Synthesis of buprestins D, E, F, G and H; structural confirmation and biological testing of acyl glucoses from jewel beetles (Coleoptera: Buprestidae)

Article abstract of DOI:10.1016/j.bmc.2008.12.038

A chemical and enzymatic synthesis was developed for five variant buprestins termed D, E, F, G and H found in jewel beetles (Coleoptera: Buprestidae). Selective acylation of the primary hydroxyl group of β-d-glucopyranose-1,2-bis(pyrrole-2-carboxylate) wi

Full text of DOI:10.1016/j.bmc.2008.12.038

Bioorganic & Medicinal Chemistry 17 (2009) 1187–1192
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Synthesis of buprestins D, E, F, G and H; structural confirmation and biological
testing of acyl glucoses from jewel beetles (Coleoptera: Buprestidae)
Sebastian Ryczek a, Konrad Dettner b, Carlo Unverzagt a,
*
a Bioorganische Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
b Tierökologie II, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A chemical and enzymatic synthesis was developed for five variant buprestins termed D, E, F, G and H
found in jewel beetles (Coleoptera: Buprestidae). Selective acylation of the primary hydroxyl group of
b-D-glucopyranose-1,2-bis(pyrrole-2-carboxylate) with substituted benzoic or cinnamic acid derivatives
followed by deprotection gave the target compounds. Using coinjection the identity with the natural
extracts was confirmed. The activity of the variant buprestins as deterrents for ants was assayed.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 14 August 2008
Revised 9 December 2008
Accepted 13 December 2008
Available online 24 December 2008
Keywords:
Acyl glucose
Buprestidae
Lipase
Carbohydrate
Deterrent
1. Introduction
the triol 1 as the final step.3 This approach should also give a direct
access to variant buprestins with altered O-6 acyl moieties. In a re-
The first isolation of acyl glucoses from Australian jewel beetles
(Buprestidae) led to the characterization of two compounds named
buprestins A and B.1 Brief biotesting of these compounds showed a
deterrent activity against ants.2 We developed a chemical and
enzymatic approach to the buprestins A and B in order to provide
sufficient material for biotests.3 In the original publication2 the
occurrence of various minor buprestins containing substituted cin-
namoyl residues was indicated. However, no structural informa-
tion was provided. In the course of our own investigations the
variant buprestins were found in crude extracts from various jewel
beetles.4 LC–MS analysis of these variant buprestins suggested4
that the variation was caused by the attachment of different acyl
residues to O-6 of the 1,2-acylated glucose core (Fig. 1). In order
to prove the structure of five variant buprestins by total synthesis
we used the previously developed precursor 13 with three OH
groups as an intermediate. We herein describe the synthesis of
the natural buprestins termed4 D, E, F, G and H from the diacyl glu-
cose precursor 1.
cently disclosed thesis4 from our lab the isolation of buprestins via
an extraction from jewel beetles indicated the presence of other
buprestins (acyl glucoses) with two pyrrole-2-carboxylic acid moi-
eties and a variable third acyl group in the crude extracts. By
deduction of the MS data obtained by LC–MS the structural varia-
tion was proposed to reside at O-6 with O-1 and O-2 acylated with
pyrrole-2-carboxylic acid.4 In order to prove this hypothesis and to
verify the identity of the natural compounds by coinjection the
synthesis of five hitherto uncharacterized buprestins was carried
out. Access to the target molecules required the incorporation of
hydroxylated cinnamoyl residues (buprestins D, E and F) or substi-
tuted benzoyl moieties (buprestins G and H). Selective acylation of
the primary OH-group of triol 1 was carried out via a Mitsunobu
reaction5 employing O-acetylated cinnamic acid derivatives. The
acetylation of OH-groups of the substituted cinnamic acids is cru-
cial in order to avoid side reactions and low acylation yields.3 Start-
ing with commercially available p-acetoxy cinnamic acid the
selective 6-O acylation of triol 1 under Mitsunobu conditions
(2 equiv of acid, 3 equiv of triphenylphosphine and 1.5 equiv of
diethylazodicarboxylate (DEAD)) gave compound 2 in an isolated
yield of 51% (Fig. 2). The subsequent enzymatic deacetylation6
using immobilized Candida antarctica lipase B (Novozym 435)3 fur-
nished the desired compound D (45% yield). Similarly, the above
procedure was carried out with p-acetoxy-m-methoxy cinnamic
acid giving compound 3 (54%), which was deprotected enzymati-
cally yielding the feruloylated compound E (48%). In comparison
2. Results and discussion
The synthesis of buprestins A and B by chemical and enzymatic
methods allows the introduction of different acyl residues at O-6 of
* Corresponding author. Tel.: +49 921 552670; fax: +49 921 555365.
E-mail address: carlo.unverzagt@uni-bayreuth.de (C. Unverzagt).
0968-0896/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2008.12.038

1188
S. Ryczek et al. / Bioorg. Med. Chem. 17 (2009) 1187–1192
R2
R2
O
O
O
R1
HN
O
HN
O
HN
O
R1
HO
HO
O
O
O
O
O
HO
HO
HO
O
O
O
HO
HO
O
O
O
O
O
N
N
1
N
H
H
H
D (Buprestin D) R1 = OH, R2 = H
E (Buprestin E) R1 = OH, R2 = OMe
F (Buprestin F) R1 = R2 = OH
G (Buprestin G) R1 = OH, R2 = OMe
H (Buprestin H) R1 = OMe, R2 = H
Figure 1. Retrosynthetic analysis of buprestins D, E, F, G and H leading to the precursor 1.
the deprotection of unrelated phenylpropanoid glycosides with a
p-benzyl feruloyl moiety proved very difficult resulting in consid-
erably lower yields.7 In the case of compound 4 di-O-acetyl caffeic
acid was synthesized initially8 and coupled via the Mitsunobu pro-
tocol (60%). Unexpectedly the enzymatic deprotection of 4 gave
only unsatisfactory results. Thus two alternative procedures were
investigated. Careful alkaline hydrolysis of 4 using potassium car-
bonate in a dichloromethane-methanol mixture9 afforded the
deprotected caffeoyl derivative F (35%). In a second approach
TBDMS protected caffeoyl chloride10 was selectively introduced
at the primary OH group of 1 giving intermediate 5 in 48% yield.
TBAF mediated deprotection of 5 was not effective, however, the
use of HF/Et3N11 rendered the target molecule F smoothly (63%).
