New diacylamino protecting groups for glucosamine

Article abstract of DOI:10.1002/ejoc.200500107

Glucosamine was 'transformed into N-diphenylmaleoyl (DPM), N-(3,3-dimethylglutaryl) (DMG), and N-diglycolyl (DG) derivatives which furnished O-acetyl-protected O-glycosyl trichloroacetimidates 3, 12, and 20, respectively, as glycosyl donors. Their reactio

Full text of DOI:10.1002/ejoc.200500107

FULL PAPER
New Diacylamino Protecting Groups for Glucosamine
Mohamed R. E. Aly[a] and Richard R. Schmidt*[a]
Dedicated to Professor András Liptak on the occasion of his 70th birthday
Keywords: Carbohydrates / Protecting groups / Amino sugars / Glycosylation / Trichloroacetimidates
Glucosamine was transformed into N-diphenylmaleoyl
(DPM), N-(3,3-dimethylglutaryl) (DMG), and N-diglycolyl
(DG) derivatives which furnished O-acetyl-protected O-gly-
cosyl trichloroacetimidates 3, 12, and 20, respectively, as gly-
cosyl donors. Their reactions with various acceptors 4 in the
presence of TMSOTf as catalyst afforded the corresponding
β-glycosides 5a–c, 13a–e, and 21a,d,f,g generally in high
yields. Investigations into the cleavage of the N-protecting
groups led to good results for the DPM and DG groups. 3-O-
Unprotected glucosamine derivative 24 with N-DG protec-
tion also served well as an acceptor, as shown in its reaction
with galactosyl donor 25 which led to disaccharide 26 in very
high yield.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
An important constituent of glycoconjugates is d-glu-
cosamine which is mainly found as an N-acetyl derivative
in β-glycosidic linkages.[1,2] Glycoside bond formation with
donors derived from N-acetylglucosamine (GlcNAc) gen-
erally occurs by neighbouring-group participation to give a
1,3-oxazolinium intermediate,[3,4] that is, a cyclic imidate,
that exhibits only weak glycosyl donor properties. In ad-
dition, O-glycosylation of acetamido groups, that is, inter-
molecular imidate formation, has also been observed as a
side-reaction.[5] Therefore, the replacement of the N-acetyl
group by strongly electron-withdrawing groups, such as the
trifluoroacetyl, trichloroacetyl,[6,7] and trichloroethoxycar-
bonyl groups,[8–12] respectively, have been investigated in or-
der to avoid the formation of stable cyclic imidate interme-
diates which impede glycoside bond formation. However,
similar to the N-acetyl group, the structural assignment of
these groups by NMR spectroscopy can be hampered when
rotation around the amidic CN bond is hindered. Hence,
C2-symmetric N,N-diacyl compounds should be ideal
amino-protecting groups, for example, two noncyclic N-acyl
groups[13] or cyclic N,N-diacyl groups such as phthaloyl
(Phth),[1–4] tetrachlorophthaloyl (TCP),[14,15] dithiasuccinyl
(DTS),[16] dimethylmaleoyl (DMM),[17] and thiodiglycolyl
(TDG) groups.[18] Indeed, formation of stable imidate inter-
mediates and difficulties in structural assignment can be
avoided by using such protecting groups (Scheme 1).
Scheme 1. Diacylamino protecting groups.
In addition, owing to the strong electron-withdrawing
character of the nitrogen substituents, these glucosamine
derivatives also exhibit increased glycosylic donor proper-
ties. The 2-azido group has also gained widespread use in
this regard[1–4,19–21] because, particularly in combination
with the nitrile effect, high β-selectivities can also be ob-
tained.[1,22] However, all these groups also exhibit some dis-
advantages which have been discussed in detail pre-
viously.[12,14] Therefore, we have turned our attention to the
use of diphenylmaleoyl (DPM), 3,3-dimethylglutaryl
(DMG), and diglycolyl (DG) groups as amino protecting
[a] Fachbereich Chemie, Universität Konstanz,
Fach M 725, 78457 Konstanz, Germany
Fax: +49-7531-88-3135
E-mail: Richard.Schmidt@uni-konstanz.de
4382
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200500107
Eur. J. Org. Chem. 2005, 4382–4392

New Diacylamino Protecting Groups for Glucosamine
FULL PAPER
groups (Scheme 1) because it was hoped that even better in satisfactory yields. Owing to the fluorescent properties
properties than those found for the DMM group would be of the products, monitoring of the reaction by TLC was
found; this group also proved to be successful in several convenient. The DPM group in 5a–c could readily be re-
complex oligosaccharide solid-support syntheses.[23,24]
moved with hydrazine hydrate in refluxing ethanol and sub-
sequent N,O-acetylation in acetic anhydride/pyridine gave
the known target molecules 6a,[12] 6b,[17] and 6c.[29] How-
ever, the much milder ring-opening of the diphenylmaleim-
ido ring with NaOH followed by removal of DPMA by
treatment with acid at pH Ϸ 5, a method that works very
well with the DMM group,[17] gave only modest results; for
instance, with compound 5c, compound 6c was obtained in
only 22% yield. Hence, the two methyl groups in the DMM
moiety seem to support ring–chain tautomerism in favour
of the amide hemiacetal required for acid-supported
DMMA cleavage more strongly than the two phenyl groups
in the DPM moiety. Therefore, besides the fluorescent prop-
erties, the DPM group exhibits no advantages over the
DMM group in terms of the ease of attachment, glycosyla-
tion yields, or ease of cleavage.
Results and Discussion
The DPM Group
The fluorescent DPM group was investigated because it
was expected that mild conditions would be sufficient for
its attachment and cleavage, as observed for the DMM
group; in addition, the presence and absence of this group
can be readily monitored by fluorescence spectroscopy.
Zehavi[25] used this group in 1976 as a protecting group for
amino functions in sugars and steroids. Glycosylation reac-
tions were studied with only methanol as an acceptor and
deprotection was effected by ethanolic hydrazine. The N-
DPM-protected per-O-acetyl glucosamine 1 was readily ob-
tained from glucosamine by treatment with DPM anhydride
(DPMA) and acetic anhydride in pyridine (Scheme 2).
Chemoselective 1-O-deacetylation with hydrazinium acetate
in DMF (Ǟ 2) and then reaction with trichloroacetonitrile
in the presence of DBU as base afforded the desired trichlo-
roacetimidate 3 as glucosyl donor.
Figure 1. HOR acceptors used in reactions with glycosyl donors 3,
12, and 20.
The DMG Group
Amino protecting groups derived from glutaric acid have
been employed in neither oligosaccharide nor peptide syn-
thesis. 3,3-Dialkylglutaryl derivatives should be reasonable
derivatives because one of the carbonyl groups provides an-
chimeric assistance for the β-glycosidic linkage and, similar
to the DMM group, convenient cleavage by base and then
acid treatment should be supported by the geminal dialkyl
effect[30] of the two alkyl substituents at the 3-position.
Therefore, commercially available 3,3-dimethylglutaric
(DMG) anhydride was chosen although attachment of this
group to glucosamine turned out to be more difficult than
the attachment of DPM. Good results were obtained in the
Scheme 2. Synthesis and reactions of DPM-protected glycosyl do-
nor 3. Reagents and conditions: (a) NaOMe, MeOH; DPMA,
Ac2O, Pyr (35%); (b) N2H4·HOAc (94%); (c) CCl3CN, DBU
(63%); (d) TMSOTf (0.01 equiv.), CH2Cl2 (5a: 68%; 5b: 68%; 5c:
68%); (e) N2H4·H2O, EtOH, reflux; Ac2O, Pyr (6a: 68%; 6b: 90%;
6c: 63%); (f) NaOH, dioxane/H2O; HCl (pH 5.0); Ac2O, Pyr (6c:
22%).
The glycosylation of known 6-O-, 3-O-, and 4-O-unpro- reaction of N-(4-methoxybenzylidene)glucosamine (7)[31]
tected sugars 4a,[26] 4b,[27] and 4c[28] as acceptors (Figure 1) with benzyl bromide and sodium hydride in DMF followed
with 3 as donor in the presence of TMSOTf as catalyst in by hydrolytic removal of the N-protecting group to afford
dichloromethane led exclusively to β-linked glycosides 5a–c the known amino derivative 8 (Scheme 3).[32]
Eur. J. Org. Chem. 2005, 4382–4392
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4383

M. R. E. Aly, R. R. Schmidt
FULL PAPER
forded only the ring-opened product, which, after acety-
lation, yielded compound 15. Hence, anchimeric assistance
of the DMG group in the glycosylation step seems to be
optimal, however the cleavage reaction needs to be im-
proved.
Scheme 4. Cleavage reactions of 9 and 13e.
The DG Group
In order to maintain the excellent anchimeric assistance
of a six-membered cyclic imido group at the 2-position of
amino sugars in glycosylation reactions yet improve its
cleavability, the dimethylmethylene group in DMG was re-
placed by an electron-withdrawing oxygen atom to give the
diglycolyl (DG) group as the amino protecting group.
