Glycosidic juvenogens: Derivatives bearing α,β-unsaturated ester functionalities

Article abstract of DOI:10.1016/j.bmc.2007.07.022

A series of the protected alkyl glycosides 5a/5b-12a/12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4′-(2″-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b-4a/4b; racemic structures) and (1a-4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs-Knorr reaction, and the products were obtained in 82-92% yields. Deprotection of the carbohydrate functionality of 5a/5b-12a/12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b-20a/20b (diastereoisomeric mixtures) and 13a-20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82-93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b-20b of the alkyl glycosides for their structure elucidation and ¹³C chemical shift assignment by ¹H and ¹³C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b-20a/20b were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism.

Full text of DOI:10.1016/j.bmc.2007.07.022

Bioorganic & Medicinal Chemistry 15 (2007) 7126–7137
Glycosidic juvenogens: Derivatives bearing a,b-unsaturated
ester functionalities
b,c
d
b
b
Zdeneˇk Wimmer,a, Lucie Pechova, Laura Sıꢀle, David Saman, Pavel Jedlicˇka,
*
ˇ
´
a
e
´
Martina Wimmerova and Erkki Kolehmainen
aInstitute of Experimental Botany AS CR, Laboratory of Chemistry, Vı´denˇska´ 1083, CZ-14220 Prague 4, Czech Republic
bInstitute of Organic Chemistry and Biochemistry AS CR, Flemingovo na´meˇstı´ 2, CZ-16610 Prague 6, Czech Republic
cInstitute of Chemical Technology, Technicka´ 5, CZ-16628 Prague 6, Czech Republic
dLatvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia
eUniversity of Jyva¨skyla¨, Department of Chemistry, PO Box, FI-40014 Jyva¨skyla¨, Finland
Received 1 February 2007; revised 29 June 2007; accepted 10 July 2007
Available online 22 August 2007
Abstract—A series of the protected alkyl glycosides 5a/5b–12a/12b was synthesized from the parent isomeric alcohols (insect juvenile
hormone bioanalogs; juvenoids), 4-[40-(200-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b–4a/4b;
racemic structures) and (1a–4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs–Knorr reac-
tion, and the products were obtained in 82–92% yields. Deprotection of the carbohydrate functionality of 5a/5b–12a/12b was care-
fully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone
part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b–20a/20b (diastereoisomeric mixtures) and 13a–
20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82–93% yields.
Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of
the respective enantiomers 13b–20b of the alkyl glycosides for their structure elucidation and 13C chemical shift assignment by
1H and 13C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b–20a/20b
were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended
effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which
results in liberation of the biologically active juvenoid in the insect organism.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
the past years.10 The compounds displayed high biolog-
ical activity on a variety of insect pests.1 One of the most
important results achieved was the finding that the
respective Z and E isomers of ethyl 4-[40-(200,200-ethylene-
dioxycyclohexyl)methylphenoxy}-3-methyl-but-2-eno-
ate, which relates to the juvenoids 1a/1b–4a/4b, used in
this investigation (Scheme 1), displayed similar level of
biological activity on aphids (Acyrthosiphon pisum).11
This important finding proved for the first time among
this series of compounds that important insect pests
can be found, on which E and Z isomers of the selected
juvenoid structure display similar (almost equal) level of
biological activity. Before this finding was observed, the
juvenoids of the 2-(40-alkoxybenzyl)cyclohexanone ser-
ies, bearing the a,b-unsaturated ester functionality in
the Z configuration in the molecule, had always been
proven to show very low biological activity on most of
insects.1 The encouraging finding11 focused again our
attention to this series of compounds. Considering
the potential target insect pests (aphids and bugs, i.e.
Insect pest management agents have been targets of our
projects for many years (for reviews, see1,2). Insect juve-
nile hormone bioanalogs (JHAs, juvenoids) represent
the environmentally most safe agents in insect pest man-
agement.1–4 These compounds mimic the mode of action
of natural insect juvenile hormones (JHs), showing their
effect either in morphological and/or gonadotropic level,
or in caste differentiation (in social insects, like ter-
mites).2,4–9
A series of a,b-unsaturated esters was designed and syn-
thesized for application as juvenoids against insects in
Keywords: Pyrrhocoris apterus; Juvenogen; Insect juvenile hormone
analog; Juvenilizing effect; Koenigs–Knorr synthesis; Enantiomer;
Diastereoisomer.
*
Corresponding author. Tel.: +420 241 062 381; fax: +420 241 062
150; e-mail: wimmer@ueb.cas.cz
0968-0896/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2007.07.022

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7127
O
O
O
O
O
O
(1)
(1)
(2)
(2)
OH
OH
1a / 1b: Z-isomer
3a / 3b: E-isomer
2a / 2b: Z-isomer
4a / 4b: E-isomer
OAc
OAc
R1
R1
O
O
R2
AcO
R2
AcO
OAc
OAc
Br
Br
18
13
O
O
11
O
O
4
1
15
16
O
O
3
2
5
OAc
6'
5'
OAc
12
14
17
R1
4'
R1
6
10
8
O
O
R2
AcO
R2
AcO
7
9
1'
O
O
2'
3'
OAc
OAc
5a / 5b: β-anomer, configuration Z; R1 = H, R2 = OAc
7a / 7b: β-anomer, configuration E; R1 = H, R2 = OAc
9a / 9b: β-anomer, configuration Z; R1 = OAc, R2 = H
6a / 6b: β-anomer, configuration Z; R1 = H, R2 = OAc
8a / 8b: β-anomer, configuration E; R1 = H, R2 = OAc
10a / 10b: β-anomer, configuration Z; R1 = OAc, R2 = H
12a / 12b: β-anomer, configuration E; R1 = OAc, R2 = H
11a / 11b: β-anomer, configuration E; R1 = OAc, R2 = H
Zn(OAc) 2 / EtOH abs.
Zn(OAc) 2 / EtOH abs.
O
O
O
O
O
O
OH
O
OH
R1
R1
O
R2
R2
O
O
HO
HO
OH
OH
13a / 13b: β-anomer, configuration Z; R1 = H, R2 = OH
14a / 14b: β-anomer, configuration Z; R1 = H, R2 = OH
15a / 15b: β-anomer, configuration E; R1 = H, R2 = OH
17a / 17b: β-anomer, configuration Z; R1 = OH, R2 = H
19a / 19b: β-anomer, configuration E; R1 = OH, R2 = H
16a / 16b: β-anomer, configuration E; R1 = H, R2 = OH
18a / 18b: β-anomer, configuration Z; R1 = OH, R2 = H
20a / 20b: β-anomer, configuration E; R1 = OH, R2 = H
Scheme 1. Reaction pathway. The numbers (1) and (2) placed in the structures 1a/1b–4a/4b indicate the chiral centers C(1) and C(2) for the
assignment of the absolute configuration, and they respect the chemical nomenclature rules. In turn, the numbering of the positions located in the
other structure should only be used for indication of the appropriate signals in the 1H and 13C NMR spectra.
herbivorous insect species), one of the possible ways of
their treatment by juvenoids is represented by the sys-
temic application of convenient derivatives, e.g. glyco-
sides of parent juvenoid alcohols, which can be more
easily ingested by insects and can also be more easily ap-
plied to the plants.
the biologically active compound (the juvenoid) under
the effect of biotic (mainly enzyme-mediated) or abiotic
(environmental) factors.12 The practical impact of hor-
monogen compounds consists in their controlled phys-
ico-chemical properties, protection of the parent
biologically active molecule for extended time period,
and an advanced feature of hormonogen compounds
to act as biochemically activated slow-release formula-
tions for biologically active compounds. Therefore,
application of juvenogens results in extended period,
during which the target insect pest is treated by the bio-
logically active compound. The rate of hydrolysis of
juvenogens, which results in liberation of the biologi-
cally active juvenoid, is dependent on the juvenogen
structure. This anticipation was proven during our pio-
neer experiments,13 for which four of the compounds
presented in this study (13a/13b–16a/16b), were already
synthesized in their diastereoisomeric forms, i.e., their
synthesis started from racemic alcohols. However, their
detailed synthesis has never been published, and their
partial 1H NMR data presented therein13 were recorded
using an old 60 MHz NMR instrument available that
The key transformation of the juvenoid molecule con-
sists in a synthesis of b-D-glucopyranoside and b-D-
galactopyranoside derivatives of the racemic isomers
1a/1b–4a/4b and of the enantiopure stereoisomers 1a–
4a of the juvenoid structures selected for the target
study; the stereoisomers 1a and 3a bear the absolute
configuration (1S,2S), 2a and 4a can be described as
(1R,2S). The reason for this transformation was to pro-
duce hormonogen substances (juvenogens, biochemi-
cally activated juvenoids)12 displaying higher polarity
than the parent alcohol, which is a key feature of the no-
vel molecule, due to its proposed systemic application
against herbivorous insect pests (aphids or bugs). The
term juvenogen has been used for describing complex
hormonogen substances generally capable of liberating

7128
Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
time. Therefore, when now focusing on the glycosidic
derivatives 5a/5b–20a/20b of the parent racemic juve-
noids 1a/1b–4a/4b and those of enantiopure juvenoids
1a–4a, for a more detailed study of the juvenogens,
and we present completed analytical data (1H and 13C
NMR, IR and mass spectra, and elemental analyses)
of the enantiopure compounds 5a–20a and 5b–20b.
The products 5a/5b–20a/20b (diastereoisomeric mix-
tures) have been synthesized and subjected to the partial
introductory screening tests on the red firebug (Pyrrhoc-
oris apterus).
the system through the whole reaction time; toluene was
used as convenient solvent due to its higher safety and
higher boiling point in comparison with benzene to assist
in maintaining anhydrous conditions during the reaction.
The second synthetic step requiredapplication ofacareful
approach to the deprotection of the carbohydrate unit
due to the presence of another ester functionality in the
aglycone part of the molecule; its presence is necessary
for keeping biological activity of the juvenoids
1a/1b–4a/4b and the juvenogens 13a/13b–20a/20b. There-
fore, removal of the acetate groups from the carbohydrate
units was performed by alcoholysis in the presence of
zinc acetate.20 The same synthetic procedure was applied
for the synthesis of the enantiopure compounds 5a–20a,
which started from the enantiopure alcohols 1a–4a. These
alcohols were obtained by a stereoselective enzymic
reduction of the corresponding parent ketones using
Saccharomyces cerevisiae whole cells.14
Recently, we have published a paper on a stereospecific
reduction of the respective E and Z isomers of ethyl
4-[40-(200-oxocyclohexyl)methylphenoxy}-3-methyl-but-
2-enoate by Saccharomyces cerevisiae whole cells,
affording the requested enantiomers 1a–4a of the corre-
sponding alcohols with > 99% enantiomeric purity.14
The described procedure14 was used to prepare the com-
pounds 1a–4a in this study and to use them in the syn-
thesis of the juvenogens 5a–20a.
It was found that the Koenigs–Knorr synthesis resulted
in higher yields of the intermediate products 9a/9b–12a/
12b (b-D-galactopyranosides), in comparison with 5a/
5b–8a/8b (b-D-glucopyranosides). The deprotection of
the compounds 5a/5b–12a/12b showed no visible prefer-
ence from any point of view. The same result was ob-
tained when the synthetic procedure started from
enantiopure alcohols 1a to 4a.
The objectives of this investigation were: (a) to synthe-
size diastereoisomeric and enantiomerically pure tar-
get alkyl glycosides; (b) to separate diastereoisomeric
mixtures of alkyl glycosides to get all possible enantio-
mers of the studied alkyl glycosides in their enantiome-
rically pure states; (c) to perform a detailed structure
elucidation and 13C chemical shift assignments of the
products 5a–20a and 5b–20b by 1H and 13C NMR spec-
troscopy; (d) to get basic introductory results on biolog-
ical activity of the prepared target alkyl glycosides by
performing the screening tests on the red firebug
(P. apterus).
Because the synthetic procedure afforded the diastereo-
isomeric compounds 5a/5b–20a/20b and the enantiopure
compounds 5a–20a directly, enough material was also
1
available for the detailed structure assignment by H
1
and 13C NMR spectroscopy. In fact, the H and 13C
NMR spectra of the enantiomers 5b–20b were extracted
from the respective spectra of the diastereoisomeric mix-
tures 5a/5b–20a/20b by using the spectra of the pure
enantiomers 5a–20a to identify signals belonging to the
enantiomers 5b–20b. Employing a chiral HPLC separa-
tion technique on a cyclodextrin-based chiral Nucleo-
dex-b-OH column, we succeeded to separate the
diastereoisomeric mixtures 13a/13b–20a/20b, and got
small quantities of 13b–20b to record their NMR spec-
tra. No separation of the enantiomers of the protected
compounds 5a/5b–12a/12b was observed under the ap-
plied isocratic chromatographic conditions; methanol/
water (9:1) was used as mobile phase. The NMR exper-
iments employed in this study though enabled finally
unambiguous structure assignment of all alkyl b-D-
glucopyranosides prepared (5a–20b). The NMR data
were determined on the basis of both, 1D and 2D
2. Results and discussion
The Koenigs–Knorr synthesis15,16 of the intermediate
products 5a/5b–12a/12b was performed using the respec-
tive 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl- and 2,3,4,6-
tetra-O-acetyl-a-D-galactopyranosyl bromide as the
activating species of the carbohydrate unit (Scheme 1).
The separated racemic isomers 1a/1b–4a/4b and the
enantiopure stereoisomers 1a–4a of the juvenoid alco-
hols were used as glycosyl acceptors. Cadmium carbon-
ate was used as optimized promoter of the Koenigs–
Knorr synthesis of alkyl glycosides.17–19 The carbohy-
drate units bring new chirality features to the intermedi-
ate products 5a/5b–12a/12b, and, therefore, these
acetylated compounds were isolated in the forms of dia-
stereoisomeric mixtures. Subsequently, the final prod-
ucts of this synthesis, the juvenogens 13a/13b–20a/20b,
were also obtained as diastereoisomeric mixtures
(Scheme 1). A 1:1 ratio of the respective diastereoiso-
mers 5a/5b–20a/20b was found in each mixture, which
means that there was no detectable preference of either
enantiomer of the isomeric racemic alcohols 1a/1b–4a/
4b during the Koenigs–Knorr synthesis. The Koenigs–
Knorr synthesis was performed under rigorously anhy-
drous conditions by careful removal of traces of humid-
ity potentially present or entering the system, by
continuous maintaining of the azeotropic conditions in
1
NMR experiments. The critical analysis of the 1D H
NMR and 1H,1H PFG COSY spectra21–23 of pure enan-
tiomers 5a–20b allowed extracting the 1H chemical shifts
and coupling constants. However, positions of the H
1
signals of the cyclohexane moiety could be extracted nei-
ther directly from the 1D NMR spectra nor from the
1H,1H PFG COSY spectra, and it was necessary to esti-
1
mate these values from the H,13C PFG HSQC spec-
tra24,25 using the knowledge of the 13C NMR chemical
shifts from the model compounds with similar struc-
1
ture.26 The 2D H,13C PFG HSQC spectra were used
for unambiguous assignment of the 13C NMR chemical
shifts of the remaining carbon atoms. The 1H NMR