Surprisingly, when attempting the deacetylation of the intermedi-
ates 2 and 3 with potassium carbonate under the abovementioned
conditions the isolated yield was very low.
showed identical retention times for the natural compounds and
the synthetic reference material. The only differences between
the analytical data of the extracts and the synthetic compounds
were occasional deviations in the intensity of the peaks and the
type of adducts in the ESI-TOF mass spectra. This can be attributed
to the low concentration of several variant buprestins in the natu-
ral samples and to the heterogeneity of the extracts. A common
feature for all buprestins in ESI–TOF–MS was the occurrence of
the base peak for a glycosyl cation fragment in which the anomeric
pyrrole-2-carboxylate was cleaved. The molecular ions were found
as adducts with ammonium or sodium in addition to dimers com-
plexed with cations. The structures of the five variant buprestins
differing only in their O-6 acyl groups suggest a common biosyn-
thetic pathway, which remains to be elucidated.
In analogy to the biotests conducted by Moore and Brown for
buprestins A and B we investigated the ability of the minor bupres-
tins D, E, F, G and H to act as deterrents in a bioassay using the
feeding behavior of ants. In order to examine quantitatively the
acceptance/deterrency of the buprestins against Lasius flavus ants
a choice test modified according to Hilker13 was conducted within
The acylation of 1 with benzoic acid derivatives was less prone
to side reactions compared with the a,b-unsaturated cinnamic acid
derivatives. Starting from acetylated vanillic acid compound 6 was
obtained (61%) and p-anisic acid directly furnished p-meth-
oxybenzoylated H in 72% (Fig. 3). Enzymatic deacetylation of 6
led to compound G in 46% yield due to competing hydrolysis to
triol 1. All compounds were thoroughly characterized12 by 2D
NMR experiments.
In order to assess the identity of the synthetic compounds D, E,
F, G and H with the natural buprestins specimens of Anthaxia hun-
garica and Chalcophora mariana were extracted according to the
established procedure.4 LC–MS analysis of the crude extracts
showed the LC peaks and the corresponding mass spectra for the
compounds D, E, F and G in A. hungarica and compounds D, E, G
and H in C. mariana. LC–MS coinjection of each synthetic reference
compound (D, E, F, G and H) with the crude jewel beetle extracts
the formicarium. The bioassay started when 7 ll each of a test
(0.15 mg of compound/20 mg of sucrose/1 ml water) and a control
solution (20 mg of sucrose/1 ml water) were offered simulta-
neously on a glass slide. For a period of 10 min the number of ants
feeding at the test and control solution was recorded. Surprisingly,
at a concentration of 0.15 mg/ml the buprestins D, E, F, G, and H
were not active, whereas synthetic buprestins A and B showed
strong response even for solutions with a tenfold dilution.
In these experiments it became evident, that buprestins A and B
exhibited a pronounced deterrency against ants as already shown
by Moore & Brown.2 Compared with buprestins A and B the
buprestins D–H required more concentrated solutions in the test
R2
R2
O
O
a or b
c, d or e
HN
HN
1
R1
R1
O
O
O
O
O
HO
HO
HO
HO
O
O
O
O
O
O
O
N
N
H
H
2 (AcBuprestin D) R1 = OAc, R2 = H (51 %)
3 (AcBuprestin E) R1 = OAc, R2 = OMe (54 %)
4 (Ac2Buprestin F) R1 = R2 = OAc (60 %)
D (Buprestin D) R1 = OH, R2 = H (c: 45 %)
E (Buprestin E) R1 = OH, R2 = OMe (c: 48 %)
F (Buprestin F) R1 = R2 = OH (d: 35 %); (e: 63 %)
5 (TBDMS2Buprestin F) R1 = R2 = OTBDMS (48 %)
Figure 2. (a) Acid, PPh3, DEAD, THF: p-acetoxy cinnamic acid (51% of 2); p-acetoxy m-methoxy cinnamic acid (54% of 3); m,p-diacetoxy cinnamic acid (60% of 4); (b) TBDMS2-
caffeoyl chloride, toluene, pyridine, (48% of 5); (c) Candidia antarctica lipase B, immobilized (Novozym 435), 0.5 M NH4OAc/CH3CN (9:1) pH 7.0, 40 °C, (45% of D; 48% of E); (d)
10 mM K2CO3 in MeOH/CH2Cl2 (1:10) (35% of F); (d) 1.6 M HF/Et3N, pyridine (63% of F).

S. Ryczek et al. / Bioorg. Med. Chem. 17 (2009) 1187–1192
1189
R2
MeO
HO
O
O
O
O
R1
a
b
HN
O
HN
O
1
O
O
O
O
HO
HO
HO
HO
O
O
O
O
N
N
H
H
6 (AcBuprestin G) R1 = OMe, R2 = H (61 %)
H (Buprestin H) R1 = OAc, R2 = OMe (72 %)
G (Buprestin G) (46 %)
Figure 3. (a) Acid, PPh3, DEAD, THF: p-methoxy benzoic acid (61% of 6); p-acetoxy m-methoxy benzoic acid (72% of H); (b) Candidia antarctica lipase B, immobilized
(Novozym 435), 0.5 M NH4OAc/CH3CN (9:1) pH 7.0, 40 °C, (46% of G).
as their biological activities were rather weak. Preliminary evalua-
tions of the data indicated that buprestins F, G and H show no
activity at all whereas buprestins D and E are even attractive for
L. flavus ants as compared with the aqueous sugar controls. This
suggests that the deterrent effect of buprestins is highly influenced
by the individual carboxylic acid moieties at O-6.