Clearly, the TDG group is closely related to the DG group,
however, it lacks the electron-withdrawing effect of the oxy-
gen atom and the presence of the sulfur atom often inter-
feres with oxidative or hydrogenolytic removal of protecting
groups, thus limiting the versatility of this group. The DG
group was readily attached starting from 8 or its hydrochlo-
ride. Heating with diglycolyl anhydride (DGA) in acetic an-
hydride/pyridine afforded N-DG-protected derivative 16
(Scheme 5).
Scheme 3. Synthesis and reactions of DMG-protected glycosyl do-
nor 12. Reagents and conditions: (a) NaH, BnBr, DMF (82%); 5 n
HCl, Me2CO; (b) DMGA, Ac2O, Pyr (quant.); (c) Pd/C, H2; Ac2O,
Pyr (98%); (d) N2H4·HOAc (99%); (e) CCl3CN, DBU (80%); (f)
TMSOTf (0.01 equiv.), CH2Cl2 (13a: 90%; 13b: 96%; 13c: 81%;
13d: 92%; 13e: 93%).
Hydrogenolytic O-debenzylation (Ǟ 17), O-acetylation
(Ǟ 18), selective 1-O-deacetylation, and then treatment
with trichloroacetonitrile in the presence of DBU as base
Then reaction with DMGA in pyridine/acetic anhydride afforded the desired trichloroacetimidate 20 in high overall
furnished the desired N-DMG-protected glucosamine 9. yield. Glycosylation of acceptors 4a,[26] 4d,[33] and 4f[34]
Hydrogenolytic O-debenzylation and O-acetylation led to with 20 under standard conditions furnished very good gly-
per-O-acetyl derivative 10. Selective removal of the 1-O-ace- cosylation results and only the β-anomers 21a, 21d, and 21f
tyl group with hydrazinium acetate (Ǟ 11) and base-cata- were obtained, thus illustrating the excellent anchimeric as-
lyzed reaction with trichloroacetonitrile led to trichloroace- sistance provided by the DG group. Similarly, with 1,3,5-
timidate 12. Glycosylation of acceptors 4a–e[27–29,33] with trimethoxybenzene as acceptor C-glycoside 21g was ob-
12 under standard conditions, that is, trimethylsilyl trifluor- tained in very good yield. Deprotection of intermediate 16
omethanesulfonate catalysis in dichloromethane, afforded with KOH in refluxing ethanol, NaOBu in butyl alcohol,
the desired β-glycosides in almost quantitative yields hydrazine hydrate, and hydrazine in refluxing ethanol fol-
(Scheme 4), thus illustrating the power of this glycosyl do- lowed by N-acetylation afforded N-acetyl-protected deriva-
nor. However, unexpectedly, the cleavage of the DMG tive 22[35,36] in 82, 69, 38, and 3% yields, respectively. Hence,
group turned out to be very difficult; neither hydrazine in deprotection of 21a, 21d, and 21g was carried out using the
ethanol nor base and ensuing acid treatment was successful. first method, providing, after acetylation, target molecules
For instance, the reaction of 13e with base and ensuing acid 6a,[12] 6d,[17] and 6g[37] in very good yields.
treatment led only to ring-opening, which, after acetylation,
This success encouraged us to investigate the acceptor
afforded compound 14 as the product (Scheme 4). Even properties of a DG-containing acceptor. Because the hy-
heating of O-benzyl-protected 9 with hydrazine hydrate af- droxy group next to the DG-protected amino group is par-
4384
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4382–4392

New Diacylamino Protecting Groups for Glucosamine
FULL PAPER
Scheme 6. Reaction of galactosyl donor 25 with acceptor 24. Rea-
gents and conditions: (a) PhCH(OMe)2, pTsOH, CH3CN/DMF
(55%); (b) TBDMS-Cl, imidazole, CH2Cl2 (79%); (c) TMSOTf
(0.01 equiv.), CH2Cl2, room temp. (91%).
with the DG group, which could also be removed under
basic conditions in high yields. In addition, the DG group
is compatible with glycosylation at a vicinal hydroxy group
which functions as an accepting group in glycosylation re-
actions. Hence, the DG group is at least as competitive as
or even superior to the standard anchimerically assisting
amino protecting groups.
Scheme 5. Synthesis and reactions of DG-protected glycosyl donor
20. Reagents and conditions: (a) DGA, Pyr, Ac2O (quant.); (b) Pd/
C, H2 (quant.); (c) Ac2O, Pyr (98%); (d) N2H4·HOAc (77%); (e)
CCl3CN, DBU (80%); (f) TMSOTf (0.01 equiv.), CH2Cl2 (21a:
quant.; 21d: 94%; 21f: 86%; 21g: 86%); (g) KOH, EtOH, reflux;
Ac2O, Pyr (6a: 83%; 6d: 83%; 6g: 76%; 22: 82%); (h) NaOBu,
BuOH, reflux; Ac2O, Pyr (69%); (i) N2H4·H2O, reflux; Ac2O, Pyr
(38%); (j) N2H4·H2O, EtOH, reflux; Ac2O, Pyr (3 %).
Experimental Section
General Remarks: Solvents were purified in the usual way. Melting
points were determined with a Gallenkamp apparatus, values were
not corrected. TLC was performed on plastic plates coated with
Silica Gel 60 F254 (E. Merck, layer thickness = 0.2 mm). Detection
was achieved by treatment with a solution of ammonium molyb-
date (20 g) and cerium(iv) sulfate (0.4 g) in 10% H2SO4 (400 mL)
ticularly affected by its proximity to the diacyl moiety, inter-
mediate 17 was transformed into 3-O-unprotected acceptor
24 by treatment with benzylidene acetal in the presence of
p-toluenesulfonic acid as catalyst (Ǟ 23) followed by anom-
eric O-silylation with tert-butyldimethylsilyl (TBDMS)
chloride and imidazole to furnish only the β-isomer 24 or with 15% H2SO4 and heating at 150 °C. Flash chromatography
was carried out on silica gel (Baker, 30–60 μm). Medium-pressure
liquid chromatography (MPLC): LiChroprep Si 60 (Merck;
Korngröße 15–25 μm) and detection was carried out with a
differential refractometer. Optical rotations were determined at
20 °C with a Perkin–Elmer 241/MC polarimeter (1-dm cell). NMR
spectra were recorded with Bruker AC 250 and 600 DRX instru-
ments using tetramethylsilane as the internal standard. The 1H
NMR spectral assignments were based on chemical shift corre-
lation (DQF COSY) and rotating frame nuclear Overhauser effect
spectroscopy (ROESY). The 13C NMR spectral assignments were
based on carbon–proton shift-correlation heteronuclear multiple
quantum coherence (HMQC). MS spectra were recorded with a
MALDI-Kompakt (Kratos) spectrometer. Microanalyses were per-
formed at the Microanalysis unit at the Fachbereich Chemie, Uni-
(Scheme 6). Reaction of 24 with known galactosyl donor
25[38,39] afforded under standard conditions the isolactosa-
mine derivative 26 in excellent yield. Thus the versatility of
the DG protecting group has been further established.
Conclusions
In conclusion, the use of DPM, DMG, and DG as amino
protecting groups of glucosamine gave varying results. In
contrast to the dimethylmaleoyl (DMM) group, the fluores-
cent DPM group did not undergo either base- or mild acid-
catalyzed cleavage in good yield. The excellent glycosylation
yields observed for the DMG group were also obtained versität Konstanz.
Eur. J. Org. Chem. 2005, 4382–4392
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4385

M. R. E. Aly, R. R. Schmidt
FULL PAPER
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-diphenylmaleimido-β-
D
-gluco- while TMSOTf (0.01 m in CH2Cl2, 0.45 mL) was added dropwise.
pyranose (1): d-glucosamine hydrochloride (1.0 g, 4.63 mmol) was
stirred at room temp. with a solution of NaOMe (1.0 m, 4.63 mL)
for 10 min and then treated with diphenylmaleic anhydride (0.58 g,
2.315 mmol). After 20 min the reaction mixture was treated with
triethylamine (0.5 mL, 4.96 mmol) and again with diphenylmaleic
anhydride (0.58 g, 2.315 mmol), then warmed to 60 °C for 75 min.
The solvent was evaporated in vacuo and the residue dried well.
The residue was stirred with pyridine/acetic anhydride (2:1, 30 mL)
at room temp., then coevaporated with toluene in vacuo after 20 h,
and purified by flash chromatography (petroleum ether/ethyl ace-
tate, 2.5:1) to yield 1 (0.930 g, 35%) as a fluorescent yellow foam.
TLC (petroleum ether/ethyl acetate, 2.5:1): Rf = 0.2. [α]D = +24.9
(c = 1.05, CHCl3). 1H NMR (250 MHz, CDCl3): δ = 1.94, 2.05,
2.10, 2.12 (4 s, 12 H, 4 CH3CO), 3.99 (m, 1 H, 5-H), 4.14 (dd, J6,6Ј
After 2 h the mixture was neutralized with Et3N and the solvents
evaporated in vacuo. The residue was purified by flash chromatog-
raphy (petroleum ether/ethyl acetate, 2.5:1) and then with MPLC
under the same conditions to afford compounds 5a–c (68%) as a
fluorescent foam.
