Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

Article abstract of DOI:10.3762/bjoc.7.189

Phenyl 3,4,6-tri-O-benzyl-2-O-(3-carboxypropionyl)-1-thio-β-D- galactopyranoside (1) was condensed via its pentafluorophenyl ester 2 with 5-aminopentyl (4a), 4-aminobutyl (4b), 3-aminopropyl (4c) and 2-aminoethyl 4,6-O-benzylidene-β-D-glucopyranoside (4d), prepared from the corresponding N-Cbz protected glucosides 3a-d, to give the corresponding 2-[3- (alkylcarbamoyl)propionyl] tethered saccharides 5a-d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the tethered β(1→3) linked disaccharides 6a-c, the a(1→3) linked disaccharides 7a-d and the a(1→2) linked disaccharide 8d in ratios depending upon the ring size formed during glycosylation. No β(1→2) linked disaccharides were formed. Molecular modeling of saccharides 6-8 revealed that a strong aromatic stacking interaction between the aromatic parts of the benzyl and benzylidene protecting groups in the galactosyl and glucosyl moieties was mainly responsible for the observed regioselectivity and anomeric selectivity of the ring-closing glycosylation step.

Full text of DOI:10.3762/bjoc.7.189

Dependency of the regio- and stereoselectivity
of intramolecular, ring-closing glycosylations
upon the ring size
Patrick Claude1, Christian Lehmann2 and Thomas Ziegler*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 1609–1619.
1Institute of Organic Chemistry, University of Tübingen, Auf der
Morgenstelle 18, 72076 Tübingen, Germany and 2Institute for Organic
Chemistry, University of Lausanne BCH-Dorigny, CH-1015 Lausanne,
Switzerland
doi:10.3762/bjoc.7.189
Received: 18 July 2011
Accepted: 08 November 2011
Published: 01 December 2011
Email:
Christian Lehmann - lehmannc.3d@a3.epfl.ch; Thomas Ziegler* -
thomas.ziegler@uni-tuebingen.de
Associate Editor: S. Flitsch
© 2011 Claude et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
intramolecular glycosylation; molecular modeling; prearranged
glycosides
Abstract
Phenyl 3,4,6-tri-O-benzyl-2-O-(3-carboxypropionyl)-1-thio-β-D-galactopyranoside (1) was condensed via its pentafluorophenyl
ester 2 with 5-aminopentyl (4a), 4-aminobutyl (4b), 3-aminopropyl (4c) and 2-aminoethyl 4,6-O-benzylidene-β-D-glucopyranoside
(4d), prepared from the corresponding N-Cbz protected glucosides 3a–d, to give the corresponding 2-[3-(alkylcarbamoyl)propion-
yl] tethered saccharides 5a–d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the
tethered β(1→3) linked disaccharides 6a–c, the α(1→3) linked disaccharides 7a–d and the α(1→2) linked disaccharide 8d in ratios
depending upon the ring size formed during glycosylation. No β(1→2) linked disaccharides were formed. Molecular modeling of
saccharides 6–8 revealed that a strong aromatic stacking interaction between the aromatic parts of the benzyl and benzylidene
protecting groups in the galactosyl and glucosyl moieties was mainly responsible for the observed regioselectivity and anomeric
selectivity of the ring-closing glycosylation step.
Introduction
Intramolecular O-glycosidic bond formation of tethered forms intramolecularly. Three different concepts for the
glycosyl donors and acceptors (prearranged glycosides) resem- intramolecularization of glycosylation reactions have been
bles to some extent enzyme-catalyzed glycosylation reactions studied so far. For recent reviews on this subject see [1-4]. In
where the glycosyl donor and glycosyl acceptor are first bound the “leaving-group-based concept”, the glycosyl acceptor is at-
in the active site of an enzyme and thus, the glycosidic bond tached to the leaving group of the glycosyl donor and O-glyco-
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sidic bond formation occurs synchronously to the cleavage of Results and Discussion
the leaving group [5-9]. In the “aglycon-delivery concept”, the For the preparation of the prearranged glycosides 5, we started
glycosyl acceptor is attached to a labile acetal [10-14] or sily- from phenyl 3,4,6-tri-O-benzyl-2-O-(3-carboxypropionyl)-1-
lene group [15-17], which is cleaved and the glycosyl acceptor thio-β-D-galactopyranoside (1), which was prepared in three
is “delivered” to the anomeric center upon its activation. In the steps from 3,4,6-tri-O-benzyl-1,2-O-methoxyethylidene-α-D-
“prearranged-glycoside concept”, the sole true intramolecular galactopyranoside as previously described [31] and condensed
glycosylation approach which was developed in our [18-20] and with pentafluorophenol (dicyclohexylcarbodiimide, ethyl
Valverde’s group [21], glycosyl donor and acceptor are linked acetate, 0 °C) to afford the pentafluorophenyl ester 2 in 87%
by a stable tether attached to positions not directly involved in yield. Aminoalkyl 4,6-O-benzylidene-β-D-glucopyranosides 4
the glycosylation step. Upon activation of the leaving group, an were prepared from the corresponding Z-protected glucosides 3.
