Polymer-bound diphenylphosphane hydrobromide, a mild acid for the activation of enol ethers: Applications in polymer-assisted glycosidations

Article abstract of DOI:10.1002/ejoc.200400069

Polymer-bound diphenylphosphane hydrobromide 2 shows excellent properties in the activation of enol ethers and glycals, the introduction and cleavage of THP ethers being promoted with excellent yields with this functionalized polymer, Glycosidations of gl

Full text of DOI:10.1002/ejoc.200400069

FULL PAPER
Polymer-Bound Diphenylphosphane Hydrobromide, a Mild Acid for the
Activation of Enol Ethers: Applications in Polymer-Assisted Glycosidations
Janis Jaunzems,[a] Dmitri Kashin,[a] Andreas Schönberger,[b] and Andreas Kirschning*[a]
Dedicated to Prof. Dr. A. Zeeck on the occasion of his 65th birthday
Keywords: Baccatin III / Glycosidation / Glycoconjugates / Multistep synthesis / Polymer-bound reagents / Protecting
group
Polymer-bound diphenylphosphane hydrobromide 2 shows
excellent properties in the activation of enol ethers and gly-
cals, the introduction and cleavage of THP ethers being pro-
moted with excellent yields with this functionalized polymer.
Glycosidations of glycals work equally well, with suppression
of the formation of undesired Ferrier rearranged products.
The reagent is sufficiently mild to leave labile 2-deoxy glyco-
sidic bonds and acid-labile protecting groups intact. It can
be employed to transfer disaccharide glycosyl donors onto
aglycons and is also selective for the promotion of two glyco-
sidations in one pot. Highly hindered glycosyl donor groups
such as the hydroxy group at C-13 of the baccatin III frame-
work can be glycosylated with glycals in the presence of this
polymer-bound reagent.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
ations relying exclusively on polymer-bound scavenging re-
agents for removal of by-products originating from conven-
tional solution-phase glycosidations.[6] Much earlier work
by Paulsen and Lockhoff[7] and later work by Capillon et
al.[8] showed that activation of glycosyl bromides can be
achieved with silver cations immobilized on a solid phase.
In this report we disclose ‘‘poly-diphenylphosphane
hydrobromide’’ (2), a new polymer-bound proton source
closely related to the soluble triphenylphosphane hydrobro-
mide studied in detail by Bestmann and later by Falck and
co-workers.[9]
Interest in the development and application of solid-sup-
ported reagents[1] and catalysts has recently seen a dramatic
increase.[2,3] This hybrid solid-/solution-phase technique
possesses all the intrinsic advantages of classical solid-phase
techniques: (a) use of excesses of reagents to drive reactions
to completion, followed by a simple filtration step to isolate
products, and (b) not every active site on the solid phase
needs to react. Additionally, all advantages associated with
solution-phase chemistry are also exploited here: (a) easy
monitoring of the reaction, and (b) no procedures for cleav-
age from the resin required.
In this context, our group has also been focusing on the
evaluation of polymer-bound promoters for glycosidations
in order to prepare 2-deoxygenated glycoconjugates with
minimum workup. We have demonstrated that glycosyl
acetates can be activated by polymer-bound silyl triflate[4]
and have also developed thiophilic reagents immobilized on
polystyrene, which promote glycosidation of thioglycosides,
followed by removal of thiol-containing by-products by
scavenging procedures.[5] In a related approach, Ley and co-
workers have recently reported polymer-assisted glycosid-
Results and Discussion
Polymer-bound reagent 2 (about 1 mmol/g) is con-
veniently prepared from ‘‘poly-diphenylphosphane’’ (1) by
treatment with hydrobromic acid (Scheme 1) and is storable
under nitrogen for months. In evaluation of the properties
of reagent 2, we first checked its ability to promote the pro-
tection of alcohols as THP (tetrahydropyranyl) ethers[10]
and their subsequent deprotection to regenerate the starting
[a]
Zentrum für Organische Chemie, Universität Hannover,
Schneiderberg 1B, 30167 Hannover, Germany
Fax: (internat.) ϩ 49-511-762-3011
E-mail: andreas.kirschning@oci.uni-hannover.de
[b]
Institut für Organische Chemie, Technischen Universität
Clausthal,
Scheme 1. Preparation of polymer-bound diphenylphosphane
hydrobromide 2
Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
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DOI: 10.1002/ejoc.200400069
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J. Jaunzems, D. Kashin, A. Schönberger, A. Kirschning
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alcohols under protic conditions. As many reagents Ϫ in- of these arising from its potential to undergo a retro-aldol
cluding several conventional protic and Lewis acids,[11,12] reaction).
pyridinium p-tosylate (PPTS),[13] Dowex 50 W,[14] and iodo-
trimethylsilane[15] Ϫ are known to promote these simple
transformations, we deliberately chose multifunctional al-
cohols 3Ϫ7, which have complexity typical of intermediate
alcohols occurring in natural product synthesis. Indeed, this
selection should allow evaluation of the mildness of reagent
2 (Table 1). Acid-labile alcohols such as digitoxygenine (5,
Entry 3), allylic silyl ether 7 (Entry 5) and allylic alcohol 6
(Entry 4) were therefore employed (the lability of the last
In all these cases, protection of selected alcohols in di-
chloromethane with use of a catalytic amount of func-
tionalized polymer 2 and 1 equiv. of dihydropyran (DHP)
proceeded almost quantitatively within 3 h. The reversed
deprotection procedure proceeded under the same con-
ditions, except that methanol was used as a solvent. Here,
extended reaction times (12 h) were required in order to
provide complete transformation. In all cases, excellent
chromatographic and NMR purity was determined for the
isolated alcohols, so no additional purification steps relative
to other published methods were necessary.
Table 1. Protection and deprotection of selected alcohols
Immobilization of reactive species often leads to a slight
to moderate reduction in activity in relation to the parent
soluble reagents or catalysts. This can be exploited to en-
hance the chemoselectivity, as is demonstrated for reagent
2 in a synthetic sequence forming part of a total synthesis
approach towards ansamycine antibiotics (Scheme 2). In
the presence of an allylic OTHP group in aniline derivative
13, only the N-bound TBS group (tert-butyldimethylsilyl)
was removed at room temp. in methanol, to yield aniline
14, while the THP ether remained intact. Finally, after in-
troduction of the allyloxycarbonyl group, the resulting THP
ether 15 was selectively cleaved in excellent yield, affording
allylic alcohol 16. Here, reagent 2 showed improved per-
formance over the soluble analogue, which yielded mixtures
during the course of the first deprotection.
In the next phase of evaluation of the properties of re-
agent 2 we directed our focus on the activation of carbo-
hydrate-based enol ether double bonds which are present in
glycals.[16] Again, many proton sources, including tri-
phenylphosphane hydrobromide,[9] are known to promote
addition of alcohols to the enol ether double bond. The
Ferrier rearrangement[17] is a common side reaction, how-
ever, resulting in the undesired unsaturated 2,3-dideoxy
hexoses. Thus, 3,4-diacylated decarestricine D 4, obtained
by a three-step protection/deprotection sequence from dec-
arestrictine D (17)[16k] via intermediates 18 and 19, was util-
ized in the first glycosidation procedure (Scheme 3). Dec-
arestrictine D (17)[18] was first isolated from the fermen-
tation broth of Penicillium species,[19] and is a ten-mem-
bered lactone analogue of larger macrolactone antibiotics.
When acceptor 4 (1 equiv.) was treated with monosilylated
fucal 20 (1 equiv.) in the presence of a catalytic amount of 2
[a] CH2Cl2, room temp., 3 h; yields refer to isolated yields. [b] Meth-
[c]
anol, room temp. 12 h; yields refer to isolated yields. For prep-
aration of alcohol 4 refer to Scheme 3 and Exp. Sect. [d] When silyl
protection was present in the glycoconjugates, Amberlite A-21 was
added prior to filtration and concentration. THP ϭ tetrahydro-
pyranyl, Ac ϭ acetate, TBS ϭ tert-butyldimethylsilyl.
Scheme 2. Chemoselective deprotection with polymer-bound reagent 2; Alloc ϭ allyloxycarbonyl
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Scheme 4. One-pot diglycosylation of dehydro-epi-androsterone 24
Scheme 3. One-pot diglycosylation of 3,4-diacetoxydecarestrictine
D (4); reagents and conditions: a) TBSCl (1.5 equiv.), CH2Cl2,
imidazole, Ϫ30 °C, 1 h; b) pyr, Ac2O (4 equiv.), 50 °C, 7 h; c)
TBAF, AcOH, pH ϭ 7, room temp., 5d; TES ϭ triethylsilyl
(0.1 mol %), the glycosidation product 21 was quantitatively
formed as a single isomer. No formation of the Ferrier
product was observed. At this point this product can be
isolated, or a second glycosidation can be initiated by ad-
dition of glycal 22 (1.2 equiv.) to the reaction mixture. The
polymer-attached catalyst 2 again smoothly promotes the
addition reaction with similar efficiency and selectivity as
seen in the first case, yielding glycoconjugate 23 in a one-
pot procedure. This orthogonal glycosidation strategy
works so well in this case because the reactivity of the
pseudoaxial hydroxy group in glycal 20 is highly reduced
relative to that at C-7, this being the most reactive of the
three hydroxy groups in decarestrictine. This reactivity dif-
ference suppresses the possible dimerization of glycal 20. It
is worth pointing out that the triethylsilyl (TES) protecting
groups, including the one attached to the highly reactive
allylic hydroxy group at C-3 in glycals 20 and 22, are not
removed under the acidic conditions employed, again a
clear indication of the mildness and selectivity of polymer-
bound catalysts 2. In all cases in which the products con-
tained O-silyl protection, Amberlite A-21 was added prior
to filtration and concentration.
Scheme 5. Glycosylation of 7-TES-protected baccatin III 26
tri-O-silylated galactal 27 (Scheme 5). The glycosyl donor
had to be employed in tenfold excess and the reaction time
had to be extended to 24 h because of the pronounced lack
of accessibility of the 13-hydroxy group in baccatin III 26.
Under these conditions, glycosylated baccatin III 28 was
isolated in 68% yield as a mixture of α/β isomers (about
15:1). Workup included chromatographic purification
mainly because it was necessary to remove excess galactal
27 and by-products derived from its degradation. Finally,
the TES protection on the monosaccharide moiety and on
the aglycon were removed by a conventional procedure, fur-
nishing glycosylated baccatin III 29.[23]
More complex glycosyl donors are deoxygenated disac-
charides containing an acid-labile glycosidic bond together
with the glycal donor group. Disaccharide glycal 30 was
activated with polymer-bound reagent 2 and coupled with
testosterone (3) (Scheme 6). Disaccharide 31 was isolated as
Likewise, dehydro-epi-androsterone 24 (1 equiv.) can be
treated with glycals 20 (1 equiv.) and 22 (1.2 equiv.) in a
similar manner to yield glycosteroid 25 in high yield and
with excellent stereoselectivity (only α-anomer for both gly-
cosidation steps) (Scheme 4).
A hydroxy group with a particular lack of reactivity is
found at C-13 in baccatin III.[20] This position is typically
esterified with N-benzoylated isoserine, which is regarded
as responsible to a great extent for the excellent antitumor
activity of paclitaxel. To the best of our knowledge, no gly-
coconjugates with carbohydrate moieties attached to C-13
of baccatin III derivatives have been published so far,[21]
and so we tested the use of polymer-bound agent 2 in the
glycosidation of protected silylated baccatin III 26[22] with Scheme 6. Glycosidation of disaccharide glycal 30
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J. Jaunzems, D. Kashin, A. Schönberger, A. Kirschning
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an anomeric mixture, because the arabino-configured glycal
exerts a lower degree of stereoselection than glycals 20 and
22 containing the stereodirecting pseudoaxial hydroxy or
siloxy group at C-4. It should be noted that glycals with
electron-withdrawing protecting groups such as 30 show re-
duced reactivity relative to O-silylated glycals in these trans-
formations.
Another complex and difficult to handle glycosyl donor
is shown in Scheme 7. Azidodeoxy sugars are ideal precur-
sors for the biologically important class of aminodeoxysac-
charides. According to Heyns,[24] Thiem[25] and Mon-
neret,[26] azidodeoxy sugars can be prepared by azidation
of glycals with sodium azide as nitrogen source and
BF3·Et2O as Lewis acid promoter. This procedure results in
a mixture of α- and β-enopyranosyl azides and 3-azido
glycals, existing in equilibrium. It has been suggested
that
a
[3,3]-sigmatropic rearrangement causes this
equilibrium.[24Ϫ26] So far, these mixtures of azido glycals
and enopyranosyl azides have not been utilized in proton-
promoted glycosidations,[27] We thus repeated the literature
procedure by treating -rhamnal (32) with sodium azide
and BF3·Et2O (Scheme 7). When the reaction was termin-
ated after 5 min and the product mixture was isolated, ex-
clusive formation of the Ferrier-type enopyranosyl azides
Scheme 8. Polymer-assisted glycosidation of 3-azido glycals
33a and 33b was noted. The use of longer reaction times yranosyl azide turned out to be unreactive under the con-
(48 h) resulted in rearranged azidoglycals 34a and 34b. The ditions employed and so could be reisolated. At this point
product mixture was now a composition of stereoisomeric the anomeric mixture was separated and the individual iso-
azidoglycals and enopyranosyl azides in an approximate ra- meric glycosides were further transformed separately. A se-
tio of 60:40. This crude product mixture was directly sub- cond glycosidation in the presence of a catalytic amount of
jected to the catalytic glycosidation conditions developed reagent 2 and glycal 22 proceeded very smoothly with both
for polymer-bound reagent 2. We had hoped that the equi- glycosides 36a and 36b, thereby furnishing disaccharides
librium depicted in Scheme 7 might be exploited for the ex- 37a and 37b, respectively. Importantly, no excess of glycosyl
clusive formation of 3-azido-3-deoxy glycosides (Scheme 8). donor was required, which allowed simplified purification.