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7129
data of the protected and unprotected alkyl glycosides
5a–20b are summarized in the Experimental section,
3. Conclusion
while their 13C NMR data are collected in Tables 1–4.
Following the specified objectives of this investigation,
several partial results were achieved and evaluated: (a)
a series of new juvenogens, insect hormonogenic com-
pounds (13a–20b), was prepared using the Koenigs–
Knorr synthesis of alkyl glycosides, followed by a
careful deprotection by alcoholysis of the acetyl
groups in the presence of zinc acetate. These sub-
stances were synthesized either in the form of diaste-
reoisomeric compounds or in the form of
enantiopure stereoisomers; (b) small quantities of the
target diastereoisomeric compounds were separated
from their diastereoisomeric mixtures using chiral
HPLC technique to get all possible stereoisomers as
enantiopure chemical species; (c) the target com-
pounds 13a–20b, as well as their protected precursors
5a–12b, were subjected to a detailed structure elucida-
tion, which enabled unambiguous structure assignment
of the products 5a–20b; (d) several compounds of this
series were subjected to the introductory screening
tests on P. apterus, and the results showed that the
juvenogens 13a/13b and 17a/17b displayed higher
activity than the parent alcohol 1a/1b, and the juveno-
gen 15a/15b was more active than its parent alcohol
3a/3b, which result clearly demonstrates the extended
effect of juvenogens, biochemically activated hormono-
genic compounds, in comparison with their parent
juvenoid alcohols.
The alkyl glycosides 13a/13b–20a/20b have been sub-
jected to biological screening tests against the red firebug
(P. apterus), employing a drinking assay (Table 5). The
ID-50 value generally indicates the amount of a biolog-
ically active compound to be used for obtaining a 50%
inhibition of metamorphosis. The ID-50 value (Table
5) represents the value calculated for each compound
from five experiments running simultaneously with dif-
ferent concentrations of the tested compound. It clearly
follows from the screening tests that a majority of juve-
nogens (13a/13b, 15a/15b, and 17a/17b) derived from the
parent alcohols 1a/1b and 3a/3b displayed higher activity
than these parent alcohols. However, when using the
juvenogens 14a/14b, 16a/16b, 18a/18b, and 20a/20b
derived from the parent alcohols 2a/2b and 4a/4b, the
results are not so convincing. The juvenogen (i.e., an al-
kyl glycoside) is metabolized by b-glycosidases present
in the insect organism, due to which process the biolog-
ically active aglycone (the juvenoid) is liberated in the in-
sect body.12,13 It has not been proved yet, if both, the
juvenogens and the juvenoids, can be transported to
the target site in the insect body. However, it has already
been proven that application of different juvenogen
structures can extend the mode of action of the parent
juvenoid.7,8,12,13
Table 1. The 13C NMR data of the protected alkyl glucosides 5a/5b–8a/8b (measured in CDCl3 at 303 K)
Carbon atom No.
Compound
5aa
5ba
6ab
6bb
7ac
7bc
8ad
8bd
1
2
79.98 (d)
43.80 (d)
26.65 (t)
25.34 (t)
20.71 (t)
31.92 (t)
37.28 (t)
133.31 (s)
129.90 (d)
114.47 (d)
156.67 (s)
67.30 (t)
156.37 (s)
117.44 (d)
165.94 (s)
59.99 (t)
14.28 (q)
21.35 (q)
101.76 (d)
71.67 (d)
73.10 (d)
68.64 (d)
71.53 (d)
62.28 (t)
74.99 (d)
43.87 (d)
26.72 (t)
25.05 (t)
20.68 (t)
28.86 (t)
37.19 (t)
133.80 (s)
130.34 (d)
114.07 (d)
156.83 (s)
67.24 (t)
156.23 (s)
117.36 (d)
165.91 (s)
59.94 (t)
14.28 (q)
21.34 (q)
98.24 (d)
71.78 (d)
73.13 (d)
68.94 (d)
71.59 (d)
62.01 (t)
85.58 (d)
45.11 (t)
29.74 (t)
24.77 (t)
24.91 (t)
33.71 (t)
37.33 (t)
132.74 (s)
130.13 (d)
114.36 (d)
156.83 (s)
67.28 (t)
156.39 (s)
117.43 (d)
165.93 (s)
59.97 (t)
14.28 (q)
21.33 (q)
102.04 (d)
71.83 (d)
73.08 (d)
68.80 (d)
71.63 (d)
62.30 (t)
81.07 (d)
44.33 (t)
29.67 (t)
24.45 (t)
24.88 (t)
31.25 (t)
37.33 (t)
133.25 (s)
130.43 (d)
114.15 (d)
156.68 (s)
67.26 (t)
156.24 (s)
117.37 (d)
165.93 (s)
59.90 (t)
14.28 (q)
21.32 (q)
98.56 (d)
71.71 (d)
73.13 (d)
68.82 (d)
71.63 (d)
62.12 (t)
80.01 (d)
43.75 (d)
26.67 (t)
25.36 (t)
20.40 (t)
29.69 (t)
37.26 (t)
133.78 (s)
129.94 (d)
114.71 (d)
156.37 (s)
71.61 (t)
153.05 (s)
115.79 (d)
166.58 (s)
59.83 (t)
14.29 (q)
15.68 (q)
101.77 (d)
71.76 (d)
73.10 (d)
68.72 (d)
71.52 (d)
62.30 (t)
a
74.70 (d)
43.86 (d)
26.82 (t)
25.05 (t)
20.23 (t)
28.80 (t)
37.11 (t)
134.19 (s)
130.39 (d)
114.28 (d)
156.54 (s)
71.61 (t)
152.85 (s)
115.70 (d)
166.52 (s)
59.78 (t)
14.29 (q)
15.68 (q)
98.17 (d)
71.84 (d)
73.13 (d)
68.97 (d)
71.76 (d)
62.12 (t)
85.59 (d)
45.13 (d)
29.78 (t)
24.76 (t)
24.92 (t)
33.71 (t)
37.35 (t)
133.22 (s)
130.17 (d)
114.58 (d)
156.52 (s)
71.70 (t)
153.05 (s)
115.76 (d)
166.57 (s)
59.82 (t)
14.28 (q)
15.68 (q)
102.02 (d)
71.83 (d)
73.07 (d)
68.79 (d)
71.61 (d)
62.30 (t)
80.93 (d)
44.34 (d)
29.72 (t)
24.77 (t)
24.90 (t)
31.25 (t)
37.32 (t)
133.70 (s)
130.48 (d)
114.35 (d)
156.38 (s)
71.64 (t)
152.90 (s)
115.70 (d)
166.54 (s)
59.78 (t)
14.28 (q)
15.68 (q)
98.50 (d)
71.81 (d)
73.11 (d)
68.82 (d)
71.12 (d)
62.12 (t)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
10
20
30
40
50
60
Signals of the protecting acetate functionalities on the monosaccharide part of the molecules: 20.48 (q), 20.61 (q), 20.65 (q), 20.70 (q), 20.71 (q),
20.74 (q), 20.74 (q), 20.84 (q), 169.21 (s), 169.22 (s), 169.44 (s), 169.45 (s), 170.33 (s), 170.37 (s), 170.59 (s), 170.71 (s); b 20.59 (q), 20.60 (q), 20.69 (q),
20.71 (q), 20.73 (q), 20.78 (q), 20.78 (q), 20.78 (q), 169.26 (s), 169.29 (s), 169.41 (s), 169.41 (s), 170.33 (s), 170.36 (s), 170.60 (s), 170.65 (s); c 20.53 (q),
20.59 (q), 20.63 (q), 20.67 (q), 20.70 (q), 20.72 (q), 20.77 (q), 20.84 (q), 169.17 (s), 169.21 (s), 169.41 (s), 169.43 (s), 170.34 (s), 170.55 (s), 170.55 (s),
170.71 (s); d 20.51 (q), 20.53 (q), 20.53 (q), 20.59 (q), 20.67 (q), 20.67 (q), 20.69 (q), 20.70 (q), 169.25 (s), 169.29 (s), 169.40 (s), 169.41 (s), 170.33 (s),
170.35 (s), 170.59 (s), 170.64 (s).