intramolecular, ring-closing condensation occurs affording a Previously, we prepared 5-(benzyloxycarbonylamino)pentyl
tethered saccharide (Figure 1).
4,6-O-benzylidene-β-D-glucopyranoside (3a) by acetalation of
5-(benzyloxycarbonylamino)pentyl β-D-glucopyranoside with
benzaldehyde and ZnCl2 [32]. Here, we used the more conve-
nient method for the acetalation step with benzaldehyde
dimethyl acetal (PhCH(OMe)2, cat. TsOH, MeCN, 25 °C) [33],
which gave 3a in 71% yield. Selective removal of the Z group
from 3a was a rather delicate task because the benzylidene
group must remain unaffected. After careful optimization,
hydrogenation of 3a with Lindlar catalyst (Pd on BaCO3) in
ethanol at room temperature gave 4a in 91% yield, which was
sufficiently pure to be used in the next step without further
purification. No hydrogenolysis of the benzylidene group was
observed under these conditions. Compound 3b has not been
described in the literature so far. It was prepared by first gluco-
Figure 1: Schematic representation of the “prearranged-glycoside
concept” for intramolecular, ring-closing glycosylation.
Despite the fact that the “prearranged-glycoside concept” for sylating 4-(benzyloxycarbonylamino)butanol [34] with 2,3,4,6-
intramolecular glycosylation has been successfully applied to tetra-O-benzoyl-α-D-glucopyranosyl trichloroacetimidate [35]
the construction of glycosidic bonds that are otherwise difficult (cat. TMSOTf, CH2Cl2, −10 °C, 2 h, 68%). Next, Zemplén
to establish (i.e., β-D-mannosidic and β-L-rhamnosidic bonds) deacylation of the intermediate glucoside (cat. NaOMe, MeOH,
and to the synthesis of complex oligosaccharides [22-24], the 25 °C, 16 h, 97%) and acetalation as described for compound
distinct effects which govern the regio- and stereoselectivity of 3a afforded compound 3b in 77% yield. Hydrogenation of the
the intramolecular formation of glycosidic bonds remain enig- latter with Lindlar catalyst then gave 4b in 80% yield. Simi-
matic. Both, the nature and the torsional flexibility of the tether larly, compounds 4c and 4d were prepared by hydrogenolysis of
and the tethered positions of the glycosyl donor and acceptor, as the known Z-protected glucosides 3c [33] and 3d [36]. Finally,
well as the size of the ring (that forms during the intramolec- compounds 4a–d were condensed with pentafluorophenyl ester
ular glycosylation step), the solvent, and the activation proce- 2 (ethyl acetate, 25 °C, 16 h) to afford the prearranged glyco-
dure all seem to play a crucial role in this respect [3,25,26]. sides 5a–d in 78–89% yield (Figure 2). As the condensation of
Previously, we have also shown for intramolecular mannosyla- ester 2 and amines 4 progressed, the products 5 precipitated
tions that double diastereodifferentiation is responsible in part from the solvent due to their poor solubility in ethyl acetate.
for the anomeric selectivity of such intramolecular glycosyla- This, however, facilitated the workup of the reaction mixtures
tions, although the exact cause of this effect has not been unam- significantly, as the prearranged glycosides 5 was isolated by
biguously identified so far [27]. Therefore, we prepared a series simple filtration and purified by recrystallization.
of prearranged glycosides constructed out of a 1-thio-galactosyl
donor and a 4,6-O-benzylidene-glucose acceptor tethered by All prearranged glycosides 5 were intramolecularly glyco-
peptide-bond-containing linkers of variable size, in order to sylated by activating the phenylthio group with the NIS-
study systematically the parameters influencing the outcome of TMSOTf reagent (Scheme 1) [37]. Attention had to be paid to
the intramolecular, ring-closing glycosylation step. In order to the choice of solvent, because the tethered glycosides 5 were
further provide a rationalization for the observed regio- and only poorly soluble in most solvents that are usually applied for
stereochemistry of the reaction, we also performed a molecular glycosylations with thioglycosides under activation with NIS.
modeling study, applying a force-field that was developed for Best results were obtained with a 1:1 mixture of CH2Cl2 and
general use in organic and pharmaceutical chemistry [28-30].
