9,10-dehydroclavine type
alkaloids.12 As for the 9,10-dihydroclavine alkaloids, two all-chair conformations seems to be imaginable
as well. 13 On the basis of NMR spectral studies our synthetic products (5, 7, 8, 9) can be found mainly in
1
13
the conformers drawn on Scheme 3. The stereostructure of 5 is of special interest. Both the H and C
spectral parameters of rings C and D were rather good agreement with those of some parent compounds14
for which the configuration and conformations were inferred from X-Ray studies. In the respective
stereochemistry ring D is in a chair form where the methyl group is close to the C10-H proton, which
explains the significant enhancement of this hydrogen upon irradiation of the methyl resonance. The trans
C/D ring junction is also corroborated by the coupling value of the C10-H with C5-H proton (10.0 Hz). In
accordance with the trans arrangement of these protons, no NOE was observed between them.
H
Me
10
H
H
8
9
C11
H
C3
5
C-4
C-5
C-7
OH
9
10
C11
4
H
H
N
H
H
H
H
5
6
7
8
9
27.28 68.15 70.03
27.25 65.38 67.24
13.91 60.87 61.75
27.26 63.45 66.81
26.82 63.28 66.21
H
Me
5
OH
8
Me
7
H
N
7
H
4
H
Me
H
C3
H
5
7
H
H
C11
C11
5
9
H
H
4
C3
C3
H
H
10
H
H
Me
Me
Me
OH
N
N
7
H
H
8
H
H
OH
Me
9
8
Scheme 3
On the contrary, the NMR parameters confirmed the cis stereochemistry at the C10-C5 ring junction for
7. The cis relationship between the C10-H and C5-H protons follows from also scalar proton coupling
(4.0 Hz). The configuration at C8, as depicted in Schemes 2 and 3, was assigned on the basis of the NOE
observed on the C10-H signal upon irradiation of the methyl resonance. The C/D ring stereochemistry
13
basically affects the C chemical shifts, as the γ-gauche relations cause noteworthy shifts of the C4, C5
and C7 carbons in comparison with their values in the trans C/D ring systems.

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295
The novel chemical proofs and correlations of the above compounds will be published in the near future.
Further examination of the reactions of 1 and 2 to synthesize other ergot alkaloids or derivatives is in
progress.
EXPERIMENTAL
Mps are uncorrected. MS spectra were run on an AEI-MS-902 (70 eV; direct insertion) and on a Kratos-
MS-902 mass spectrometer. FAB-MS spectra were measured on a ZAB 2SEQ spectrometer. IR spectra
were taken on a Nicolet 7795 FT-IR spectrophotometer. NMR spectroscopy measurements were carried
1
13
out on a Varian Unity Inova (400 MHz for H and 100 MHz for C) instrument. Chemical shifts are
given relative to TMS=0.00 ppm. Elemental analyses (C, H, N, S) were carried out by Vario EL III
(Elementar Analysen System Gmbh) automatic microanalyzer. Preparative separations were performed
by column chromatography on Merck Kieselgel 60 (0.063-0.200).