7130
Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
Table 2. The 13C NMR data of the protected alkyl galactosides 9a/9b–12a/12b (measured in CDCl3 at 303 K)
Carbon atom No.
Compound
9aa
9ba
10ab
10bb
11ac
11bc
12ad
12bd
1
2
80.14 (d)
43.75 (d)
26.58 (t)
25.28 (t)
20.89 (t)
31.92 (t)
37.27 (t)
133.34 (s)
129.91 (d)
114.44 (d)
156.62 (s)
67.19 (t)
156.48 (s)
117.41 (d)
165.96 (s)
60.91 (t)
14.30 (q)
21.39 (q)
102.32 (d)
69.17 (d)
71.16 (d)
67.17 (d)
70.44 (d)
61.39 (t)
75.45 (d)
43.79 (d)
26.65 (t)
24.80 (t)
21.03 (t)
28.94 (t)
37.04 (t)
133.87 (s)
130.32 (d)
114.09 (d)
156.81 (s)
67.29 (t)
156.32 (s)
117.33 (d)
165.95 (s)
59.97 (t)
14.30 (q)
21.37 (q)
98.93 (d)
69.31 (d)
71.17 (d)
67.19 (d)
70.48 (d)
61.39 (t)
85.81 (d)
45.09 (t)
29.76 (t)
24.76 (t)
24.92 (t)
33.80 (t)
37.32 (t)
132.73 (s)
130.15 (d)
114.28 (d)
156.76 (s)
67.08 (t)
156.48 (s)
117.36 (d)
165.94 (s)
59.98 (t)
14.28 (q)
21.35 (q)
102.55 (d)
69.21 (d)
71.15 (d)
67.23 (d)
70.41 (d)
61.25 (t)
81.38 (d)
44.27 (t)
29.57 (t)
24.43 (t)
24.81 (t)
31.31 (t)
37.37 (t)
133.28 (s)
130.38 (d)
114.10 (d)
156.59 (s)
67.08 (t)
156.34 (s)
117.32 (d)
165.94 (s)
59.96 (t)
14.28 (q)
21.35 (q)
99.28 (d)
69.27 (d)
71.15 (d)
67.20 (d)
70.48 (d)
61.36 (t)
80.09 (d)
43.65 (d)
26.57 (t)
25.27 (t)
20.40 (t)
31.88 (t)
37.22 (t)
133.75 (s)
129.92 (d)
114.63 (d)
156.27 (s)
71.65 (t)
153.12 (s)
115.66 (d)
166.57 (s)
59.83 (t)
14.27 (q)
15.68 (q)
102.30 (d)
69.12 (d)
71.11 (d)
67.11 (d)
70.42 (d)
61.35 (t)
a
75.11 (d)
43.74 (d)
26.70 (t)
24.90 (t)
20.86 (t)
28.85 (t)
37.19 (t)
134.20 (s)
130.35 (d)
114.25 (d)
156.45 (s)
71.72 (t)
152.90 (s)
115.54 (d)
166.53 (s)
59.79 (t)
14.27 (q)
15.68 (q)
98.82 (d)
69.28 (d)
71.13 (d)
67.14 (d)
70.42 (d)
61.33 (t)
85.84 (d)
45.14 (d)
29.79 (t)
24.78 (t)
24.95 (t)
33.83 (t)
37.35 (t)
133.24 (s)
130.21 (d)
114.53 (d)
156.47 (s)
71.73 (t)
153.11 (s)
115.67 (d)
166.60 (s)
59.86 (t)
14.30 (q)
15.71 (q)
102.55 (d)
69.22 (d)
71.16 (d)
67.10 (d)
70.43 (d)
61.25 (t)
81.30 (d)
44.31 (d)
29.64 (t)
24.45 (t)
24.85 (t)
31.32 (t)
37.40 (t)
133.79 (s)
130.46 (d)
114.34 (d)
156.31 (s)
71.75 (t)
153.00 (s)
115.61 (d)
166.58 (s)
59.83 (t)
14.30 (q)
15.71 (q)
99.27 (d)
69.30 (d)
71.16 (d)
67.10 (d)
70.51 (d)
61.37 (t)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
10
20
30
40
50
60
Signals of the protecting acetate functionalities on the monosaccharide part of the molecules: 20.59 (q), 20.59 (q), 20.65 (q), 20.67 (q), 20.71 (q),
20.76 (q), 20.76 (q), 20.78 (q), 169.38 (s), 169.38 (s), 169.91 (s), 169.99 (s), 170.26 (s), 170.44 (s), 170.45 (s), 170.53 (s); b 20.57 (q), 20.60 (q), 20.63 (q),
20.65 (q), 20.67 (q), 20.72 (q), 20.73 (q), 20.86 (q), 169.97 (s), 170.23 (s), 170.27 (s), 170.37 (s), 170.41 (s), 170.42 (s), 170.43 (s), 170.50 (s); c 20.40 (q),
20.56 (q), 20.62 (q), 20.63 (q), 20.67 (q), 20.73 (q), 20.75 (q), 21.00 (q), 169.38 (s), 169.87 (s), 169.96 (s), 170.22 (s), 170.26 (s), 170.40 (s), 170.42 (s),
170.49 (s); d 20.56 (q), 20.65 (q), 20.67 (q), 20.69 (q), 20.74 (q), 20.75 (q), 20.85 (q), 20.88 (q), 169.40 (s), 169.46 (s), 170.24 (s), 170.26 (s), 170.37 (s),
170.39 (s), 170.43 (s), 170.48 (s).
Table 3. The 13C NMR data of the alkyl glucosides 13a/13b–16a/16b (measured in CD3OD at 303 K)
Carbon atom No.
Compound
13a
13b
14a
14b
15a
15b
16a
16b
1
2
80.52 (d)
45.21 (d)
28.32 (t)
26.10 (t)
23.31 (t)
33.24 (t)
37.40 (t)
135.94 (s)
131.82 (d)
115.73 (d)
158.56 (s)
68.62 (t)
158.44 (s)
118.92 (d)
167.95 (s)
61.61 (t)
15.11 (q)
21.93 (q)
105.65 (d)
76.08 (d)
78.83 (d)
72.28 (d)
78.22 (d)
63.35 (t)
76.57 (d)
45.58 (d)
28.25 (t)
26.60 (t)
22.33 (t)
30.13 (t)
38.37 (t)
136.10 (s)
131.92 (d)
115.64 (d)
158.53 (s)
68.62 (t)
158.40 (s)
118.90 (d)
167.93 (s)
61.61 (t)
15.09 (q)
21.92 (q)
102.23 (d)
75.77 (d)
78.83 (d)
72.37 (d)
78.29 (d)
63.46 (t)
85.34 (d)
46.85 (d)
30.89 (t)
25.89 (t)
26.17 (t)
35.15 (t)
38.50 (t)
134.99 (s)
131.37 (d)
115.24 (d)
157.79 (s)
68.18 (t)
158.11 (s)
118.47 (d)
167.46 (s)
61.11 (t)
14.57 (q)
21.41 (q)
105.65 (d)
75.65 (d)
78.31 (d)
71.77 (d)
77.78 (d)
62.88 (t)
80.77 (d)
46.18 (d)
31.10 (t)
25.68 (t)
26.33 (t)
32.22 (t)
38.58 (t)
135.19 (s)
131.45 (d)
115.20 (d)
157.77 (s)
68.18 (t)
158.06 (s)
118.47 (d)
167.46 (s)
61.11 (t)
14.57 (q)
21.40 (q)
101.35 (d)
75.21 (d)
78.28 (d)
71.98 (d)
77.90 (d)
63.07 (t)
80.53 (d)
45.21 (d)
28.31 (t)
25.46 (t)
24.53 (t)
33.23 (t)
37.45 (t)
136.22 (s)
131.84 (d)
115.97 (d)
158.25 (s)
73.03 (t)
155.98 (s)
116.51 (d)
168.62 (s)
61.41 (t)
15.09 (q)
16.25 (q)
105.65 (d)
76.08 (d)
78.83 (d)
72.28 (d)
78.22 (d)
63.35 (t)
76.50 (d)
45.59 (d)
28.28 (t)
26.61 (t)
24.24 (t)
30.58 (t)
38.42 (t)
136.37 (s)
131.96 (d)
115.87 (d)
158.20 (s)
73.01 (t)
155.94 (s)
116.49 (d)
168.60 (s)
61.41 (t)
15.09 (q)
16.25 (q)
102.22 (d)
75.77 (d)
78.83 (d)
72.37 (d)
78.29 (d)
63.46 (t)
85.90 (d)
47.43 (d)
31.40 (t)
26.43 (t)
26.71 (t)
35.73 (t)
39.00 (t)
135.73 (s)
131.90 (d)
115.92 (d)
158.25 (s)
73.02 (t)
155.96 (s)
116.52 (d)
168.61 (s)
61.41 (t)
15.08 (q)
16.25 (q)
106.21 (d)
76.14 (d)
78.76 (d)
72.21 (d)
78.29 (d)
63.32 (t)
81.18 (d)
46.69 (d)
31.59 (t)
26.20 (t)
26.86 (t)
32.74 (t)
39.05 (t)
135.91 (s)
132.00 (d)
115.87 (d)
158.21 (s)
73.02 (t)
155.94 (s)
116.50 (d)
168.61 (s)
61.41 (t)
15.08 (q)
16.25 (q)
101.81 (d)
75.68 (d)
78.75 (d)
72.42 (d)
78.42 (d)
63.52 (t)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
10
20
30
40
50
60

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7131
Table 4. The 13C NMR data of the alkyl galactosides 17a/17b–20a/20b (measured in CD3OD at 303 K)
Carbon atom No.
Compound
17a
17b
18a
18b
19a
19b
20a
20b
1
2
80.52 (d)
45.30 (d)
28.33 (t)
26.13 (t)
23.28 (t)
33.26 (t)
37.46 (t)
135.99 (s)
131.83 (d)
115.72 (d)
158.55 (s)
68.62 (t)
158.44 (s)
118.92 (d)
167.95 (s)
61.62 (t)
15.08 (q)
21.93 (q)
106.31 (d)
73.53 (d)
75.70 (d)
70.75 (d)
76.86 (d)
62.79 (t)
76.63 (d)
45.67 (d)
28.29 (t)
26.57 (t)
22.35 (t)
30.17 (t)
38.26 (t)
136.14 (s)
131.93 (d)
115.62 (d)
158.50 (s)
68.62 (t)
158.41 (s)
118.90 (d)
167.93 (s)
61.62 (t)
15.08 (q)
21.92 (q)
102.96 (d)
73.24 (d)
75.74 (d)
70.75 (d)
76.89 (d)
62.83 (t)
85.83 (d)
47.45 (d)
31.41 (t)
26.44 (t)
26.71 (t)
35.76 (t)
39.03 (t)
135.50 (s)
131.88 (d)
115.67 (d)
158.56 (s)
68.62 (t)
158.41 (s)
118.92 (d)
167.94 (s)
61.61 (t)
15.08 (q)
21.93 (q)
106.84 (d)
73.57 (d)
75.66 (d)
70.75 (d)
76.92 (d)
62.88 (t)
81.25 (d)
46.71 (d)
31.60 (t)
26.22 (t)
26.86 (t)
32.78 (t)
39.03 (t)
135.64 (s)
131.98 (d)
115.62 (d)
158.52 (s)
68.62 (t)
158.40 (s)
118.91 (d)
167.94 (s)
61.61 (t)
15.08 (q)
21.92 (q)
102.53 (d)
73.13 (d)
75.64 (d)
70.81 (d)
77.01 (d)
62.91 (t)
80.54 (d)
45.29 (d)
28.31 (t)
26.10 (t)
23.27 (t)
33.26 (t)
37.48 (t)
136.27 (s)
131.84 (d)
116.00 (d)
158.23 (s)
73.00 (t)
155.98 (s)
116.51 (d)
168.63 (s)
61.41 (t)
15.08 (q)
16.25 (q)
106.31 (d)
73.53 (d)
75.70 (d)
70.78 (d)
76.86 (d)
62.83 (t)
76.90 (d)
45.68 (d)
28.30 (t)
26.58 (t)
22.31 (t)
30.17 (t)
38.26 (t)
136.42 (s)
131.97 (d)
115.85 (d)
158.18 (s)
73.00 (t)
155.95 (s)
116.48 (d)
168.61 (s)
61.41 (t)
15.08 (q)
16.25 (q)
102.96 (d)
73.23 (d)
75.73 (d)
70.74 (d)
76.90 (d)
62.86 (t)
85.83 (d)
47.44 (d)
31.41 (t)
26.44 (t)
26.72 (t)
35.77 (t)
39.04 (t)
135.78 (s)
131.90 (d)
115.91 (d)
158.24 (s)
73.03 (t)
155.97 (s)
116.51 (d)
168.63 (s)
61.41 (t)
15.08 (q)
16.25 (q)
106.83 (d)
73.58 (d)
75.66 (d)
70.75 (d)
76.93 (d)
62.88 (t)
81.24 (d)
46.71 (d)
31.61 (t)
26.22 (t)
26.87 (t)
32.80 (t)
39.04 (t)
135.91 (s)
132.01 (d)
115.85 (d)
158.20 (s)
73.03 (t)
155.95 (s)
116.50 (d)
168.61 (s)
61.41 (t)
15.08 (q)
16.25 (q)
102.53 (d)
73.13 (d)
75.64 (d)
70.83 (d)
77.02 (d)
62.95 (t)
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
10
20
30
40
50
60
Table 5. Juvenilizing effect of selected compounds on the red firebug
(P. apterus)
(FAB) were recorded on a VG analytical 70 - 250 SE
mass spectrometer, ZAB-EQ (BEQQ configuration) at
70 eV. Preparative column chromatography was per-
formed on a silica gel type 60 (particle size 0.04–
0.063 mm; Fluka, Switzerland). TLC was performed
on aluminum sheets precoated with silica gel 60 (Merck,
Germany). Analytical HPLC was carried out on a TSP
Compound ID-50
(drinking assay)
[lg.ind.ꢀ1
Compound ID-50
(drinking assay)
[lg.ind.ꢀ1
]
]
1a/1b
18.0
1.1
2a/2b
inactive
inactive
3.0
13a/13b
17a/17b
3a/3b
14a/14b
18a/18b
4a/4b
2.3
(Thermoseparation
Products,
USA)
instrument
0.05
0.0021
0.11
0.32
1.3
equipped with a ConstaMetric 4100 Bio pump and a
SpectroMonitor 5000 UV DAD. The purity of the prod-
ucts was checked using a Sepharon SGX C-18 reverse
phase column (250 · 4 mm, particle size 5 lm; Watrex,
Czech Republic) and/or on a chiral Nucleodex b-OH
column (150 · 4 mm; Macherey–Nagel, Germany) using
methanol / water (4:1, v/v) as mobile phase at
0.5 mL minꢀ1 (Sepharon SGX C-18 RP column) or at
0.3 mL minꢀ1 (Nucleodex b-OH column). The eluate
was monitored at 220, 254, and 275 nm and UV spectra
were run from 200 to 300 nm. Optical rotations were
measured on an Autopol IV polarimeter (Rudolph Re-
search Analytical, USA). Elemental analyses were per-
formed on a Perkin Elmer 2400, series II CHNS/O
analyzer (USA).
15a/15b
19a/19b
16a/16b
20a/20b
1.9
4. Experimental
4.1. General
1
The H NMR and the 13C NMR spectra were recorded
on a Bruker AVANCE 500 spectrometer (in a FT mode)
at 500.1 and 125.8 MHz, respectively, in CDCl3 or in
CD3OD at 303 K. For standardization, in the 1H
NMR either internal signal of tetramethylsilane (d0.0)
or a proton trace signal (d3.31 for CHD2OD) was used,
and in the 13C NMR spectra solvent signals for both
CDCl3 (d 77.00) and CD3OD (d49.50) were used. 2D
NMR experiments were measured using following char-
acteristic parameters: 1H,1H PFG COSY–spectral width
9 ppm in both f1, f2 dimensions, delay 1 s, data matrix
for processing 2048 · 2048 data points; 1H,13C PFG
HSQC – spectral width 9 ppm in f2 and 160 ppm in f1,
delay 1 s, data matrix for processing 2048 · 2048 data
points (lists of all acquisition and processing parameters
4.2. Ethyl 4-{40-[200-[(2000,3000,4000,6000- tetra-O-acetyl-b-D-
glucopyranosyloxy)cyclohexyl]methylphenoxy}-3-methyl-
but-2-enoate(5a/5b–8a/8b) and ethyl 4-{40-[200-[(2000,3000,4000,6-
tetra-O-acetyl-b-D-galactopyranosyloxy)cyclohexyl]meth-
ylphenoxy}-3-methyl-but-2-enoate(9a/9b–12a/12b)
The respective isomers of the alcohol (1–4; 200 mg;
0.6 mmol) were dissolved in toluene (45 mL), and
cadmium carbonate (335 mg; 2.0 mmol) was added. A
part of toluene (7–10 mL) was distilled off under the
azeotropic conditions to remove traces of water from
ˇ
are available from D. Saman on request). IR spectra
were recorded either in a solution (CCl4) or using a
KBr technique on a Bruker IFS 88 instrument. MS