MeCN. All intramolecular couplings proceeded smoothly at
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Figure 2: Structures of compounds 1–5.
Scheme 1: Intramolecular, ring-closing glycosylation of prearranged glycosides 5a–d.
−5 °C within one hour. The products 6−8 were purified by was proven by HMBC NMR experiments, which revealed a
conventional chromatography on silica gel with mixtures of weak 3J-CH-correlation between H-1 of the galactosyl residues
CH2Cl2 and acetone as the eluent.
and C-3 of the glucosyl residues. The structure of 6a was
further proven by the opening of the peptide bridge at the ester
For the prearranged glycoside 5a, only the β(1→3)-linked prod- function, to give β(1→3)-linked disaccharide 9 in 84% yield
uct 6a (50%) and the α(1→3)-linked product 7a (6%) were (Scheme 2). Similar results were obtained for the intramolec-
obtained upon intramolecular glycosylation, forming an ular glycosylation of prearranged glycoside 5b, which afforded
18-membered macrocyclic ring. No (1→2)-linked disaccha- the β(1→3)-linked 17-membered macrocyclic ring 6b in 58%
rides 8 were detected. The structures of 6a and 7a were unam- yield and the corresponding α(1→3)-linked ring 7b in 8% yield.
biguously assigned by NMR spectroscopy. In compound 6a C-1 Again, no (1→2)-linked disaccharides 8 were found in this
of the galactosyl residue resonated at 103.2 ppm, indicating a case, and the structures of 6b and 7b were unambiguously
β-linkage, while in compound 7a it resonated at 96.6 ppm, indi- assigned by NMR spectroscopy showing C-1 of the galactose
cating an α-linkage. The (1→3)-linkage for both disaccharides residue at 102.8 ppm for 6b and at 94.7 ppm for 7b. HMBC
Scheme 2: Ring opening of compound 6a.
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NMR experiments revealed 3J-CH-correlation between C-1 of glycosylation between a glycosyl donor and an acceptor that
the galactosyl residues and H-3 of the glucosyl residues. For the are tethered by a specially designed tripeptide through their
prearranged glycoside 5c, the results for the intramolecular respective 6-OH groups, depends on the peptide tether (peptide-
16-membered ring-forming glycosylation were also similar. templated saccharide synthesis) [41,42]. Therefore, in order to
Only the β(1→3)-linked disaccharide 6c (58%) and the understand these factors better, we performed a molecular
α(1→3)-linked disaccharide 7c (15%) were obtained, although modeling study for the intramolecular glycosylation of
7c was contaminated with traces of 6c. However, the structures the prearranged glycosides 5 and their cyclization products
of both 6c and 7c were again unambiguously assigned by NMR 6–8.
spectroscopy showing C-1 of the galactose residue at 102.7 ppm
for 6c and at 95.4 ppm for 7c, and significant weak 3J-CH- Molecular modeling studies
correlations between H-1 of the galactosyl residue and C-3 of Molecular models of the intramolecular glycosylation products
the glucosyl residue in 6c and C-1 of the galactosyl residue and 6–8 were built by using the molecular modeling program suite
H-3 of the glucosyl residue in 7c.
Moloc [28,29]. First, the β(1→3)-selective cyclization junction
was modelled and energy minimized in a recently reparame-
Surprisingly, the prearranged glycoside 5d gave no β(1→3)- trized version of the MAB force field [30], revealing that a
linked disaccharide 6d and only a small amount (13%) of the strong aromatic triad is formed between the 4,6-O-benzylidene
corresponding α(1→3)-linked 15-membered ring 7d. Instead, group of the glucose moieties and the 4- and 6-O-benzylether
the 14-membered α(1→2)-linked ring 8d was formed as the groups of the adjacent galactose residues (Figure 4).
major product and was isolated in 59% yield. Here, no β(1→2)-
linked product was detected. The α(1→2)-linkage for 8d was
evident from its NMR spectra showing a signal at 97.3 ppm for
C-1 of the galactosyl residue and a weak 3J-CH-correlation
between C-1 of the galactosyl residue and H-2 of the glucosyl
residue. Likewise, compound 7d showed C-1 of its galactosyl
residue resonating at 97.2 ppm and a weak 3J-CH-correlation
between C-1 of the galactosyl and H-3 of the glucosyl residue.