Methyl 3,4,6-Tri-O-acetyl-2-deoxy-2-diphenylmaleimido-β-
D-gluco-
pyranosyl-(1Ǟ6)-2,3,4-tri-O-benzyl-β- -glucopyranoside (5a): TLC
D
(petroleum ether/ethyl acetate, 2.5:1): Rf = 0.1. [α]D = +26.0 (c =
1
0.4, CHCl3). H NMR (600 MHz, CDCl3): δ = 1.92, 2.03, 2.07 (3
s, 9 H, 3 CH3CO), 3.27 (s, 3 H, OCH3), 3.37 (dd, J3,4 = 9.2, J4,5
=
9.5 Hz, 1 H, 4a-H), 3.46 (dd, J1,2 = 3.2, J2,3 = 9.6 Hz, 1 H, 2a-H),
3.66 (dd, Jgem = 10.3, J5,6 = 4.4 Hz, 1 H, 6a-H), 3.72 (m, 1 H, 5a-
H), 3.82 (m, 1 H, 5b-H), 3.92 (dd, J2,3 = 9.6, J3,4 = 9.2 Hz, 1 H,
3a-H), 4.10 (dd, J6,6Ј = 10.3, J5,6Ј Ͻ 1 Hz, 1 H, 6Јa-H), 4.16 (dd,
J6,6Ј = 12.1, J5,6 Ͻ 1 Hz, 1 H, 6b-H), 4.31–4.34 (m, 2 H, 2b-H, 6Јb-
= 12.5, J5,6 = 1.9 Hz, 1 H, 6-H), 4.38 (dd, J6,6Ј = 12.5, J5,6Ј
=
4.4 Hz, 1 H, 6Ј-H), 4.41 (dd, J1,2 = 8.9, J2,3 = 10.3 Hz, 1 H, 2-H),
5.23 (dd, J3,4 = 9.3, J4,5 = 9.8 Hz, 1 H, 4-H), 5.84 (dd, J2,3 = 10.3,
J3,4 = 9.3 Hz, 1 H, 3-H), 6.47 (d, J1,2 = 8.9 Hz, 1 H, 1-H), 7.32–
7.48 (m, 10 H, 2 Ph) ppm. MALDI MS (positive ion mode, DHB–
THF matrix): m/z = 601.8 [M + Na]+ , 617.7 [M + K]+ .
C30H29NO11 (579.6): C 62.17, H 5.04, N 2.41; found C 61.73, H
5.09, N 2.43.
H), 4.52 (d, J1,2 = 2.3 Hz, 1 H, 1a-H), 4.33, 4.66 (2 d, Jgem
=
10.5 Hz, 2 H, CH2Ph), 4.59, 4.73 (2 d, Jgem = 12 Hz, 2 H, CH2Ph),
4.71, 4.92 (2 d, Jgem = 10.5 Hz, 2 H, CH2Ph), 5.18 (dd, J3,4 = J4,5
= 9.6 Hz, 1 H, 4b-H), 5.35 (d, J1,2 = 8.4 Hz, 1 H, 1b-H), 5.76 (dd,
J2,3 = 10.1, J3,4 = 9.6 Hz, 1 H, 3b-H), 7.02–7.30 (m, 25 H, 5
Ph) ppm. 13C NMR (150.9 MHz, CDCl3): δ = 20.54, 20.64, 20.75
(3 CH3CO), 54.81 (C-2b), 55.06 (OCH3), 62.03 (C-6b), 68.50 (C-
6a), 68.82 (C-4b), 69.24 (C-5a), 70.72 (C-3b), 71.86 (C-5b), 73.40,
3,4,6-Tri-O-acetyl-2-deoxy-2-diphenylmaleimido-β-D-glucopyranose
(2): A mixture of 1 (0.879 g, 1.5 mmol) and hydrazine acetate 74.89, 75.58 (3 CH2Ph), 77.66 (C-4a), 81.84 (C-3a), 97.83 (C-2a),
(0.17 g, 1.8 mmol) in dry DMF (3 mL) was stirred at room temp.
After 2 h the mixture was diluted with ethyl acetate (50 mL) and
treated with saturated NaHCO3 solution (3 mL). The organic layer
was separated and the aqueous layer extracted with ethyl acetate
(10 mL); the combined organic layers were dried with MgSO4, fil-
tered, and the solvents evaporated in vacuo. The residue was puri-
fied by flash chromatography (petroleum ether/ethyl acetate, 3:2)
to yield 2 (0.773 g, 94%) as a yellow fluorescent foam. TLC (petro-
leum ether/ethyl acetate, 3:2): Rf = 0.19. [α]D = +69.0 (c = 0.2,
97.97 (C-1a), 98.42 (C-1b), 127.43–138.73 (5 Ph), 169.42, 170.34,
170.72 (5 CO) ppm. MALDI MS (positive ion mode, DHB/THF
matrix): m/z = 1006.2 [M + K]+. C56H57NO15 (984.1): C 68.33, H
5.84, N 1.42; found C 67.68, H 6.00, N 1.52.
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-diphenylmaleimido-β-
pyranosyl-(1Ǟ3)-2,4,6-tri-O-benzyl-β- -galactopyranosyl-(1Ǟ4)-
2,3,6-tri-O-benzyl-β- -glucopyranoside (5b): TLC (petroleum ether/
D-gluco-
D
D
1
ethyl acetate, 2.5:1): Rf = 0.25. [α]D = –16.6 (c = 0.3, CHCl3). H
NMR (600 MHz, CDCl3): δ = 1.91, 1.97, 2.05 (3 s, 9 H, 3 CH3CO),
2.80 (m, 1 H, 5a-H), 3.34–3.38 (m, 5 H, 2a-H, 6a-H, 6b-H, 5b-H,
3a-H), 3.50–3.53 (m, 2 H, 6Јa-H, 6Јb-H), 3.60–3.61 (m, 2 H, 2b-H,
3b-H), 3.82 (m, 1 H, 5c-H), 3.88 (dd, J3,4 = 9.0, J4,5 = 9.3 Hz, 1 H,
4a-H), 3.98 (dd, J3,4 = J4,5 Ͻ 1.0 Hz, 1 H, 4b-H), 4.19–4.36 (m, 8
1
CHCl3). H NMR (250 MHz, CDCl3): δ = 1.94, 2.04, 2.05 (3 s, 9
H, 3 CH3CO), 3.58 (br. s, 1 H, OH), 3.88 (m, 1 H, 5-H), 4.10–4.31
(m, 3 H, 6Ј-H, 2-H, 6-H), 5.19 (dd, J3,4 = 9.2, J4,5 = 9.8 Hz, 1 H,
4-H), 5.57 (d, J1,2 = 8.3 Hz, 1 H, 1-H), 5.79 (dd, J2,3 = 10.6, J3,4
=
9.2 Hz, 1 H, 3-H), 7.31–7.47 (m, 10 H, 2 Ph) ppm. MALDI MS
(positive ion mode, DHB–THF matrix): m/z = 559.8 [M + Na]+,
575.8 [M + K]+. C28H27NO10 (537.5): C 62.56, H 5.06; N 2.60;
found C 62.12, H 5.21, N 2.61.
H, 6Јc-H, 6c-H, 1a-H, 1b-H, 2c-H, 1.5 CH2Ph), 4.43 (d, Jgem
=
11.7 Hz, 1 H, 0.5 CH2Ph), 4.48 (d, Jgem = 12.1 Hz, 1 H, 0.5
CH2Ph), 4.52–4.58 (m, 4 H, 2 CH2Ph), 4.69 (d, Jgem = 10.8 Hz, 1
H, 0.5 CH2Ph), 4.84–4.90 (m, 3 H, 1.5 CH2Ph), 5.00 (d, Jgem
11.4 Hz, 1 H, 0.5 CH2Ph), 5.15 (dd, J3,4 = 9.3, J4,5 = 9.8 Hz, 1 H,
nosyl) Trichloroacetimidate (3): A mixture of 2 (0.66 g, 1.13 mmol) 4c-H), 5.60 (d, J1,2 = 8.3 Hz, 1 H, 1c-H), 5.80 (dd, J2,3 = 10.3, J3,4
=
O-(3,4,6-Tri-O-acetyl-2-deoxy-2-diphenylmaleimido-D-glucopyra-
and trichloroacetonitrile (0.8 mL, 7.9 mmol) in dry dichlorometh-
ane (3 mL) was stirred at room temp. while DBU (0.14 mL,
0.93 mmol) was added dropwise. After 4 h the solvent was evapo-
rated in vacuo and the residue purified by flash chromatography
(petroleum ether/ethyl acetate, 1:1 + 1% Et3N) to yield 3 (0.496 g,
63%) as a fluorescent green foam in an α/β ratio of 1:8. TLC (pe-
troleum ether/ethyl acetate, 1:1 + 1% Et3N): Rf = 0.73 (α-form),
= 9.3 Hz, 1 H, 3c-H), 7.05–7.32 (m, 45 H, 9 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 20.49, 20.57, 20.65 (3 CH3CO), 55.46 (C-
2c), 62.09 (C-6c), 68.01 (C-6a, C-6b), 68.90 (C-4c), 70.61 (C-3c),
70.81 (CH2Ph), 71.58 (C-5c), 72.59–76.79 (C-5a, C-5b, 6 CH2Ph),
77.00 (C-4a), 77.21 (C-4b), 78.83 (C-2b), 81.65 (C-2a), 82.54 (C-
3b), 82.85 (C-3a), 99.32 (C-1c), 102.10 (C-1b), 102.39 (C-1a),
127.14–139.26 (9 Ph) ppm. MALDI MS (positive ion mode, DHB/
THF matrix): m/z = 1514.1 [M + Na]+, 1527.5 [M + K]+.