(1 ml). The mixture was concentrated and purified by flash chro-
matography (dichloromethane/methanol 45:1) affording 15.6 mg
of 2 (51%). Rf = 0.35 (cyclohexane/ethyl acetate 1:2); ½a D23
= ꢁ34.5
ꢀ
(c 0.3, dichloromethane); 1H NMR (360 MHz, DMSO-d6): d = 11.98
(s, 1H, NH), 11.87 (s, 1H, NH0), 7.81, 7.78 (2s, 2H, Ar-2/6), 7.66 (d,
Jtrans = 16.0 Hz, 1H, @CHb), 7.18, 7.16 (2s, 2H, Ar-3/5), 7.02, 6.97
(2s, 2H, Pyrr, Pyrr0), 6.73–6.67 (m, 3H, Pyrr, @CH , Pyrr0), 6.11 (m,
a
2H, Pyrr, Pyrr0), 5.85 (d, J1,2 = 8.4 Hz, 1H, H-1), 5.61 (d, JOH,4 = 5.6 Hz,
1H, OH-4), 5.57 (d, JOH,3 = 5.6 Hz, 1H, OH-3), 4.99 (dd, J1,2 = 8.4 Hz,
J2,3 = 8.7 Hz, 1H, H-2), 4.46 (dd, Jgem = 12.2 Hz, J5,6a < 2Hz, 1H, H-6a),
4.26 (dd, Jgem = 12.2 Hz, J5,6b = 5.6 Hz, 1H, H-6b), 3.75 (m, 1H, H-5),
3.68 (m, 1H, H-3), 3.46 (m, 1H, H-4), 2.27 (s, 3H, Ac); 13C NMR
(67.5 MHz, DMSO-d6): d = 169.0 (C@O Ac), 166.1 (C@O Ar), 159.3,
158.4 (C@O Pyrr, Pyrr0), 152.0 (C-4 Ar), 143.9 (@CHb), 131.6 (C-1
Ar), 129.7 (C-2/6 Ar), 122.4 (C-3/5 Ar), 121.5, 120.4 (Pyrr, Pyrr0),
3. Conclusion
In summary, a short chemical and enzymatic route was devel-
oped for the five novel buprestins D, E, F, G, and H. Due to the acid
and base sensitivity of the buprestins mild conditions for deprotec-
tion were required. Based on extracts obtained from European jew-
el beetles the occurrence and the identity of five compounds
corresponding to modified buprestins was confirmed by total syn-
thesis and coinjection. These minor compounds do not display the
known deterrent activity of the major buprestins A and B.
117.9 (CH ), 116.4, 115.3 (Pyrr, Pyrr0), 109.8, 109.4 (Pyrr, Pyrr0),
a
91.8 (C-1), 74.7 (C-5), 73.6 (C-3), 72.2 (C-2), 69.8 (C-4), 63.3 (C-
6); ESI-MS (CH3CN/H2O, 0.1% HCOOH), C27H26N2O11 Mr (calcd)
554.15, Mr (found) 577.10 (M+Na)+, 444.09 (MꢁPyrrCO2)+,
1131.23 (2M+Na)+.
4. Experimental
4.1. General
4.3. 6-O-(p-Acetoxy-m-methoxycinnamoyl)-1,2-di-O-(pyrrol-2-
Solvents were dried according to standard methods. Optical
rotations were measured on a Perkin–Elmer 241 polarimeter at
589 nm. NMR spectra were recorded on Bruker AC 250, Avance
360 and AMX 500 instruments. Coupling constants are reported
in Hz. ESI-TOF mass spectra were recorded on a Micromass LCT
instrument coupled to an Agilent 1100 HPLC. Flash chromatogra-
phy was performed on silica gel 60, (230–400 mesh, Merck Darms-
tadt). The reactions were monitored by thin layer chromatography
on coated aluminum plates (silica gel 60 GF254, Merck Darmstadt).
Spots were detected by UV-light or by charring with a 1:1 mixture
of 2 N H2SO4 and 0.2% resorcine monomethylether in ethanol. Sev-
eral colonies of L. flavus (Formicinae) where collected at Weiden-
berg (near Bayreuth/Northern Bavaria, Germany). Ants where
kept in climate chamber at 25 °C (16L: 6D) at constant humidity.
carbonyl)-b-D-glucopyranose (3)
Triol 1 (20 mg, 55
l
mol), p-acetoxy-m-methoxycinnamic acid
mol) were
(26 mg, 110 mol) and triphenylphosphine (43 mg, 165
l
l
dissolved in freshly distilled tetrahydrofuran (2 ml) and stirred un-
der nitrogen for 40 min at 0 °C. Diethylazodicarboxylate (DEAD,
17
lowed to attain room temperature. After 19 h, an additional amount
of DEAD (7.5 l, 47 mol) was slowly added to the mixture after
ll, 107 lmol) was added dropwise to the mixture, which was al-
l
l
cooling to 0 °C. After 24 h the reaction was terminated with metha-
nol (1 ml). The mixture was concentrated and purified by flash chro-
matography (dichloromethane/methanol 45:1) affording 17.3 mg of
3 (54%). Rf = 0.33 (cyclohexane/ethyl acetate 1:2); ½a D23
= ꢁ22.1 (c
ꢀ
0.4, dichloromethane); 1H NMR (360 MHz, DMSO-d6): d = 11.98 (s,
1H, NH), 11.86 (s, 1H, NH0), 7.64 (d, Jtrans = 15.9 Hz, 1H, @CHb), 7.56
(s, 1H, H-2’ Ar), 7.29 (d, J5 ,6 = 8.1 Hz, 1H, H-50 Ar), 7.11 (d,
0
0
4.2. 6-O-(p-Acetoxycinnamoyl)-1,2-di-O-(pyrrol-2-carbonyl)-b-
J6 5 = 8.1 Hz, 1H, H-60 Ar), 7.03, 6.97 (2s, 2H, Pyrr, Pyrr0), 6.78 (d,
0
0
D
-glucopyranose (2)
Jtrans = 16.0 Hz, 1H, @CH ), 6.73, 6.70 (2s, 2H, Pyrr, Pyrr0), 6.10 (m,
a
Triol
1
(20 mg, 55
l
mol), p-acetoxycinnamic acid (23 mg,
2H, Pyrr, Pyrr0), 5.86 (d, J1,2 = 8.4 Hz, 1H, H-1), 5.61 (d, JOH,4 = 5.8 Hz,
1H, OH-4), 5.58 (d, JOH,3 = 5.6 Hz, 1H, OH-3), 5.00 (dd, J1,2 = 8.4 Hz,
J2,3 = 8.8 Hz, 1H, H-2), 4.46 (dd, Jgem = 12.2 Hz, J5,6a < 2 Hz, 1H, H-
6a), 4.27 (dd, Jgem = 12.2 Hz, J5,6b = 5.7 Hz, 1H, H-6b), 3.82 (s, 3H,
Me), 3.72 (m, 1H, H-5), 3.68 (m, 1H, H-3), 3.46 (m, 1H, H-4); 2.25
(s, 3H, Ac); 13C NMR (67.5 MHz, DMSO-d6): d = 168.3 (C@O Ac),
166.2 (C@O Ar), 159.3, 158.4 (C@O Pyrr, Pyrr0), 151.2 (C-4 Ar),
144.3 (@CHb), 141.1 (C-3 Ar), 132.0 (C-1 Ar), 123.2, 122.0 (Pyrr,
11
l
mol) and triphenylphosphine (43 mg, 165 l
mol) were dis-
solved in freshly distilled tetrahydrofuran (2 ml) and stirred under
nitrogen for 40 min at 0 °C. Diethylazodicarboxylate (DEAD, 17 l,
107 mol) was added dropwise to the mixture, which was allowed
to attain room temperature. After 19 h, an additional amount of
DEAD (7.5 l, 47 mol) was slowly added to the mixture after cool-
ing to 0 °C. After 24 h the reaction was terminated with methanol
l
l
l
l

1190
S. Ryczek et al. / Bioorg. Med. Chem. 17 (2009) 1187–1192
Pyrr0), 121.5, 120.4 (Ci-Pyrr, Ci-Pyrr0), 118.1 (C-5 Ar), 116.4, 115.3
(Pyrr, Pyrr0), 111.8 (C-6 Ar), 109.8, 109.5 (Pyrr, Pyrr0), 91.8 (C-1),
74.7 (C-5), 73.5 (C-3), 72.2 (C-2), 69.8 (C-4), 63.3 (C-6), 56.0 (Me),
20.4 (Ac); ESI-MS (CH3CN/H2O, 0.1% HCOOH), C28H28N2O12 Mr
(calcd) 584.16, Mr (found) 607.24 (M+Na)+, 474.16 (MꢁPyrrCO2)+,
1191.50 (2M+Na)+.