Conventional desilylation was achieved with tetrabutylam-
monium fluoride (TBAF) at room temperature in THF
within 4 h, after which polymer-bound diphenylphosphane
1 was added to the reaction mixture. This procedure liber-
ated the amino groups by a Staudinger reaction and gave
aminoglycosides 38a and 38b, respectively, in very good
yield.
Finally, we evaluated polymer-assisted deprotection
methods for silyl ethers, which are commonly the final steps
in the preparation of glycoconjugates. Protic removal of si-
lyl groups present in glycoconjugates is not a suitable pro-
cedure, because of the labile glycosidic linkage present in 2-
deoxyhexoses. Here, neutral or basic conditions are more
appropriate and can be achieved by use of different fluor-
ide sources.
Scheme 7. Equilibrium of azido glycals and enopyranosyl azides
The glycosidation with testosterone (3) was complete
Disaccharide 39 was prepared in a one-pot fashion by
within 24 h, and purification afforded an anomeric mixture the procedure described in Schemes 3 and 4, with testoster-
of ribo-configured glycosides, which were directly deacyl- one (3) as aglycon (Scheme 9). This per-O-silylated product
ated with Amberlyst A-26 (hydroxide form) 35 to yield 3- served for testing of different polymer-assisted deprotection
azido-3-deoxy glycosides 36a and 36b. The isolated yield methods. DeShong and co-workers developed a new fluor-
was excellent (47% with reference to the starting mixture ide salt formed from triphenylsilyl fluoride and TBAF.[28]
Ϫ in fact about 80% with reference to the ribo-configured The resulting tetrabutylammonium difluorotriphenylsilicate
fraction of the glycals and the enopyranosides derived from (TBAT) is stable, compatible with most organic solvents
them) in view of the observation that the arabino-config- and not hygroscopic. It has mainly been employed because
ured azidoglycal and the corresponding β-configured enop- of its non-basic character. Because of these properties we
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respectively, with use of tetramethylsilane as the internal standard.
If not otherwise noted, CDCl3 is the solvent for all NMR experi-
ments. Multiplicities are described with the following abbreviations:
s ϭ singlet, d ϭ doublet, t ϭ triplet, q ϭ quadruplet, m ϭ mul-
tiplet, br. ϭ broad. NMR data for oligosaccharides are labelled
with a prime (first sugar) and a double prime (second sugar cou-
pled to the first through the anomeric centre). Chemical shift values
of 13C NMR spectra are reported as values in ppm relative to re-
sidual CHCl3 (δ ϭ77 ppm) or CD3OD (49) as internal standards.
The multiplicities refer to the resonances in the off-resonance spec-
tra and were elucidated by use of the distortionless enhancement
by polarisation transfer (DEPT) spectral editing technique, with
secondary pulses at 90° and 135°. Multiplicities are reported with
the following abbreviations: s ϭ singlet (due to quaternary C), d ϭ
doublet (methine), q ϭ quadruplet (methyl), t ϭ triplet (methyl-
ene). Mass spectra were recorded with a type LCT spectrometer
(Micromass) and with a type VG autospec (Micromass). Ion mass
(m/z) signals are reported as values in atomic mass units, followed,
in parentheses, by the peak intensities relative to the base peak
(100%). Optical rotations [α] were collected with a Polarimeter 341
(PerkinϪElmer) at a wavelength of 589 nm and are given in 10Ϫ1
deg·cm2·gϪ1. Combustion analyses were performed at the Institut
für Organische Chemie, Universität Hannover. All solvents used
were of reagent grade and were further dried. Reactions were moni-
tored by thin layer chromatography (TLC) on silica gel 60 F254 (E.
Merck, Darmstadt) and spots were detected either by UV absorp-
tion or by charring with H2SO4/4-methoxybenzaldehyde in meth-
anol. Preparative column chromatography was performed on silica
gel 60 (E. Merck, Darmstadt). In most cases this chromatographic
step was employed to obtain analytically pure compounds (e.g., for
combustion analysis or for the separation of anomeric mixtures).
Steroids 3, 5, 24 and 27 are commercially available. Reagent 1 was
obtained from NovaBiochem. Amberlite A-21 was obtained from
Fluka. Glycals 20 and 22 were prepared from -fucal by partial
and exhaustive silylation, respectively, under standard conditions.
Similarly, glycals 27 and 32 were obtained from -galactal and -
rhamnal, respectively, as in ref.[31] Polymer-bound fluoride 41 was
prepared as in ref.[29]
Scheme 9. Glyconjugate synthesis by polymer-assisted glycosid-
ation and desilylation
prepared the ion-exchange analogue 42 of TBAT. Fluoride
exchange resin 41 was prepared as reported by Colonna and
co-workers[29] and treated with triphenylsilyl fluoride, with
Amberlite A-26 as polymeric source. The functionalized
polymer 42 obtained was evaluated as a fluoride source for
cleavage of silyl ether protection groups on glycoconjugate
39.[30] The resin showed good properties as a silyl group
cleaving agent in selected systems. In a parallel experiment,
fluoride exchange resin 41 was utilized for the deprotection
of the same disaccharide 39, but turned out not to be suited
because partial cleavage of the glycosidic bond was ob-
served. Only traces of the desired deprotected triol 40
were formed.
Conclusion
Preparation of Polymer-Bound Reagent 2: A suspension of polymer-
bound diphenylphosphane (0.5 g, 1.12 mmol/g) in HBr/AcOH
(33%, 5 mL) was gently shaken at room temperature for 24 h. The
slurry was washed with CH2Cl2 (20 ϫ 5 mL) and dried under re-
duced pressure to afford the dark yellow polymer 2.[32]
In summary, polymer-bound diphenylphosphane hydro-
bromide 2 shows excellent properties in the activation of
enol ethers and glycals. Introduction and cleavage of THP
ethers in excellent yields can be promoted with this func-
tionalized polymer. The mildness of the procedure allows
chemoselective manipulations of acid-labile protecting
groups (e.g., THP, TES, TBS). Glycosidations of glycals
works equally well; formation of undesired Ferrier re-
arranged products is suppressed. The reagent is sufficiently
mild to leave labile 2-deoxy glycosidic bonds intact. It can
be employed to transfer disaccharide glycosyl donors onto
aglycons and is selective for promotion of two glycosida-
tions in one pot. Studies towards automated solution-phase
glycosidations in continuous flow systems are in progress in
our laboratories.
Preparation of Polymer-Bound Tetramethylammonium Difluorotri-
phenylsilicate TBAT (42): Triphenylsilanol was recrystallized from
petroleum ether/ethyl acetate prior to use. Triphenylsilanol (25 g,
90.4 mmol) was dissolved in methanol (90 mL) in a polyethylene
bottle and cooled to 5 °C. Aqueous HF (13 mL, 49%, 360 mmol)
was slowly added, and the resulting reaction mixture was allowed
to warm to room temperature. Stirring was continued for an ad-
ditional 30 min, resulting in the crystallization of the product as a
fine white powder. Distilled water (50 mL) was added to induce
further product precipitation. The resulting slurry was filtered in
vacuo and washed with water. The crude product was recrystallized
(MeOH/water, 15:1) and dried in vacuo to afford pure triphenylsilyl
fluoride (23.9 g, 86 mmol; 95%). Polymer-supported fluoride 41
was washed with acetonitrile/ethyl acetate prior to use. A mixture
of fluoride exchange resin 41 (2 g, Amberlite A-26) and triphenylsi-
lyl fluoride (3.3 g, 12 mmol; 2 equiv.) in dichloromethane (100 mL)
was shaken for 30 min, and the solvent was slowly evaporated un-
der reduced pressure. The resulting polymer was taken up with
ethyl acetate (50 mL) and the organic solvent was removed under
Experimental Section
General Remarks and Starting Materials: 1H NMR, 13C NMR and
1H, 13C-COSY and NOESY spectra were measured with Avance
200/DPX (Bruker) 200 MHz (50 MHz), Avance 400/DPX (Bruker)
400 MHz (100 MHz) and Avance 500/DRX (Bruker) instruments,
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J. Jaunzems, D. Kashin, A. Schönberger, A. Kirschning
FULL PAPER
reduced pressure. This procedure was repeated three times, and the
resulting polymer-bound TBAT (42) was filtered, washed with ethyl
acetate and dried in high vacuum.
0.363 mmol; 96%) as a semisolid material. [α]2D3 ϭ ϩ46.4 (c ϭ 0.5,
CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 1.18 (d, J ϭ 6.2 Hz, 3
1
H, 10-H), 1.83Ϫ1.73 (m, 2 H, CH2-8), 2.08, 2.07 (2 s, 6 H, 2 ϫ
CH3CO), 2.61, 2.52 (2 ddd, J ϭ 14.3, 10.0, 2.6 Hz and J ϭ 14.3,
2.6, 2.6 Hz, 2 H, CH2-2), 2.68 (br. s, 1 H, 7-OH), 4.12 (ddd, J ϭ
10.6, 7.9, 3.4 Hz, 1 H, 7-H), 5.08 (m, 1 H, 9-H), 5.22, 5.00 (2 ddd,
J ϭ 5.2, 2.6, 2.6 Hz and J ϭ 10.0, 5.2, 2.6 Hz, 2 H, 4-H, 3-H), 5.66
(dd, J ϭ 16.0, 2.6 Hz, 1 H, 5-H), 5.72 (dd, J ϭ 16.0, 7.9 Hz, 1 H,
6-H) ppm. 13C NMR (100 MHz, CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ
20.8, 20.9 (2 q, 2 ϫ CH3CO), 21.2 (q, C-10), 33.7 (t, C-2), 42.3 (t,
C-8), 68.0 (d, C-9), 70.8, 72.1 (3 d, C-3, C-4, C-7), 123.4 (d, C-5),
136.9 (d, C-6), 169.2, 169.4, 169.8 (3 s, C-1, 2 ϫ CH3CO) ppm.
C14H20O7 (300.30): calcd. C 55.99, H 6.71; found C 55.88, H 6.65.
Preparation of 3-O-Benzoyl-2,6-dideoxy-4-O-(3,4-di-O-acetyl-2,6-
dideoxy-α-
L
-arabino-hexopyranosyl)-
L
-arabino-hex-1-enitol (30):[5b]
˚
Powdered molecular sieves (4 A, 50 mg) were added to a stirred
solution of 3,4-di-O-acetyl-2,6-dideoxy-1-phenylthio-α--arabino-
pyranoside (33 mg, 0.1 mmol) and 3-O-benzoyl-2,6-dideoxy--ara-
bino-hex-1-enit (23.4 mg, 0.1 mmol) in acetonitrile (5 mL). The sus-
pension was cooled to 0 °C, and SelectfluorTM (0.105 mmol) was
added. The mixture was shaken for 20 min, and the reaction was
then terminated by addition of dry Amberlite A-21. The resulting
suspension was filtered through a pad of Al2O3. The solvent was
evaporated under reduced pressure, and the residue was redissolved
in 2-propanol (5 mL). After addition of polymer-supported
borohydride (100 mg), the mixture was shaken overnight in order
to remove thio-derived impurities. The suspension was filtered and
concentrated under reduced pressure to afford pure compound 30
General Procedure for the Introduction of THP Ethers: The alcohol
(33 µmol) was dissolved in dry CH2Cl2 (3 mL). Dihydropyran
(DHP, 2.8 mg, 3.3 µL; 1 equiv.) and a catalytic amount of polymer-
bound reagent 2 (0.5 mg, 1.5 mol %) were added, and the suspen-
sion was gently shaken at room temperature for 3 h. The reaction
mixture was filtered through a pad of Celite, and the filtrate was
concentrated under reduced pressure to yield the pure THP-pro-
tected product.