(-)-6-Methylergolin-8-one (6)
To a solution of 21 (200 mg; 0.839 mmol) in dry MeOH (30 mL) 10% Pd/C (100 mg) was added at rt and
the suspension stirred under H2 atmosphere for 8 h. The catalyst was removed by filtration, washed with
MeOH (3x20 mL), the filtrate was evaporated under reduced pressure and the residue was purified by
column chromatography (eluent: CHCl3 – MeOH, 10/1) to yield 6 (100 mg; 50%) as a pale semisolid
o
product, mp 182-190 C (from ether/hexane; decomp); [α]D = - 64o (c=0.25, MeOH). IR (KBr): 3408,
2930, 2794, 1661, 1618, 1445, 1346, 1062 cm-1. MS (m/z, %): 241 (100, M+), 212 (33), 197 (10), 181 (9),
168 (23), 154 (26) 127 (9). 1H NMR (400 MHz, CDCl3 + DMSO-d6), δ: 2.50 (3H, s, N-Me), 2.51 (1H,
dd, J= 15.2 + 12.8 Hz, H-9ax), 2.67 (1H, ddd, J= 11.1 + 9.1 + 4.0 Hz, H-5), 2.76 (1H, ddd, J= 14.4 + 11.1
+ 1.6 Hz, H-4ax), 3.06 (1H, d, J= 14.5 Hz, H-7ax), 3.26 (1H, ddd, J= 15.2 + 5.0 + 2.1 Hz, H-9eq), 3.35 (1H,
ddd, J= 12.8 + 9.1 + 5.0 Hz, H-10), 3.35 (1H, dd, J= 14.5 + 2.1 Hz, H-7eq), 3.42 (1H, dd, J= 14.4 + 4.0
Hz, H-4eq), 6.74 (1H, dd, J= 7.2 + 1.2 Hz, H-14), 6.93 (1H, t, J= 1.6 Hz, H-2), 7.10 (1H, dd, J= 7.2 + 8.1
13
Hz, H-13), 7.20 (1H, dd, J= 8.1 + 1.2 Hz, H-12), 9.82 (1H, d, J= 1.6 Hz, NH). C NMR (100 MHz,
CDCl3 + DMSO-d6), δ: 27.25 (C-4), 40.57 (C-10), 41.89 (N-Me), 43.00 (C-9), 65.38 (C-5), 67.24 (C-7),
109.59 (C-14), 110.63 (C-3), 112.67 (C-12), 118.79 (C-2), 122.80 (C-13), 126.44 (C-16), 131.93 (C-11),
133.80 (C-15), 206.13 (C-8). Anal. Calcd for C15H16N2O: C, 74.97, H, 6.71, N, 11.65. Found: C, 74.85,
H, 6.79, N, 11.61.
(-)-9,10-Dihydroisosetoclavine (5) and (+)- 8α-hydroxycostaclavine (7)
Grignard reagent was prepared from Mg (120 mg, 049 mg atom) and MeI (1.1 g, 8.03 mmol) in dry ether
(20 mL). The formed methylmagnesium iodide was dropped into a solution of 6 (160 mg, 0.66 mmol) in
benzene (20 mL) at 50 oC and the reaction mixture was stirred for 1 h at 60 oC, then was cooled to 0 oC.

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The mixture was decomposed by adding aqueous saturated NH4Cl solution (5 mL). The phases were
separated and the aqueous layer was extracted with CHCl3 (2x20 mL). The combined organic phase was
washed with saturated NaCl solution (10 mL) and dried (Na2SO4). The filtrate was evaporated under
reduced pressure, the residue was separated by column chromatography (eluent: CHCl3 – MeOH, 5/1; Rf
of 7 ≈ 0.3, Rf of 5 ≈ 0.5).
o
Compound (5): white crystals (38 mg; 22%), mp 245-250 C (decomp) (from ether) [lit.,4 mp 276-278
oC]; [α]D = - 48o (c=0.25, MeOH) [lit.,4 [α]D = - 51o ± 5o (c=0.2, pyridine)]. IR (KBr): 3404, 3099, 2847,
2792, 1609, 1444, 1328, 1126 cm-1. MS (m/z, %): 256 (100, M+), 197 (15), 167 (9), 154 (26), 127 (9). 1H
NMR (400 MHz, CDCl3, + DMSO-d6), δ: 1.43 (3H, s, C8-Me), 1.48 (1H, dd, J= 13.0 + 12.2 Hz, H-9ax),
1.98 (1H, ddd, J= 10.2 + 10.0 + 4.2 Hz, H-5), 2.14 (1H, d, J= 10.7 Hz, H-7ax), 2.38 (3H, s, N-Me), 2.51
(1H, ddd, J= 13.0 + 4.0 + 2.0 Hz, H-9eq), 2.57 (1H, dd, J= 14.6 + 10.2 Hz, H-4ax), 2.69 (1H, dd, J= 10.7 +
2.0 Hz, H-7eq), 2.86 (1H, ddd, J= 12.2 + 10.0 + 4.0 Hz, H-10), 3.32 (1H, dd, J= 14.6 + 4.2 Hz, H-4eq),
4.42 (1H, s, OH), 6.75 (1H, dd, J= 7.2 + 1.2 Hz, H-12), 6.87 (1H, br s, H-2), 7.02 (1H, dd, J= 8.1 + 7.2
13
Hz, H-13), 7.12 (1H, dd, J= 8.1 + 1.2 Hz, H-14), 10.24 (1H, br s, NH). C NMR (100 MHz, CDCl3 +
DMSO-d6), δ: 26.91 (C8-Me), 27.28 (C-4), 39.65 (C-10), 42.44 (C-9), 43.75 (N-Me), 68.00 (C-8), 68.15
(C-5), 70.03 (C-7), 109.11 (C-14), 111.03 (C-3), 112.40 (C-12), 118.64 (C-2), 122.60 (C-13), 126.73 (C-
16), 133.36 (C-11), 133.72 (C-15). Anal. Calcd for C16H20N2O: C, 74.96, H, 7.86, N, 10.92. Found: C,
74.91, H, 7.89, N, 10.83.