7132
Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
the system.
A
solution of 2,3,4,6-tetra-O-acetyl-
(m, 1H, H-3a), 1.06 (m, 1H, H-5a), 1.20 (m, 1H, H-
4a), 1.29 (t, J = 7.1, 3H, H-17), 1.40 (m, 1H, H-6a),
1.54 (m, 1H, H-5b), 1.59 (m, 1H, H-2), 1.64 (m, 1H,
H-3b), 1.71 (m, 1H, H-4b), 2.02 (dt, J = 0.8, 0.8, 1.5,
3H, H-18), 2.12 (m, 1H, H-6b), 2.17 (dd, J = 9.0, 13.6,
1H, H-7a), 3.13 (dd, J = 3.5, 13.6, 1H, H-7b), 3.32 (dt,
J = 4.3, 9.5, 9.5, 1H, H-1), 3.67 (ddd, J = 2.7, 4.9,
10.0, 1H, H-50), 4.16 (dd, J = 2.7, 12.1, 1H, H-60a),
4.17 (q, J = 7.1, 2H, H-16), 4.26 (dd, J = 4.9, 12.1, 1H,
H-60b), 4.61 (d, J = 7.8, 1H, H-10), 5.01 (dd, J = 7.8,
9.7, 1H, H-20), 5.10 (dd, J = 9.4, 10.0, 1H, H-40), 5.16
(dq, J = 0.8, 0.8, 0.8, 1.6, 2H, H-12), 5.22 (t, J = 9.5,
1H, H-30), 5.81 (m, J = 1.5, 1H, H-14), 6.82 (m, 2H,
H-10), 7.06 (m, 2H, H-9); signals (CH3CO-): 2.01 (s,
3H), 2.03 (s, 3H), 2.04 (s, 3H), 2.07 (s, 3H). IR (CCl4):
3030 (w), 1761 (s), 1753 (s), 1716 (m), 1649 (w), 1612
(w), 1511 (m), 1340 (w), 1246 (s), 1220 (s), 1151 (s),
1098 (m), 1039 (s), 906 (w), 880 (w). MS: m/z = 663 (1;
[M+H]+), 369 (5), 331 (30), 233 (6), 187 (8), 169 (81),
139 (10), 127 (100), 109 (68), 99 (65). For C34H46O13
(662.74) calculated C, 61.62; H, 7.00. Found: C, 61.69;
H, 6.46.
a-D-glucopyranosyl bromide or 2,3,4,6-tetra-O-acetyl-
a-D-galactopyranosyl bromide (800 mg; 2.0 mmol) in
toluene (2 mL) was added during 5 min to the reaction
mixture, which was stirred and heated under azeotropic
condition for additional 16 h. A mixture of inorganic
salts was removed by filtration, and the solvent was
evaporated from the filtrate, affording a dry residue.
Column chromatography on silica gel yielded the pure
products in the respective yields: 5a/5b: 46%; 6a/6b:
34%; 7a/7b: 32%; 8a/8b: 33%; 9a/9b: 92%; 10a/10b:
91%; 11a/11b: 49%; 12a/12b: 35%.
1
Compound 5a/5b: H NMR (CDCl3): 5a: 1.17–1.46 (m,
6H, H-3, H-4a, H-5, H-6a), 1.29 (t, J = 7.1, 3H, H-17),
1.55–1.69 (m, 3H, H-2, H-4b, H-6b), 2.01 (dt, J = 0.7,
0.7, 1.5, 3H, H-18), 2.40 (dd, J = 7.7, 13.6, 1H, H-7a),
2.52 (dd, J = 6.9, 13.6, 1H, H-7b), 3.65 (ddd, J = 2.7,
4.6, 9.8, 1H, H-50), 3.65 (dt, J = 2.3, 2.3, 4.4, 1H, H-
1), 4.10 (dd, J = 2.7, 11.8, 1H, H-60a), 4.17 (q, J = 7.1,
2H, H-16), 4.21 (dd, J = 4.6, 11.8, 1H, H-60b), 4.55 (d,
J = 7.9, 1H, H-10), 5.10 (dd, J = 7.9, 9.7, 1H, H-20),
5.14 (t, J = 9.6, 1H, H-40), 5.18 (dq, J = 0.7, 0.7, 0.7,
1.7, 2H, H-12), 5.22 (t, J = 9.5, 1H, H-30), 5.83 (m,
J = 1.5, 1H, H-14), 6.86 (m, 2H, H-10), 7.04 (m, 2H,
H-9); signals (CH3CO-): 2.02 (s, 3H), 2.04 (s, 3H), 2.07
(s, 3H), 2.08 (s, 3H); 5b: 1.17–1.46 (m, 6H, H-3, H-4a,
H-5, H-6a), 1.30 (t, J = 7.1, 3H, H-17), 1.55–1.69 (m,
3H, H-2, H-4b, H-6b), 2.01 (dt, J = 0.7, 0.7, 1.5, 3H,
H-18), 2.52 (dd, J = 6.9, 13.6, 1H, H-7a), 2.70 (dd,
J = 7.5, 13.6, 1H, H-7b), 3.65 (ddd, J = 2.7, 4.6, 9.8,
1H, H-50), 3.81 (dt, J = 2.3, 2.3, 4.4, 1H, H-1), 4.15
(dd, J = 2.7, 11.8, 1H, H-60a), 4.18 (q, J = 7.1, 2H, H-
16), 4.29 (dd, J = 4.6, 11.8, 1H, H-60b) 4.55 (d, J = 7.9,
1H, H-10), 5.06 (t, J = 9.6, 1H, H-40), 5.08 (dd, J = 7.9,
9.7, 1H, H-20), 5.15 (dq, J = 0.7, 0.7, 0.7, 1.7, 2H, H-
12), 5.23 (t, J = 9.5, 1H, H-30), 5.81 (m, J = 1.5, 1H,
H-14), 6.83 (m, 2H, H-10), 7.11 (m, 2H, H-9); signals
(CH3CO-): 2.02 (s, 3H), 2.03 (s, 3H), 2.03 (s, 3H), 2.06
(s, 3H). IR (CCl4): 3029 (w), 1760 (s), 1753 (s), 1715
(m), 1648 (w), 1612 (w), 1511 (m), 1340 (w), 1246 (s),
1221 (s), 1151 (s), 1097 (m), 1039 (s), 898 (w). MS:
m/z = 663 (1; [M+H]+), 331 (30), 315 (8), 289 (4), 271
(13), 233 (9), 217 (7), 169 (100), 127 (93), 109 (85). For
C34H46O13 (662.74) calculated C, 61.62; H, 7.00. Found:
C, 61.78; H, 6.92.
1
Compound 7a/7b: H NMR (CDCl3): 7a: 1.16–1.46 (m,
4H, H-3, H-5), 1.21-1.25 (m, 1H, H-4a), 1.29 (t, J = 7.1,
3H, H-17), 1.29-1.36 (m, 1H, H-6a), 1.62-1.65 (m, 1H,
H-4b), 1.63 (m, 1H, H-2), 1.87 (m, 1H, H-6b), 2.20
(dt, J = 0.6, 0.6, 1.5, 3H, H-18), 2.41 (dd, J = 6.2,
13.7, 1H, H-7a), 2.53 (dd, J = 6.9, 13.5, 1H, H-7b),
3.65 (dt, J = 2.3, 2.3, 4.5, 1H, H-1), 3.84 (ddd, J = 2.3,
4.6, 10.0, 1H, H-50), 4.13 (dd, J = 2.3, 12.1, 1H, H-
60a), 4.18 (q, J = 7.1, 2H, H-16), 4.26 (dd, J = 4.6,
12.1, 1H, H-60b), 4.48 (dq, J = 0.5, 0.5, 0.5, 1.5, 2H,
H-12), 4.55 (d, J = 7.9, 1H, H-10), 5.11 (dd, J = 7.9,
9.4, 1H, H-20), 5.15 (t, J = 9.8, 1H, H-40), 5.22 (t,
J = 9.5, 1H, H-30), 6.07 (m, J = 1.6, 1H, H-14), 6.83
(m, 2H, H-10), 7.05 (m, 2H, H-9); signals (CH3CO-):
2.01 (s, 3H), 2.05 (s, 3H), 2.07 (s, 3H), 2.07 (s, 3H);
7b: 1.16-1.46 (m, 4H, H-3, H-5), 1.21-1.25 (m, 1H, H-
4a), 1.29 (t, J = 7.1, 3H, H-17), 1.29-1.36 (m, 1H, H-
6a), 1.62-1.65 (m, 1H, H-4b), 1.63 (m, 1H, H-2), 1.87
(m, 1H, H-6b), 2.19 (dt, J = 0.6, 0.6, 1.5, 3H, H-18),
2.39 (dd, J = 7.1, 13.5, 1H, H-7a), 2.71 (dd, J = 7.8,
13.7, 1H, H-7b), 3.65 (ddd, J = 2.6, 5.7, 10.2, 1H, H-
50), 3.80 (dt, J = 2.3, 2.3, 4.3, 1H, H-1), 4.10 (dd,
J = 2.6, 12.0, 1H, H-60a), 4.17 (q, J = 7.1, 2H, H-16),
4.20 (dd, J = 5.7, 12.0, 1H, H-60b), 4.45 (dq, J = 0.5,
0.5, 0.5, 1.5, 2H, H-12), 4.54 (d, J = 7.9, 1H, H-10),
5.06 (dd, J = 9.4, 10.2, 1H, H-40), 5.10 (dd, J = 7.9,
9.4, 1H, H-20), 5.23 (t, J = 9.5, 1H, H-30), 6.05 (m,
J = 1.5, 1H, H-14), 6.77 (m, 2H, H-10), 7.12 (m, 2H,
H-9); signals (CH3CO-): 2.02 (s, 3H), 2.03 (s, 3H),
2.03 (s, 3H), 2.06 (s, 3H). IR (CCl4): 3030 (w), 1761
(s), 1753 (s), 1720 (m), 1665 (w), 1612 (w), 1511 (m),
1327 (w), 1247 (s), 1224 (s), 1149 (s), 1097 (s), 1040
(s), 897 (w), 849 (w). MS: m/z = 663 (2; [M+H]+), 408
(1), 331 (49), 233 (19), 188 (10), 169 (100), 139 (13),
109 (77). For C34H46O13 (662.74) calculated C, 61.62;
H, 7.00. Found: C, 61.60; H, 6.89.
1
Compound 6a/6b: H NMR (CDCl3): 6a: 0.86 (m, 1H,
H-3a), 1.06 (m, 1H, H-5a), 1.19 (m, 1H, H-6a), 1.20
(m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-17), 1.54 (m,
1H, H-5b), 1.59 (m, 1H, H-2), 1.64 (m, 1H, H-3b),
1.71 (m, 1H, H-4b), 1.98 (m, 1H, H-6b), 2.02 (dt,
J = 0.8, 0.8, 1.5, 3H, H-18), 2.10 (dd, J = 8.8, 13.7,
1H, H-7a), 3.07 (dd, J = 3.5, 13.7, 1H, H-7b), 3.20 (dt,
J = 4.2, 9.5, 9.5, 1H, H-1), 3.70 (ddd, J = 2.7, 4.9,
10.0, 1H, H-50), 4.13 (dd, J = 2.7, 12.1, 1H, H-60a),
4.17 (q, J = 7.1, 2H, H-16), 4.25 (dd, J = 4.9, 12.1, 1H,
H-60b), 4.63 (d, J = 7.7, 1H, H-10), 5.07 (dd, J = 9.4,
10.0, 1H, H-40), 5.07 (dd, J = 7.7, 9.7, 1H, H-20), 5.16
(dq, J = 0.8, 0.8, 0.8, 1.6, 2H, H-12), 5.22 (t, J = 9.5,
1H, H-30), 5.81 (m, J = 1.5, 1H, H-14), 6.83 (m, 2H,
H-10), 7.00 (m, 2H, H-9); signals (CH3CO-): 1.95 (s,
3H), 2.00 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H), 6b: 0.86
1
Compound 8a/8b: H NMR (CDCl3): 8a: 0.87 (m, 1H,
H-3a), 1.07 (m, 1H, H-5a), 1.18 (m, 1H, H-6a), 1.20
(m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-17), 1.53 (m,