The results obtained in this study mirror to some extent the
trend observed by Fairbanks for the intramolecular mannosyla-
tion of compound 10, where the donor and the acceptor were
tethered at their 6-positions by di- through to tetrapeptides
(Figure 3) [38-40]. As observed in our cases, the size of the ring
that forms during intramolecular glycosylation influences
the anomeric outcome of the glycosylation. However, the
distinct regio- and stereoselectivities in such cases are also
strongly influenced by the nature of the tether and thus, by the
preferred conformations that the prearranged glycosides adopt
Figure 4: Isolated β(1→3)-glycosidic linkage favored by triad aromatic-
stacking interactions (ASI).
during the ring-closing condensation. Likewise, Warriner
showed that the anomeric selectivity of an intramolecular
Figure 3: Intramolecular glycosylation of peptide-tethered mannosides according to Fairbanks [38-40].
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Further, the main glycosylation products 6–8 for interlinking related with intra- and interresidual molecular hydrogen
chains (CH2)n with n = 5, 4, 3, 2 were constructed and energy bonding and non-bonding ASI terms in the most stable product
minimized (Figure 5). A strain-free β(1→3)-junction is possible conformation.
for all constitutions, whereby the family of conformations
(including the case n = 2) is compatible with the aforemen- Mechanistically, the complex reaction is thought to be initiated
tioned stacking effect. It is expected, that the hydroxy group at by a fast [43], exergonic glycosyl cation formation, which is
position 2 of disaccharide 6a is buried within the ring, and thus, then followed by the comparatively slow, entropy-reducing
is less reactive and hence difficult to acylate or to glycosylate: intramolecular cyclization step. Within the frame of an overall
Indeed, all attempts to benzoylate the disaccharide 6a under SN1 reaction, the cyclization step is regarded as the rate-deter-
various conditions failed.
mining step; therefore, the transition state for the nucleophilic
addition to the glycosyl cyclic oxonium intermediate may allow
In spite of this favourable arrangement, for the case n = 2 for a rationalization of the observed regioselectivity over the
predominant formation of the α(1→2)-linked product 8d was course of the reaction. If the rate-determining step of the reac-
observed, justifying a more profound conformational analysis of tion is endergonic, then differences in productlike transition
this product (Figure 6). Conformational molecular dynamics states will account for the observed selectivity according to
runs (MD) were performed on both anomers of the two regio- Hammond’s postulate [44].
isomers of 8d to simulate the behavior of the molecule during
more than 5000 ps of molecular motion. Thereby, it was found For the reaction path to the most constrained macrocylic ring
that for the observed regio- and stereochemistry an alternative system (constitution series d with n = 2), this argument holds,
conformation with two ASIs (2 + 2 ASI) and two intramolec- even to the extent of regarding the most stable product con-
ular hydrogen bonds is significantly (2.2 kcal/mol) more stable formation as a valid model for the transition state: The observed
than the virtual β(1→3)-linked product 6d; however, the triad- major diastereomer 8d, α(1→2), emerges as the most stable
stabilized starting conformation for the MD is energetically product conformation by more than 2.2 kcal/mol compared to
significantly higher (4.8 kcal/mol) than the MD optimized con- its next highest diastereomer 6d, β(1→3), as documented in
formation, since the latter profits from two hydrogen bonds and Figure 6. Nevertheless, a closer approximation to the real tran-
also two ASIs, even though it is decoupled. Thus, for the prod- sition state involving the pyranose cyclic oxonium intermediate
uct constitution 8d with the highest relative macrocyclic ring is possible within our calibrated force field approach: Figure 7
constraint, the observed regio- and stereoselectivity can be highlights the stereoelectronic course of the reaction, which
Figure 5: Stereo view of the superposition of β(1→3)-linked disaccharide models of 6a–d in stable triad-ASI conformations. 6a (n = 5) orange,
6b (n = 4) green, 6c (n = 3) pink, 6d (n = 2) magenta.
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Figure 6: Most-stable product conformations for the cyclo-glycosidation reaction with ring size spacer n = 2 (constitutions 6d, 7d, 8d, and further the
isomer β(1→2), were not observed). The various regio- and stereoisomers were modeled and subjected to molecular dynamics (MD) runs of at least
5000 ps, wherefrom the observed major diastereomer 8d emerged with a lowest free energy by more than 2.2 kcal/mol with respect to the β(1→3)
isomer 6d.