63.1 (C-6), 25.6 (tBu), 2.2 (Me); ESI-MS (CH3CN/H2O, 0.1% HCOOH),
C37H52N2O11Si2 Mr (calcd) 756.31, Mr (found) 779.22 (M+Na)+,
774.25 (M+NH4)+, 535.21 (MꢁPyrrCO2HꢁPyrrCO2)+, 646.21
(MꢁPyrrCO2)+, 1535. 46 (2M+Na)+.
4.6. 6-O-(p-Acetoxy-m-methoxybenzoyl)-1,2-di-O-(pyrrol-2-
carbonyl)-b-D-glucopyranose (6)
4.4. 6-O-(m,p-Diacetoxycinnamoyl)-1,2-di-O-(pyrrol-2-
carbonyl)-b-
D-glucopyranose (4)
Triol 1 (5 mg, 14
lmol), p-acetoxy-m-methoxybenzoic acid
(6 mg, 28 mol) and triphenylphosphine (3 equiv, 11 mg) were
l
Triol 1 (5 mg, 14
mol) and triphenylphosphine (11 mg, 42
in freshly distilled tetrahydrofuran (2 ml) and stirred under nitro-
gen for 40 min at 0 °C. Diethylazodicarboxylate (DEAD, 10 l,
63 mol) was added dropwise to the mixture, which was allowed
to attain room temperature. After 21 h, an additional amount of
DEAD (5 l, 32 mol) was slowly added to the mixture after cool-
l
mol), m,p-diacetoxycinnamic acid (7.4 mg,
dissolved in freshly distilled tetrahydrofuran (1 ml) and stirred un-
der nitrogen for 40 min at 0 °C. Diethylazodicarboxylate (DEAD,
28
l
lmol) were dissolved
10
lowed to attain room temperature. After 21 h, an additional
amount of DEAD (5 l, 32 mol) was slowly added to the mixture
ll, 63 lmol) was added dropwise to the mixture, which was al-
l
l
l
l
after cooling to 0 °C. After 72 h the reaction was terminated with
methanol (0.5 ml). The mixture was concentrated and purified by
flash chromatography (dichloromethane/methanol 45:1) affording
l
l
ing to 0 °C. After 72 h the reaction was terminated with methanol
(1 ml). The mixture was concentrated and purified by flash chro-
matography (dichloromethane/methanol 45:1) affording 5.1 mg
4.7 mg of
6 (61%). Rf = 0.31 (cyclohexane/ethyl acetate 1:2);
½
a 2D3
ꢀ
= ꢁ27.3 (c 0.3, dichloromethane); 1H NMR (360 MHz, DMSO-
of 4 (60%). Rf = 0.29 (cyclohexane/ethyl acetate 1:2); ½a D23
ꢀ
= ꢁ28.7
d6): d = 11.95 (s, 1H, NH), 11.87 (s, 1H, NH0), 7.59–7.58 (m, 2H, H-
20/50 Ar), 7.27 (d, J5,6 = 8.6 Hz, 1H, H-60 Ar), 7.01, 6.97 (2s, 2H, Pyrr,
Pyrr0), 6.74, 6.69 (2s, 2H, Pyrr, Pyrr0), 6.11 (m, 2H, Pyrr, Pyrr0), 5.84
(d, J1,2 = 8.3 Hz, 1H, H-1), 5.65 (d, JOH,4 = 5.8 Hz, 1H, OH-4), 5.56 (d,
JOH,3 = 5.8 Hz, 1H, OH-3), 5.01 (dd, J1,2 = 8.3 Hz, J2,3 = 8.9 Hz, 1H, H-
2), 4.58 (dd, J6a,6b = 12.0 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.37 (dd,
J6a,6b = 12.0 Hz, J5,6b = 5.8 Hz, 1H, H-6b), 3.86–3.82 (m, 4H, H-5,
Me), 3.70 (m, 1H, H-3), 3.47 (m, 1H, H-4), 2.28 (s, 3H, Ac); 13C
NMR (67.5 MHz, DMSO-d6): d = 168.1 (C@O Ac), 164.9 (C@O Ar),
159.3, 158.4 (C@O Pyrr, Pyrr0), 151.0 (C-4 Ar), 143.3 (C-3 Ar),
128.4 (C-1 Ar), 125.6 (C-5 Ar), 124.2 (C-6 Ar), 123.3, 122.1 (Pyrr,
Pyrr0), 121.5, 120.4 (Ci-Pyrr, Ci-Pyrr0), 116.5, 115.3 (Pyrr, Pyrr0),
113.1 (C-2 Ar), 109.8, 109.5 (Pyrr, Pyrr0), 91.9 (C-1), 74.7 (C-5),
73.7 (C-3), 72.2 (C-2), 70.0 (C-4), 63.9 (C-6), 56.0 (Me), 20.4 (Ac);
ESI-MS (CH3CN/H2O, 0.1% HCOOH), C26H26N2O10 Mr (calcd)
558.15, Mr (found) 580.94 (M+Na)+, 447.95 (MꢁPyrrCO2)+,
1138.89 (2M+Na)+.