1
(43.4 mg, 97 µmol; 97%). H NMR (500 MHz, CDCl3): δ ϭ 1.18
(d, J ϭ 6.3 Hz, 3 H, 6-HЈ), 1.46 (d, J ϭ 6.5 Hz, 3 H, 6-H), 1.75
(ddd, J ϭ 13.0, 11.5, 3.7 Hz, 1 H, 2-HЈeq), 2.04, 1.96 (2s, 6 H, 2 ϫ
CH3CO), 2.15 (dd, J ϭ 13.0, 5.2 Hz, 1 H, 2-HЈax), 3.94 (dq, J ϭ
9.6, 6.3 Hz, 1 H, 5-HЈ), 3.93 (m, 1 H, 4-H), 4.18 (dq, J ϭ 6.7,
6.3 Hz, 1 H, 5-H), 4.71 (dd, J ϭ 9.6, 9.6 Hz, 1 H, 4-HЈ), 4.87 (dd,
J ϭ 6.1, 3.5 Hz, 1 H, 2-H), 5.23 (ddd, J ϭ 11.5, 9.6, 5.2 Hz, 1 H,
3-HЈ), 5.25 (d, J ϭ 3.7 Hz, 1 H, 1-HЈ), 5.51 (br. dd, J ϭ 4.1, 3.5 Hz,
1 H, 3-H), 6.45 (d, J ϭ 6.1 Hz, 1 H, 1-H), 7.45 (dd, J ϭ 7.1, 7.1 Hz,
2 H, Phmeta), 7.57 (dd, J ϭ 7.1, 7.1 Hz, 1 H, Phpara), 8.01 (d, J ϭ
7.1 Hz, 2 H, Phortho) ppm. 13C NMR (125 MHz, CDCl3, CDCl3,
δ ϭ 77 ppm): δ ϭ 17.3 (q, C-6), 17.4 (q, C-6Ј), 20.8, 20.9 (2q, 2 ϫ
CH3CO), 35.4 (t, C-2Ј), 66.5 (d, C-5Ј), 68.6 (d, C-3Ј), 70.8 (d, C-
3), 73.3 (d, C-5), 74.7 (d, C-4Ј), 75.4 (d, C-4), 96.4 (d, C-1Ј), 98.5
(d, C-2), 128.5 (d, Phmeta), 129.6 (d, Phortho), 129.9 (s, Phipso), 133.2
(d, Phortho), 146.0 (d, C-1), 165.9 (s, PhCO), 170.11 (s, CH3CO),
170.1 (s, CH3CO) ppm. HRMS (C23H28O9): calcd. 448.1733 [M]ϩ,
found 448.1745.
17-O-(Tetrahydropyran-2Ј-yloxy)testosterone (8): Testosterone (3)
(10 mg, 34.7 µmol) was converted into compound 8 (12.5 mg, 33.7
µmol; 97%) by the general procedure for the introduction of THP
ethers. 1H NMR (400 MHz, CDCl3): δ ϭ 0.7Ϫ2.5 (m, 31 H,
THPϪH, testosteroneϪH), 3.5 (m, 1 H, CHHOCHO), 3.67 (ddd,
1H J ϭ 8.5, 8.1, 4.7 Hz, 1 H, 17-H), 3.91 (ddd, J ϭ 10.9, 7.9, 2.9
Hz, 1 H, CHHOCHO), 4.65 (br. d, J ϭ 3.7 Hz, 1 H, ϪOCHOϪ),
5.75 (s, 1 H, 4-H) ppm. HRMS (C24H36O3): calcd. 373.2743 [M ϩ
H]ϩ, found 373.2748.
3,4-Di-O-acetyl-7-O-(tetrahydropyran-2Ј-yloxy)decarestrictine D (9):
Diacylated decarestrictine 4 (10 mg, 33 µmol) was converted into
compound 9 (12.6 mg, 32.8 µmol; 99%) as a diastereomeric mixture
(dr ϭ 2:1*) by the general procedure for the introduction of THP
1
ethers. H NMR (400 MHz, CDCl3): δ ϭ 1.22, (d, J ϭ 6.3 Hz, 3
H, CH3-10), 1.4Ϫ2.0 (m, 8 H, THP, CH2-8), 2.14, 2.12, 2.11 (3 s,
6 H, 2 ϫ CH3CO), 2.55 (ddd, J ϭ 14.2, 11.6, 2.2 Hz, 1 H, CHH-
2), 2.66 (ddd, J ϭ 14.2, 14.2, 7.0 Hz, 1 H, CHH-2), 3.43 (m, 1 H,
THP), 3.80 (m, 1 H, THP), 4.12* (ddd, J ϭ 10.5, 9.6, 3.2 Hz, 1 H,
7-H), 4.24* (ddd, J ϭ 10.5, 9.6, 3.5 Hz, 1 H, 7-H), 4.52* (dd, J ϭ
4.5, 2.9 Hz, 1 H, THP), 4.61* (dd, J ϭ 4.3, 2.9 Hz, 1 H, THP),
5.03 (m, 1 H, 9-H), 5.13 (2 ϫ ddd, J ϭ 21.7, 11.6, 7.0, 2.2 Hz, 1
H, 3-H), 5.32 (dddd, J ϭ 16.0, 5.0, 3.5, 1.3 Hz, 1 H, 4-H), 5.63*
(ddd, J ϭ 16.0, 9.4, 1.3 Hz, 1 H, 5-H), 5.71 (dd, J ϭ 16.0, 3.5 Hz,
1 H, 5-H), 5.80* (dd, J ϭ 16.0, 3.3 Hz, 1 H, 6-H), 5.87 (ddd, J ϭ
16.0, 9.4, 1.3 Hz, 1 H, 6-H) ppm. 13C NMR (125 MHz, CDCl3):
δ ϭ 19.7 (t, THP), 19.8* (t, THP), 20.9 (q, CH3CO), 20.9 (q,
CH3CO), 21.0 (q, C-10), 21.4* (q, C-10), 21.4 (t, THP), 25.2 (t,
THP), 25.4* (t, THP), 30.7(d), 30.7* (t, THP), 30.8 (t, THP), 33.4
(t, C-2), 33.9* (t, C-2), 40.1 (t, C-8), 41.1* (t, C-8), 62.7 (t, C-5Ј),
62.9* (t, C-5Ј), 68.3 (d, C-9), 68.4* (C-9), 70.9, 72.0, 72.2*, 74.9
(4d, C-3, C-4, C-7), 95.2* (d, THP-1), 97.2 (d, THP-1), 122.9* (d,
C-5), 125.7 (d, C-5), 134.7* (d, C-6), 136.1 (d, C-6), 169.1, 169.1,
3,4-Di-O-acetyl-7-O-(tert-butyldimethylsilyl)decarestrictine D (19):
tert-Butyldimethylsilyl chloride (69 mg, 0.46 mmol) was added at
Ϫ30 °C to a solution of decarestrictine D (17) (100 mg, 0.46 mmol)
and imidazole (47 mg, 0.69 mmol, 1.5 equiv.) in CH2Cl2 (30 mL).
The reaction mixture was stirred at this temperature for 1 h, after
which the solvent was evaporated under a nitrogen flow while the
system was allowed to warm to room temp. Dry pyridine (5 mL)
and Ac2O (187 µL, 4 equiv.) were added, and stirring was continued
at 50 °C for 7 h. Pyridine was removed under reduced pressure and
the crude product was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate, 2:1; Rf ϭ 0.53), affording pure
19 (185 mg, 0.446 mmol; 97%) as a colourless oil. 1H NMR
(400 MHz, CDCl3): δ ϭ Ϫ0.04, Ϫ0.08 [2 s, 6 H, Si(CH3)2], 0.79 (s,
9 H, tBu), 1.16 (d, J ϭ 6.4 Hz, 1 H, 3 H, 10-H), 1.73 (m, 2 H,
CH2-8), 2.06, 2.05 (2 s, 6 H, 2 ϫ CH3CO), 2.54 (m, 2 H, CH2-2),
4.08 (ddd, J ϭ 9.0, 8.4, 5.7 Hz, 1 H, 7-H), 5.20, 5.03 (2 m, 3 H, 9-
H, 4-H, 3-H), 5.59 (dd, J ϭ 16.2, 3.3 Hz, 1 H, 5-H), 5.70 (dd, J ϭ
16.2, 9.0 Hz, 1 H, 6-H) ppm. HRMS (C20H34O7Si): calcd. 415.2152
[M ϩ H]ϩ, found 415.2154.
169.4, 169.5, 169.9 (5 s, C-1,
2 ϫ CH3CO) ppm. HRMS
(C19H28O8): calcd. 385.1862 [M ϩ H]ϩ, found 385.1860.
Preparation of 3,4-Di-O-acetyldecarestrictine D (4): O-Silylated dec-
arestrictine 19 (160 mg, 0.38 mmol) was dissolved in a minimal
amount of THF, added to the buffered THF solution of tetrabu-
3-O-(Tetrahydropyran-2Ј-yloxy)digitoxygenine (10): Digitoxygenine
(5) (10 mg, 26.7 µmol) was converted into compound 10 (12.2 mg,
tylammonium fluoride[23] (3 mL), and stirred for 5 d. The solvent 26.5 µmol; 99%) by the general procedure for the introduction of
1
was removed under reduced pressure, and the crude product was
purified by column chromatography on silica gel (petroleum ether/
ethyl acetate, 2:1; Rf ϭ 0.1) to yield compound 4 (109 mg,
THP ethers. H NMR (400 MHz, CDCl3): δ ϭ 2.4Ϫ0.7 (m, 33 H,
THP, digitoxygenine), 2.80 (m, 1 H, 17-H), 3.50 (m, 1 H, THP),
3.90 (m, 1 H, 3-H), 3.98 (br. s, 1 H, THP), 4.63 (m, 1 H, THP),
3440
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3435Ϫ3446

Applications in Polymer-Assisted Glycosidations
FULL PAPER
4.82 (dd, J ϭ 18.1, 1.6 Hz, 1 H, 21-H), 5.01 (ddd, J ϭ 18.1, 1.6, 1.2
Celite and concentrated under reduced pressure. The product was
Hz, 1 H5 Hz, 21-H), 5.88 (s, 1 H, 22-H) ppm. 13C NMR (125 MHz, additionally dried under high vacuum to remove remaining traces
CDCl3): δ ϭ 15.7 (q, C-18), 19.7 (t, THP), 20.0 (t, THP), 21.2 (t, of THP-methyl ether.
C-11), 21.4 (t, C-7), 23.7 (q, C-19), 24.1, 25.4, 25.5, 25.6 (4 t, THP),
Deprotection of 17-O-(Tetrahydropyran-2Ј-yloxy)testosterone (8):
17-O-(Tetrahydropyran-2Ј-yloxy)testosterone (8; 12.5 mg, 33.7
µmol) was deprotected to afford testosterone (3) (9.9 mg, 33.4
µmol, 99%) by the general procedure for the cleavage of THP
ethers. Spectroscopic and physical data are identical with those of
authentic testosterone.
26.6, 26.7 (2 t, C-16), 26.8 (t, C-6), 26.9 (t, C-2), 29.9, 30.0 (2 t, C-
1), 30.4, 30.7 (2 t, C-15), 31.4, 32.2 (2 t, THP), 33.1, 33.2 (2 t, C-
4), 35.2 (s, C-10), 35.7 (d, C-9), 36.4, 36.5 (2 d, C-5), 40.0 (t, C-12),
41.9 (d, C-8), 49.6 (s, C-13), 50.9 (d, C-17), 62.8, 62.9 (2 t, THP),
70.8, 71.1 (2 d, C-3), 73.4 (t, C-21), 85.6 (s, C-14), 96.7, 96.9 (2 d,
THP-1), 117.6 (d, C-22), 174.5 (s, C-23), 174.6 (s, C-20) ppm.
HRMS (C28H42O5): calcd. 459.3111 [M ϩ H]ϩ, found 459.3113.
Deprotection of 3,4-Di-O-acetyl-7-O-(tetrahydropyran-2Ј-yloxy)de-
carestrictine D (9): 3,4-Di-O-acetyl-7-O-(tetrahydropyran-2Ј-yloxy-
Ethyl (3R)-3-O-(Tetrahydropyran-2Ј-yloxy)pent-4-enoate (11): Ethyl
)decarestrictine D (9; 12.6 mg, 32.8 µmol) was deprotected to afford
(3R)-3-hydroxypent-4-enoate (6; 20 mg, 0.139 mmol) was converted
compound 4 (9.75 mg, 32.5 µmol; 99% yield) by the general pro-
into a diastereomeric mixture (dr ϭ 2:1*) of THP ethers 11
cedure for the cleavage of THP ethers. Spectroscopic and physical
(31.2 mg, 0.137 mmol; 99%) by the general procedure for the intro-
data are mentioned above.
duction of THP ethers. 1H NMR (400 MHz, CDCl3): δ ϭ 1.25,
1.23* (2 t, J ϭ 7.3 Hz, 3 H, CH2ϪCH3), 1.4Ϫ1.8 (m, 6 H, THP),
Deprotection of 3-O-(Tetrahydropyranyl)digitoxygenine (10): 3-O-
2.47* (dd, J ϭ 15.0, 5.5 Hz, 1 H, 2-H), 2.48 (dd, J ϭ 14.9, 5.7 Hz,
(Tetrahydropyranyl)digitoxygenine (10; 12.2 mg, 26.5 µmol) was
1 H, 2-H), 2.61* (dd, J ϭ 15.0, 8.0 Hz, 1 H, 2-H), 2.64 (dd, J ϭ
deprotected to afford digitoxygenine (5; 9.8 mg, 26.2 µmol; 99%)
14.9, 8.1 Hz, 1 H, 2-H), 3.84, 3.48 (2 m, 2 H, OCHOCH2), 4.14,
by the general procedure for the cleavage of THP ethers. Spectro-
scopic and physical data are identical with those of authentic digi-
toxygenine.