Figure 7: Most-stable product conformations for the cyclo-glycosidation reaction with ring size spacer n = 3 (constitutions 6c, 7c, 8c, and further the
isomer β(1→2), were not observed). As in Figure 6, the various regio- and stereoisomers were modeled and subjected to molecular dynamics (MD)
runs of at least 5000 ps, wherefrom the observed major diastereomer 8c, α(1→2), in its lowest conformation was again obtained with a free energy
that was 2.3 kcal/mol lower than that for the next highest diastereomer 7c, α(1→3).
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involves the 2’-OH nucleophilic center in a favorable, 1,2- α(1→2)-stereoisomer; indeed, extensive MD calculations
diaxial addition to the cyclic C=O(+) moiety, resulting in the (>5000 ps) on each of the possible product diastereomers
α(1→2)-anomer. This reaction path not only leads directly to (Figure 7, Figure 8 and Figure 9) converge into most-stable,
the establishment of the most-stable, chair conformation in the rearranged product conformations with most having the
pyranose ring, but moreover proves to be entirely consistent α(1→2)-stereochemistry.
with accepted stereoelectronic principles in organic chemistry
[45-47]. Given these arguments, the obvious question for the As summarized in Table 1, the most stable product conforma-
alternative stereochemical outcome of the cyclo-glycosidation tions are generally supportive of the formation of the α(1→2)
reaction for the cases n = 3, 4 and 5 (series c, b and a) arises: In stereo- and regiochemistry, which would occur over a tran-
terms of the canonical stereochemical principles, we do not sition state as depicted in Figure 10 for the case n = 2. For the
perceive a clear reason why they should not also cyclize to the comparatively unconstrained cases n > 2 our analysis appears
Table 1: Calculated free energies of the most stable isomers of compounds 6–8 and the isomers not found during cyclization of compounds 5.
Compounds
Length of
Energy [kcal∙mol−1] of the most stable isomersb
(CH2)n groupa
6a–d β(1→3)
7a–d α(1→3)
8a–d β(1→2)c
8a–d α(1→2)
6–8a
6–8b
6–8c
6–8d
n = 5
n = 4
n = 3
n = 2
42.77
49.61
47.51
46.89c
40.76
42.99
44.29
53.01
45.79c
50.55c
47.22c
47.28c
39.70c
44.75c
42.01c
44.62
aSee Scheme 1; bEnergies were calculated by molecular dynamics, >5000 ps, for each isomer. Individual aromatic stacking patterns and H-bond
contributions in the respective product conformations are illustrated in composite Figures 6–9; cIsomers not obtained during the intramolecular cycliza-
tion of compounds 5a–d.
Figure 8: Most-stable product conformations for the cyclo-glycosidation reaction with ring size spacer n = 4 (constitutions 6b, 7b, 8b, and further the
isomer β(1→2), were not observed). As in Figure 6, the various regio- and stereoisomers were modeled and subjected to molecular dynamics (MD)
runs of at least 5000 ps, wherefrom the observed major diastereomer 7b, α(1→3), in its lowest conformation was obtained with a free energy that was
1.8 kcal/mol lower than that for the next highest diastereomer 8b, α(1→2).
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Figure 9: Most-stable product conformations for the cyclo-glycosidation reaction with ring size spacer n = 5 (constitutions 6a, 7a, 8a, and further the
isomer β(1→2), was not observed). As in Figure 6, the various regio- and stereoisomers were modeled and subjected to molecular dynamics (MD)
runs of at least 5000 ps, wherefrom the observed major diastereomer 8a, α(1→2), in its lowest conformation invariably emerged with a free energy
that was 1.0 kcal/mol lower than that for the next higher diastereomer 7a, α(1→3).
Figure 10: Canonical stereoelectronic course of the intramolecular glycosylation reaction leading to the α(1→2)-linked product 8d favored by two
independent aromatic-stacking interactions (2 + 2 ASI). Notably, the diaxial attack of the nucleophile in this case allows the direct formation of a chair
conformation out of the pyranose cyclic oxonium intermediate.