C89H89NO20 (1492.8): C 71.60, H 6.02, N 0.93; found C 70.97, H
1
0.64 (β-form). H NMR (250 MHz, CDCl3): δ = 1.94–2.13 (sev. s,
9 H, 3 CH3CO), 4.01–4.49 (m, 3 H, 6Ј-H, 6-H, 5-H), 4.57 (dd, J1,2
= 8.9 Hz, J2,3 = 10.7 Hz, 0.89 H, 2β-H), 4.73 (dd, J1,2 = 3.7, J2,3 6.04, N 1.06.
= 11.5 Hz, 0.11 H, 2α-H), 5.15–5.37 (m, 1 H, 4-H), 5.79–5.94 (m,
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-diphenylmaleimido-β-D-gluco-
1 H, 3-H), 6.42 (d, J1,2 = 3.7 Hz, 0.11 H, 1α-H), 6.52 (d, J1,2
=
pyranosyl-(1Ǟ4)-2,3,6-tri-O-benzyl-β-O-glucopyranoside (5c): TLC
(petroleum ether/ethyl acetate, 2.5:1): Rf = 0.19. [α]D = +30.4 (c =
8.9 Hz, 0.89 H, 1β-H), 7.26–7.47 (m, 10 H, 2 Ph) ppm.
C30H27Cl3N2O10 (681.9): C 52.84, H 3.99; N. 4.10; found C 53.03,
H 4.22, N 4.30.
1
0.25, CHCl3). H NMR (600 MHz, CDCl3): δ = 1.90, 1.96–1.98 (3
s, 9 H, 3 CH3CO), 3.35–3.39 (m, 2 H, 5a-H, 5b-H), 3.47 (dd, J1,2
= 7.8, J2,3 = 8.4 Hz, 1 H, 2a-H), 3.53 (dd, J6,6Ј = 11.2, J5,6 = 4.3 Hz,
1 H, 6a-H), 3.57 (dd, J6,6Ј = 12.3, J5,6 = 1,4 Hz, 1 H, 6b-H), 3.61–
3.65 (m, 2 H, 6Јa-H, 3a-H), 4.00 (dd, J3,4 = J4,5 = 9.1 Hz, 1 H, 4a-
General Procedure for the Synthesis of Compounds 5a–c: A solution
of 3 (0.3 g, 0.44 mmol) and 4a,[26] 4b,[27] or 4c[28] (0.36 mmol) in
dry dichloromethane (2 mL) was stirred at room temp. under argon
4386
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4382–4392

New Diacylamino Protecting Groups for Glucosamine
FULL PAPER
H), 4.02 (dd, J6,6Ј = 12.3, J5,6Ј = 3.7 Hz, 1 H, 6Јb-H), 4.19 (dd, J1,2
= 8.4, J2,3 = 10.4 Hz, 1 H, 2b-H), 4.43 (d, J1,2 = 7.8 Hz, 1 H, 1a-
and stirred with 3,3-dimethylglutaric anhydride (0.9 g, 6.3 mmol)
at room temp. Et3N (1.0 mL) was added after 2 h and the solution
was warmed at 80 °C for 30 min, acetic anhydride (1 mL) was then
added, and the mixture was stirred at this temperature overnight.
The mixture was coevaporated with toluene in vacuo and the resi-
due purified by flash chromatography (petroleum ether/ethyl ace-
tate, 4:1) to yield 9 (3.4 g, quant.) as a colourless oil. TLC (petro-
leum ether/ethyl acetate, 4:1): Rf = 0.2. [α]D = + 1.46 (c = 1.05,
H), 4.45, 4.52 (2 d, Jgem = 12.1 Hz, 2 H, CH2Ph), 4.60 (d, Jgem
=
11.6 Hz, 1 H, 0.5 CH2Ph), 4.61 (d, Jgem = 10.4 Hz, 1 H, 0.5
CH2Ph), 4.85–4.91 (m, 3 H, 1.5 CH2Ph), 4.95 (d, Jgem = 11.8 Hz,
1 H, 0.5 CH2Ph), 5.11 (dd, J3,4 = 9.5, J4,5 = 9.7 Hz, 1 H, 4b-H),
5.60 (d, J1,2 = 8.4 Hz, 1 H, 1b-H), 5.66 (dd, J2,3 = 10.4, J3,4
=
9.5 Hz, 1 H, 3b-H), 7.19–7.44 (m, 30 H, 6 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 20.49, 20.59, 20.68 (3 CH3CO), 55.63 (C-
2b), 61.40 (C-6b), 67.91 (C-6a), 68.31 (C-4b), 70.81 (CH2Ph), 70.88
1
CHCl3). H NMR (600 MHz, CDCl3): δ = 0.76, 0.83 (2 s, 6 H, 2
CH3), 1.74 (d, Jgem = 16.8 Hz, 1 H, 0.5 -CH2-), 2.07 (m, 2 H, -
(C-3b), 71.64 (C-5b), 72.93 (CH2Ph), 74.43 (C-5a), 74.79 (2 CH2-), 2.34 (d, Jgem = 18.5 Hz, 1 H, 0.5 -CH2-), 3.61 (m, 1 H, 5-
CH2Ph), 76.11 (C-4a), 81.96 (C-2a), 82.91 (C-3a), 97.64 (C-1b), H), 3.74 (dd, J3,4 = 8.5, J4,5 = 9.5 Hz, 1 H, 4-H), 4.42–4.46 (m, 2
102.26 (C-1a), 126.68–139.17 (6 Ph), 169.37, 170.29, 170.67 (5 H, 6Ј-H, 6-H), 4.42–4.46 (m, 3 H, 2 CH2Ph, 3-H), 4.58, 4.66 (2 d,
CO) ppm. MALDI MS (positive ion mode, DHB/THF matrix): m/ Jgem = 12.2 Hz, 2 H, CH2Ph), 4.60 (d, Jgem = 11.5 Hz, 1 H, 0.5
z = 1081.8 [M + K]+. C62H61NO15 (1060.2): C 70.23, H 5.81, N CH2Ph), 4.79–4.87 (m, 4 H, 1.5 CH2Ph, 2-H), 5.27 (d, J1,2
=
1.32; found C 69.77, H 5.87, N 1.33.
8.2 Hz, 1 H, 1-H), 7.21–7.38 (m, 20 H, 4 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 25.86, 28.60 (2 CH3), 46.65 (2 -CH2-),
56.02 (C-2), 68.81 (C-6), 70.80 (CH2Ph), 73.47 (CH2Ph), 74.57,
74.79, 75.08 (2 CH2Ph, C-5), 79.77 (C-3), 80.21 (C-4), 98.17 (C-1),
127.47–128.45, 137.37–139.01 (4 Ph), 172.18, 172.84 (2 CO) ppm.
MALDI MS (positive ion mode, DHB/THF matrix): m/z = 684.2
[M + Na]+, 700.1 [M + K]+. C41H45NO7 (663.9): C 74.17, H 6.84,
N 2.11; found C 73.80, H 6.77, N 2.23.
Deprotection of the DPM Group. Method A: Compounds 5
(0.06 mmol) dissolved in dry ethanol (5 mL) were treated with hy-
drazine hydrate (0.3 mL, 6.1 mmol, 0.309 g) and refluxed over-
night. The mixture was coevaporated with toluene in vacuo and
the dry residue was treated with pyridine (Pyr)/Ac2O, (2:1, 6 mL).
This mixture was stirred at room temp. for 6 h and then coevapo-
rated with toluene in vacuo. The residue was purified by flash
chromatography to give compounds 6b (90%), 6a (68%), and 6c
(63%). The physical data obtained for these compounds are iden-
tical to those given in the literature.[12,17,29]
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-D-glu-
copyranose (10): A solution of 9 (3.4 g, 5.12 mmol) in dry methanol
(30 mL) was stirred under hydrogen in the presence of Pd/C (10%,
0.6 g). After 24 h the reaction mixture was filtered through Celite,
washed with aqueous methanol (1:1, 50 mL), evaporated in vacuo,
and dried well. The residue was stirred with pyridine (20 mL) and
acetic anhydride (10 mL) overnight then coevaporated with toluene
in vacuo and the residue was purified by flash chromatography
(petroleum ether/ethyl acetate, 2:1) to yield 10 (2.364 g, 98%) as a
white powder. TLC (petroleum ether/ethyl acetate, 2:1): Rf = 0.13;
m.p. 139–140 °C. [α]D = +16.9 (c = 0.95, CHCl3). 1H NMR
(250 MHz, CDCl3): δ = 1.01, 1.06 (2 s, 2 CH3), 1.95, 2.03, 2.03,
2.10 (4 s, 12 H, 4 CH3CO), 2.37–2.57 (m, 4 H, 2 -CH2-), 3.92–3.99
(2 m, 1 H, 5-H), 4.10 (dd, J6,6Ј = 12.5, J5,6 = 2.2 Hz, 1 H, 6-H),
4.32 (dd, J6,6Ј = 12.5, J5,6 = 4.5 Hz, 1 H, 6Ј-H), 5.01 (dd, J1,2 = 8.6,
J2,3 = 10.4 Hz, 1 H, 2-H), 5.17 (m, J3,4 = 8.9, J4,5 = 10.2 Hz, 1 H,
Method B: Compound 5c (0.176 g, 0.17 mmol) in a dioxane/water
mixture (5:1, 6 mL) was stirred with NaOH (0.2 g) at room temp.