(c 0.5, dichloromethane); 1H NMR (360 MHz, DMSO-d6): d = 11.98
(s, 1H, NH), 11.87 (s, 1H, NH0), 7.74 (s, 1H, H-20 Ar), 7.70–7.67
(m, 1H, H-50 Ar), 7.64 (d, Jtrans = 16.3 Hz, 1H, @CHb), 7.30 (d,
J5 6 = 8.3 Hz, 1H, H-60 Ar), 7.02, 6.97 (2s, 2H, Pyrr, Pyrr0), 6.74–
0
0
6.70 (m, 3H, Pyrr, @CH , Pyrr0), 6.11 (m, 2H, Pyrr, Pyrr0), 5.85 (d,
a
J1,2 = 8.4 Hz, 1H, H-1), 5.61 (d, JOH,4 = 5.8 Hz, 1H, OH-4), 5.57 (d,
JOH,3 = 5.6 Hz, 1H, OH-3), 4.99 (dd, J1,2 = 8.4 Hz, J2,3 = 8.9 Hz, 1H,
H-2), 4.45 (dd, Jgem = 12.2 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.26 (dd,
Jgem = 12.2 Hz, J5,6b = 5.6 Hz, 1H, H-6b), 3.77 (m, 1H, H-5), 3.68
(m, 1H, H-3), 3.43 (m, 1H, H-4), 2.28, 2.27 (2s, 6H, Ac); 13C NMR
(67.5 MHz, DMSO-d6): d = 168.1, 168.0 (C@O Ac), 165.9 (C@O Ar),
159.3, 158.4 (C@O Pyrr, Pyrr0), 143.5 (C-4 Ar), 143.1 (@CHb),
142.3 (C-3 Ar), 132.8 (C-1 Ar), 127.0 (C-2 Ar), 125.6 (C-6 Ar),
124.1 (C-5 Ar), 124.1, 123.2 (Pyrr, Pyrr0), 121.5, 120.4 (Ci-Pyrr, Ci-
Pyrr0), 118.9 (@CH ), 116.4, 115.3 (Pyrr, Pyrr0), 109.8, 109.5 (Pyrr,
a
Pyrr0), 91.8 (C-1), 74.7 (C-5), 73.6 (C-3), 72.2 (C-2), 69.8 (C-4),
63.3 (C-6), 56.0 (Me), 20.3 (Ac, Ac0); ESI-MS (CH3CN/H2O, 0.1%
HCOOH), C29H28N2O13 Mr (calcd) 612.16, Mr (found) 634.93
(M+Na)+, 501.93 (M-PyrrCO2)+.
4.7. 6-O-(p-Anisoyl)-1,2-di-O-(pyrrol-2-carbonyl)-b-D-
glucopyranose H
4.5. 6-O-(m,p-Bis(tert-butyldimethylsilyloxy)cinnamoyl)-1,2-
Triol 1 (20 mg, 55
triphenylphosphine (43 mg 165
distilled tetrahydrofuran (2 ml) and stirred under nitrogen for
40 min at 0 °C. Diethylazodicarboxylate (DEAD, 25 l, 157 mol)
l
mol), p-anisic acid (17 mg, 110
lmol) and
di-O-(pyrrol-2-carbonyl)-b-
D-glucopyranose (5)
lmol) were dissolved in freshly
To a stirred solution of freshly prepared tert-butyldimethylsilyl-
protected caffeoyl chloride (17 mg, 41 mol) in toluene (10 ml)
were added triol 1 (10 mg, 27 mol) and pyridine (1.5 ml). The
l
l
l
was added dropwise to the mixture, which was allowed to attain
room temperature. After 4 h the reaction was terminated with
methanol (1 ml). The mixture was concentrated and purified by
flash chromatography (dichloromethane/methanol 45:1) affording
19.7 mg of H (72%). Rf = 0.22 (dichloromethane/methanol 24:1);
l
mixture was stirred at room temperature for two days. The solvent
was removed under reduced pressure and the residue was purified
by flash chromatography (dichloromethane/methanol 60:1)
affording 11 mg of 5 (56%). Rf = 0.20 (dichloromethane/methanol
½
a 2D3
ꢀ
= ꢁ76.0 (c 0.4, MeOH); 1H NMR (360 MHz, DMSO-d6):
24:1); ½a 2D3
ꢀ
= ꢁ25.9 (c 0.3, dichloromethane); 1H NMR (360 MHz,
d = 11.98 (s, 1H, NH), 11.87 (s, 1H, NH), 7.91 (d, J = 8.8 Hz, 2H, H-
20/60 Ar), 7.06 (d, J = 8.8 Hz, 2H, H-30/50 Ar), 7.02 (s, 1H, Pyrr), 6.97
(s, 1H, Pyrr0), 6.74 (s, 1H, Pyrr), 6.70 (s, 1H, Pyrr0), 6.10 (m, 2H, Pyrr,
Pyrr0), 5.85 (d, J1,2 = 8.4 Hz, 1H, H-1), 5.64 (m, 1H, OH-4), 5.58 (d,
JOH,3 = 5.1 Hz, 1H, OH-3), 5.02 (dd, J1,2 = 8.4 Hz, J2,3 = 8.8 Hz, 1H,
H-2), 4.52 (dd, Jgem = 12.1 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.33 (dd,
Jgem = 12.1 Hz, J5,6b = 5.2 Hz, 1H, H-6b), 4.12 (s, 3H, OMe), 3.82 (m,
1H, H-5), 3.69 (m, 1H, H-3), 3.49 (m, 1H, H-4); 13C NMR
(67.5 MHz, DMSO-d6): d = 165.2 (C@O Ar), 163.2 (C-4 Ar), 159.3,
158.4 (C@O Pyrr), 131.3 (C-2/6 Ar), 125.5 (Pyrr), 124.2 (Pyrr0),
121.8, 121.5 (Ci-Pyrr, Ci-Pyrr0), 120.4 (C-1 Ar), 116.4 (Pyrr), 115.4
(Pyrr0), 114.0 (C-3/5 Ar), 109.8 (Pyrr), 109.5 (Pyrr0), 91.9 (C-1),
74.8 (C-5), 73.7 (C-3), 72.2 (C-2), 69.8 (C-4), 63.3 (C-6), 55.5
(OMe); ESI-MS (CH3CN/H2O, 0.1% HCOOH), C24H24N2O10 Mr (calcd)
500.14, Mr (found) 523.26 (M+Na)+.