4.12* (2 q, J ϭ 7.3 Hz, 2 H, CH2ϪCH3), 4.50* (ddd, J ϭ 8.0, 6.5,
5.5 Hz, 1 H, 3-H), 4.55 (ddd, J ϭ 8.1, 7.7, 5.7 Hz, 1 H, 3-H), 4.69
(dd, J ϭ 3.1, 3.1 Hz, 1 H, ϪOCHOϪ), 4.7* (dd, J ϭ 4.1, 3.0 Hz,
Ethyl (3R)-3-Hydroxypent-4-enoate (6): Ethyl (3R)-3-O-(tetra-
hydropyran-2Ј-yloxy)pent-4-enoate (11; 31.2 mg, 0.137 mmol) was
deprotected to afford compound 6 (19.59 mg, 0.136 mmol; 99%) by
the general procedure for the cleavage of THP ethers. 1H NMR
(400 MHz, CDCl3): δ ϭ 1.26 (t, J ϭ 7.1 Hz, 3 H, CH2ϪCH3), 2.50
(dd, J ϭ 16.1, 8.7 Hz, 1 H, 2-H), 2.57 (dd, J ϭ 16.1, 4.6 Hz, 1 H,
2-H), 3.02 (br. s, 1 H, OH), 4.16 (q, J ϭ 7.1 Hz, 2 H, CH2ϪCH3),
4.53 (ddd, J ϭ 8.7, 4.6, 2.8 Hz, 1 H, 3-H), 5.14 (ddd, J ϭ 10.5, 1.4,
1.4 Hz, 1 H, 5-H), 5.31 (ddd, J ϭ 17.1, 1.4, 1.4 Hz, 1 H, 5-H), 5.87
(ddd, J ϭ 17.1, 10.5, 1.4 Hz, 1 H, 4-H) ppm. 13C NMR (100 MHz,
CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ 14.13 (q, CH3), 41.13 (t, C-2),
60.75 (t, CH2ϪCH3), 68.90 (d, C-3), 115.35 (t, C-5), 138.78 (d, C-
4), 172.22 (s, CϭO) ppm. C7H10O3 (144.17): calcd. C 58.32, H 8.39;
found C 58.35, H 8.31.
1 H, ϪOCHO), 5.11* (ddd, J ϭ 10.5, 1.5, 1.2 Hz, 1 H, 5-HЈ), 5.21,
(dd, J ϭ 10.2, 1.5 Hz, 1 H, 5-HЈ), 5.25* (d, J ϭ 17.2 Hz, 1 H,
1.2 Hz, 5-H), 5.29 (dd, J ϭ 17.1, 1.5 Hz, 1 H, 5-H), 5.66 (ddd, J ϭ
17.1, 10.2, 7.7 Hz, 1 H, 4-H), 5.91* (ddd, J ϭ 17.2, 10.5, 6.5 Hz,
1 H, 4-H) ppm. 13C NMR (100 MHz, CDCl3, CDCl3, δ ϭ 77 ppm):
δ ϭ 14.19 (q, CH2ϪCH3), 18.9, 19.5*, 25.3*, 25.5, 30.4*, 30.7 (6t,
THP), 40.58 (t, C-2), 41.23* (t, C-2), 60.40* (t, CH2ϪCH3), 61.59
(t, CH2ϪCH3), 72.80 (d, C-3), 74.94 (d, C-3), 94.56 (d, THP-1),
98.68* (d, THP-1), 115.53 (t, ϪCHϭCH2), 118.37 (t, ϪCHϭCH2),
136.75 (d, ϪCHϭCH2), 138.34 (d, ϪCHϭCH2), 170.79 (s, CϭO),
170.92 (s, CϭO) ppm. HRMS (C12H20O4): calcd. 229.1440 [M ϩ
H]ϩ, found 229.1441.
(Z)-4-(tert-Butyldimethylsiloxy)-2-methyl-1-(tetrahydropyran-2Ј-
yloxy)-2-butene (12): Dihydropyran (48 µL, 0.53 mmol) and poly-
mer-bound reagent 2 (2 mg) were added to a solution of (Z)-4-(tert-
butyldimethylsiloxy)-2-methyl-2-buten-1-ol (7; 0.1 g, 0.44 mmol) in
dichloromethane (2 mL). After 10 min, the reaction was terminated
by addition of dry Amberlite A-21. After filtration and washing of
the solids with methanol (2 ϫ 2 mL), the combined filtrates were
concentrated under reduced pressure. The crude product was puri-
fied by flash column chromatography on silica gel (petroleum ether/
ethyl acetate, 6:1), yielding compound 12 (0.13 g, 0.43 mmol; 98%)
{(Z)-2,5-Dimethoxy-3-[4-methyl-5-(tetrahydropyran-2Ј-yloxy)pent-
3-enyl]phenyl}amine (14): Amine 13 (98 mg, 0.22 mmol) was dis-
solved in methanol (5 mL), and polymer-bound reagent 2 (1 mg)
was added. The mixture was stirred for 10 min, and the reaction
was terminated by addition of dry Amberlite A-21. After filtration,
the solids were washed with methanol (2 ϫ 5 mL) and the com-
bined filtrates were concentrated under reduced pressure. The crude
product 14 (74 mg, 0.22 mmol) was directly used in the next step
without further purification or analysis.
1
as a colourless oil. H NMR (400 MHz, CDCl3): δ ϭ 0.06 [s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, Si(CCH3)3], 1.86Ϫ1.78 and 1.73Ϫ1.47 (br.
m, 6 H, THP), 1.79 (2 s, 3 H, CH3), 3.54Ϫ3.48 (m, 1 H, THP-5),
3.89Ϫ3.83 (m, 1 H, THP-5), 4.04 (dd, J ϭ 11.7, 0.7 Hz, 1 H, CH2-
1), 4.11 (d, J ϭ 11.7 Hz, 1 H, CH2-1), 4.23 (dq, J ϭ 6.4, 1.1 Hz, 2
H, CH2-4), 4.57 (dd, J ϭ 3.8, 3.1 Hz, 1 H, THP-1), 5.50 (t, J ϭ
6.4 Hz, 1 H, 3-H) ppm. 13C NMR (100 MHz, CDCl3, δ ϭ
77.0 ppm): δ ϭ Ϫ5.1 [q, Si(CH3)2], 18.4 [q, Si(CCH3)3], 19.4 (s, C-
3), 21.6 (q, CH3), 25.5 (s, C-2), 26.0 [q, Si(CCH3)3], 30.6 (s, C-4),
59.6 (s, C-9), 62.1 (s, C-1), 65.5 (s, C-6), 97.6 (t, C-5), 128.9 (t, C-
8), 133.6 (q, C-7) ppm. HRMS (C16H32O3Si): calcd. 301.2199 [M
ϩ H]ϩ, found 301.2201.
(Allyloxycarbamoyl){2,5-dimethoxy-3-[(Z)-4-methyl-5-(tetrahydro-
pyran-2Ј-yloxy)pent-3-enyl]phenyl}amine (15): An aqueous solution
of potassium carbonate (4.2 ; 94 mg, 30 equiv.) and allyloxycar-
bonyl chloride (0.25 mL, 10 equiv.) was added to a solution of
aniline 14 (74 mg, 0.22 mmol) in acetone (5 mL). The reaction mix-
ture was stirred for 20 min and then diluted with brine. The product
was extracted with diethyl ether (3 ϫ 5 mL), the organic phase was
separated and dried (Na2SO4), and the solvent was removed under
reduced pressure. The crude material was purified by column chro-
matography on silica gel (petroleum ether/ethyl acetate, 4:1) to af-
ford compound 15 (90 mg, 0.21 mmol; 95% from 13) as a colourless
1
General Procedure for the Cleavage of THP Ethers: Polymer-bound
diphenylphosphane hydrobromide 2 (2 mg, 6 mol %) was added at
room temperature to a stirred solution of the THP-protected al-
cohol (0.033 mmol) in methanol (5 mL). The mixture was gently
shaken at room temperature for 12 h, filtered through a pad of
oil. H NMR (200 MHz, CDCl3): δ ϭ 1.71Ϫ1.53 (m, 6 H, 2 ϫ 2-
HЈ, 2 ϫ 3-HЈ, 2 ϫ 4-HЈ, ϪTHP), 1.77 (m, 3 H, 2-CH3), 2.42Ϫ2.34
(m, 2 H, 2-H, Ϫpentenyl), 2.69Ϫ2.58 (m, 2 H, 1-H, Ϫpentenyl),
3.55Ϫ3.44 (m, 1 H, 1-HЈ), 3.69 (s, 3 H, OCH3), 3. 77 (s, 3 H,
OCH3), 3.93Ϫ3.81 (m, 1 H, 1-H), 4.08 (m, 2 H, 2 ϫ 6Ј-H), 4.68
Eur. J. Org. Chem. 2004, 3435Ϫ3446
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3441

J. Jaunzems, D. Kashin, A. Schönberger, A. Kirschning
FULL PAPER
(dt, J ϭ 5.7, 1.4 Hz, 2 H, ϪCH2CHϭCH2), 5.28 (dd, J ϭ 10.4, 2.8 3-O-[(2-Deoxy-3,4-di-O-triethylsilyl-α-
L
-fuco-pyranosyl)-(1Ǟ4)-(2-
Hz, 1 H, 1.4 Hz, ϪCH2CHϭCHH), 5.38 (ddd, J ϭ 17.2, 2.8, 1.4
Hz, 1 H, ϪCH2CHϭCHH), 5.40Ϫ5.47 (m, 1 H, 8-H), 5.99 (dddd,
J ϭ 17.2, 10.4, 5.7, 5.7 Hz, 1 H, ϪCH2CHϭCH2), 6.41 (d, J ϭ 3.1
deoxy-3-O-triethylsilyl-α-L-fuco-pyranosyl)]dehydro-epi-andro-
sterone (25): Polymer-bound reagent 2 (1 mg) was added to a solu-
tion of fucal 18 (24 mg, 0.1 mmol) and dehydro-epi-androsterone
Hz, 1 H, Ar), 7.22 (s, 1 H, Ar), 7.61 (s, 1 H, NϪH) ppm. HRMS (24) (28 mg, 0.1 mmol) in dichloromethane (5 mL). The reaction
(C23H33NO6): calcd. 420.2386 [M ϩ H]ϩ, found 420.2390.
mixture was shaken at room temp. for 2 h, after which di-O-silyl-
ated -fucal 22 (40 mg, 0.12 mmol) in dichloromethane (1 mL) was
added. The solution was shaken for another 5 h, and Amberlite A-
21 was then added to terminate the reaction, after which the solvent
was removed under reduced pressure. The crude product was puri-
fied by column chromatography (ethyl acetate/petroleum ether, 1:3,
Rf ϭ 0.62) to yield glycoconjugate 25 (71 mg, 84 µmol; 84%). [α]
(Allyloxycarbamoyl){3-[(Z)-5-hydroxy-4-methyl)pent-3-enyl]-2,5-
(dimethoxy)phenyl}amine (16): Polymer-bound reagent 2 (1 mg) was
added to a solution of THP ether 15 (90 mg, 0.21 mmol) in meth-
anol (5 mL). After 30 h at room temp., the reaction was terminated
by addition of dry Amberlite A-21. After filtration, the solids were
washed with methanol (2 ϫ 5 mL) and the combined filtrates were
concentrated under reduced pressure. The crude product was puri-
fied by flash chromatography on silica gel (petroleum ether/ethyl
acetate, 2:1), yielding compound 16 (64 mg, 0.19 mmol; 90%) as a
23
1
ϭ Ϫ85.6 (c ϭ 1.0, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ
D
0.55Ϫ0.7 [m, 18 H, 3 ϫ Si(CH2CH3)3], 0.88 (s, 3 H, CH3-18),
0.93Ϫ1.02 [m, 27 H, 3 ϫ Si(CH2CH3)3], 1.03 (s, 3 H, CH3-19), 1.13
(d, J ϭ 6.4 Hz, 3 H, CH3-6ЈЈ), 1.17 (d, J ϭ 6.7 Hz, 3 H, CH3-6Ј),
0.9Ϫ2.5 (m, 24 H, CH2-2ЈЈ, CH2-2Ј, androsterone-H), 3.39 (dddd,
J ϭ 11.1, 11.1, 4.6, 4.6 Hz, 1 H, 3-H), 3.56, (br. s, 1 H, 4-HЈЈ), 3.65
(br. d, J ϭ 2.5 Hz, 1 H, 4-HЈ), 3.86 (br. q, J ϭ 6.7 Hz, 1 H, 5-HЈ),
4.05Ϫ4.15 (m, 2 H, 3-HЈ, 3-HЈЈ), 4.31 (br. q, J ϭ 6.4 Hz, 1 H, 5-
HЈЈ), 5.02 (d, J ϭ 2.5 Hz, 1 H, 1-HЈЈ), 5.09 (d, J ϭ 3.1 Hz, 1 H,
1-HЈ), 5.35 (br. d, J ϭ 5.1 Hz, 1 H, 6-H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 5.3, 4.9, 4.8 [3 t, 3 ϫ Si(CH2CH3)3], 7.0,
6.8 [2 q, 3 ϫ Si(CH2CH3)3], 13.5 (q, C-18), 17.6 (q, C-6ЈЈ), 18.0 (q,
C-6Ј), 19.4 (q, C-19), 20.4 (t, C-11), 21.9 (t, C-15), 29.6 (t, C-2),
30.8 (t, C-1), 31.5 (t, C-12), 31.6 (d, C-8), 32.9 (t, C-2ЈЈ), 34.5 (t,
C-2Ј), 35.8 (t, C-16), 36.9 (s, C-10), 37.3 (t, C-7), 38.7 (t, C-4), 47.5
(s, C-13), 50.3 (d, C-9), 51.8 (d, C-14), 66.9 (d, C-3Ј), 67.3 (d, C-
3ЈЈ), 67.5 (d, C-5ЈЈ), 67.6 (d, C-5Ј), 74.0 (d, C-4ЈЈ), 74.9 (d, C-4Ј),
76.1 (d, C-3), 96.0 (d, C-1ЈЈ), 97.8 (d, C-1Ј), 120.7 (d, C-6), 141.2
(s, C-5), 220.9 (s, C-17) ppm. HRMS (C49H90O8Si3): calcd.