Compound (7): white crystals (15 mg; 9%), mp 165-170 oC (decomp) (from ether); [α]D = + 24o (c=0.54,
MeOH). IR (KBr): 3410, 2929, 2852, 1667, 1444, 1108. cm-1. MS (m/z, %): 256 (100, M+), 197 (14), 167
(9), 154 (27), 127 (7). 1H NMR (400 MHz, CDCl3, 70 oC), δ: 1.37 (3H, s, C8-Me), 1.83 (1H, dd, J= 13.4
+ 5.0 Hz, H-9β), 2.22 (1H, dd, J= 13.4 + 9.4 Hz, H-9α), 2.37 (1H, d, J= 11.0 Hz, H-7β), 2.40 (3H, s, N-
Me), 2.62 (1H, d, J= 11.0 Hz, H-7α), 2.92 (1H, ddd, J= 15.4 + 3.7 + 1.0 Hz, H-4β), 2.98 (1H, ddd, J= 6.7
+ 4.0 + 3.7 Hz, H-5), 3.18 (1H, ddd, J= 15.4 + 6.7 + 1.5 Hz, H-4α), 3.34 (1H, ddd, J= 9.4 + 5.0 + 4.0 Hz,
H-10), 3.85 (1H, br s, in CDCl3 + DMSO-d6), 6.84 (1H, dd, J= 1.5 + 1.0 Hz, H-2), 6.97 (1H, m, H-13),
13
o
7.12 (2H, m, H-12 + H-14), 7.80 (1H, br s, NH). C NMR (100 MHz, CDCl3 + DMSO-d6, 80 C), δ:
13.91 (C-4) 27.31 (C8-Me), 38.59 (C-10), 43.07 (N-Me), 43.73 (C-9), 60.87 (C-5), 61.75 (C-7), 68.87 (C-
8), 108.87 (C-14), 110.53 (C-3), 114.92 (C-12), 119.07 (C-2), 122.44 (C-13), 126.69 (C-16), 134.52 (C-
15), 135.05 (C-11). Anal. Calcd for C16H20N2O: C, 74.96, H, 7.86, N, 10.92. Found: C, 74.90, H, 7.84, N,
11.03.
(+)-Setoclavine (8) and (+)-isosetoclavine (9)
To cold solution of THF (5 mL, -50oC) and methyllithium (2 mL in THF, 2 mmol) a solution of 2 (160
mg, 0.67 mmol) in anisole (5 mL) was added. The temperature of the reaction mixture was allowed to

HETEROCYCLES, Vol. 67, No. 1, 2006
297
o
o
warm up to 0 C and stirred for 1 h then was cooled again to - 40 C. The mixture was decomposed by
adding water (3 mL) and the organic solvent was removed by evaporation in reduced pressure (bath: 30
oC). The residue was dissolved in a mixture of CHCl3 (100 mL) and water (7 mL). The phases were
separated and the organic layer was washed with saturated NaCl solution (20 mL). The filtrate was
evaporated under reduced pressure (4 g). The residue was purified by column chromatography (eluent:
hexane - AcOEt, 1/1) to remove anisole. The residue was separated by column chromatography (eluent:
hexane – AcOEt - MeOH, 5/5/1; Rf of 8 ≈ 0.4, Rf of 9 ≈ 0.6) to yield yield 8 and 9.