DMSO-d6): d = 11.97 (s, 1H, NH), 11.87 (s, 1H, NH0), 7.56 (d,
Jtrans = 16.2 Hz, 1H, @CHb), 7.25 (d, J5 ,6 = 8.3 Hz, 1H, H-50 Ar), 7.20
0
0
(s, 1H, H-20 Ar), 7.02, 6.96 (2s, 2H, Pyrr, Pyrr0), 6.86 (d, J5 6 = 8.3 Hz,
1H, H-60 Ar) 6.72–6.70 (m, 2H, Pyrr, Pyrr0), 6.50 (d, Jtrans = 15.8 Hz,
0
0
1H @CH ), 6.11 (m, 2H, Pyrr, Pyrr0), 5.85 (d, J1,2 = 8.2 Hz, 1H, H-
a
1), 5.59 (d, JOH,4 = 5.3 Hz, 1H, OH-4), 5.57 (d, JOH,3 = 5.9 Hz, 1H,
OH-3), 4.99 (dd, J1,2 = 8.2 Hz, J2,3 = 9.0 Hz, 1H, H-2), 4.44 (dd,
Jgem = 12.7 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.22 (dd, Jgem = 12.7 Hz,
J5,6b = 6.5 Hz, 1H, H-6b), 3.71 (m, 1H, H-5), 3.66 (m, 1H, H-3),
3.39 (m, 1H, H-4), 0.93–0.94 (m, 18H, tBu), 0.19 (s, 12H, Me); 13C
NMR (67.5 MHz, DMSO-d6), from HMQC-COSY): d = 144.5 (@CHb),
125.3 (C-2 Ar), 125.2, 124.0 (Pyrr, Pyrr0), 122.6 (C-5 Ar), 120.6 (C-
6 Ar), 116.1, 115.3 (Pyrr, Pyrr0), 115.2 (@CH ), 109.8, 109.5 (Pyrr,
a
Pyrr0), 91.9 (C-1), 75.0 (C-5), 73.4 (C-3), 72.0 (C-2), 69.6 (C-4),

S. Ryczek et al. / Bioorg. Med. Chem. 17 (2009) 1187–1192
1191
4.8. 6-O-Cumaroyl-1,2-di-O-(pyrrol-2-carbonyl)-b-
glucopyranose D
D
-
(C-4), 63.0 (C-6), 55.7 (OMe); ESI-MS (CH3CN/H2O, 0.1% HCOOH),
C26H26N2O11 Mr (calcd) 542.15, Mr (found) 565.26 (M+Na)+.
Compound 2 (5 mg, 9
lmol) was suspended in a mixture of ace-
4.10. 6-O-Caffeoyl-1,2-di-O-(pyrrol-2-carbonyl)-b-D-
tonitrile/0.5 M ammonium acetate, pH 7 (1 ml, 1:9) and stirred at
40 °C. To the milky suspension was added immobilized CAL B
(20 mg) and stirring was continued at 40 °C. With progressing
reaction the suspension cleared. After 3–4 h (monitored by LC–
MS) the reaction was terminated by filtration. The solids were
washed with water/acetonitrile (2 ml, 9:1) and the filtrate was
lyophilized twice. The remainder was dissolved in water (10 ml)
and passed over a SepPak C18 Classic cartridge (Waters). Elution
was carried out using a step gradient of acetonitrile/water (10 ml
each) with concentrations of 0–40% acetonitrile (5% steps). The tar-
get compound eluted in the fractions with 25–30% of acetonitrile.
The fractions were combined and lyophilized giving 2 mg of D
glucopyranose F
1. Deprotection of 4: To a stirred solution of 4 (2 mg, 0.33
dichloromethane (1 ml), a solution of K2CO3 in methanol (0.01 M,
25 l) was added dropwise. The reaction was monitored by LC/MS
and after each 24 h additional K2CO3-solution (25 l) was added.
After 4 days the reaction was terminated with acetic acid (50 l).
lmol) in
l
l
l
The mixture was dried in high vacuo and purified by RP-HPLC (Äkta
Basic, Amersham, water/acetonitrile 10–95%, 9.5 ml/min, YMC
ODS-A, 250 ꢂ 4.6 mm, 120 Å, S-5
2. Deprotection of 5: To a solution of 5 (9 mg, 12
(2 ml), a solution of 3HF/Et3N in pyridine (100 l, 1.56 M) was added
dropwise. The mixture was stirred for 20 h and the solvent was
evaporated under reduced pressure. The residue was purified using
RP-HPLC (Äkta Basic, Amersham, water/acetonitrile 10–95%, 9.5 ml/
l
m) to afford 0.6 mg of F (35%).