891.6022 [M ϩ H]ϩ, found 891.6018.
1
colourless oil. H NMR (400 MHz, CDCl3): δ ϭ 1.77 (m, 3 H, 2-
CH3), 2.35 (dd, J ϭ 15.0, 7.6 Hz, 2 H, 2 ϫ 4-H), 2.63 (m, 2 H, 2
ϫ 5-H), 3.69 (s, 3 H, OCH3), 3.77 (s, 3 H, OCH3), 4.05 (s, 2 H, 1-
H and 1-HЈ), 4.68 (d, J ϭ 5.7 Hz, 2 H, ϪCH2CHϭCH2), 5.27 (dd,
J ϭ 10.5, 1.4 Hz, 1 H, ϪCH2CHϭCHH), 5.32Ϫ5.36 (m, 1 H, 3-
H), 5.37 (dd, J ϭ 17.2, 1.4 Hz, 1 H, ϪCH2CHϭCHH), 5.98 (dddd,
J ϭ 17.2, 10.5, 5.7, 5.7 Hz, 1 H, ϪCH2CHϭCH2), 6.39 (d, J ϭ 3.0
Hz, 1 H, Ar), 7.20 (s, 1 H, Ar), 7.61 (s, 1 H, NϪH) ppm. 13C NMR
(100 MHz, CDCl3, δ ϭ 77.0 ppm): δ ϭ 21.2 (q, 2-CH3), 28.3 (s, C-
4), 30.1 (s, C-5), 55.5 (q, OCH3), 61.1 (p, OCH3), 61.5 (s, C-1),
65.9 (s, ϪCH2CHϭCH2), 109.7 (t, C-3), 118.3 (s, ϪCH2CHϭCH2),
127.2 (t, Ar), 131.9 (q, Ar), 132.4 (t, Ar), 134.9 (q, Ar), 135.4 (q,
C-2), 140.4 (q, Ar), 153.1 (q, Ar), 156.1 (q, CϭO) ppm. HRMS
(C18H25NO5): calcd. 358.1630 [M ϩ Na]ϩ, found 358.1636.
3,4-Di-O-acetyl-7-O-[(2-deoxy-3,4-di-O-triethylsilyl-α-
L-fuco-
pyranosyl)-(1Ǟ4)-(2-deoxy-3-O-triethylsilyl-α- -fuco-pyranosyl)]-
L
decarestrictine D (23): Polymer-bound reagent 2 (1 mg) and LiBr
(5 mg) were added to a solution of -fucal 20 (24 mg, 0.1 mmol)
and decarestrictine (4) (30 mg, 0.1 mmol) in dry dichloromethane.
The reaction mixture was shaken at room temp. for 2 h, after which
fully silylated -fucal 22 (40 mg, 0.12 mmol) in dichloromethane (1
mL) was added. The resulting solution was stirred at room temp.
for another 4 h and the reaction was terminated by the addition of
Amberlite A-21. Filtration was followed by washing of the solid
with ethyl acetate and the concentration of the combined filtrates
under reduced pressure. The crude material was purified by column
chromatography on silica gel (ethyl acetate/petroleum ether, 1:2),
13-O-Glycosylated Baccatin III 28: 7-O-(Triethylsilyl)baccatin III
(26; 68.5 mg, 98 µmol; prepared according to ref.[22]) and tri-O-
silylated galactal 27 (479 mg, 0.98 mmol) were dissolved in dry di-
chloromethane (25 mL), and polymer-bound reagent 2 (50 mg) was
added. The reaction mixture was shaken at room temp. for 24 h
and the reaction was terminated by the addition of Amberlite A-
21. Filtration was followed by washing of the solid with ethyl acet-
ate and the concentration of the combined filtrates under reduced
pressure. The crude material was purified by column chromatogra-
phy on silica gel (ethyl acetate/petroleum ether, 1:8), which afforded
glycosylated baccatin α/β-28.
1
which afforded disaccharide 23 (56 mg, 62 µmol; 62%). H NMR
(400 MHz, CDCl3): δ ϭ 0.6 [m, 18 H, 3 ϫ Si(CH2CH3)3], 0.9 [m,
27 H, 3 ϫ Si(CH2CH3)3], 1.26, 1.23, 1.19 (3 d, J ϭ 6.6, J ϭ 6.5, α-28: First fraction (Rf ϭ 0.54; ethyl acetate/petroleum ether, 1:4):
1
J ϭ 6.4 Hz, 9 H, 10-H, 6-HЈ, 6-HЈ’), 2.1Ϫ1.4 (m, 6 H, 2-H, 2-HЈ, 74 mg, 62 µmol; 63%. [α]2D2 ϭ Ϫ2.5 (c ϭ 1.02, CHCl3). H NMR
2-HЈЈ), 2.17, 2.14 (2 s, 6 H, 2 ϫ OAc), 2.51 (dd, J ϭ 14.0, 2.2 Hz,
1 H, 8-H), 2.67 (dd, J ϭ 14.0, 6.6 Hz, 1 H, 8-H), 3.53 (br. s, 1 H,
(400 MHz, CDCl3): δ(aglycon) ϭ 0.71Ϫ0.5 [m, 6 H, Si(CH2CH3)3],
0.99Ϫ0.87 [m, 9 H, Si(CH2CH3)3], 1.01 (s, 3 H, CH3-16), 1.14 (s, 3
4-HЈЈ), 3.63 (br. d, J ϭ 2.5 Hz, 1 H, 4-HЈ), 3.75 (br. q, J ϭ 6.5 Hz, H, CH3-17), 1.59 (s, 1 H, OH-1), 1.68 (s, CH3-19), 1.88 (ddd, J ϭ
1 H, 5-HЈ), 4.15Ϫ4.0 (m, 3 H, 7-H, 3-HЈ, 3-HЈЈ), 4.30 (br. q, J ϭ
6.4 Hz, 1 H, 5-HЈЈ), 4.83 (d, J ϭ 3.1 Hz, 1 H, 1-HЈЈ), 5.02 (ddd,
14.4, 10.6, 2.0 Hz, 1 H, 6-HЈ), 2.05 (dd, J ϭ 14.6, 9.2 Hz, 1 H, 14-
HЈ), 2.15 (s, 3 H, CH3-18), 2.16 (s, 3 H, CH3CO2Ϫ at position 10),
J ϭ 7.2, 5.0, 2.5 Hz, 1 H, 3-H), 5.06 (d, J ϭ 3.0 Hz, 1 H, 1-HЈ), 2.25 (dd, J ϭ 14.6, 9.2 Hz, 1 H, 14-H), 2.26 (s, 3 H, CH3CO2Ϫ at
5.14 (ddd, J ϭ 9.8, 6.6, 2.2 Hz, 1 H, H-9), 5.33 (m, 1 H, 4-H), 5.60 position 4), 2.53 (ddd, J ϭ 14.4, 9.6, 6.8 Hz, 1 H, 6-H), 3.81 (d,
(ddd, J ϭ 16.0, 9.5, 1.5 Hz, 1 H,, 6-H), 5.77 (ddd, J ϭ 16.0, 8.5, J ϭ 7.0 Hz, 1 H, 3-H), 4.15 (d, J ϭ 8.4 Hz, 1 H, 20-HЈ), 4.30 (d,
3.5 Hz, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3, CDCl3, δ ϭ J ϭ 8.4 Hz, 1 H, 20-H), 4.50 (dd, J ϭ 10.6, 6.8 Hz, 1 H, 7-H), 4.96
77 ppm): δ ϭ 4.7, 4.9, 5.2, 6.8, 7.0 (3 q, 2 t, 3 ϫ TES), 17.3 (q, C-
6ЈЈ), 18.0 (q, C-6Ј), 20.9, 21.0 (2 q, 2 ϫ COCH3), 21.4 (q, C-10),
(dd, J ϭ 9.6, 2.0 Hz, 1 H, 5-H), 5.04 (dd, J ϭ 9.2, 9.2 Hz, 1 H,
13-H), 5.68 (d, J ϭ 7.0 Hz, 1 H, 2-H), 6.51 (s, 1 H, 10-H), 7.48
32.9 (t, C-2Ј), 33.5 (t, C-2), 33.8 (t, C-2ЈЈ), 40.9 (t, C-8), 66.8 (d, C- (dd, J ϭ 8.4, 7.6 Hz, 2 H, Phmeta), 7.61 (tt, J ϭ 7.6, 1.4 Hz, 1 H,
3Ј), 67.3 (d, C-3ЈЈ), 67.5 (d, C-5ЈЈ), 67.7 (d, C-5Ј), 68.3 (d, C-9), Phpara), 8.08 (dd, J ϭ 8.4, 1.4 Hz, 2 H, Phortho) ppm; δ(glycan) ϭ
70.8, 71.8, 71.9 (3 d, C-3, C-4, C-7), 73.8 (d, C-4ЈЈ), 74.5 (d, C-4Ј),
0.71Ϫ0.5 [m, 18 H, Si(CH2CH3)3], 0.99Ϫ0.87 [m, 27 H,
93.5 (d, C-1Ј), 97.7 (d, C-1ЈЈ), 125.9 (d, C-5), 134.0 (d, C-6), 169.0, Si(CH2CH3)3], 1.62 (dd, J ϭ 12.8, 4.2 Hz, 1 H, 2-Heq), 2.21 (ddd,
169.5, 169.9 (3 s, 2 ϫ COCH3, C-1) ppm. HRMS (C44H82O13Si3): J ϭ 12.8, 11.7, 3.0 Hz, 1 H, 2-Hax), 3.52 (dt, J ϭ 6.2, 1.0 Hz, 1 H,
calcd. 903.5142 [M ϩ H]ϩ, found 903.5146.
5-H), 3.66 (d, J ϭ 6.2 Hz, 2 H, 6-H), 3.86 (dd, J ϭ 2.0, 1.0 Hz, 1
3442
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3435Ϫ3446

Applications in Polymer-Assisted Glycosidations
FULL PAPER
H, 4-H), 4.10 (ddd, J ϭ 11.7, 4.2, 2.0 Hz, 1 H, 3-H), 5.13 (d, J ϭ (dd, J ϭ 12.0, 5.0 Hz, 1 H, 6-H), 4.03 (dd, J ϭ 2.6, 1.0 Hz, 1 H,
3.0 Hz, 1 H, 1-H) ppm. 13C NMR (100 MHz, CDCl3): δ(agly-
4-H), 4.10 (ddd, J ϭ 12.0, 5.0, 2.6 Hz, 1 H, 3-H), 5.16 (d, J ϭ 3.0
con) ϭ 5.8Ϫ4.2 [t, Si(CH2CH3)3], 7.0Ϫ6.6 [q, Si(CH2CH3)3], 10.1 Hz, 1 H, 1-H) ppm. 13C NMR (100 MHz, CDCl3): δ(aglycon) ϭ
(q, C-19), 13.9 (q, C-18), 20.8 (q, CH3CO2Ϫ at position 10), 21.5
(q, C-17), 22.4 (q, CH3CO2Ϫ at position 4), 26.4 (q, C-16), 33.4 (t,
9.6 (q, C-19), 14.9 (q, C-18), 20.9 (q, CH3CO2Ϫ at position 10),
22.2 (q, C-17), 22.4 (q, CH3CO2Ϫ at position 4), 26.5 (q, C-16),
C-14), 37.1 (t, C-6), 43.2 (s, C-15), 46.9 (d, C-3), 58.3 (s, C-8), 67.3 35.8, 35.4 (t, 2 C, C-6, C-14), 43.1 (s, C-15), 45.7 (d, C-3), 58.3 (s,
(d, C-13), 72.2 (d, C-7), 75.1 (d, C-2), 75.2 (d, C-10), 76.5 (t, C- C-8), 69.9 (d, C-13), 75.2 (d, C-2), 75.7 (d, C-10), 76.3 (t, C-20),
20), 79.7 (s, C-1), 80.9, (s, C-4), 84.2 (d, C-5), 128.6 (d, 2 C, Phmeta), 77.0 (t, C-7), 80.9, 79.9 (2 s, 2 C, C-4, C-1), 84.4 (d, C-5), 128.7 (d,
129.4 (s, Phipso), 130.1 (d, 2 C, Phortho), 131.9 (s, C-11), 133.6 (d, 2 C, Phmeta), 129.2 (s, Phipso), 130.0 (d, 2 C, Phortho), 131.6 (s, C-
Phpara), 143.5 (s, C-12), 167.1 (s, PhCO2Ϫ), 169.2 (s, CH3CO2Ϫ at 11), 133.8 (d, Phpara), 145.1 (s, C-12), 171.4, 169.8, 167.0 (3 s,
position 10), 171.1 (s, CH3CO2Ϫ at position 4), 202.3. (s, C-9) ppm; CH3CO2Ϫ at positions 4 and 10, PhCO2Ϫ), 204.0. (s, C-9) ppm;
δ(glycan) ϭ 5.8Ϫ4.2 [t, Si(CH2CH3)3], 7.0Ϫ6.6 [q, Si(CH2CH3)3],
δ(glycan) ϭ 32.9 (t, C-2), 63.5 (t, C-6), 65.3 (d, C-3), 69.5 (d, C-4),
35.1 (t, C-2), 62.9 (t, C-6), 67.4 (d, C-3), 70.4 (d, C-4), 73.7 (d, C- 70.3 (d, C-5), 95.2 (d, C-1) ppm. HRMS (C37H48O15): calcd.