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7133
1H, H-5b), 1.55 (m, 1H, H-2), 1.62 (m, 1H, H-3b), 1.72
(m, 1H, H-4b), 2.00 (m, 1H, H-6b), 2.00-2.23 (m, 1H, H-
7a), 2.19 (dt, J = 0.6, 0.6, 1.5, 3H, H-18), 3.07 (dd,
J = 3.1, 13.5, 1H, H-7b), 3.20 (dt, J = 4.1, 9.5, 9.5, 1H,
H-1), 3.71 (ddd, J = 2.6, 5.3, 10.0, 1H, H-50), 4.13 (dd,
J = 2.6, 12.1, 1H, H-60a), 4.18 (q, J = 7.1, 2H, H-16),
4.29 (dd, J = 4.7, 12.1, 1H, H-60b), 4.47 (bd, J = 1.5,
1H, H-14), 4.63 (d, J = 8.0, 1H, H-10), 5.07 (dd,
J = 8.0, 9.5, 1H, H-20), 5.11 (t, J = 9.8, 1H, H-40), 5.22
(t, J = 9.5, 1H, H-30), 6.06 (m, J = 1.5, 2H, H-12), 6.80
(m, 2H, H-10), 7.01 (m, 2H, H-9); signals (CH3CO-):
2.01 (s, 3H), 2.03 (s, 3H), 2.09 (s, 3H), 2.11 (s, 3H);
8b: 0.87 (m, 1H, H-3a), 1.07 (m, 1H, H-5a), 1.18 (m,
1H, H-6a), 1.20 (m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-
17), 1.53 (m, 1H, H-5b), 1.55 (m, 1H, H-2), 1.62 (m,
1H, H-3b), 1.72 (m, 1H, H-4b), 2.00 (m, 1H, H-6b),
2.00-2.23 (m, 1H, H-7a), 2.19 (dt, J = 0.6, 0.6, 1.5, 3H,
H-18), 3.13 (dd, J = 3.7, 13.7, 1H, H-7b), 3.32 (dt,
J = 4.0, 9.5, 9.5, 1H, H-1), 3.68 (ddd, J = 2.8, 4.7,
10.0, 1H, H-50), 4.12 (dd, J = 2.8, 12.5, 1H, H-60a),
4.18 (q, J = 7.1, 2H, H-16), 4.26 (dd, J = 5.3, 12.5, 1H,
H-60b), 4.47 (m, 1H, H-14), 4.62 (d, J = 8.0, 1H, H-10),
5.01 (dd, J = 8.0, 9.5, 1H, H-20), 5.09 (t, J = 9.8, 1H,
H-40), 5.25 (t, J = 9.5, 1H, H-30), 6.06 (m, J = 1.5, 2H,
H-12), 6.80 (m, 2H, H-10), 7.08 (m, 2H, H-9); signals
(CH3CO-): 2.04 (s, 3H), 2.07 (s, 3H), 2.11 (s, 3H), 2.16
(s, 3H). IR (CCl4): 3031 (w), 1762 (s), 1753 (s), 1720
(m), 1665 (w), 1612 (w), 1511 (m), 1327 (w), 1248 (s),
1224 (s), 1149 (m), 1099 (s), 1040 (s), 907 (w), 880 (w).
MS: m/z = 663 (1; [M+H]+), 408 (1), 353 (2), 331 (38),
271 (6), 233 (8), 169 (100), 139 (11), 109 (75). For
C34H46O13 (662.74) calculated C, 61.62; H, 7.00. Found:
C, 61.58; H 7.01.
(CH3CO-): 2.05 (s, 3H), 2.10 (s, 3H), 2.12 (s, 3H),
2.14 (s, 3H). IR (CCl4): 2982 (w), 1716 (m), 1650 (w),
1612 (w), 1511 (m), 1369 (s), 1340 (w), 1245 (s), 1050
(s), 1221 (s), 1152 (s), 1099 (m), 1080 (s). MS: m/z =
685 (1; [M+Na]+), 662 (1; [M]+), 331 (16), 269 (6), 188
(6), 169 (29), 127 (100), 99 (89). For C34H46O13
(662.74) calculated C, 61.62; H, 7.00. Found: C, 61.70;
H 6.92.
1
Compound 10a/10b: H NMR (CDCl3): 10a: 0.88 (m,
1H, H-3a), 1.05 (m, 1H, H-5a), 1.18 (m, 1H, H-6a),
1.20 (m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-17), 1.54
(m, 1H, H-5b), 1.57 (m, 1H, H-2), 1.63 (m, 1H, H-
3b), 1.71 (m, 1H, H-4b), 1.95 (m, 1H, H-6b), 2.00-
2.18 (m, 1H, H-7a), 2.01 (dt, J = 0.6, 0.6, 1.5, 3H,
H-18), 3.08 (dd, J = 3.2, 13.2, 1H, H-7b), 3.22 (dt,
J = 4.3, 9.6, 9.6, 1H, H-1), 3.92 (dt, J = 1.2, 5.9, 6.5,
1H, H-50), 4.10 (dd, J = 5.9, 11.2, 1H, H-60a), 4.17
(q, J = 7.1, 2H, H-16), 4.23 (dd, J = 6.5, 11.2, 1H,
H-60b), 4.60 (d, J = 7.9, 1H, H-10), 5.04 (dd, J = 3.4,
10.5, 1H, H-30), 5.17 (bd, J = 1.5, 2H, H-12), 5.31
(dd, J = 7.9, 10.5, 1H, H-20), 5.39 (dd, J = 1.2, 3.4,
1H, H-40), 5.82 (m, J = 1.5, 1H, H-14), 6.84 (m, 2H,
H-10), 7.05 (m, 2H, H-9); signals (CH3CO-): 1.99 (s,
3H), 2.04 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H); 10b:
0.88 (m, 1H, H-3a), 1.05 (m, 1H, H-5a), 1.18 (m,
1H, H-6a), 1.20 (m, 1H, H-4a), 1.29 (t, J = 7.1, 3H,
H-17), 1.54 (m, 1H, H-5b), 1.57 (m, 1H, H-2), 1.63
(m, 1H, H-3b), 1.71 (m, 1H, H-4b), 1.95 (m, 1H, H-
6b), 2.00-2.18 (m, 1H, H-7a), 2.02 (dt, J = 0.6, 0.6,
1.5, 3H, H-18), 3.20 (dd, J = 3.6, 13.5, 1H, H-7b),
3.32 (dt, J = 4.2, 9.5, 9.5, 1H, H-1), 3.89 (dt, J = 1.2,
6.4, 6.4, 1H, H-50), 4.11 (dd, J = 6.2, 11.1, 1H, H-
60a), 4.17 (q, J = 7.1, 2H, H-16), 4.19 (dd, J = 6.5,
11.1, 1H, H-60b), 4.55 (d, J = 7.9, 1H, H-10), 5.04
(dd, J = 3.4, 10.5, 1H, H-30), 5.17 (bd, J = 1.5, 2H,
H-12), 5.20 (dd, J = 7.9, 10.5, 1H, H-20), 5.39 (dd,
J = 1.2, 3.4, 1H, H-40), 5.81 (m, J = 1.5, 1H, H-14),
6.83 (m, 2H, H-10), 7.06 (m, 2H, H-9); signals
(CH3CO-): 2.03 (s, 3H), 2.05 (s, 3H), 2.12 (s, 3H),
2.14 (s, 3H). IR (CCl4): 2982 (w), 1757 (s), 1716
(m), 1649 (w), 1612 (w), 1511 (m), 1370 (s), 1340
(w), 1247 (s), 1220 (s), 1172 (s), 1098 (m), 1051 (s),
911 (w), 879 (w), 602 (w). MS: m/z = 685 (2;
[M+Na]+), 662 (1; [M]+), 331 (18), 269 (6), 233 (3),
188 (6), 169 (18), 127 (100), 99 (81). For C34H46O13
(662.74) calculated C, 61.62; H, 7.00. Found: C,
61.43; H, 7.05.
1
Compound 9a/9b: H NMR (CDCl3): 9a: 0. 90 (m, 1H,
H-3a), 1.17 (m, 1H, H-5a), 1.20 (m, 1H, H-4a), 1.29 (t,
J = 7.1, 3H, H-17), 1.36 (m, 1H, H-6a), 1.50 (m, 1H, H-
5b), 1.62 (m, 1H, H-3b), 1.63 (m, 1H, H-2), 1.65 (m, 1H,
H-4b), 1.83 (m, 1H, H-6b), 2.00 (dt, J = 0.7, 0.7, 1.5,
3H, H-18), 2.39 (dd, J = 8.0, 13.6, 1H, H-7a), 2.53
(dd, J = 6.6, 13.6, 1H, H-7b), 3.66 (dt, J = 2.4, 2.4,
4.8, 1H, H-1), 3.85 (dt, J = 1.2, 6.6, 6.6, 1H, H-50),
4.08 (dd, J = 6.4, 11.3, 1H, H-60a), 4.16 (dd, J = 6.7,
11.3, 1H, H-60b), 4.17 (q, J = 7.1, 2H, H-16), 4.51 (d,
J = 8.0, 1H, H-10), 5.03 (dd, J = 3.5, 10.5, 1H, H-30),
5.16 (dq, J = 0.7, 0.7, 0.7, 1.5, 2H, H-12), 5.26 (dd,
J = 7.9, 10.5, 1H, H-20), 5.39 (dd, J = 1.2, 3.5, 1H, H-
40), 5.80 (m, J = 1.5, 1H, H-14), 6.86 (m, 2H, H-10),
7.05 (m, 2H, H-9); signals (CH3CO-): 2.03 (s, 3H),
2.05 (s, 3H), 2.06 (s, 3H), 2.08 (s, 3H); 9b: 0. 90 (m,
1H, H3a), 1.17 (m, 1H, H-5a), 1.20 (m, 1H, H-4a),
1.29 (t, J = 7.1, 3H, H-17), 1.36 (m, 1H, H-6a), 1.50
(m, 1H, H-5b), 1.62 (m, 1H, H-3b), 1.63 (m, 1H, H-
2), 1.65 (m, 1H, H-4b), 1.83 (m, 1H, H-6b), 2.02 (dt,
J = 0.7, 0.7, 1.5, 3H, H-18), 2.43 (dd, J = 7.2, 13.8,
1H, H-7a), 2.73 (dd, J = 7.1, 13.8, 1H, H-7b), 3.81 (dt,
J = 2.4, 2.4, 4.8, 1H, H-1), 3.87 (dt, J = 1.3, 6.5, 6.5,
1H, H-50), 4.16 (d, J = 6.5, 2H, H-60), 4.17 (q, J = 7.1,
2H, H-16), 4.50 (d, J = 7.9, 1H, H-10), 5.04 (dd,
J = 3.5, 10.5, 1H, H-30), 5.17 (dq, J = 0.7, 0.7, 0.7, 1.5,
2H, H-12), 5.30 (dd, J = 8.0, 10.5, 1H, H-20), 5.40 (dd,
J = 1.3, 3.5, 1H, H-40), 5.81 (m, J = 1.5, 1H, H-14),
6.82 (m, 2H, H-10), 7.11 (m, 2H, H-9); signals
1
Compound 11a/11b: H NMR (CDCl3): 11a: 0.90 (m,
1H, H-3a), 1.18 (m, 1H, H-5a), 1.20 (m, 1H, H-4a),
1.29 (t, J = 7.1, 3H, H-17), 1.37 (m, 1H, H-6a), 1.44
(m, 1H, H-5b), 1.61 (m, 1H, H-3b), 1.63 (m, 1H, H-
2), 1.66 (m, 1H, H-4b), 1.83 (m, 1H, H-6b), 2.20 (bd,
J = 1.5, 3H, H-18), 2.40 (dd, J = 8.0, 13.7, 1H, H-7a),
2.54 (dd, J = 6.7, 13.7, 1H, H-7b), 3.66 (dt, J = 2.4,
2.4, 4.8, 1H, H-1), 3.85 (dt, J = 1.2, 6.7, 6.7, 1H, H-
50), 4.08 (dd, J = 6.8, 11.2, 1H, H-60a), 4.16 (dd,
J = 6.6, 11.2, 1H, H-60b), 4.17 (q, J = 7.1, 2H, H-16),
4.48 (dq, J = 0.6, 0.6, 0.6, 1.5, 2H, H-12), 4.51 (d,
J = 8.0, 1H, H-10), 5.04 (dd, J = 3.4, 10.5, 1H, H-30),
5.26 (dd, J = 7.9, 10.5, 1H, H-20), 5.38 (dd, J = 1.2,
3.4, 1H, H-40), 6.06 (m, J = 1.5, 1H, H-14), 6.83 (m,