l
mol) in pyridine
l
(45%). Rf = 0.61 (dichloromethane/methanol 7:1); ½a D23
ꢀ
= ꢁ28.2 (c
0.1, MeOH); 1H NMR (360 MHz, DMSO-d6): d = 11.97 (s, 1H, NH),
11.87 (s, 1H, NH0), 10.04 (s, 1H, OH-Ar), 7.65–7.53 (m, 2H, H-20/60
Ar), 7.55 (d, Jtrans = 15.7 Hz, 1H, @CHb), 7.08 (m, 1H, Pyrr), 7.02
(m, 1H, Pyrr0), 6.78–6.70 (m, 2H, H-30/50 Ar), 6.53 (d, Jtrans = 15.9 Hz,
min, YMC ODS-A, 250 ꢂ 20 mm, 120 Å, S-5
lm) to afford 10 mg of F
(63%). Rf = 0.68 (dichloromethane/methanol 7:1); ½a D23
= ꢁ27.7 (c
ꢀ
1H, @CH ), 5.84 (d, J1,2 = 8.4 Hz, 1H, H-1), 5.58 (m, 2H, OH-4, OH-3),
0.4, MeOH); 1H NMR (360 MHz, DMSO-d6): d = 11.94 (s, 1H, NH),
11.84 (s, 1H, NH0), 9.35 (m, 2H, OH-3/4 Ar), 7.47 (d, Jtrans = 15.8 Hz,
1H, @CHb), 7.02 (m, 1H, Pyrr), 7.00 (s, 1H, H-20 Ar), 6.96 (m, 1H, Pyrr0),
6.76 (m, 1H, Pyrr), 6.73 (m, 1H, Pyrr0), 6.71 (m, 1H, H-50 Ar), 6.70 (d,
a
4.99 (dd, J1,2 = 8.4 Hz, J2,3 = 8.8 Hz, 1H, H-2), 4.41 (dd,
Jgem = 11.9 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.37 (dd, Jgem = 11.9 Hz,
J5,6b = 5.9 Hz, 1H, H-6b), 3.75 (m, 1H, H-5), 3.69 (m, 1H, H-3),
3.37 (m, 1H, H-4). 13C NMR (67.5 MHz, DMSO-d6): d = 166.5
(C@O Ar), 159.9 (C-4 Ar), 159.3, 158.4 (C@O Pyrr, Pyrr0), 145.1
(@CHb), 132.7, 130.4 (2H, C-2/6 Ar), 125.6 (Pyrr), 125.0 (C-1 Ar),
124.2 (Pyrr0), 121.5 (Ci-Pyrr), 120.4 (Ci-Pyrr0), 116. 5 (Pyrr), 115.8
J5 ,6 = 1.3 Hz, 1H, H-60 Ar), 6.30 (d, Jtrans = 15.9 Hz, 1H, @CH ), 6.12–
0
0
a
6.10 (m, 2H, Pyrr, Pyrr0), 5.84 (d, J1,2 = 8.3 Hz, 1H, H-1), 5.53 (m, 2H,
OH-4, OH-3), 4.99 (dd, J1,2 = 8.3 Hz, J2,3 = 8.6 Hz, 1H, H-2), 4.44 (dd,
Jgem = 12.0 Hz, J5,6a < 2 Hz, 1H, H-6a), 4.20 (dd, Jgem = 12.0 Hz,
J5,6b = 5.8 Hz, 1H, H-6b), 3.79 (m, 1H, H-5), 3.70 (m, 1H, H-3), 3.42
(m, 1H, H-4); 13C NMR (67.5 MHz, DMSO-d6): d = 166.5 (C@O Ar),
159.3, 158.4 (C@O Pyrr, Pyrr0), 148.5 (C-4 Ar), 145.6 (C-3 Ar), 145.5
(@CHb), 125.6 (Pyrr), 125.4 (C-1 Ar), 124.1 (Pyrr0), 121.5 (Ci-Pyrr),
121.4 (C-2 Ar), 124.1 (Ci-Pyrr0), 116.5, 115.7 (Pyrr, Pyrr0), 115.3 (C-
(C-3/5 Ar), 115.3 (Pyrr0), 114.9 (1H, C-3/5 Ar), 113.8 (@CH ),
a
109.8, 109.5 (Pyrr, Pyrr0), 91.8 (C-1), 74.8 (C-5), 73.6 (C-3), 72.2
(C-2), 69.8 (C-4), 63.1 (C-6); ESI-MS (CH3CN/H2O, 0.1% HCOOH),
C25H24N2O10 Mr (calcd) 512.14, Mr (found) 535.27 (M+Na)+.
4.9. 6-O-Feruloyl-1,2-di-O-(pyrrol-2-carbonyl)-b-
D-
5 Ar), 115.0 (C-6 Ar), 113.6 (@CH ), 109.8, 109.5 (Pyrr, Pyrr0), 91.8
a
glucopyranose E
(C-1), 74.8 (C-5), 73.6 (C-3), 72.2 (C-2), 69.9 (C-4), 63.0 (C-6); ESI-
MS (CH3CN/H2O, 0.1% HCOOH), C25H24N2O11 Mr (calcd) 528.14, Mr
(found) 551.27 (M+Na)+.
Compound 3 (5 mg, 8 lmol) was suspended in a mixture of ace-
tonitrile/0.5 M ammonium acetate, pH 7 (1 ml, 1:9) and stirred at
40 °C. To the milky suspension was added immobilized CAL B
(20 mg) and stirring was continued at 40 °C. With progressing
reaction the suspension cleared. After 3–4 h (monitored by LC/
MS) the reaction was terminated by filtration. The solids were
washed with water/acetonitrile (2 ml, 9:1) and the filtrate was
lyophilized twice. The remainder was dissolved in water (10 ml)
and passed over a SepPak C18 Classic cartridge (Waters). Elution
was carried out using a step gradient of acetonitrile/water (10 ml
each) with concentrations of 0–40% acetonitrile (5% steps). The tar-
get compound eluted in the fractions with 20–30% of acetonitrile.
The fractions were combined and lyophilized giving 2 mg of E
4.11. 6-O-Vanilloyl-1,2-di-O-(pyrrol-2-carbonyl)-b-D-
glucopyranose G
Compound 6 (14 mg, 25 lmol) was suspended in a mixture of
acetonitrile/0.5 M ammonium acetate, pH 7 (3 ml, 1:9) and stirred
at 40 °C. To the milky suspension was added immobilized CAL B
(20 mg) and stirring was continued at 40 °C. With progressing reac-
tion the suspension cleared. After 1–2 h (monitored by LC–MS) the
reaction was terminated by filtration. The solids were washed with
water/acetonitrile (2 ml, 9:1) and the filtrate was lyophilized twice.