5), 93.8 (d, C-1) ppm. HRMS (C61H104O15Si4): calcd. 1189.6531
733.3071 [M ϩ H]ϩ, found 733.3074.
[M ϩ H]ϩ, found 1189.6536.
17-O-[4-O-(3,4-Di-O-acetyl-2,6-dideoxy-α-
L
-arabino-hexopy-
-arabino-hexopy-
ranosyl]testosterone (31b) and 17-O-[4-O-(3,4-Di-O-acetyl-2,6-dide-
oxy-α- -arabino-hexopyranosyl)-(1Ǟ4)-(3-O-benzoyl-2,6-dideoxy-α-
-arabino-hexopyranosyl)]testosterone (31a): Polymer-bound re-
ranosyl)-(1Ǟ4)-(3-O-benzoyl-2,6-dideoxy-β-
L
β-28: Second fraction (Rf ϭ 0.37; ethyl acetate/petroleum ether,
1
1:4): 4.7 mg, 4 µmol; 4.8%. H NMR (400 MHz, CDCl3): δ(agly-
L
con) ϭ 0.71Ϫ0.5 [m, 6 H, Si(CH2CH3)3], 0.99Ϫ0.87 [m, 9 H,
Si(CH2CH3)3], 1.39, 1.07 (2s, 6 H, CH3-16, CH3-17), 1.68 (s, 1 H,
OH), 1.80Ϫ1.72 (m, 1 H, 6Ј-H), 1.87 (s, CH3-19), 2.17 (s, 3 H,
CH3-10), 2.18 (s, 3 H, CH3CO2Ϫ at position 18), 2.27Ϫ2.05 (m, 2
H, 14-H, 14-HЈ), 2.26 (s, 3 H, CH3CO2Ϫ at position 4), 2.50Ϫ2.37
(m, 1 H, 6-H), 3.83 (d, J ϭ 7.0 Hz, 1 H, 3-H), 4.15, 4.07 (2d, J ϭ
12.8 Hz, 2 H, 20-H, 20-HЈ), 4.38 (dd, J ϭ 10.6, 4.4 Hz, 1 H, 7-H),
5.14 (dd, J ϭ 10.4, 2.8 Hz, 1 H, 5-H), 5.20Ϫ5.15 (m, 1 H, 13-H),
5.74 (d, J ϭ 7.0 Hz, 1 H, 2-H), 6.47 (s, 1 H, 10-H), 7.48 (dd, J ϭ
8.4, 7.6 Hz, 2 H, Phmeta), 7.60 (tt, J ϭ 7.6, 1.4 Hz, 1 H, Phpara),
7.79 (dd, J ϭ 8.4, 1.4 Hz, 2 H, Phortho) ppm; δ(glycan) ϭ 0.70Ϫ0.48
[m, 18 H, Si(CH2CH3)3], 1.02Ϫ0.85 [m, 27 H, Si(CH2CH3)3],
1.67Ϫ1.60 (m, 1 H, 2-Heq), 2.27Ϫ2.05 (m, 1 H, 2-Hax), 3.68 (d, J ϭ
7.2 Hz, 2 H, 6-H), 3.74 (dt, J ϭ 7.2, 1.0 Hz, 1 H, 5-H), 3.90 (dd,
J ϭ 2.0, 1.0 Hz, 1 H, 4-H), 4.02Ϫ3.93 (m, 1 H, 3-H), 4.70 (d, J ϭ
7.0 Hz, 1 H, 1-H) ppm. Not all 13C NMR spectroscopic data could
be collected, due to the small amount of material available.
L
agent 2 (2 mg) was added to a mixture of testosterone (3) (28 mg,
0.1 mmol) and disaccharide 30 (44 mg, 0.1 mmol) in dry aceto-
nitrile (5 mL). The resulting suspension was shaken at room temp.
for 24 h, and the reaction was terminated by addition of Amberlite
A-21 (10 mg). The mixture was filtered through a pad of Celite, and
the filtrate was concentrated under reduced pressure. The anomeric
isomers were finally separated by flash column chromatography
(ethyl acetate/petroleum ether, 1:5) to afford two fractions.
31b: First fraction: 10.3 mg, 14 µmol, 14%. 1H NMR (500 MHz,
CDCl3): δ ϭ 2.5Ϫ0.7 (m, 43 H, 2 ϫ CH3CO, 6-HЈ, 6-HЈЈ, 2-HЈ, 2-
HЈЈ, testosterone-H), 3.44 (dq, J ϭ 9.0, 6.1 Hz, 1 H, 5-HЈ), 3.59
(dd, J ϭ 9.0, 9.0 Hz, 1 H, 4-HЈ), 3.69 (t, J ϭ 8.3 Hz, 1 H, 17-H),
3.93 (dq, J ϭ 9.6, 6.2 Hz, 1 H, 5-HЈЈ), 4.56 (dd, J ϭ 9.5, 1.7 Hz,
1 H, 1-HЈ), 4.65 (dd, J ϭ 9.6, 9.5 Hz, 1 H, 4-HЈЈ), 5.15 (m, 2 H,
3-HЈ, 3-HЈЈ), 5.23 (d, J ϭ 3.3 Hz, 1 H, 1-HЈЈ), 5.72 (s, 1 H, 4-H),
7.45 (dd, J ϭ 7.5, 7.5 Hz, 2 H, Phmeta), 7.58 (dd, J ϭ 7.5, 7.5 Hz,
1 H, Phpara), 7.99 (d, J ϭ 7.5 Hz, 2 H, Phortho) ppm. 13C NMR
(125 MHz, CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ 11.6 (q, C-18), 17.3
(q, C-6ЈЈ), 17.4 (q, C-19), 18.6 (q, C-6Ј), 20.6 (t, C-11), 20.8, 20.9
(2 q, 2 ϫ COCH3), 23.2 (t, C-15), 27.5 (t, C-16), 31.6 (t, C-7), 32.8
(t, C-6), 34.0 (t, C-2), 35.3 (d, C-8), 35.5 (t, C-2ЈЈ), 35.7 (t, C-1),
36.6 (t, C-2Ј), 37.1 (t, C-12), 38.7 (s, C-10), 42.4 (s, C-13), 50.6 (d,
C-14), 54.0 (d, C-9), 66.4 (d, C-5ЈЈ), 68.5(d, C-3ЈЈ), 70.5 (d, C-5Ј),
74.7 (d, C-4ЈЈ), 75.0 (d, C-3Ј), 79.6 (d, C-4Ј), 87.2 (d, C-17), 97.7
(d, C-1ЈЈ), 98.1 (d, C-1Ј), 123.8 (d, C-4), 128.6 (d, Phmeta), 129.5 (d,
Phortho), 129.7 (d, Phpara), 133.3 (s, Phipso), 165.4 (s, COPh), 170.0,
170.1 (2s, COCH3), 171.3 (s, C-5), 199.5 (s, C-3) ppm. HRMS
(C42H56O11): calcd. 737.3901 [M ϩ H]ϩ, found 737.3904.
13-O-Glycosylated Baccatin III 29: Tetrabutylammonium fluoride
trihydrate (395 mg, 1.25 mmol) was dissolved under N2 in THF
(12.5 mL), and the mixture was treated with AcOH (0.225 mL,
3.9 mmol; 3.1 equiv. with reference to TBAF). A proportion of this
solution (4 mL; 8 equiv.) was taken, glycosylated baccatin III α-28
(60 mg, 51 µmol) was added, and the mixture was heated under
reflux for 70 h. After the mixture had cooled to room temp., neu-
tralization was achieved by addition of an aqueous solution of hy-
drogencarbonate. After extraction with ethyl acetate and drying of
the organic phase (MgSO4), the filtrate was concentrated in vacuo.
The crude material was purified by column chromatography on
Sephadex (acetone) followed by a second chromatographic step on
silica gel (dichloromethane/MeOH, 20:1) and finally on Sephadex
again (acetone) to yield α-29 (14.9 mg, 20.3 µmol; 40.3%). [α]2D2
ϭ
31a: Second fraction: 33.9 mg, 46 µmol; 46%. 1H NMR (500 MHz,
ϩ121.2 (c ϭ 0.50, CHCl3). 1H NMR (400 MHz, CDCl3): δ(agly- CDCl3): δ ϭ 2.5Ϫ0.7 (m, 43 H, 2 ϫ CH3CO, 6-HЈ, 6-HЈ, 2-HЈ, 2-
con) ϭ 1.11 (s, 3 H, CH3-17), 1.18 (s, 3 H, CH3-16), 1.65 (s, CH3-
HЈЈ, testosterone-H), 3.52 (t, J ϭ 8.5 Hz, 1 H, 8.5 Hz, 17-H), 3.55
19), 1.90Ϫ1.82 (m, 1 H, 6-HЈ), 1.99 (s, 3 H, CH3-18), 2.08 (dd, J ϭ (dd, J ϭ 9.3, 9.1 Hz, 1 H, 4-HЈ), 3.91 (dq, J ϭ 9.3, 6.2 Hz, 1 H,
15.0, 8.4 Hz, 1 H, 14-HЈ), 2.24 (s, 3 H, CH3CO2Ϫ at position 10), 5-HЈ), 3.96 (dq, J ϭ 9.5, 6.2 Hz, 1 H, 5-HЈЈ), 4.66 (dd, J ϭ 9.5, 9.2
2.28 (s, 3 H, CH3CO2Ϫ at position 4), 2.32 (dd, J ϭ 15.0, 8.4 Hz, Hz, 1 H, 4-HЈЈ), 4.91 (d, J ϭ 2.7 Hz, 1 H, 1-HЈ), 5.19 (ddd, J ϭ
1 H, 14-H), 2.54 (ddd, J ϭ 14.4, 9.4, 6.8 Hz, 1 H, 6-H), 3.79 (d,
11.4, 9.2, 5.1 Hz, 1 H, 3-HЈЈ), 5.24 (d, J ϭ 3.1 Hz, 1 H, 1-HЈЈ),
J ϭ 7.2 Hz, 1 H, 3-H), 4.14 (d, J ϭ 8.4 Hz, 1 H, 20-HЈ), 4.31 (d, 5.47 (ddd, J ϭ 11.2, 9.1, 5.1 Hz, 1 H, 3-HЈ), 5.73 (s, 1 H, 4-H),
J ϭ 8.4 Hz, 1 H, 20-H), 4.44 (dd, J ϭ 10.6, 6.8 Hz, 1 H, 7-H), 4.96
7.45 (dd, J ϭ 7.5, 7.5 Hz, 2 H, Phmeta), 7.58 (dd, J ϭ 7.5, 7.5 Hz,
(dd, J ϭ 9.4, 2.4 Hz, 1 H, 5-H), 4.99 (dd, J ϭ 8.4, 8.4 Hz, 1 H, 1 H, Phpara), 8.0 (d, J ϭ 7.5 Hz, 2 H, Phortho) ppm. 13C NMR
13-H), 5.66 (d, J ϭ 7.2 Hz, 1 H, 2-H), 6.30 (s, 1 H, 10-H), 7.50 (125 MHz, CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ 11.7 (q, C-18), 17.3
(dd, J ϭ 8.4, 7.6 Hz, 2 H, Phmeta), 7.62 (t, J ϭ 7.6 Hz, 1 H, Phpara),
8.08 (dd, J ϭ 8.4, 1.4 Hz, 2 H, Phortho) ppm; δ(glycan) ϭ 1.90Ϫ1.82 (2 q, COCH3), 23.4 (t, C-15), 28.5 (t, C-16), 31.6 (t, C-7), 32.8 (t,
(m, 1 H, 2-Heq), 2.12Ϫ2.04 (m, 1 H, 2-Hax), 3. 74 (ddd, J ϭ 5.0, C-6), 33.9 (t, C-2), 35.4 (d, C-8), 35.5 (t, C-2Ј), 35.7 (t, C-2ЈЈ), 35.7
4.2, 1.0 Hz, 1 H, 5-H), 3.85 (dd, J ϭ 12.0, 4.2 Hz, 1 H, 6-HЈ), 3.89 (t, C-1), 37.2 (t, C-12), 38.7 (s, C-10), 42.9 (s, C-13), 50.3 (d, C-14),
(q, C-6ЈЈ), 17.4 (q, C-19), 18.4 (q, C-6Ј), 20.6 (t, C-11), 20.8, 20.9
Eur. J. Org. Chem. 2004, 3435Ϫ3446
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3443

J. Jaunzems, D. Kashin, A. Schönberger, A. Kirschning
FULL PAPER
53.9 (d, C-9), 66.4 (d, C-5Ј), 66.4 (d, C-5ЈЈ), 68.5 (d, C-3ЈЈ), 73.4 O), 171.2 (s, C-5), 199.5 (s, C-3) ppm. HRMS (C25H37N3O4): calcd.
(d, C-3Ј), 74.8 (d, C-4ЈЈ), 80.6 (d, C-4Ј), 87.5 (d, C-17), 97.4 (d, C-
1Ј), 97.8 (d, C-1ЈЈ), 123.8 (d, C-4), 128.6 (d, Phmeta), 129.5 (d, Phor-
tho), 129.9 (d, Phpara), 133.2 (s, Phipso), 165.4(s, COPh), 170.0, 170.1
(2 s, 2 ϫ COCH3), 171.3 (s, C-5), 199.5 (s, C-3) ppm. HRMS
(C42H56O11): calcd. 737.3901 [M ϩ H]ϩ, found 737.3903.