After 24 h the pH was adjusted to and kept at 5 by the addition of
1 n HCl while stirring. After 24 h the mixture was made basic with
ethanolamine and the solvents evaporated in vacuo. The residue
was treated with Pyr/Ac2O, (2:1, 12 mL) and stirred overnight and
then coevaporated with toluene in vacuo. The residue was purified
by flash chromatography (2:1 toluene/acetone) to yield 6c (31.0 mg,
22%). The data obtained for 6c are identical to those of an authen-
tic sample prepared in a previous work.[17]
2-Amino-1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucose Hydrochloride
(8): A mixture of 7[31] (44.22 g, 148.7 mmol) and benzyl bromide
(81.8 mL, 689.15 mmol, 117.87 g) in dry DMF (300 mL) was
stirred vigorously in an ice/salt bath while NaH (95% in oil, 17.7 g,
737.2 mmol) was added in 17 portions. The mixture was then al-
lowed to reach room temp. overnight. Ethyl acetate (100 mL) was
added dropwise while stirring and then the solvent was evaporated
in vacuo. The residue was taken up in ethyl acetate (900 mL) and
water (100 mL), the organic layer was separated, dried with
MgSO4, and the solvents evaporated in vacuo. Flash chromatog-
raphy of the residue on alumina (150 g) (petroleum ether/ethyl ace-
tate, 4:1, plus 1% Et3N) afforded the β-tetra-O-benzyl derivative
(97.0 g, quant.) as a yellow oil. TLC on alumina (petroleum ether/
ethyl acetate, 4:1, plus 1% Et3N): Rf = 0.75. The product from the
last step was dissolved in acetone (200 mL), treated with HCl (5 n,
31.2 mL), refluxed for 20 min, and then refrigerated after having
cooled to room temp. The white mass was broken, filtered at a
vacuum pump, washed with acetone, and recrystallized from aque-
ous ethanol to yield 8[32] (69.6 g, 82%) as white crystals, which were
immediately used in the next step.
4-H), 5.87 (dd, J2,3 = 10.4, J3,4 = 8.9 Hz, 1 H, 3-H), 6.53 (d, J1,2
=
8.6 Hz, 1 H, 1-H) ppm. MALDI MS (positive ion mode, DHB/
THF matrix): m/z = 494.7 [M + Na]+ , 510.8 [M + K]+ .
C21H29NO11 (471.5): C 53.48, H 6.21, N 2.97; found C 53.16, H
6.06, N 2.94.
3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-D-gluco-
pyranose (11): A solution of 10 (0.937 g, 1.98 mmol) in dry DMF
(6 mL) was stirred at room temp. with hydrazine acetate (0.2 g,
2.17 mmol). After 2 h the reaction mixture was diluted with ethyl
acetate (50 mL) and then washed with saturated NaHCO3 (15 mL)
and water (2×20 mL). The combined aqueous layer was extracted
with ethyl acetate (2×25 mL) and the combined organic layer was
dried with MgSO4 and the solvents evaporated in vacuo. The resi-
due was purified by flash chromatography (petroleum ether/ethyl
acetate, 1:1) to yield 11 (0.848 g, 99%) as an amorphous mass. TLC
(petroleum/ethyl acetate, 1:1.5): Rf = 0.21. [α]D = +5.6 (c = 1.5,
1
CHCl3) H NMR (250 MHz, CDCl3): δ = 1.05, 1.09 (2 s, 6 H, 2
CH3), 1.94, 2.02, 2.11 (3 s, 9 H, 3 CH3CO), 2.41–2.61 (m, 4 H, 2-
1,3,4,6-Tetra-O-benzyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-D-glu- CH2-), 3.51 (d, J1,OH = 8.2 Hz, 1 H, OH), 3.82–3.89 (2 m, 1 H, 5-
copyranoside (9): Crystalline 8 (3.0 g, 5.2 mmol) suspended in
dichloromethane (50 mL) was neutralized by shaking with a solu-
tion of sodium acetate (3.0 g, 36.5 mmol) in water (30 mL). The
organic layer was separated, dried with MgSO4, and the solvents
evaporated in vacuo. The residue was taken up in pyridine (10 mL)
H), 4.11 (m, 1 H, 6-H), 4.27 (dd, J6,6Ј = 12.3, J5,6 = 4.6 Hz, 1 H,
6Ј-H), 4.79 (dd, J1,2 = 8.2, J2,3 = 10.6 Hz, 1 H, 2-H), 5.13 (dd, J3,4
= 8.9, J4,5 = 10.2 Hz, 1 H, 4-H), 5.59 (dd, J1,2 = J1,OH = 8.2 Hz, 1
H, 1-H), 5.86 (dd, J2,3 = 10.6, J3,4 = 8.9 Hz, 1 H, 3-H) ppm.
MALDI MS (positive ion mode, DHB/THF matrix): m/z = 452.0
Eur. J. Org. Chem. 2005, 4382–4392
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4387

M. R. E. Aly, R. R. Schmidt
FULL PAPER
[M + Na]+, 468.0 [M + K]+. C19H27NO10 (429.5): C 53.13, H 6.34,
N 3.26; found C 52.99, H 6.52, N 3.13.
H, 2b-H, 3b-H), 3.66 (dd, J6,6Ј = 10.8, J5,6Ј = 3.7 Hz, 1 H, 6Јa-H),
3.79 (m, 1 H, 5c-H), 3.96–3.98 (m, 2 H, 4a-H, 4b-H), 4.17 (dd, J6,6Ј
= 10.7, J5,6 Ͻ 1 Hz, 1 H, 6c-H), 4.22–4.24 (m, 2 H, 6Јc-H, CH2Ph),
4.34 (d, Jgem = 12.1 Hz, 1 H, 0.5 CH2Ph), 4.35 (d, Jgem = 11.7 Hz,
O-[3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimetylglutarimido)-D-gluco-
pyranosyl] Trichloroacetimidate (12): A mixture of 11 (1.0 g,
2.3 mmol) and tricloroacetonitrile (1.5 mL, 15.0 mmol, 2.16 g) in
dry dichloromethane (5 mL) was treated with DBU (0.1 mL,
0.66 mmol) and stirred at room temp. overnight. The reaction mix-
ture was evaporated in vacuo and the residue purified by flash
chromatography (petroleum ether/ethyl acetate, 1:1 + 2% Et3N) to
yield 12 (1.077 g, 80%) as a faint yellow foam in an α/β ratio of
1:2.3. TLC (petroleum ether/ethyl acetate, 1:1 + 2% Et3N): Rf =
0.47 (α-form), 0.42 (β-form). 1H NMR (250 MHz, CDCl3): δ =
1.02, 1.12 (2 s, 6 H, 2 CH3), 1.96, 2.03, 2.10 (3 s, 9 H, 3 CH3CO),
2.30, 2.59 (m, 4 H, 2 -CH2-), 3.95–4.40 (m, 3 H, 5-H, 6Ј-H, 6-H),
5.06–5.26 (m, 2 H, 2-H, 4-H), 5.42 (dd, J2,3 = 7.2, J3,4 = 6.0 Hz,
1 H, 0.5 CH2Ph), 4.39–4.40 (m, 2 H, 1a-H, 1b-H), 4.49 (d, Jgem
11.6 Hz, 1 H, 0.5 CH2Ph), 4.54 (2 d, Jgem = 12.9 Hz, 1 H, 0.5
CH2Ph), 4.56 (d, Jgem = 12.8 Hz, 1 H, 0.5 CH2Ph), 4.59 (d, Jgem
12.1 Hz, 1 H, 0.5 CH2Ph), 4.65 (d, Jgem = 10.5 Hz, 1 H, 0.5
CH2Ph), 4.71 (d, Jgem = 10.9 Hz, 1 H, 0.5 CH2Ph), 4.74 (d, Jgem
=
=
=
12.1 Hz, 1 H, 0.5 CH2Ph), 4.87–4.90 (m, 2 H, CH2Ph), 4.93–4.98
(m, 3 H, CH2Ph, 2c-H), 5.07 (dd, J3,4 = 8.9, J4,5 = 9.8 Hz, 1 H, 4c-
H), 5.65 (d, J1,2 = 8.0 Hz, 1 H, 1c-H), 5.86 (dd, J2,3 = 10.4, J3,4
=
8.9 Hz, 1 H, 3c-H), 7.10–7.34 (m, 35 H, 7 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 20.56, 20.67 (2 CH3), 26.15, 28.12, 28.42
(3 CH3CO), 45.79, 46.20 (2 -CH2-), 55.11 (C-2c), 62.13 (C-6c),
67.90 (C-6a), 69.82 (C-4c, C-6b), 70.37 (C-3c), 70.85 (CH2Ph),
71.31 (C-5c), 73.00 (C-5b), 73.13, 73.93, 74.73 (3 CH2Ph), 74.90
(C-5a), 75.02, 75.38, 75.93 (3 CH2Ph), 76.10 (C-4a, C-4b), 79.14
(C-2b), 80.99 (C-3b), 81.63 (C-2a), 82.89 (C-3a), 99.45 (C-1c),
102.48 (C-1a, C-1b), 126.37 (7 Ph), 169.68, 170.17 (5 CO) ppm.