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Figure 11: Unusual stereoelectronic course of the intramolecular glycosylation reaction leading to the β(1→3)-linked products 8a–c induced by a
cumulated tetrad aromatic-stacking interaction (4 ASI), and further by a strong transannular amide N–H···OH(2’) hydrogen bond (yellow) as well as an
assisting neighboring H-bond (3’)O–H···O=C(ester) (blue). Extended MD runs (>10.000 ps) do not lead to a dissociation of the relayed aromatic
tetrad.
thus to have failed, since for these cases the β(1→3) isomers formation only after formation of an initial pyranose envelope/
have predominantly been isolated from the reaction. Can we boat conformation, which however easily flips to the chair con-
nevertheless find a stringent, modeling-based argument for the formation with the anomeric hydrogen in the axial and the
alternative course of the reaction with extended linker geome- glycosidic oxygen in the equatorial orientation.
tries?
Similar, possibly less-spectacular cases of product-controlling
Figure 11 illustrates what we intuitively anticipated at the ASI effects have notably been found in peptide cyclization reac-
beginning of the discussion, namely that the aromatic stacking tions [48,49] and very generally for the case of the induction of
interactions have a remarkable influence on the course of an handedness in nucleic acid constructs ([50] and references cited
intramolecular cyclization reaction: If the precyclized (seco) therein). A remarkable differentiation of the regioselectivity of
cyclic oxonium ion is modeled as an approximation for its tran- acylation reactions at differently exposed hydroxy groups was
sition state, the established stereoelectronic principles are over- found for chiral 2’-O-tetrahydropyranyl nucleotides [51],
ruled not only by a triple ASI, but rather by a quadruply aligned whereby a particular hydroxy group is significantly deshielded
stack: A tetrad ASI. In extended MD runs (>10,000 ps), the in 1H NMR and consequently its nucleophilicity is thought to be
tetrad does not dislocate into aggregates with alternate stacking enhanced by intramolecular hydrogen bonding.
patterns, whereas the corresponding constitution with a shorter
tether bridge n = 2 rearranges after a short time of MD. The Conclusion
“non-canonical” tetrad ASI transition state is further stabilized We showed, for the intramolecular glycosylation reaction via
by a strong transannular amide N–H···OH(2’) hydrogen bond “prearranged” glycosides, that the stereo- and regioselectivity of
as well as by an assisting, neighboring H-bond this condensation reaction does not only depend upon the rela-
(3’)O–H···O=C(ester), which renders the previous more nucleo- tive configuration of the involved hydroxyls of the glycosyl
philic. In this case, the attack occurs from the opposite side of donor and acceptor, as was previously anticipated. Rather, in
the oxonium intermediate and leads to stable product con- addition to these factors, interactions (π-stacking) of the
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18.Ziegler, T.; Lau, R. Tetrahedron Lett. 1995, 36, 1417–1420.
protecting groups in close proximity to, as well as distant from,
the reaction centers play an important role in determining the
stereoselectivity of intramolecular glycosylations.
doi:10.1016/0040-4039(95)00010-A
19.Lau, R.; Schüle, G.; Schwaneberg, U.; Ziegler, T. Liebigs Ann. 1995,
1745–1754. doi:10.1002/jlac.1995199510245
20.Ziegler, T.; Lemanski, G.; Rakoczy, A. Tetrahedron Lett. 1995, 36,
8973–8976. doi:10.1016/0040-4039(95)01952-E
21.Valverde, S.; Gómez, A. M.; Hernández, A.; Herradón, B.; López, J. C.
J. Chem. Soc., Chem. Commun. 1995, 2005–2006.
doi:10.1039/C39950002005
Supporting Information
Supporting Information File 1
Experimental data.
22.Schüle, G.; Ziegler, T. Liebigs Ann. 1996, 1599–1607.
doi:10.1002/jlac.199619961016
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-189-S1.pdf]
23.Lemanski, G.; Ziegler, T. Eur. J. Org. Chem. 2000, 181–186.
doi:10.1002/(SICI)1099-0690(200001)2000:1<181::AID-EJOC181>3.0.
CO;2-7
24.Lemanski, G.; Ziegler, T. Eur. J. Org. Chem. 2006, 2618–2630.
doi:10.1002/ejoc.200600078
Acknowledgment
This work was financially supported by the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen Industrie.
We thank the groups of Professor K. Albert and Professor K.
Zeller for measuring the NMR and MS spectra.
25.Lemanski, G.; Ziegler, T. Tetrahedron 2000, 56, 563–579.
doi:10.1016/S0040-4020(99)01053-4
26.Abdel-Rahman, A. A.-H.; El Ashry, E. S. H.; Schmidt, R. R.
Carbohydr. Res. 2002, 337, 195–206.
doi:10.1016/S0008-6215(01)00306-8
27.Ziegler, T.; Lemanski, G. Eur. J. Org. Chem. 1998, 163–170.
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