444.2862 [M ϩ H]ϩ, found 444.2865.
36b: 1H NMR (500 MHz, CDCl3): δ ϭ 2.5Ϫ0.7 (m, 32 H, 6-HЈ, 2-
HЈ testosterone-H), 1.20 (d, J ϭ 6.2 Hz, 3 H, 6-HЈ), 1.68 (ddd, J ϭ
14.3, 13.9, 4.8 Hz, 1 H), 2.26 (ddd, J ϭ 14.3, 4.0, 2.3 Hz, 1 H), 3.64
(dd, J ϭ 8.4, 8.4 Hz, 1 H, 17-H), 3.89 (dq, J ϭ 9.3, 6.2 Hz, 1 H,
5-HЈ), 4.16 (ddd, J ϭ 3.5, 3.5, 3.5 Hz, 1 H, 3-HЈ), 4.65 (dd, J ϭ
9.3, 3.5 Hz, 1 H, 4-HЈ), 4.66 (dd, J ϭ 9.2, 2.3 Hz, 1 H, 1-HЈ),
5.71 (s, 1 H, 4-H) ppm. 13C NMR (125 MHz, CDCl3, CDCl3, δ ϭ
77 ppm): δ ϭ 11.6 (q, C-18), 17.4 (q, C-19), 17.9 (q, C-6Ј), 20.6 (t,
C-11), 20.6 (q, COCH3), 23.1 (t, C-15), 27.5 (t, C-16), 31.6 (t, C-
7), 32.8 (t, C-6), 33.9 (t, C-2), 35.5 (d, C-8), 35.7 (t, C-1), 36.6 (t,
C-2Ј), 37.0 (t, C-12), 38.6 (s, C-10), 42.4 (s, C-13), 50.6 (d, C-14),
53.9 (d, C-9), 58.0 (d, C-3Ј), 68.0 (d, C-5Ј), 74.4 (d, C-4Ј), 87.2 (d,
C-17), 96.4 (d, C-1Ј), 123.8 (d, C-4), 170.1 (s, CϭO), 171.2 (s, C-
5), 199.5 (s, C-3) ppm. HRMS (C25H37N3O4): calcd. 444.2862 [M
ϩ H]ϩ, found 444.2865.
4-O-Acetyl-α-
tyl-β- -erythro-hex-2-enopyranosyl Azide (33b), 4-O-Acetyl-1,5-
anhydro-3-azido-2,3,6-trideoxy- -ribo-hex-1-enitol (34a) and 4-O-
Acetyl-1,5-anhydro-3-azido-2,3,6-trideoxy- -arabino-hex-1-enitol
L-erythro-hex-2-enopyranosyl Azide (33a), 4-O-Ace-
L
L
L
(34b): 3,4-Di-O-acetyl--rhamnal (32; 1 g, 4.7 mmol) and solid
NaN3 (0.79 g, 12 mmol) were suspended in absol. acetonitrile (10
˚
mL), and powdered molecular sieves (4 A, 1 g) were added. After
the mixture had been cooled to Ϫ30 °C, boron trifluorideϪdiethyl
ether (1.35 mL, 10 mmol) was slowly added dropwise over 30 min.
The suspension was stirred at the same temperature for another
1 h, and sodium hydrogencarbonate (1 g) was added to the reaction
mixture for neutralization. The mixture was allowed to warm to
room temp. over 30 min while stirring was continued. The resulting
slurry was filtered and washed with ethyl acetate, and the combined
filtrates were concentrated. The crude material obtained was dis-
solved in ethyl acetate and washed with brine. The organic phase
was separated, and the solvent was removed under reduced press-
ure. The crude product mixture was purified by column chromatog-
raphy (ethyl acetate/petroleum ether, 1:10) to yield 33a, 33b, 34a
and 34b (0.9 g, 4.6 mmol, 98% yield) as a colourless oil, which was
directly subjected to the subsequent reaction. The spectroscopic
data are identical to those reported in the literature.[24Ϫ26]
17-O-[(2-Deoxy-3,4-di-O-triethylsilyl-α-
L-fuco-pyranosyl)-(1Ǟ4)-(3-
azido-2,3,6-dideoxy-α- -allo-pyranosyl)]testosterone (37a): Polymer-
L
bound reagent 2 (0.5 mg, 1.5 mol %) was added to a stirred solution
of 36a (11.2 mg, 25.3 µmol) and glycal 22 (10 mg, 2.66 mmol) in
dry dichloromethane (5 mL). The stirring was continued for 24 h,
and was followed by addition of Amberlite A-21 (5 mg). The mix-
ture was filtered through a pad of Celite, and the filtrate was con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography on silica gel (ethyl acetate/petroleum ether,
1
1:3) to afford 37a (16.1 mg, 20 µmol; 80%) as a colourless oil. H
NMR (500 MHz, CDCl3): δ ϭ 2.5Ϫ0.5 (m, 67 H, 6-HЈ, 6-HЈЈ, 2-
HЈ, 2-HЈЈ, testosterone-H, 2 ϫ TES), 3.37 (dd, J ϭ 9.0, 3.2 Hz, 1
H, 4-HЈ), 3.45 (dd, J ϭ 8.5, 8.5 Hz, 1 H, 17-H), 3.59 (s, 1 H, 4-
HЈЈ), 3.74 (q, J ϭ 6.3 Hz, 1 H, 5-HЈЈ), 3.96 (ddd, J ϭ 11.6, 2.4, 4.1
Hz, 1 H, 3-HЈЈ), 4.12 (m, 2 H, 3-HЈ, 5-HЈ), 4.80 (d, J ϭ 3.8 Hz, 1
H, 1-HЈ), 5.09 (d, J ϭ 3.1 Hz, 1 H, 1-HЈЈ), 5.72 (s, 1 H, 4-H) ppm.
13C NMR (125 MHz, CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ 4.8, 5.2,
6.8, 7.0 (2 t, 2 q, 2 ϫ TES), 11.7 (q, C-18), 17.3 (q, C-6ЈЈ), 17.4 (q,
C-6Ј), 17.8 (q, C-19), 20.6 (t, C-11), 23.4 (t, C-15), 28.7 (t, C-16),
31.6 (t, C-7), 32.3 (t, C-2ЈЈ), 32.3 (t, C-2Ј), 32.8 (t, C-6), 33.9 (t, C-
2), 35.5 (d, C-8), 35.7 (t, C-1), 37.1 (t, C-12), 38. 7 (s, C-10), 43.0
(s, C-13), 50.2 (d, C-14), 52.9 (d, C-5Ј), 54.0 (d, C-9), 63.2 (d, C-
3Ј), 67.5 (d, C-3ЈЈ), 68.3 (d, C-5ЈЈ), 73.4 (d, C-4ЈЈ), 74.2 (d, C-4Ј),
88.2 (d, C-17), 93.4 (d, C-1ЈЈ), 96.5 (d, C-1Ј), 123.8 (d, C-4), 171.2
(s, C-5), 199.5 (s, C-3) ppm. HRMS (C43H75N3O7Si2): calcd.
802.5222 [M ϩ H]ϩ, found 802.5218.
Testosteryl 3-Azido-2,3,6-trideoxy-α-
L-allo-pyranoside (36a) and Te-
stosteryl 3-Azido-2,3,6-trideoxy-β- -allo-pyranoside (36b): Polymer-
L
bound reagent 2 (2 mg) was added to a stirred solution of testoster-
one (3) (73 mg, 0.25 mmol) and the azidoglycal mixture 33a/33b/
34a/33b (50 mg, 0.25 mmol) in dry dichloromethane (5 mL). The
stirring was continued for 24 h, and was followed by addition of
Amberlite A-21 (10 mg). The mixture was filtered through a pad
of Celite, and the filtrate was concentrated under reduced pressure.
The products were finally separated by flash column chromatogra-
phy on silica gel (ethyl acetate/petroleum ether, 1:3) to afford the
α-configured glycoconjugate (16 mg, 33 µmol; 13.2%) and the β-
glycoconjugate (15 mg, 31 µmol; 12.4%), together with a mixture
of the two diastereomers (26 mg, 54 µmol; 21.6%). Both anomeric
glycosidation products were separately deacetylated by use of Am-
berlite A-26 (hydroxide form) with 35 in methanol. This was
achieved by dissolving the respective compounds (16 mg, 33 µmol,
and 15 mg, 31 µmol) separately in methanol (5 mL) and addition
of Amberlite A-26 (hydroxide form; 0.1 g) to each reaction vessel.
The resulting suspensions were shaken for 24 h, after which the
reaction mixtures were filtered. The filtrates were concentrated un-
der reduced pressure to afford alcohols 36a (11.2 mg, 25.3 µmol;
82%) and 36b (11.6 mg, 26.2 µmol, 80% yield).
17-O-[(2-Deoxy-3,4-di-O-triethylsilyl-α-L-fuco-pyranosyl)-(1Ǟ4)-(3-
azido-2,3,6-dideoxy-β- -allo-pyranosyl)]testosterone (37b): The β-
L
configured glycoconjugate 36b (11.6 mg, 26 µmol) was transformed
into disaccharide 37b (14.6 mg, 18.2 µmol; 70%) under conditions
identical to those described for glycoside 36a. 1H NMR (500 MHz,
CDCl3): δ ϭ 2.5Ϫ0.7 (m, 67 H, 6-HЈ, 6-HЈЈ, 2-HЈ, 2-HЈЈ, testoster-
one-H, 2 ϫ TES), 3.37 (dd, J ϭ 9.0, 3.2 Hz, 1 H, 4-HЈ), 1.16 (d,
J ϭ 6.3 Hz, 3 H, 6-HЈЈ), 1.25 (d, J ϭ 6.2 Hz, 3 H, 6-HЈ), 3.53 (dd,
1
36a: H NMR (500 MHz, CDCl3): δ ϭ 2.5Ϫ0.7 (m, 32 H, 6-HЈ, 2- J ϭ 8.9, 3.2 Hz, 1 H, 4-HЈ), 3.60 (br. s, 1 H, 4-HЈЈ), 3.64 (dd, J ϭ
HЈ testosterone-H), 3.45 (dd, J ϭ 8.5, 8.5 Hz, 1 H, 17-H), 4.15
(ddd, J ϭ 3.4, 3.4, 3.4 Hz, 1 H, 3-HЈ), 4.22 (dq, J ϭ 9.6, 6.2 Hz,
8.3, 8.3 Hz, 1 H, 17-H), 3.79 (br. q, J ϭ 6.3 Hz, 1 H, 5-HЈЈ), 3.85
(dq, J ϭ 8.9, 6.2 Hz, 1 H, 5-HЈ), 3.95 (ddd, J ϭ 11.7, 4.1, 2.4 Hz,
1 H, 5-HЈ), 4.57 (dd, J ϭ 9.6, 3.4 Hz, 1 H, 4-HЈ), 4.83 (d, J ϭ 3.8 1 H, 3-HЈЈ), 4.17 (ddd, J ϭ 3.2, 3.2, 3.2 Hz, 1 H, 3-HЈ), 4.65 (dd,
Hz, 1 H, 1-HЈ), 5.72 (s, 1 H, 4-H) ppm. 13C NMR (125 MHz, J ϭ 9.0, 1.5 Hz, 1 H, 1-HЈ), 5.08 (d, J ϭ 3.1 Hz, 1 H, 1-HЈЈ),
CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ 11.6 (q, C-18), 17.1 (q, C-6Ј), 5.72 (s, 1 H, 4-H) ppm. 13C NMR (125 MHz, CDCl3, CDCl3, δ ϭ
17.4 (q, C-19), 20.6 (t, C-11), 20.8 (q, COCH3), 23.4 (t, C-15), 28.6
77 ppm): δ ϭ 4.8, 5.2, 6.8, 7.0 (2 t, 2 q, 2 ϫ TES), 11.6 (q, C-18),
(t, C-16), 31.5 (t, C-7), 32.3 (t, C-2Ј), 32.8 (t, C-6), 33.9 (t, C-2), 17.2 (q, C-6ЈЈ), 17.4 (q, C-19), 18.5 (q, C-6Ј), 20.6 (t, C-11), 23.2
35.4 (d, C-8), 35.7 (t, C-1), 37.0 (t, C-12), 38.6 (s, C-10), 43.0 (s, C-
13), 50.1 (d, C-14), 53.9 (d, C-9), 55.0 (d, C-3), 62.0 (d, C-5Ј), 73.5
(d, C-4Ј), 88.4 (d, C-17), 96.3 (d, C-1Ј), 123.8 (d, C-4), 170.1 (s, Cϭ
(t, C-15), 27.5 (t, C-16), 31.6 (t, C-7), 31.9 (t, C-2ЈЈ), 32.8 (t, C-6),
34.0 (t, C-2), 35.5 (d, C-8), 35.7 (t, C-2Ј), 35.7 (t, C-1), 36.6 (t, C-
12), 38.7 (s, C-10), 42.4 (s, C-13), 50.6 (d, C-14), 54.0 (d, C-9), 55.8
3444
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3435Ϫ3446

Applications in Polymer-Assisted Glycosidations
FULL PAPER
(d, C-3Ј), 67.4 (d, C-3ЈЈ), 68.4 (d, C-5ЈЈ), 69.0 (d, C-5Ј), 73.4 (d, C-
chromatography on silica gel (ethyl acetate/petroleum ether, 1:4) to
4ЈЈ), 75.4 (d, C-4Ј), 87.1 (d, C-17), 94.3 (d, C-1ЈЈ), 96.6 (d, C-1Ј), afford disaccharide 39 (77.5 mg, 87 µmol; 87%). 1H NMR
123.8 (d, C-4), 171.3 (s, C-5), 199.5 (s, C-3) ppm. HRMS
(400 MHz, CDCl3): δ ϭ 2.5Ϫ0.5 (m, 82 H, 3 ϫ TES, 6-HЈ, 6-HЈЈ,
2-HЈ, 2-HЈЈ, testosterone-H), 3.45 (t, J ϭ 8.2 Hz, 1 H, 17-H), 3.55
(br. s, 1 H, 4-HЈЈ), 3.65 (br. d, J ϭ 2.4 Hz, 1 H, 4-HЈ), 3.80 (br. q,
J ϭ 6.8 Hz, 1 H, 5-HЈ), 4.10 (m, 2 H, 3-HЈ, 3-HЈЈ), 4.30 (br. q, J ϭ
6.3 Hz, 1 H, 5-HЈЈ), 4.89 (d, J ϭ 2.9 Hz, 1 H, 1-HЈЈ), 5.09 (d, J ϭ
2.8 Hz, 1 H, 1-HЈ), 5.72 (s, 1 H, 4-H), 5.09 (d, J ϭ 2.8 Hz, 1 H, 1-
HЈ) ppm. 13C NMR (100 MHz, CDCl3, CDCl3, δ ϭ 77 ppm): δ ϭ
4.8 4.9, 5.1, 5.2, 6.7, 6.8, 7.0, (3 ϫ TES), 11.5 (q, C-18), 17.4 (q,
C-6ЈЈ), 17.5 (q, C-6Ј), 17.9 (q, C-19), 20.6 (t, C-11), 23.4 (t, C-15),
26.9(t), 28.6 (t, C-16), 31.5 (t, C-7), 32.9 (t, C-6), 33.9 (t, C-2), 34.3
(t, C-2ЈЈ), 35.4 (d, C-8), 35.5 (t, C-2Ј), 35.7 (t, C-1), 37.1 (t, C-12),
38.6 (s, C-10), 42.8 (s, C-13), 50.1 (d, C-14), 53.9 (d, C-9), 66.9,
67.3, 67.6, 67.8, 73.9, 74.9, (6d, C-3Ј, C-4Ј, C-5Ј, C-3ЈЈ, C-4ЈЈ, C-
5ЈЈ), 87.5 (d, C-17), 97.7 (d, C-1Ј), 98.9 (d, C-1ЈЈ), 123.8 (d, C-4),
171.1 (s, C-5), 199.4 (s, C-3) ppm. HRMS (C48H86O8Si3): calcd.