MALDI MS (positive ion mode, DHB/THF matrix): m/z = 1404.7
[M + Na]+, 1420.4 [M + K]+. C80H89NO20 (1384.7): C 69.38, H
6.49, N 1.01; found C 68.99, H 6.19, N 1.07.
0.3 H, 3α-H), 5.75 (d, J1,2 = 5.6 Hz, 0.3 H, 1α-H), 5.93 (dd, J2,3
=
10.5, J3,4 = 8.8 Hz, 0.7 H, 3β-H), 6.69 (d, J1,2 = 8.5 Hz, 0.7 H, 1β-
H), 8.67 (s, 1 H, NH) ppm. C21H27Cl3N2O10 (573.8).
General Procedure for the Synthesis of Compounds 13a–e: A mixture
of 12 (0.63 mmol) and the appropriate acceptor 4a–e[27–29]
(0.42 mmol) in dry dichloromethane (1 mL) was stirred under ar-
gon at room temp. while TMSOTf (0.01 m in CH2Cl2, 0.65 mL)
was added dropwise. After 75 min the mixture was neutralized with
Et3N and the solvents evaporated in vacuo.
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-
D-
glucopyranosyl-(1Ǟ4)-2,3,6-tri-O-benzyl-β- -glucopyranoside (13c):
D
Methyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-
D-
The residue was purified by flash chromatography (petroleum
ether/ethyl acetate, 2:1) to afford 13c (81%) as a white foam. TLC
(petroleum ether/ethyl acetate, 2:1): Rf = 0.16. [α]D = –11.3 (c =
glucopyranosyl-(1Ǟ6)-2,3,4-tri-O-benzyl-α- -glucopyranoside (13a):
D
The residue was purified by flash chromatography (petroleum
ether/ethyl acetate, 1.5:1) to afford 13a (90%) as a white foam. TLC
(petroleum ether/ethyl acetate, 1.5:1): Rf = 0.16. [α]D = +6.5 (c =
1.1, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 0.93, 0.98 (2 s, 6
H, CH3), 1.92, 2.01, 2.03 (3 s, 9 H, 3 CH3CO), 2.30, 2.40 (2 d, 2
H, Jgem = 17.0 Hz, -CH2-), 2.36 (m, 2 H, -CH2-), 3.28 (dd, J3,4
9.2, J4,5 = 9.5 Hz, 1 H, 4a-H), 3.31 (s, 3 H, -OCH3), 3.44 (dd, J1,2
= 3.7, J2,3 = 9.6 Hz, 1 H, 2a-H), 3.55 (dd, J5,6 = 6.0, J6,6Ј = 10.5 Hz,
1
0.65, CHCl3). H NMR (600 MHz, CDCl3): δ = 0.91, 0.99 (2 s, 6
H, 2 CH3), 1.91, 1.95, 1.97 (3 s, 9 H, 3 CH3CO), 2.36–2.43 (m, 3
H, 1.5 -CH2-), 2.52 (d, Jgem = 16.6 Hz, 1 H, 0.5 -CH2-), 3.28 (m, 1
H, 5a-H), 3.34 (m, 1 H, 5b-H), 3.47 (dd, J1,2 = 7.7, J2,3 = 8.7 Hz,
1 H, 2a-H), 3.56 (dd, J2,3 = 8.7, J3,4 = 8.9 Hz, 1 H, 3a-H), 3.62
(dd, J5,6 = 3.8, J6,6Ј = 10.8 Hz, 1 H, 6a-H), 3.69 (dd, J5,6Ј Ͻ 1.0,
J6,6Ј = 10.8 Hz, 1 H, 6Јa-H), 3.82 (dd, J5,6 = 1.7, J6,6Ј = 12.4 Hz, 1
H, 6b-H), 4.04 (dd, J5,6 = 4.0, J6,6Ј = 12.4 Hz, 1 H, 6Јb-H), 4.08
(dd, J3,4 = 8.9, J4,5 = 9.2 Hz, 1 H, 4a-H), 4.43 (d, J1,2 = 7.7 Hz, 1
H, 1a-H), 4.63–4.66 (m, 2 H, CH2Ph), 4.61, 4.69 (2 d, 2 H, CH2Ph),
4.79 (d, Jgem = 11.5 Hz, 1 H, 0.5 CH2Ph), 4.83–4.96 (m, 4 H, 1.5
CH2Ph, 2b-H), 5.05 (dd, J3,4 = 8.9, J4,5 = 9.9 Hz, 1 H, 4b-H), 5.58
(d, J1,2 = 8.1 Hz, 1 H, 1b-H), 5.73 (dd, J2,3 = 10.6, J3,4 = 8.9 Hz,
1 H, 3b-H), 7.21–7.39 (m, 20 H, 4 Ph) ppm. 13C NMR (150.9 MHz,
CDCl3): δ = 20.64, 20.70 (2 CH3), 27.07, 27.54, 27.87 (3 CH3CO),
46.06, 46.82 (2 -CH2-), 55.40 (C-2b), 61.66 (C-6b), 68.37 (C-6a),
69.23 (C-4b), 70.69 (C-3b), 70.95 (CH2Ph), 71.44 (C-5b), 73.33
(CH2Ph), 74.69 (C-4a), 74.87 (C-5a, 2 CH2Ph), 81.76 (C-2a), 82.17
(C-3a), 97.17 (C-1b), 102.44 (C-1a), 127.28–138.34 (4 Ph), 172.89
(5 CO) ppm. MALDI MS (positive ion mode, DHB/THF matrix):
m/z = 974.0 [M + Na]+. C53H61NO15 (952.1): C 66.85, H 6.47, N
1.47; found C 66.51, H 6.47, N 1.55.
=
1 H, 6a-H), 3.76 (m, 2 H, 5a-H, 5b-H), 3.95 (dd, J2,3 = 9.6, J3,4
=
9.2 Hz, 1 H, 3a-H), 3.98 (dd, J5,6Ј = 1.1, Jgem = 10.5 Hz, 1 H, 6Јa-
H), 4.10 (dd, J5,6 = 1.9, J6,6Ј = 12.1 Hz, 1 H, 6b-H), 4.25 (dd, J5,6Ј
= 4.6, J6,6Ј = 12.1 Hz, 1 H, 6Јb-H), 4.47 (d, J1,2 = 3.7 Hz, 1 H, 1a-
H), 4.48 (2 d, Jgem = 10.8 Hz, 2 H, CH2Ph), 4.63 (d, Jgem = 12.1 Hz,
1 H, 0.5 CH2Ph), 4.76 (m, 2 H, CH2Ph), 4.91 (dd, J1,2 = 8.2, J2,3
= 10.5 Hz, 1 H, 2b-H), 4.96 (d, Jgem = 10.8 Hz, 1 H, 0.5 CH2Ph),
5.11 (dd, J3,4 = 9.0, J4,5 = 9.8 Hz, 1 H, 4b-H), 5.40 (d, J1,2 = 8.2 Hz,
1 H, 1b-H), 5.78 (dd, J2,3 = 10.5, J3,4 = 9.0 Hz, 1 H, 3b-H), 7.25–
7.34 (m, 15 H, 3 Ph) ppm. 13C NMR (600 MHz, CDCl3): δ = 20.67,
20.73 (2 CH3), 27.22, 27.60, 28.78 (3 CH3CO), 46.18, 46.85 (2 -
CH2-), 54.71 (C-2b), 55.11 (-OCH3), 62.14 (C-6b), 68.45 (C-6a),
69.36 (C-5b), 69.42 (C-4b), 70.72 (C-3b), 71.66 (C-5a), 73.29, 74.68,
75.70 (3 CH2Ph), 78.05 (C-4a), 81.76 (C-3a), 97.66 (C-1a), 97.80
(C-2a), 98.82 (C-1b), 127.62–137.98 (3 Ph-C) ppm. MALDI MS
(positive ion mode, DHB/THF matrix): m/z = 898.3 [M + Na]+.
C47H57NO15 (876.0): C 64.43, H 6.57, N 1.59; found C 63.93, H
6.87, N 1.68.
Allyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylgluarimido)-β-
D-
glucopyranosyl-(1Ǟ2)-3,4,6-tri-O-benzyl-α- -mannopyranoside
D
(13d): The residue was purified by flash chromatography (petro-
leum ether/ethyl acetate, 2:1) to afford 13d (92%) as a white foam.