Theremainder was dissolved in water (10 ml) and passed over a Sep-
Pak C18 Classic cartridge (Waters). Elution was carried out using a
step gradient of acetonitrile/water (10 ml each) with concentrations
of 0–40% acetonitrile (5% steps). The target compound eluted in the
fractions with 20–30% of acetonitrile. The fractions were combined
and lyophilized giving 6mg of G (48%). Rf = 0.62 (dichloromethane/
(48%). Rf = 0.65 (dichloromethane/methanol 7:1); ½a D23
= ꢁ49.3 (c
ꢀ
0.4, MeOH); 1H NMR (360 MHz, DMSO-d6): d = 11.95 (s, 1H, NH),
11.84 (s, 1H, NH), 9.56 (s, 1H, OH Ar), 7.68 (m, 1H, H-50 Ar), 7.54
(d, Jtrans = 15.8 Hz, 1H, @CHb), 7.35 (m, 1H, H-60 Ar), 7.02 (s, 1H,
H-20 Ar), 6.96 (m, 2H, Pyrr, Pyrr0), 6.73 (m, 2H, Pyrr, Pyrr0), 6.53
(d, Jtrans = 15.9 Hz, 1H, @CH ), 6.11 (m, 2H, Pyrr, Pyrr0), 5.85 (d,
methanol 7:1); ½a D23
ꢀ
= ꢁ60.7 (0.3, MeOH); 1H NMR (360 MHz,
a
J1,2 = 8.3 Hz, 1H, H-1), 5.64–5.49 (m, 2H, OH-4, OH-3), 4.99 (dd,
J1,2 = 8.3 Hz, J2,3 = 9.3 Hz, 1H, H-2), 4.44 (dd, Jgem = 12.3 Hz,
J5,6a < 2 Hz, 1H, H-6a), 4.23 (dd, Jgem = 12.3 Hz, J5,6b = 4.9 Hz, 1H,
H-6b), 3.81 (s, 3H, OMe), 3,74 (m, 1H, H-5), 3.68 (m, 1H, H-3),
3.39 (m, 1H, H-4); 13C NMR (67.5 MHz, DMSO-d6): d = 166.6
(C@O Ar), 159.3, 158.4 (C@O Pyrr, Pyrr0), 149.4 (C-4 Ar), 148.0 (C-
3 Ar), 145.4 (@CHb), 125.6 (C-2 Ar), 125.4 (C-1 Ar), 124.2 (Pyrr),
123.5 (Pyrr0), 121.5 (Ci-Pyrr), 120.4 (Ci-Pyrr0), 116.5 (Pyrr), 115.4
DMSO-d6): d = 11.91 (s, 1H, NH), 11.82 (s, 1H, NH0), 9.92 (s, 1H, OH
Ar), 7.47 (d, J5 ,6 = 8.2 Hz, 1H, H-50 Ar), 7.43 (s, 1H, H-20 Ar), 7.01
0
0
(m, 1H, Pyrr), 6.96 (m, 1H, Pyrr0), 6.88 (d, J5 ,6 = 8.2 Hz, 1H, H-60
Ar), 6.74 (m, 1H, Pyrr), 6.69 (m, 1H, Pyrr0), 6.10 (m, 2H, Pyrr, Pyrr0),
5.85 (d, J1,2 = 8.4 Hz, 1H, H-1), 5.58 (d, JOH,4 = 3.6 Hz, 1H, OH-4),
5.52 (d, JOH,3 = 3.6 Hz, 1H, OH-3), 5.00 (dd, J1,2 = 8.4 Hz, J2,3 = 8.6 Hz,
1H, H-2), 4.56 (m, Jgem = 12.0 Hz, J5,6a < 2 Hz, 1H, H-6a) 4.28 (dd,
Jgem = 12.0 Hz, J5,6b = 5.8 Hz, 1H, H-6b), 3.82 (m, 1H, H-5), 3.80 (s,
3H, OMe), 3.69 (m, 1H, H-3), 3.48 (m, 1H, H-4); 13C NMR
(67.5 MHz, DMSO-d6): d = 165.4 (C@O Ar), 159.4, 158.5 (C@O Pyrr),
0
0
(Pyrr0), 114.9 (C-5 Ar), 114.1 (@CH ), 111.0 (C-6 Ar), 109.8 (Pyrr),
a
109.5 (Pyrr0), 91.7 (C-1), 74.7 (C-5), 73.5 (C-3), 72.2 (C-2), 69.8

1192
S. Ryczek et al. / Bioorg. Med. Chem. 17 (2009) 1187–1192
151.9 (C-4 Ar), 147.4 (C-3 Ar), 125.6 (Pyrr), 124.2 (Pyrr0), 123.5 (C-2
Ar), 121.5, 120.4 (Ci-Pyrr, Ci-Pyrr0), 120.2 (C-1 Ar), 116.5 (Pyrr), 115.4
(Pyrr0), 115.2 (C-5 Ar), 112.6 (C-6 Ar), 109.9 (Pyrr), 109.5 (Pyrr0), 91.9
(C-1), 74.8 (C-5), 73.7 (C-3), 72.2 (C-2), 70.0 (C-4), 63.3 (C-6), 55.6
(OMe); ESI-MS (CH3CN/H2O, 0.1% HCOOH), C24H24N2O11 Mr (calcd)
516.14, Mr (found) 539.24 (M+Na)+.
2. Moore, B. P.; Brown, W. V. J. Aust. Entomol. Soc. 1985, 24, 81.
3. Schramm, S.; Dettner, K.; Unverzagt, C. Tetrahedron Lett. 2006, 47,
7741.
4. Schramm, S., Dissertation, Universität Bayreuth, 2006; see also: Schramm, S.
Bekannte und neue Acylglucoside aus Prachtkäfern: Von der Synthese zur
biologischen Bedeutung; Shaker, 2007.
5. Mitsunobu, O. Synthesis 1981, 1.
6. Lambusta, D.; Nicolosi, G.; Patti, A.; Sanfilippo, C. J. Mol. Catal. B: Enzym. 2003,
22, 271.
7. Das, S. K.; Reddy, K. A.; Mukkanti, K. Carbohydr. Res. 2007, 342, 2309.
8. Patnam, R.; Chang, F.-R.; Kuo, R.-Y.; Pan, W.-B.; Wu, Y.-C. J. Chem. Res. (S) 2002,
301.
Acknowledgments
9. Duynstee, H. I.; De Koning, M. C.; Van der Marel, G. A.; Van Boom, J. H.
Tetrahedron 1999, 55, 9881.
10. Zhang, X.; Lee, Y. K.; Kelley, J. A.; Burke, T. R., Jr. J. Org. Chem. 2000, 65,
6237.
11. Duynstee, H. I.; De Koning, M. C.; Ovaa, H.; Van der Marel, G. A.; Van Boom, J. H.
Eur. J. Org. Chem. 1999, 2623.
12. Kessler, H.; Gehrke, M.; Griesinger, C. Angew. Chem., Int. Ed. Engl. 1988, 27,
490.
We are grateful to the Deutsche Forschungsgemeinschaft (DFG)
Graduate College 678 and the Fonds der Chemischen Industrie for
financial support.
References and notes
1. Brown, W. V.; Jones, A. J.; Lacey, M. J.; Moore, B. P. Aust. J. Chem. 1985, 38, 197.
13. Hilker, M.; Eschbach, U.; Dettner, K. Naturwiss 1992, 79, 271.