890.5934 [M ϩ H]ϩ, found 890.5937.
(C43H75N3O7Si2): calcd. 802.5222 [M ϩ H]ϩ, found 802.5221.
17-O-[(2-Dideoxy-α-
L-fuco-pyranosyl)-(1Ǟ4)-(3-amino-2,3,6-
dideoxy-α- -allo-pyranosyl)]testosterone (38a): A solution of TBAF
L
in THF (1 , 60 µL, 60 µmol) was added to a solution of glycocon-
jugate 37a (16.1 mg, 20 µmol) in THF (1 mL). After the solution
had been stirred for 4 h at room temp., polymer-bound diphenyl-
phosphane 1 (20 mg, 1.1 mmol/g) was added. The suspension was
stirred at room temperature for 24 h and the polymers were filtered
off. The resulting filtrate was concentrated under reduced pressure,
and the residue was purified by column chromatography (ethyl
acetate/EtOH, 6:1) to yield glycoconjugate 38a (10 mg, 18.3 µmol;
91%) as a colourless film. 1H NMR (500 MHz): δ ϭ 2.6Ϫ0Ϫ7 (m,
37 H, 6-HЈ, 6-HЈЈ, 2-HЈ, 2-HЈЈ, testosterone-H), 3.46 (dd, J ϭ 9.4,
3.8 Hz, 1 H, 4-HЈ), 3.52 (dd, J ϭ 7.1, 3.8 Hz, 1 H, 3-HЈ), 3.59 (t,
J ϭ 8.5 Hz, 1 H, 17-H), 3.61 (br. d, J ϭ 2.6 Hz, 1 H, 4-HЈЈ), 3.98
(m, 3 H, 3-HЈЈ, 5Ј-H, 5ЈЈ-H), 4.92 (d, J ϭ 2.8 Hz, 1 H, 1-HЈ), 5.10
(d, J ϭ 3.3 Hz, 1 H, 1-HЈЈ), 5.75 (s, 1 H, 4-H) ppm. 13C NMR
(125 MHz, CD3OD, δ ϭ 49 ppm): δ ϭ 12.2 (q, C-18), 17.7, 17.1 (2
q, C-6Ј, C-6ЈЈ), 18.6 (q, C-19), 21.7 (t, C-11), 23.0 (q,
CH3COOϪ),24.3 (t, C-15), 29.8 (t, C-16), 32.8 (t, C-7), 33.0 (t, C-
2ЈЈ), 33.9 (t, C-6), 34.2 (t, C-2Ј), 34.7 (t, C-2), 36.7 (d, C-8), 36.8
(t, C-1), 38.3 (t, C-12), 40.0 (s, C-10), 44.0 (s, C-13), 45.6 (d, C-
3ЈЈ), 51.3 (d, C-14), 55.4 (d, C-9), 63.4 (d, C-5Ј), 66.8, 68.5 (2 d, C-
3ЈЈ, C-5ЈЈ), 72.1 (d, C-4ЈЈ), 76.3 (d, C-4Ј), 89.7 (d, C-17), 95.4 (d,
C-1ЈЈ), 99.1 (d, C-1Ј), 124.2 (d, C-4), 175.0 (s, C-5), 202.3 (s, C-3)
ppm. LC-LRMS (ESI): m/z (%) ϭ 546.34 (60) [M Ϫ H]Ϫ. HRMS
(C31H48NO7): calcd. 546.3431, found 546.3431.
17-O-[(2-Dideoxy-α-L-fuco-pyranosyl)-(1Ǟ4)-(2-dideoxy-α-L-fuco-
pyranosyl)]-testosterone (40): Glycoconjugate 39 (67 mg, 75 µmol)
was mixed with polymer-bound TBAT 42 (200 mg, 10 equiv.) in
acetonitrile (10 mL). This suspension was shaken at room temp.
for 48 h and the polymer was filtered off. The solid was washed
with methanol, and the combined filtrates were concentrated under
reduced pressure. The crude product was purified by column chro-
matography on silica gel (ethyl acetate; Rf ϭ 0.14) to afford com-
1
pound 40 (29 mg, 52 µmol; 70%). H NMR (500 MHz, CD3OD):
δ ϭ 2.5Ϫ0.7 (m, 31 H, 2-HЈ, 2-HЈ, testosterone-H), 1.26, 1.21 (2d,
J ϭ 6.5 and J ϭ 6.4 Hz, 6 H, 6-HЈ, 6-HЈЈ), 3.54 (t, J ϭ 8.5 Hz, 1
H, 17-H), 3.59 (br. d, J ϭ 2.2 Hz, 1 H, 4-HЈЈ), 3.62 (br. d, J ϭ
2.0 Hz, 1 H, 4-HЈ), 3.95 (br. q, J ϭ 6.5 Hz, 1 H, 5-HЈ), 3.98 (ddd,
J ϭ 11.8, 4.9, 2.0 Hz, 1 H, 3-HЈ), 4.04 (ddd, J ϭ 11.8, 5.9, 2.2 Hz,
1 H, 3-HЈЈ), 4.28 (br. q, J ϭ 6.4 Hz, 5-HЈЈ), 4.95 (d, J ϭ 3.7 Hz, 1
H, 1-HЈ), 4.96 (d, J ϭ 4.6 Hz, 1 H, 1-HЈЈ), 5.73 (s, 1 H, 4-H) ppm.
13C NMR (125 MHz, CD3OD, δ ϭ 49 ppm): δ ϭ 12.1 (q, C-18),
17.1, 17.5 (2 q, C-6Ј, C-6ЈЈ), 17.7 (q, C-19), 21.8 (t, C-11), 24.3 (t,
C-15), 29.6 (t, C-16), 32.8 (t, C-7), 33.3 (t, C-2ЈЈ), 33.9 (t, C-6), 34.7
(2 t, C-2Ј, C-2), 36.7 (d, C-8), 36.8 (t, C-1), 38.4 (t, C-12), 40.0 (s,
C-10), 44.0 (s, C-13), 51.5 (d, C-14), 55.5 (d, C-9), 66.7, 66.7 (2 d,
C-3ЈЈ, C-3Ј), 68.1 (d, C-5Ј), 68.5 (d, C-5ЈЈ), 72.3 (d, C-4ЈЈ), 81.7 (d,
C-4Ј), 88.6 (d, C-17), 99.9 (d, C-1Ј), 101.4 (d, C-1ЈЈ), 124.1 (d, C-
4), 175.1 (s, C-5), 202.3 (s, C-3) ppm. LCMS (ESI): m/z (%) ϭ
547.33 (90) [M Ϫ H]Ϫ, 548.33 (25) [M]. HRMS (C31H47O8): calcd.
547.3271[M ϩ H]ϩ, found 547.3278.
17-O-[(2-Dideoxy-α-
L-fuco-pyranosyl)-(1Ǟ4)-(3-amino-2,3,6-
dideoxy-β- -allo-pyranosyl)]testosterone (38b): The β-configured
L
glycoconjugate 37b (14.6 mg, 18.2 µmol) was transformed into di-
saccharide 38b (7.1 mg, 13 µmol; 71%) under reaction conditions
identical to those described for the preparation of glycoside 38a.
1H NMR (500 MHz, CD3OD): δ ϭ 2.5Ϫ0.7 (m, 37 H, 6-HЈ, 6-HЈЈ,
2-HЈ, 2-HЈЈ, testosterone-H), 3.53 (dd, J ϭ 7.0, 3.6 Hz, 1 H, 4-HЈ),
3.61 (br. s, 1 H, 4-HЈЈ), 3.73 (br. q, J ϭ 6.2 Hz, 1 H, 5-HЈЈ), 3.77
(dd, J ϭ 8.1, 8.1 Hz, 1 H, H-17), 3.97 (m, 3 H, 3-HЈ, 3-HЈЈ, 5-HЈ),
4.93 (dd, J ϭ 7.1, 2.6 Hz, 1 H, 1-HЈ), 5.07 (d, J ϭ 3.4 Hz, 1 H, 1-
HЈЈ), 5.75 (s, 1 H, 4-H) ppm. 13C NMR (125 MHz, CD3OD, δ ϭ
49 ppm): δ ϭ 12.1 (q, C-18), 17.1 (q, C-6ЈЈ), 17.7 (q, C-19), 19.8
(q, C-6Ј), 21.7 (q, CH3COOϪ), 22.7 (t, C-11), 24.2 (t, C-15), 28.3
(t, C-16), 32.9 (t, C-2ЈЈ), 33.0 (t, C-7), 33.9 (t, C-6), 34.7 (t, C-2),
35.0 (t, C-2Ј), 36.7 (d, C-8), 36.8 (t, C-1), 38.1 (t, C-12), 40.0 (s, C-
10), 43.6 (s, C-13), 45.5 (d, C-5Ј), 51.9 (d, C-14), 55.5 (d, C-9), 66.8
(d, C-5ЈЈ), 68.5 (d, C-3ЈЈ), 70.7 (d, C-3Ј), 72.1 (d, C-4ЈЈ), 77.1 (d,
C-4Ј), 87.3 (d, C-17), 97.0 (d, C-1Ј), 97.7 (d, C-1ЈЈ), 124.1 (d, C-
4), 175.1 (s, C-5), 202.3 (s, C-3) ppm. HRMS (C31H49NO7): calcd.
547.3497 [M ϩ H]ϩ, found 547.3512.
Acknowledgments
This work was supported by the DFG (SFB 416, project B2) and
the Fonds der Chemischen Industrie. D. K. thanks the Ministerium
für Wissenschaft and Kultur (MWK), Niedersachsen for a scholar-
ship. We thank Markus Kalesse (Hannover) for providing alcohol
6. We are grateful to AnalytiCon Discovery (Potsdam) for a do-
nation of deacetyl-baccatin III.
17-O-[(2-Deoxy-3,4-di-O-triethylsilyl-α-
L-fuco-pyranosyl)-(1Ǟ4)-(2-
deoxy-3-O-triethylsilyl-α- -fuco-pyranosyl)]testosterone (39): Poly-
L
mer-bound reagent 2 (1 mg) and LiBr (5 mg) were added to a solu-
tion of fucal 20 (24 mg, 0.1 mmol) and testosterone (3) (28 mg,
0.1 mmol) in dichloromethane (3 mL). The reaction mixture was
shaken at room temp. for 2 h, after which di-O-silylated -fucal 22
(40 mg, 0.12 mmol) in dichloromethane (1 mL) was added. The
resulting suspension was shaken at room temp. for another 4 h, and
the reaction was finally terminated after addition of Amberlite A-
21 (10 mg). The polymers were filtered off and washed with ethyl
acetate, and the combined filtrates were concentrated under re-
duced pressure. The crude material was finally purified by column
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3445

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Received February 2, 2004
3446
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Eur. J. Org. Chem. 2004, 3435Ϫ3446