7134
Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
2H, H-10), 7.06 (m, 2H, H-9); signals (CH3CO-): 2.05
(s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 2.12 (s, 3H); 11b:
0.90 (m, 1H, H-3a), 1.18 (m, 1H, H-5a), 1.20 (m, 1H,
H-4a), 1.29 (t, J = 7.1, 3H, H-17), 1.37 (m, 1H, H-6a),
1.44 (m, 1H, H-5b), 1.61 (m, 1H, H-3b), 1.63 (m, 1H,
H-2), 1.66 (m, 1H, H-4b), 1.83 (m, 1H, H-6b), 2.20
(bd, J = 1.5, 3H, H-18), 2.44 (dd, J = 7.0, 13.8, 1H, H-
7a), 2.74 (dd, J = 7.4, 13.8, 1H, H-7b), 3.81 (dt,
J = 2.3, 2.3, 4.6, 1H, H-1), 3.87 (dt, J = 1.3, 6.7, 6.7,
1H, H-50), 4.17 (dd, J = 6.8, 11.0, 1H, H-60a), 4.17 (q,
J = 7.1, 2H, H-16), 4.19 (dd, J = 6.6, 11.0, 1H, H-60b),
4.47 (dq, J = 0.6, 0.6, 0.6, 1.5, 2H, H-12), 4.50 (d,
J = 7.9, 1H, H-10), 5.05 (dd, J = 3.4, 10.5, 1H, H-30),
5.30 (dd, J = 8.0, 10.5, 1H, H-20), 5.40 (dd, J = 1.3,
3.4, 1H, H-40), 6.06 (m, J = 1.5, 1H, H-14), 6.80 (m,
2H, H-10), 7.12 (m, 2H, H-9); signals (CH3CO-): 2.08
(s, 3H), 2.14 (s, 3H), 2.18 (s, 3H), 2.20 (s, 3H). IR
(CCl4): 1758 (s), 1720 (m), 1665 (w), 1612 (w), 1511
(m), 1369 (s), 1328 (w), 1250 (s), 1046 (s), 1222 (s),
1172 (s), 1149 (s), 1098 (m), 989 (w), 849 (w). MS:
m/z = 685 (3; [M+Na]+), 662 (2; [M]+), 331 (49), 269
(6), 233 (46), 188 (16), 169 (51), 127 (44), 99 (100).
For C34H46O13 (662.74) calculated C, 61.62; H, 7.00.
Found: C, 62.01; H, 6.73.
4.3. Ethyl 4-{40-[200-(b-D-glucopyranosyloxy)cyclo-
hexyl]methylphenoxy}-3-methyl-but-2-enoate (13a/13b–
16a/16b) and ethyl 4-{40-[200-(b-D-galactopyranosyloxy)cyclo-
hexyl-methyl]phenoxy}-3-methyl-but-2-enoate (17a/17b–20a/
20b)
Zinc acetate dihydrate (62 mg; 0.282 mmol) was added
to a solution of 5a/5a–12a/12b (186 mg; 0.282 mmol) in
absolute ethanol (15 mL), and the reaction mixture
was heated at the solvent boiling point for 32 h. When
completed, the solvent was evaporated under reduced
pressure and the residue was applied on the top of a col-
umn for chromatographic purification, affording the
products in the respective yields: 13a/13b: 83%; 14a/
14b: 71%; 15a/15b: 67%; 16a/16b: 62%; 17a/17b: 61%;
18a/18b: 74%; 19a/19b: 93%; 20a/20b: 64%.
1
Compound 13a/13b: H NMR (CD3OD): 13a: 1.28 (t,
J = 7.1, 3H, H-17), 1.29 (m, 1H, H-4a), 1.33 (m, 1H,
H-3a), 1.37 (m, 1H, H-5a), 1.39 (m, 1H, H-6a), 1.52
(m, 1H, H-3b), 1.66 (m, 1H, H-4b), 1.74 (m, 1H, H-
5b), 1.75 (m, 1H, H-2), 2.00 (dt, J = 0.8, 0.8, 1.5, 3H,
H-18), 2.03 (m, 1H, H-6b), 2.52 (dd, J = 8.4, 13.6, 1H,
H-7a), 2.85 (dd, J = 6.6, 13.6, 1H, H-7b), 3.20 (ddd,
J = 2.4, 5.7, 9.7, 1H, H-50), 3.27 (dd, J = 7.9, 9.2, 1H,
H-20), 3.32 (t, J = 9.5, 1H, H-40), 3.37 (t, J = 9.4, 1H,
H-30), 3.65 (dd, J = 5.7, 11.8, 1H, H-60a), 3.73 (dt,
J = 2.4, 2.4, 4.8, 1H, H-1), 3.82 (dd, J = 2.4, 11.8, 1H,
H-60b), 4.16 (q, J = 7.1, 2H, H-16), 4.32 (d, J = 7.8,
1H, H-10), 5.14 (dq, J = 0.8, 0.8, 0.8, 1.5, 2H, H-12),
5.85 (m, J = 1.5, 1H, H-14), 6.81 (m, 2H, H-10), 7.15
(m, 2H, H-9); 13b: 1.28 (t, J = 7.1, 3H, H-17), 1.29 (m,
1H, H-4a), 1.32 (m, 1H, H-6a), 1.33 (m, 1H, H-3a),
1.33 (m, 1H, H-5a), 1.52 (m, 1H, H-3b), 1.66 (m, 1H,
H-4b), 1.67 (m, 1H, H-2), 1.77 (m, 1H, H-5b), 1.96
(m, 1H, H-6b), 2.00 (dt, J = 0.8, 0.8, 1.5, 3H, H-18),
2.42 (dd, J = 7.9, 13.7, 1H, H-7a), 2.81 (dd, J = 6.5,
13.7, 1H, H-7b), 3.25 (ddd, J = 2.4, 5.6, 9.6, 1H, H-50),
3.25 (dd, J = 7.8, 9.3, 1H, H-20), 3.27 (t, J = 9.7, 1H,
H-40), 3.35 (dd, J = 9.3, 9.7, 1H, H-30), 3.72 (dd,
J = 5.6, 11.6, 1H, H-60a), 3.89 (dd, J = 2.4, 11.6, 1H,
H-60b), 3.92 (dt, J = 2.5, 2.5, 4.6, 1H, H-1), 4.16 (q,
J = 7.1, 2H, H-16), 4.34 (d, J = 7.9, 1H, H-10), 5.14
(dq, J = 0.8, 0.8, 0.8, 1.5, 2H, H-12), 5.85 (m, J = 1.5,
1H, H-14), 6.81 (m, 2H, H-10), 7.15 (m, 2H, H-9).
13a/13b: IR (KBr): 3607 (w), 3534 (m), 1712 (s), 1664
(m), 1511 (s), 1329 (m), 1232 (s), 1177 (m), 1152 (s),
1093 (s), 1074 (s), 1030 (s), 1014 (s), 894 (w), 843 (w).
MS: m/z = 517 (14; [M+Na]+), 494 (4; [M]+), 391 (1),
333 (5), 315 (3), 233 (1), 149 (19), 127 (100), 105 (5),
99 (97), 79 (22), 57 (27). For C26H38O9 (494.59) calcu-
lated C, 63.14; H, 7.74. Found: C, 63.20; H, 7.69.
1
Compound 12a/12b: H NMR (CDCl3): 12a: 0.87 (m,
1H, H-3a), 1.05 (m, 1H, H-5a), 1.18 (m, 1H, H-6a),
1.20 (m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-17), 1.55
(m, 1H, H-5b), 1.57 (m, 1H, H-2), 1.63 (m, 1H, H-
3b), 1.72 (m, 1H, H-4b), 1.93 (m, 1H, H-6b), 2.00-
2.17 (m, 1H, H-7a), 2.20 (bt, J = 1.5, 3H, H-18), 3.08
(dd, J = 3.2, 13.5, 1H, H-7b), 3.22 (dt, J = 4.3, 9.6,
9.6, 1H, H-1), 3.92 (ddd, J = 1.3, 5.9, 6.2, 1H, H-50),
4.10 (dd, J = 6.2, 11.3, 1H, H-60a), 4.17 (q, J = 7.1,
2H, H-16), 4.22 (dd, J = 6.2, 11.3, 1H, H-60b), 4.48
(dq, J = 0.6, 0.6, 0.6, 1.5, 2H, H-12), 4.60 (d, J = 8.0,
1H, H-10), 5.04 (dd, J = 3.1, 10.5, 1H, H-30), 5.31
(dd, J = 8.0, 10.5, 1H, H-20), 5.39 (dd, J = 1.4, 3.1,
1H, H-40), 6.07 (m, J = 1.5, 1H, H-14), 6.81 (m, 2H,
H-10), 7.02 (m, 2H, H-9); signals (CH3CO-): 1.96 (s,
3H), 1.98 (s, 3H), 2.03 (s, 3H), 2.04 (s, 3H); 12b: 0.87
(m, 1H, H-3a), 1.05 (m, 1H, H-5a), 1.18 (m, 1H, H-
6a), 1.20 (m, 1H, H-4a), 1.29 (t, J = 7.1, 3H, H-17),
1.55 (m, 1H, H-5b), 1.57 (m, 1H, H-2), 1.63 (m, 1H,
H-3b), 1.72 (m, 1H, H-4b), 1.93 (m, 1H, H-6b), 2.00-
2.17 (m, 1H, H-7a), 2.20 (bt, J = 1.5, 3H, H-18), 3.20
(dd, J = 3.6, 13.2, 1H, H-7b), 3.32 (dt, J = 4.2, 9.7,
9.7, 1H, H-1), 3.88 (dt, J = 1.3, 6.2, 6.2, 1H, H-50),
4.11 (dd, J = 5.9, 11.1, 1H, H-60a), 4.17 (q, J = 7.1,
2H, H-16), 4.19 (dd, J = 6.2, 11.1, 1H, H-60b), 4.47
(dq, J = 0.6, 0.6, 0.6, 1.5, 2H, H-12), 4.55 (d, J = 7.9,
1H, H-10), 5.04 (dd, J = 3.1, 10.5, 1H, H-30), 5.20
(dd, J = 7.9, 10.5, 1H, H-20), 5.39 (dd, J = 1.4, 3.1,
1H, H-40), 6.06 (m, J = 1.5, 1H, H-14), 6.80 (m, 2H,
H-10), 7.09 (m, 2H, H-9); signals (CH3CO-): 1.99 (s,
3H), 2.00 (s, 3H), 2.04 (s, 3H), 2.06 (s, 3H). IR
(CCl4): 1757 (s), 1721 (m), 1665 (w), 1612 (w), 1511
(m), 1369 (s), 1328 (w), 1249 (s), 1048 (s), 1222 (s),
1150 (s), 1098 (m), 912 (w), 879 (w), 602 (w). MS: m/z =
685 (1; [M+Na]+), 662 (1; [M]+), 331 (70), 269 (8), 233
(51), 188 (24), 169 (81), 127 (63), 99 (100). For
C34H46O13 (662.74) calculated C, 61.62; H, 7.00.
Found: C, 60.99; H 6.87.
20
20
13a/13b: ½aꢁ ꢀ13.2 (c 0.25, CH3OH). 13a: ½aꢁ +14.0
D
D
20
D
(c 0.19, CH3OH). 13b: ½aꢁ ꢀ36.2 (c 0.17, CH3OH).
1
Compound 14a/14b: H NMR (CD3OD): 14a: 0.91 (m,
1H, H-3a), 1.07 (m, 1H, H-5a), 1.23 (m, 1H, H-6a),
1.25 (m, 1H, H-4a), 1.28 (t, J = 7.1, 3H, H-17), 1.60
(m, 1H, H-5b), 1.61 (m, 1H, H-2), 1.63 (m, 1H, H-3b),
1.73 (m, 1H, H-4b), 2.01 (dt, J = 0.7, 0.7, 1.4, 3H, H-
18), 2.13 (m, 1H, H-6b), 2.16 (dd, J = 9.9, 13.4, 1H,
H-7a), 3.23-3.40 (m, 5H, H-1, H-7b, H-30, H-40, H-50),
3.24 (dd, J = 7.9, 9.0, 1H, H-20), 3.68 (dd, J = 5.3,