Compound (8): white crystals (40 mg; 24%), mp 216-222 oC (from ether; decomp) [lit.,9 mp 229-234 oC];
[α]D = +160o (c=0.25, pyridine) [lit.,9 [α]D = + 174o (c= 1.1, pyridine)]. IR (KBr): 3537, 2929, 2844,
1650, 1601, 1450, 1341, 1103, 928 cm-1. MS (m/z, %): 254.1424 (calcd 254.1419, C16H18N2O, 100, M+),
1
235 (8), 211 (29), 196 (34), 181 (22), 168 (28), 154 (72), 127 (7). H NMR (400 MHz, CDCl3), δ: 1.91
(3H, s, C8-Me), 2.47 (1H, d, J= 11.3, H-7ax), 2.54 (3H, s, N-Me), 2.66 (1H, ddd, J= 14.6 + 11.3 + 1.7 Hz,
H-4ax), 2.78 (1H, dd, J= 11.4 + 1.3 Hz, H-7eq), 2.98 (1H, ddd, J= 11.3 + 5.5 + 1.9 Hz, H-5), 3.51 (1H, dd,
J= 14.6 + 5.5, H-4eq), 3.63 (1H, br s, OH), 6.30 (1H, dd, J= 1.9 + 1.3 Hz, H-9), 6.90 (1H, dd, J= 1.7 + 1.7
Hz, H-2), 7.08 (2H, m, H-13 + H-14), 7.18 (1H, m, H-12), 10.22 (1H, d, J= 1.7 Hz, NH). 13C NMR (100
MHz, CDCl3 + DMSO-d6), δ: 26.09 (C8-Me), 27.26 (C-4), 43.88 (N-Me), 63.45 (C-5), 66.58 (C-8), 66.81
(C-7), 109.67 (C-3), 110.47 (C-14), 111.87 (C-12), 119.33 (C-2), 122.79 (C-13), 126.86 (C-16), 127.01
(C-9), 127.60 (C-11), 134.40 (C-15), 135.90 (C-10).
Compound (9): white crystals (64 mg; 38%), mp 208-226 oC (from ether; decomp) [lit.,9 mp 234-237 oC];
[α]D = + 102o (c=0.25, pyridine) [lit.,9 [α]D = + 107o (c=0.5, pyridine)]. IR (KBr): 3374, 2777, 1660,
1604, 1446, 1378, 1220, 1109, 922 cm-1. MS (m/z, %): 254.1424 (calcd 254.1419, C16H18N2O, 100, M+),
235 (11), 211 (37), 196 (34), 181 (24), 168 (32), 154 (79), 127 (9). 1H NMR (400 MHz, CDCl3 + DMSO-
d6), δ: 1.44 (3H, s, C8-Me), 2.51 (1H, d, J= 10.6, H-7ax), 2.53 (3H, s, N-Me), 2.58 (1H, ddd, J= 14.5 +
11.4 + 1.7 Hz, H-4ax), 2.78 (1H, dd, J= 10.6 + 1.3 Hz, H-7eq), 3.07 (1H, ddd, J= 11.4 + 5.6+ 2.1 Hz, H-5),
3.46 (1H, dd, J= 14.5 + 5.6 Hz, H-4eq), 4.36 (1H, br s, OH), 6.29 (1H, dd, J= 2.1 + 1.3 Hz, H-9), 6.90
(1H, dd, J= 1.7 + 1.7 Hz, H-2), 7.07 (2H, m, H-13 + H-14), 7.17 (1H, m, H-12), 10.05 (1H, d, J= 1.7 Hz,
NH). 13C NMR (100 MHz, CDCl3 + DMSO-d6), δ: 26.82 (C-4), 28.24 (C8-Me), 43.80 (N-Me), 63.28 (C-
5), 66.21 (C-7), 67.97 (C-8), 110.09 (C-3), 110.12 (C-14), 111.56 (C-12), 119.19 (C-2), 122.80 (C-13),
126.78 (C-16), 126.20 (C-11), 129.01 (C-9), 134.0 (C-10), 134.39 (C-15).
ACKNOWLEDGEMENTS
The authors wish to thank Ms Mónika Huber and Ms Gabriella Hanek for technical assistance. Support
for this research under grant No. T-046015 from the National Scientific Research Foundation (OTKA)
and NKFP Medichem 2 (Nr.: 1/A/005/2004) is gratefully acknowledged.

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REFERENCES AND NOTES
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Studies on the Ergot Alkaloids and Related Compounds,’ Vol. 54, The Alkaloids, ed. by A. G.
Cordell, Academic Press, Inc., San Diego, 2000, pp. 191-257; I. Ninomiya and T. Kiguchi, ‘Ergot
Alkaloids,’ Vol. 38, The Alkaloids, ed. by A. Brossi, Academic Press, Inc., New York, 1990, pp 1-
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