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7135
1
11.8, 1H, H-60a), 3.85 (dd, J = 2.3, 11.8, 1H, H-60b),
4.17 (q, J = 7.1, 2H, H-16), 4.40 (d, J = 7.9, 1H, H-10),
5.14 (m, 2H, H-12), 5.84 (m, 1H, H-14), 6.81 (m, 2H,
H-10), 7.10 (m, 2H, H-9); 14b: 0.91 (m, 1H, H-3a),
1.07 (m, 1H, H-5a), 1.23 (m, 1H, H-6a), 1.25 (m, 1H,
H-4a), 1.28 (t, J = 7.1, 3H, H-17), 1.60 (m, 1H, H-5b),
1.61 (m, 1H, H-2), 1.63 (m, 1H, H-3b), 1.73 (m, 1H,
H-4b), 2.01 (dt, J = 0.7, 0.7, 1.4, 3H, H-18), 2.13 (m,
1H, H-6b), 2.23 (dd, J = 9.4, 13.8, 1H, H-7a), 3.23-
3.40 (m, 4H, H-7b, H-30, H-40, H-50), 3.22 (dd, J = 7.9,
9.0, 1H, H-20), 3.49 (m, w = 12.0, 1H, H-1), 3.70 (dd,
J = 5.6, 11.8, 1H, H-60 0a), 3.89 (dd, J = 2.3, 11.8, 1H,
H-60b), 4.17 (q, J = 7.1, 2H, H-16), 4.41 (d, J = 7.9,
1H, H-10), 5.14 (m, 2H, H-12), 5.84 (m, 1H, H-14),
6.82 (m, 2H, H-10), 7.09 (m, 2H, H-9). 14a/14b: IR
(KBr): 3597 (w), 3418 (m), 1706 (s), 1647 (m), 1612
(w), 1511 (s), 1341 (m), 1230 (s), 1177 (m), 1154 (s),
1095 (m), 1074 (s), 1038 (s), 1020 (s), 912 (w), 879 (w).
MS: m/z = 517 (12; [M+Na]+), 494 (3; [M]+), 391 (9),
333 (2), 315 (1), 269 (2), 233 (2), 219 (1), 167 (13), 149
(86), 127 (51), 105 (10), 99 (44), 79 (40), 57 (100). For
Compound 16a/16b: H NMR (CD3OD): 16a: 0.91 (m,
1H, H-3a), 1.07 (m, 1H, H-5a), 1.16 (m, 1H, H-6a),
1.27 (m, 1H, H-4a), 1.28 (t, J = 7.1, 3H, H-17), 1.58
(m, 1H, H-5b), 1.59 (m, 2H, H-2, H-3b), 1.73 (m, 1H,
H-4b), 2.14 (m, 1H, H-6b), 2.15 (dd, J = 10.0, 13.5,
1H, H-7a), 2.17 (bd, J = 1.4, 3H, H-18), 3.20-3.41 (m,
4H, H-7b, H-30, H-40, H-50), 3.24 (dd, J = 7.8, 9.0, 1H,
H-20), 3.24 (dt, J = 4.2, 9.8, 9.8, 1H, H-1), 3.68 (dd,
J = 5.2, 11.8, 1H, H-60a), 3.85 (dd, J = 2.2, 11.8, 1H,
H-60b), 4.15 (q, J = 7.1, 2H, H-16), 4.41 (d, J = 7.8,
1H, H-10), 4.48 (bd, J = 1.4, 2H, H-12), 6.01 (m,
J = 1.4, 1H, H-14), 6.83 (m, 2H, H-10), 7.11 (m, 2H,
H-9); 16b: 0.91 (m, 1H, H-3a), 1.07 (m, 1H, H-5a),
1.16 (m, 1H, H-6a), 1.27 (m, 1H, H-4a), 1.28 (t,
J = 7.1, 3H, H-17), 1.58 (m, 1H, H-5b), 1.59 (m, 2H,
H-2, H-3b), 1.73 (m, 1H, H-4b), 2.14 (m, 1H, H-6b),
2.17 (bd, J = 1.4, 3H, H-18), 2.24 (dd, J = 9.3, 13.6,
1H, H-7a), 3.20-3.41 (m, 3H, H-30, H-40, H-50), 3.22
(dd, J = 7.8, 9.0, 1H, H-20), 3.40 (dd, J = 3.7, 13.6, 1H,
H-7b), 3.50 (dt, J = 4.2, 10.0, 10.0, 1H, H-1), 3.70 (dd,
J = 5.7, 11.7, 1H, H-60a), 3.90 (dd, J = 2.3, 11.7, 1H,
H-60b), 4.15 (q, J = 7.1, 2H, H-16), 4.40 (d, J = 7.8,
1H, H-10), 4.48 (bd, J = 1.4, 2H, H-12), 6.01 (m,
J = 1.4, 1H, H-14), 6.84 (m, 2H, H-10), 7.10 (m, 2H,
H-9). 16a/16b: IR (KBr): 3593 (w), 3416 (m), 1712 (s),
1664 (m), 1611 (w), 1511 (s), 1328 (m), 1232 (s), 1177
(m), 1152 (s), 1095 (s), 1075 (s), 1040 (s), 1021 (s), 913
(w), 879 (w). MS: m/z = 517 (3; [M+Na]+), 495 (1;
[M+H]+), 459 (5), 413 (2), 391 (6), 333 (1), 315 (2),
306 (1), 233 (8), 167 (14), 149 (100), 127 (6), 99 (16),
71 (29), 57 (86). For C26H38O9 (494.59) calculated C,
63.14; H, 7.74. Found: C, 63.09; H, 7.55. 16a/16b:
C26H38O9 (494.59) calculated C, 63.14; H, 7.74. Found:
20
D
C, 63.52; H, 7.58. 14a/14b: ½aꢁ +12.3 (c 0.21, CH3OH).
20
D
0.14, CH3OH).
20
D
14a: ½aꢁ +40.0 (c 0.16, CH3OH). 14b: ½aꢁ ꢀ63.1 (c
1
Compound 15a/15b: H NMR (CD3OD): 15a: 1.25 (m,
1H, H-4a), 1.27 (t, J = 7.1, 3H, H-17), 1.32 (m, 1H, H-
3a), 1.41 (m, 1H, H-5a), 1.45 (m, 1H, H-6a), 1.52 (m,
1H, H-3b), 1.67 (m, 1H, H-4b), 1.72 (m, 1H, H-5b),
1.75 (m, 1H, H-2), 2.05 (m, 1H, H-6b), 2.17 (bd,
J = 1.5, 3H, H-18), 2.53 (dd, J = 8.5, 13.6, 1H, H-7a),
2.85 (dd, J = 6.5, 13.6, 1H, H-7b), 3.20 (ddd, J = 2.4,
5.6, 9.6, 1H, H-50), 3.26 (dd, J = 7.9, 9.2, 1H, H-20),
3.33 (t, J = 9.5, 1H, H-40), 3.38 (t, J = 9.3, 1H, H-30),
3.65 (dd, J = 5.6, 11.8, 1H, H-60a), 3.73 (dt, J = 2.5,
2.5, 4.6, 1H, H-1), 3.82 (dd, J = 2.4, 11.8, 1H, H-60b),
4.15 (q, J = 7.1, 2H, H-16), 4.34 (d, J = 7.9, 1H, H-
10), 4.53 (bd, J = 1.5, 2H, H-12), 6.01 (m, J = 1.5,
1H, H-14), 6.83 (m, 2H, H-10), 7.17 (m, 2H, H-9);
15b: 1.25 (m, 1H, H-4a), 1.27 (t, J = 7.1, 3H, H-17),
1.32 (m, 1H, H-3a), 1.33 (m, 1H, H-6a), 1.37 (m, 1H,
H-5a), 1.52 (m, 1H, H-3b), 1.67 (m, 1H, H-4b), 1.69
(m, 1H, H-2), 1.75 (m, 1H, H-5b), 1.97 (m, 1H, H-
6b), 2.17 (bd, J = 1.5, 3H, H-18), 2.43 (dd, J = 7.8,
13.7, 1H, H-7a), 2.82 (dd, J = 6.7, 13.7, 1H, H-7b),
3.25 (dd, J = 7.9, 9.3, 1H, H-20), 3.26 (ddd, J = 2.5,
5.6, 9.6, 1H, H-50), 3.27 (t, J = 9.7, 1H, H-40), 3.36
(dd, J = 9.3, 9.7, 1H, H-30), 3.72 (dd, J = 5.6, 11.6,
1H, H-60a), 3.89 (dd, J = 2.5, 11.6, 1H, H-60b), 3.92
(dt, J = 2.6, 2.6, 4.6, 1H, H-1), 4.15 (q, J = 7.1, 2H,
H-16), 4.33 (d, J = 7.9, 1H, H-10), 4.53 (bd, J = 1.5,
2H, H-12), 6.01 (m, J = 1.5, 1H, H-14), 6.84 (m, 2H,
H-10), 7.16 (m, 2H, H-9). 15a/15b: IR (KBr): 3594
(w), 3417 (m), 1705 (s), 1647 (w), 1611 (w), 1511 (s),
1340 (m), 1231 (s), 1177 (m), 1154 (s), 1093 (m), 1074
(s), 1037 (s), 1018 (s), 894 (w), 846 (w). MS:
m/z = 517 (7; [M+Na]+), 495 (1; [M+H]+), 391 (2),
191 (6), 149 (29), 127 (6), 105 (8), 79 (22), 57 (100).
20
D
20
D
½aꢁ ꢀ 17.5 (c 0.28, CH3OH). 16a: ½aꢁ ꢀ 5.0 (c 0.18,
20
D
CH3OH). 16b: ½aꢁ ꢀ 30.5 (c 0.15, CH3OH).
1
Compound 17a/17b: H NMR (CD3OD): 17a: 1.28 (t,
J = 7.1, 3H, H-17), 1.29 (m, 1H, H-4a), 1.34 (m, 1H,
H-3a), 1.36 (m, 1H, H-5a), 1.39 (m, 1H, H-6a), 1.52
(m, 1H, H-3b), 1.64 (m, 1H, H-4b), 1.73 (m, 1H, H-
5b), 1.75 (m, 1H, H-2), 2.00 (bd, J = 1.3, 3H, H-18),
2.03 (m, 1H, H-6b), 2.52 (dd, J = 8.4, 13.7, 1H, H-7a),
2.85 (dd, J = 6.5, 13.7, 1H, H-7b), 3.44 (dt, J = 1.1,
6.2, 6.2, 1H, H-50), 3.49 (dd, J = 3.5, 9.7, 1H, H-30),
3.60 (dd, J = 7.8, 9.7, 1H, H-20), 3.69 (dd, J = 6.4,
11.2, 1H, H-60a), 3.72 (dd, J = 6.1, 11.2, 1H, H-60b),
3.74 (dt, J = 2.4, 2.4, 4.8, 1H, H-1), 3.84 (dd, J = 1.1,
3.4, 1H, H-40), 4.16 (q, J = 7.1, 2H, H-16), 4.28 (d,
J = 7.7, 1H, H-10), 5.14 (dq, J = 0.6, 0.6, 0.6, 1.7, 2H,
H-12), 5.85 (m, J = 1.4, 1H, H-14), 6.80 (m, 2H, H-
10), 7.15 (m, 2H, H-9); 17b: 1.28 (t, J = 7.1, 3H, H-
17), 1.29 (m, 1H, H-4a), 1.32 (m, 1H, H-6a), 1.34 (m,
2H, H-3a, H-5a), 1.52 (m, 1H, H-3b), 1.64 (m, 1H, H-
4b), 1.69 (m, 1H, H-2), 1.77 (m, 1H, H-5b), 1.96 (m,
1H, H-6b), 2.00 (bd, J = 1.3, 3H, H-18), 2.42 (dd,
J = 7.8, 13.6, 1H, H-7a), 2.81 (dd, J = 6.6, 13.6, 1H,
H-7b), 3.48 (dt, J = 1.1, 6.2, 6.2, 1H, H-50), 3.48 (dd,
J = 3.4, 9.7, 1H, H-30), 3.57 (dd, J = 7.7, 9.7, 1H, H-
20), 3.75 (dd, J = 6.1, 11.0, 1H, H-60a), 3.79 (dd,
J = 6.3, 11.0, 1H, H-60b), 3.88 (dt, J = 1.1, 3.5, 1H, H-
40), 3.91 (dt, J = 2.5, 2.5, 4.5, 1H, H-1), 4.16 (q,
J = 7.1, 2H, H-16), 4.30 (d, J = 7.8, 1H, H-10), 5.14
(dq, J = 0.6, 0.6, 0.6, 1.7, 2H, H-12), 5.84 (m, J = 1.4,
1H, H-14), 6.79 (m, 2H, H-10), 7.14 (m, 2H, H-9).
For C26H38O9 (494.59) calculated C, 63.14; H, 7.74.
20
D
Found: C, 63.02; H, 7.45. 15a/15b: ½aꢁ ꢀ11.0 (c
20
20
0.27, CH3OH). 15a: ½aꢁ + 5.7 (c 0.17, CH3OH). 15b:
D
½aꢁ ꢀ 27.2 (c 0.16, CH3OH).
D

7136
Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
17a/17b: IR (KBr): 3585 (w), 3433 (m), 1705 (s), 1648
(w), 1611 (w), 1511 (s), 1340 (m), 1238 (s), 1177 (s),
1154 (s), 1098 (m), 1074 (s), 1062 (s), 1038 (s), 898 (w),
840 (w). MS: m/z = 495 (2; [M+H]+), 333 (2), 269 (4),
221 (3), 187 (3), 149 (4), 127 (48), 99 (100). For
1.34 (m, 1H, H-5a), 1.51 (m, 1H, H-3b), 1.65 (m, 1H,
H-4b), 1.69 (m, 1H, H-2), 1.77 (m, 1H, H-5b), 1.96
(m, 1H, H-6b), 2.17 (bd, J = 1.4, 3H, H-18), 2.43 (dd,
J = 7.8, 13.7, 1H, H-7a), 2.82 (dd, J = 6.6, 13.7, 1H,
H-7b), 3.48 (dt, J = 1.2, 6.2, 6.2, 1H, H-50), 3.48 (dd,
J = 3.4, 9.7, 1H, H-30), 3.58 (dd, J = 7.8, 9.7, 1H, H-
20), 3.76 (dd, J = 6.2, 11.0, 1H, H-60a), 3.80 (dd,
J = 6.2, 11.0, 1H, H-60b), 3.88 (dt, J = 1.2, 3.4, 1H, H-
40), 3.91 (dt, J = 2.5, 2.5, 4.8, 1H, H-1), 4.15 (q,
J = 7.1, 2H, H-16), 4.30 (d, J = 7.7, 1H, H-10), 4.53
(bd, J = 1.4, 2H, H-12), 6.01 (m, J = 1.4, 1H, H-14),
6.82 (m, 2H, H-10), 7.17 (m, 2H, H-9). 19a/19b: IR
(KBr): 3584 (w), 3433 (m), 1710 (s), 1664 (m), 1611
(w), 1511 (s), 1329 (m), 1231 (s), 1152 (s), 1099 (m),
1075 (s), 1061 (s), 1042 (s), 898 (w), 844 (w). MS:
m/z = 495 (1; [M+H]+), 333 (3), 315 (8), 233 (22), 187
(5), 149 (14), 127 (29), 99 (100), 73 (21). For C26H38O9
(494.59) calculated C, 63.14; H, 7.74. Found: C, 63.12;
C26H38O9 (494.59) calculated C, 63.14; H, 7.74. Found:
20
D
C ,63.23; H, 7.68. 17a/17b: ½aꢁ ꢀ 10.1 (c 0.25, CH3OH).
20
D
0.17, CH3OH).
20
D
17a: ½aꢁ +17.0 (c 0.15, CH3OH). 17b: ½aꢁ ꢀ36.1 (c
1
Compound 18a/18b: H NMR (CD3OD): 18a: 0.90 (m,
1H, H-3a), 1.08 (m, 1H, H-5a), 1.21 (m, 1H, H-6a),
1.28 (t, J = 7.1, 3H, H-17), 1.25 (m, 1H, H-4a), 1.57
(m, 2H, H-2, H-5b), 1.61 (m, 1H, H-3b), 1.72 (m, 1H,
H-4b), 2.00 (dt, J = 0.7, 0.7, 1.6, 3H, H-18), 2.14 (m,
1H, H-6b), 2.14 (dd, J = 9.9, 13.7, 1H, H-7a), 3.31 (dt,
J = 4.2, 9.5, 9.5, 1H, H-1), 3.40 (dd, J = 3.4, 13.4, 1H,
H-7b), 3.47 (dd, J = 3.4, 9.8, 1H, H-30), 3.50 (dt,
J = 1.2, 6.3, 6.3, 1H, H-50), 3.57 (dd, J = 7.7, 9.8, 1H,
H-20), 3.72 (dd, J = 6.3, 11.1, 1H, H-60a), 3.75 (dd,
J = 6.1, 11.1, 1H, H-60b), 3.85 (dd, J = 1.2, 3.4, 1H, H-
40), 4.16 (q, J = 7.1, 2H, H-16), 4.37 (d, J = 7.5, 1H,
H-10), 5.14 (dq, J = 0.7, 0.7, 0.7, 1.6, 2H, H-12), 5.85
(m, J = 1.6, 1H, H-14), 6.80 (m, 2H, H-10), 7.09 (m,
2H, H-9); 18b: 0.90 (m, 1H, H-3a), 1.08 (m, 1H, H-
5a), 1.21 (m, 1H, H-6a), 1.28 (t, J = 7.1, 3H, H-17),
1.25 (m, 1H, H-4a), 1.57 (m, 2H, H-2, H-5b), 1.61 (m,
1H, H-3b), 1.72 (m, 1H, H-4b), 2.00 (dt, J = 0.7, 0.7,
1.6, 3H, H-18), 2.14 (m, 1H, H-6b), 2.21 (dd, J = 9.4,
13.4, 1H, H-7a), 3.24 (dd, J = 3.6, 13.7, 1H, H-7b),
3.49 (dd, J = 3.4, 9.7, 1H, H-30), 3.49 (dt, J = 4.3, 9.6,
9.6, 1H, H-1), 3.50 (dt, J = 1.2, 6.2, 6.2, 1H, H-50),
3.55 (dd, J = 7.5, 9.7, 1H, H-20), 3.76 (d, J = 6.3, 2H,
H-60), 3.86 (dd, J = 1.2, 3.4, 1H, H-40), 4.16 (q,
J = 7.1, 2H, H-16), 4.36 (d, J = 7.7, 1H, H-10), 5.14
(dq, J = 0.7, 0.7, 0.7, 1.6, 2H, H-12), 5.85 (m, J = 1.6,
1H, H-14), 6.81 (m, 2H, H-10), 7.08 (m, 2H, H-9).
18a/18b: IR (KBr): 3590 (w), 3425 (m), 1705 (s), 1648
(m), 1611 (w), 1511 (s), 1340 (m), 1229 (s), 1177 (m),
1154 (s), 1073 (s), 1060 (s), 1048 (m), 1038 (s), 910 (w),
879 (w). MS: m/z = 495 (1; [M+H]+), 333 (5), 315 (2),
269 (3), 233 (6), 187 (3), 149 (6), 127 (87), 113 (10), 99
20
20
D
H, 7.52. 19a/19b: ½aꢁ ꢀ9.9 (c 0.22, CH3OH). 19a: ½aꢁ
D
20
D
+7.1 (c 0.15, CH3OH). 19b: ½aꢁ ꢀ26.0 (c 0.14, CH3OH).
1
Compound 20a/20b: H NMR (CD3OD): 20a: 0.92 (m,
1H, H-3a), 1.08 (m, 1H, H-5a), 1.26 (m, 1H, H-4a),
1.27 (t, J = 7.1, 3H, H-17), 1.28 (m, 1H, H-6a), 1.56
(m, 1H, H-5b), 1.60 (m, 1H, H-2), 1.62 (m, 1H, H-3b),
1.70 (m, 1H, H-4b), 2.18 (bd, J = 1.5, 3H, H-18), 2.22
(m, 1H, H-6b), 2.22 (dd, J = 9.6, 13.4, 1H, H-7a), 3.32
(dt, J = 4.5, 9.5, 9.5, 1H, H-1), 3.41 (dd, J = 3.4, 13.4,
1H, H-7b), 3.47 (dd, J = 3.4, 9.7, 1H, H-30), 3.50 (dt,
J = 1.2, 6.2, 6.2, 1H, H-50), 3.57 (dd, J = 7.6, 9.7, 1H,
H-20), 3.86 (dd, J = 1.2, 3.4, 1H, H-40), 3.72 (dd,
J = 6.4, 11.3, 1H, H-60a), 3.75 (dd, J = 6.1, 11.3, 1H,
H-60b), 4.15 (q, J = 7.1, 2H, H-16), 4.37 (d, J = 7.6,
1H, H-10), 4.53 (bd, J = 1.5, 2H, H-12), 6.03 (m,
J = 1.5, 1H, H-14), 6.87 (m, 2H, H-10), 7.11 (m, 2H,
H-9); 20b: 0.92 (m, 1H, H-3a), 1.08 (m, 1H, H-5a),
1.26 (m, 1H, H-4a), 1.27 (t, J = 7.1, 3H, H-17), 1.36
(m, 1H, H-6a), 1.54 (m, 1H, H-2), 1.56 (m, 1H, H-5b),
1.62 (m, 1H, H-3b), 1.70 (m, 1H, H-4b), 2.14 (m, 1H,
H-6b), 2.14 (dd, J = 10.1, 13.7, 1H, H-7a), 2.17 (bd,
J = 1.5, 3H, H-18), 3.24 (dd, J = 3.6, 13.7, 1H, H-7b),
3.48 (dt, J = 4.4, 9.6, 9.6, 1H, H-1), 3.49 (dd, J = 3.4,
9.7, 1H, H-30), 3.50 (dt, J = 1.2, 6.2, 6.2, 1H, H-50),
3.55 (dd, J = 7.7, 9.7, 1H, H-20), 3.77 (d, J = 6.2, 2H,
H-60), 3.85 (dd, J = 1.2, 3.4, 1H, H-40), 4.15 (q,
J = 7.1, 2H, H-16), 4.36 (d, J = 7.7, 1H, H-10), 4.53
(bd, J = 1.5, 2H, H-12), 6.01 (m, J = 1.5, 1H, H-14),
6.88 (m, 2H, H-10), 7.10 (m, 2H, H-9). 20a/20b: IR
(KBr): 3591 (w), 3425 (m), 1712 (s), 1664 (w), 1611
(w), 1511 (s), 1329 (m), 1231 (s), 1177 (m), 1153 (s),
1098 (m), 1074 (s), 1040 (s), 1002 (m), 880 (w). MS:
m/z = 495 (3; [M+H]+), 391 (3), 333 (10), 315 (10), 233
(40), 187 (13), 149 (71), 127 (35), 99 (100), 73 (33). For
(100), 73 (13). For C26H38O9 (494.59) calculated C,
20
D
63.14; H, 7.74. Found: C, 63.27; H, 7.52. 18a/18b: ½aꢁ
20
20
ꢀ10.4 (c 0.20, CH3OH). 18a: ½aꢁ +42.0 (c 0.16,
D
CH3OH). 18b: ½aꢁ ꢀ63.0 (c 0.19, CH3OH).
D
1
Compound 19a/19b: H NMR (CD3OD): 19a: 1.25 (m,
1H, H-4a), 1.27 (t, J = 7.1, 3H, H-17), 1.33 (m, 1H, H-
3a), 1.36 (m, 1H, H-5a), 1.39 (m, 1H, H-6a), 1.51 (m,
1H, H-3b), 1.65 (m, 1H, H-4b), 1.74 (m, 1H, H-5b),
1.75 (m, 1H, H-2), 2.03 (m, 1H, H-6b), 2.17 (bd,
J = 1.4, 3H, H-18), 2.53 (dd, J = 8.4, 13.6, 1H, H-7a),
2.86 (dd, J = 6.5, 13.6, 1H, H-7b), 3.44 (dt, J = 1.2,
6.2, 6.2, 1H, H-50), 3.49 (dd, J = 3.4, 9.7, 1H, H-30),
3.60 (dd, J = 7.7, 9.7, 1H, H-20), 3.69 (dd, J = 6.3,
11.2, 1H, H-60a), 3.72 (dd, J = 6.1, 11.2, 1H, H-60b),
3.74 (dt, J = 2.4, 2.4, 4.9, 1H, H-1), 3.84 (dd, J = 1.2,
3.4, 1H, H-40), 4.15 (q, J = 7.1, 2H, H-16), 4.28 (d,
J = 7.8, 1H, H-10), 4.53 (bd, J = 1.4, 2H, H-12), 6.01
(m, J = 1.4, 1H, H-14), 6.83 (m, 2H, H-10), 7.16 (m,
2H, H-9); 19b: 1.25 (m, 1H, H-4a), 1.27 (t, J = 7.1,
3H, H-17), 1.28 (m, 1H, H-6a), 1.33 (m, 1H, H-3a),
C26H38O9 (494.59) calculated C, 63.14; H, 7.74. Found:
20
D
C, 63.07; H, 7.80. 20a/20b: ½aꢁ ꢀ13.9 (c 0.24, CH3OH).
20
20a/20b: ½aꢁ ꢀ1.0 (c 0.18, CH3OH). 20a/20b: ½aꢁ
20
D
D
ꢀ25.8 (c 0.14, CH3OH).
4.4. Methodology of the screening tests on Pyrrhocoris
apterus
The red firebug (P. apterus) is a well-known experimen-
tal model,27 kept in breeding chambers on linden seeds

Z. Wimmer et al. / Bioorg. Med. Chem. 15 (2007) 7126–7137
7137
ˇ
7. Wimmer, Z.; Saman, D.; Kuldova, J.; Hrdy, I.; Bennet-
´
tova, B. Bioorg. Med. Chem. 2002, 10, 1305.
´
at a constant rearing temperature (27 ꢁC) using a photo-
period set up for the constant long day (18 h light/6 h
dark). For the per-oral application, drinking assay13
was used. Each compound was diluted into four concen-
trations (0.01, 0.1, 1 and 10 lg in 22 lL of the tested
solution per individual), and offered to the insects during
their last larval instar. The dilution rate was based on
the knowledge that water consumption for the last larval
instar of this species is approximately 22 lL for one indi-
vidual in the first day after ecdysis.28 Glass vials contain-
ing the test solutions were plugged with pieces of cotton
and offered to 30 specimens in a Petri dish. In summary,
150 specimens (for the reference experiment and for the
experiments with four above-given concentrations of the
tested compounds) were used for one tested compound.
The results of the biological screening tests are summa-
rized in Table 5.
´
8. Hrdy´, I.; Kuldova, J.; Wimmer, Z. Pest Manag. Sci. 2004,
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60, 1035.
9. Hrdy´, I.; Kuldova, J.; Hanus, R.; Wimmer, Z. Pest
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Manag. Sci. 2006, 62, 848.
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10. Wimmer, Z.; Romanuk, M. Coll. Czech. Chem. Commun.
1981, 46, 2573.
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11. Kuldova, J.; Hrdy, I.; Wimmer, Z. Pesticide Sci. 1994, 41,
319.
´
ˇ
12. Slama, K.; Romanuk, M. Insect Biochem. 1976, 6, 579.
13. Slama, K.; Wimmer, Z.; Romanuk, M. Hoppe-Seyler’s Z.
´
ˇ
Physiol. Chem. 1978, 359, 1407.
ˇ
14. Wimmer, Z.; Saman, D.; Zarevu´cka, M.; Wimmerova, M.
´
Tetrahedron: Asymmetry 2005, 16, 2810.
15. Schmidt, R. R. Angew. Chem. Int. Ed. Engl. 1986, 25,
212.
16. Schmidt, R. R.; Jung, K.-H. Oligosaccharide synthesis
with trichloroacetimidates. In Preparative Carbohydrate
Chemistry; Hanessian, S., Ed.; Dekker: New York, 1997;
pp 283–312.
ˇ
Acknowledgement
´
17. Wimmer, Z.; Pechova, L.; Saman, D. Molecules 2004, 9,
902.
ˇ
18. Saman, D.; Wimmerova, M.; Wimmer, Z. Coll. Czech.
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Chem. Commun. 2006, 71, 1186.
The authors thank the Ministry of Education of the
Czech Republic (Project D29.001) for financial support
of a part of this work, and the EU (COST Project
D29/0014/04) for mobility funds.
ˇ
´
´
19. Saman, D.; Kratina, P.; Moravcova, J.; Wimmerova, M.;
Wimmer, Z. Coll. Czech. Chem. Commun. 2006, 71,
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20. Kuhn, M.; von Wartburg, A. Helv. Chim. Acta 1968, 51,
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