TLC (petroleum ether/ethyl acetate, 2:1): Rf = 0.15. [α]D = +6.0 (c
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-
glucopyranosyl-(1Ǟ3)-2,4,6-tri-O-benzyl-β- -galactopyranosyl-
(1Ǟ4)-2,3,6-tri-O-benzyl-β- -glucopyranoside (13b): The residue
D-
D
1
D
= 0.3, CHCl3). H NMR (600 MHz, CDCl3): δ = 0.91, 0.96 (2 s, 6
was purified by flash chromatography (petroleum ether/ethyl ace- H, 2 CH3), 1.93, 2.02 (2 s, 9 H, 3 CH3CO), 2.18 (d, Jgem = 16.3 Hz,
tate, 1:2) to yield 13b (96%) as a white foam. TLC (petroleum ether/ 1 H, 0.5 -CH2-), 2.42 (d, Jgem = 16.6 Hz, 1 H, 0.5 -CH2-), 2.49 (m,
ethyl acetate, 2:1): Rf = 0.16. [α]D = –9.0 (c = 0.2, CHCl3). 1H 2 H, -CH2-), 3.57 (dd, J6,6Ј = 10.5, J5,6 = 4.5 Hz, 1 H, 6a-H), 3.64
NMR (600 MHz, CDCl3): δ = 0.68, 0.82 (2 s, 6 H, 2 CH3), 1.78,
2.17 (2 d, Jgem = 17.2 Hz, 2 H, -CH2-), 1.89, 1.95, 2.01 (3 s, 9 H, 3
CH3CO), 1.97, 2.26 (2 d, Jgem = 16.4 Hz, 2 H, -CH2-), 3.14 (m, 1
H, 5a-H), 3.39–3.62 (m, 8 H, 6Јb-H, 5b-H, 2a-H, 3a-H, 6b-H, 6a-
(dd, J6,6Ј = 10.5, J5,6Ј Ͻ 1.0 Hz, 1 H, 6Јa-H), 3.71 (m, 2 H, 4a-H,
5a-H), 3.82 (m, 1 H, 5b-H), 3.87–3.95 (m, 2 H, -CHH-CH=CH2,
3a-H), 4.12–4.14 (m, 2 H, -CHH-CH=CH2, 2a-H), 4.18 (dd, J6,6Ј
= 10.7, J5,6 Ͻ 1.0 Hz, 1 H, 6b-H), 4.25 (dd, J6,6Ј = 10.7, J5,6Ј
=
4388
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org Eur. J. Org. Chem. 2005, 4382–4392

New Diacylamino Protecting Groups for Glucosamine
5.1 Hz, 1 H, 6Јb-H), 4.42, 4.87 (d, Jgem = 10.7 Hz, 2 H, CH2Ph), CHCl3). H NMR (250 MHz, CDCl3): δ = 1.04, 1.05 (2 s, 6 H, 2
FULL PAPER
1
4.45–4.51 (m, 3 H, 1.5 CH2Ph), 4.61 (d, J1,2 Ͻ 1.0 Hz, 1 H, 1a-H),
4.79 (d, Jgem = 11.3 Hz, 1 H, 0.5 CH2Ph), 5.01 (dd, J1,2 = 8.2, J2,3
= 10.4 Hz, 1 H, 2b-H), 5.13 (dd, J3,4 = 9.3, J4,5 = 9.6 Hz, 1 H, 4b-
CH3), 1.84–2.35 (m, 7 H, 2 -CH2-, CH3CO), 3.46–4.95 (m, 15 H),
7.12–7.36 (m, 21 H, 4 Ph, NH), 7.62 (br. s, 1 H, NH), 8.98 (br. s,
1 H, NH) ppm. MALDI MS (positive ion mode, DHB/THF ma-
H), 5.20 (m, 2 H, -CH2-CH=CH2), 5.47 (d, J1,2 = 8.2 Hz, 1 H, 1b- trix): m/z = 758.5 [M + Na]+, 774.5 [M + K]+. C43H51N3O8 (738.0):
H), 5.84–5.87 (m, 1 H, -CH2-CH=CH2), 5.86 (dd, J2,3 = 10.4, J3,4
= 9.3 Hz, 1 H, 3b-H), 7.16–7.39 (m, 15 H, 3 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 20.65, 20.73 (2 CH3), 26.40, 28.58 (3
CH3CO), 45.87, 46.92 (2 -CH2-), 54.55 (C-2b), 62.53 (C-6b), 68.07
(-CH2-CH=CH2), 69.60 (C-4b), 70.48 (C-3b), 69.51 (C-6a), 70.78
(CH2Ph), 71.10 (C-5a), 71.93 (C-5b), 73.10 (CH2Ph), 73.93 (C-2a),
74.07 (C-4a), 75.08 (CH2Ph), 78.09 (C-3a), 82.00 (-CH2-CH=CH2),
96.76 (C-1a), 97.72 (C-1b), 117.57–138.42 (3 Ph, CH2CH=CH2),
169.51–173.42 (5 CO) ppm. MALDI MS (positive ion mode, DHB/
THF matrix): m/z = 923.5 [M + Na]+ , 939.5 [M + K]+ .
C49H59NO15 (902.1): C 65.23, H 6.60, N 1.55; found C 65.21, H
6.58, N 1.53.
C 69.97, H 6.97, N 5.69; found C 69.64, H 6.86, N 5.56.
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-diglycolylimido-β-D-glucopyr-
anoside (16): Crystalline 8 (4.20 g, 7.28 mmol) suspended in dichlo-
romethane (75 mL) was neutralized by shaking with saturated
Na2CO3 solution (15 mL). The organic layer was separated, dried
with MgSO4, and the solvent evaporated in vacuo. The residue was
stirred with diglycolic anhydride (1.13 g, 9.7 mmol) in pyridine
(10 mL) at room temp. Et3N (0.5 mL) was added after 1 h and the
solution heated at 80 °C for 30 min. Acetic anhydride (0.5 mL) was
then added and heating was continued for a further 6 h. The mix-
ture was coevaporated with toluene in vacuo and the residue puri-
fied by flash chromatography (petroleum ether/ethyl acetate, 4:1)
to yield 16 (4.64 g, quant.) as a colourless oil which solidified in
the form of an amorphous mass upon standing. TLC (petroleum
ether/ethyl acetate, 4:1): Rf = 0.22. [α]D = +4.2 (c = 0.35, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 3.50 (d, Jgem = 18.5 Hz, 1 H, -
CH2-), 3.58 (m, 1 H, 5-H), 3.75–3.81 (m, 4 H, 0.5 -CH2-, 6Ј-H, 6-
H, 4-H), 3.91, 4.19 (2 d, Jgem = 16.2 Hz, 2 H, -CH2-), 4.37 (m, 1
H, 3-H), 4.41–4.51 (m, 2 H, CH2Ph), 4.57–4.63 (m, 2 H, CH2Ph),
4.66–4.69 (m, 2 H, 0.5 CH2Ph, 2-H), 4.81–4.84 (m, 3 H, 1.5
CH2Ph), 5.12 (d, J1,2 = 8.3 Hz, 1 H, 1-H), 7.20–7.37 (m, 20 H, 4
Ph) ppm. 13C NMR (150.9 MHz, CDCl3): δ = 55.87 (C-2), 67.25,
67.55 (2 -CH2-), 68.63 (C-6), 70.68, 73.47, 74.70, 74.83 (4 CH2Ph),
74.96 (C-5), 78.94 (C-3), 80.06 (C-4), 97.17 (C-1), 127.58–138.59 (4
Ph) ppm. MALDI MS (positive ion mode, DHB/THF matrix): m/
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutarimido)-β-D-
glucopyranoside (13e): The residue was purified by flash chromatog-
raphy (petroleum ether/ethyl acetate, 1.5:1) to yield 13e (0.254 g,
93%) as a colourless oil. TLC (petroleum ether/ethyl acetate, 1:1):
Rf = 0.36. [α]D = –19.0 (c = 0.55, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 0.91, 0.98 (2 s, 6 H, 2 CH3), 1.92, 2.02, 2.12 (3 s, 9 H,
3 CH3CO), 2.23–2.47 (m, 4 H, 2 -CH2-), 3.38, 3.77 (2 m, 1 H, 5-
H), 4.16 (dd, J6,6Ј = 12.3, J5,6 = 2.2 Hz, 1 H, 6-H), 4.30 (dd, J6,6Ј
= 12.3, J5,6Ј = 4.6 Hz, 1 H, 6Ј-H), 4.48, 4.85 (2 d, Jgem = 11.8 Hz,
2 H, CH2Ph), 4.92 (dd, J1,2 = 8.2, J2,3 = 10.6 Hz, 1 H, 2-H), 5.15
(dd, J3,4 = 8.8, J4,5 = 10.1 Hz, 1 H, 4-H), 5.47 (d, J1,2 = 8.2 Hz, 1
H, 1-H), 5.79 (dd, J2,3 = 10.6, J3,4 = 8.8 Hz, 1 H, 3-H), 7.20–7.32
(m, 5 H, Ph) ppm. MALDI MS (positive ion mode, DHB/THF
matrix): m/z = 543.3 [M + Na]+. C26H33NO10 (519.6): C 60.09, H z = 659.4 [M + Na]+, 675.3 [M + K]+. C38H39NO8 (637.8): C 71.55,
6.41, N 2.69; found C 59.58, H 6.41, N 2.76.
H 6.17, N 2.19; found C 71.16, H 6.27, N 2.22.
Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-(3,3-dimethylglutaramido)-β-
D-
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-diglycolylimido-β-D-glucopyranose
glucopyranoside (14): Compound 13e (0.225 g, 0.433 mmol) and
NaOH (0.25 g, 6.2 mmol) in MeOH/dioxane/water (1:1:1, 6 mL)
was stirred at room temp. overnight and then warmed to 60 °C.
After 5 h the pH of the mixture was adjusted to 4.5 by the addition
(18): A solution of 16 (4.28 g, 6.71 mmol) in dry methanol (30 mL)
was stirred under hydrogen in the presence of Pd/C (10%, 0.78 g).
After 24 h the reaction mixture was filtered through Celite, washed
with aqueous methanol (1:1, 50 mL), evaporated in vacuo, and
of 2 n HCl and maintained at this pH for 24 h. The mixture was dried to give 17 (quant.) as a white powder. Compound 17 was
then neutralized with K2CO3 and dried in vacuo. The residue was
treated with Pyr/Ac2O, (2:1, 12 mL), stirred for 14 h, and then co-
evaporated with toluene in vacuo. The residue was purified by flash
chromatography (toluene/acetone, 2.5:1) to afford 14 (quant.) as a
stirred overnight with pyridine (20 mL) and acetic anhydride
(10 mL), and then coevaporated with toluene in vacuo. The residue
was purified by flash chromatography (petroleum ether/ethyl ace-
tate, 1:1) to yield 18 (2.93 g, 98%) as a colourless foam. TLC (pe-
troleum ether/ethyl acetate, 1:1): Rf = 0.21. [α]D = +6.6 (c = 0.15,
yellow oil. TLC (toluene/acetone, 2.5:1): Rf = 0.2. [α]D = –45.0 (c
1
= 0.4, CHCl3). H NMR (250 MHz, CDCl3): δ = 0.99, 1.01 (2 s, 6 CHCl3). 1H NMR (250 MHz, CDCl3): δ = 1.98, 2.05, 2.08, 2.11 (4
H, 2 CH3), 2.01, 2.02, 2.11 (3 s, 9 H, 3 CH3CO), 2.20–2.36 (m, 2 s, 12 H, 4 CH3CO), 3.93–3.99 (2 m, 1 H, 5-H), 4.11 (dd, J6,6Ј
=
H, 2 -CH2-), 3.70 (m, 1 H, 5-H), 4.00 (m, 1 H, 2-H), 4.18 (m, 1 H, 12.5, J5,6 = 2.1 Hz, 1 H, 6-H), 4.27–4.40 (m, 5 H, 2 -CH2-, 6Ј-H),
6-H), 4.29 (dd, J5,6Ј = 4.8, J6,6Ј = 12.3 Hz, 1 H, 6Ј-H), 4.72 (d, J1,2
= 8.3 Hz, 1 H, 1-H), 4.56, 4.90 (2 d, Jgem = 11.7 Hz, 2 H, CH2Ph),
5.09 (dd, J3,4 = 9.3, J4,5 = 9.8 Hz, 1 H, 4-H), 5.30 (dd, J2,3 = 10.6,
4.88 (dd, J1,2 = 8.6, J2,3 = 10.3 Hz, 1 H, 2-H), 5.20 (dd, J3,4 = 9.0,
J4,5 = 10.2 Hz, 1 H, 4-H), 5.82 (dd, J2,3 = 10.3, J3,4 = 9.0 Hz, 1 H,
3-H), 6.52 (d, J1,2 = 8.6 Hz, 1 H, 1-H) ppm. MALDI MS (positive
J3,4 = 9.3 Hz, 1 H, 3-H), 6.43 (br. d, J2,NH = 8.4 Hz, 1 H, NH), ion mode, DHB/THF matrix): m/z = 468.0 [M + Na]+, 483.9 [M
7.25–7.36 (m, 5 H, Ph) ppm. C26H35NO11 (537.6): C 58.08, H 6.57, + K]+. C18H23NO12 (445.4): C 48.53, H 5.21, N 3.14; found C
N 2.60; found C 57.91, H 6.88, N 2.70.
48.36, H 5.29, N 3.09.
Benzyl 3,4,6-Tri-O-benzyl-2-deoxy-2-(N3-acetyl-3,3-dimethyl-
3,4,6-Tri-O-acetyl-2-deoxy-2-diglycolylimido-β-D-glucopyranose
hydrazidoglutaramido)-β-
D
-glucopyranoside (15): A mixture of 3
(19): A solution of 18 (7.0 g, 15.7 mmol) in dry DMF (15 mL) was
stirred at room temp. with hydrazine acetate (1.55 g, 16.8 mmol).
After 1.5 h the reaction mixture was diluted with ethyl acetate
(200 mL) and washed with HCl (5%, 3×20 mL), H2O (20 mL),
and saturated NaHCO3 (20 mL). The organic layer was dried with
MgSO4 and the solvents evaporated in vacuo. The residue was puri-
fied by flash chromatography (toluene/acetone, 3:1) to yield 19
(4.88 g, 77%) as an amorphous mass. TLC (toluene/acetone, 3:1):
Rf = 0.27. [α]D = +14.1 (c = 0.6, CHCl3). 1H NMR (250 MHz,
(0.23 g, 0.34 mmol) and hydrazine hydrate (6 mL) was refluxed
overnight and then cooled to room temp. The mixture was diluted
with dichloromethane (50 mL), washed with water (3 × 10 mL),
dried with MgSO4, and coevaporated in vacuo. The residue was
stirred with Pyr/Ac2O, (2:1, 12 mL) for 2 h, then evaporated with
toluene in vacuo, and purified by flash chromatography (toluene/
acetone, 2:1) to yield 15 (63.0 mg, 24%) as an amorphous white
mass. TLC (toluene/acetone, 2:1): Rf = 0.22. [α]D = –9.0 (c = 1.1,
Eur. J. Org. Chem. 2005, 4382–4392
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4389

M. R. E. Aly, R. R. Schmidt
FULL PAPER
CDCl3): δ = 1.05, 1.09 (2 s, 6 H, 2 CH3), 1.98, 2.04, 2.11 (3 s, 9 H,
3 CH3CO), 3.58 (br. s, 1 H, OH), 3.86 (m, 1 H, 5-H), 4.11–4.42
(m, 6 H, 2 -CH2-, 6Ј-H, 6-H), 4.68 (dd, J1,2 = 8.2, J2,3 = 10.6 Hz,
1 H, 2-H), 5.16 (dd, J3,4 = 8.9, J4,5 = 10.2 Hz, 1 H, 4-H), 5.64 (dd,
J1,2 = 8.2 Hz, 1 H, 1-H), 5.76 (dd, J2,3 = 10.6, J3,4 = 8.9 Hz, 1 H,
3-H) ppm. MALDI MS (positive ion mode, DHB/THF matrix): m/
(m, 1 H, 5b-H), 4.33–4.88 (m, 10 H, 2 -CH2-, 6Јb-H, 6b-H, 2a-H, -
CH2-CH=CH2, 3a-H), 4.43–4.46 (d, 2 H, CH2Ph), 4.52–4.54 (m, 2
H, CH2Ph), 4.59 (d, J1,2 Ͻ 1.0 Hz, 1 H, 1a-H), 4.75 (d, Jgem
=
11.3 Hz, 1 H, 0.5 CH2Ph), 4.88 (d, Jgem = 10.4 Hz, 1 H, 0.5
CH2Ph), 4.90 (dd, J1,2 = 8.3, J2,3 = 10.8 Hz, 1 H, 2b-H), 5.15 (dd,
J3,4 = 9.0, J4,5 = 9.6 Hz, 1 H, 4b-H), 5.17–5.24 (m, 2 H, -CH2-
z = 426.0 [M + Na]+, 441.9 [M + K]+. C16H21NO11 (403.4): C CH=CH2), 5.46 (d, J1,2 = 8.3 Hz, 1 H, 1b-H), 5.77 (dd, J2,3 = 10.8,
47.63, H 5.25, N 3.47; found C 47.55, H 5.33, N 3.40.
J3,4 = 9.0 Hz, 1 H, 3b-H), 5.84 (m, 1 H, -CH2-CH=CH2), 7.18–
7.39 (m, 15 H, 3 Ph) ppm. 13C NMR (150.9 MHz, CDCl3): δ =
20.55, 20.65, 20.73 (3 CH3CO), 54.26 (C-2b), 62.40 (C-6b), 67.08
(-CH2-CH=CH2), 68.07, 68.10 (2 -CH2-), 69.18 (C-6a), 69.26 (C-
4b), 70.11 (C-3b), 70.96 (CH2Ph), 71.13 (C-5a), 72.09 (C-5b), 73.23
(CH2Ph), 73.98 (C-4a), 74.02 (C-2a), 75.16 (CH2Ph), 78.02 (C-3a),
81.80 (-CH2CH=CH2), 96.40 (C-1a), 97.07 (C-1b), 117.61–138.42
(3 Ph, -CH2-CH=CH2), 168.90, 169.41, 170.48, 170.70, 170.83 (5
CO) ppm. MALDI MS (positive ion mode, DHB/THF matrix): m/
z = 896.1 [M + Na]+, 912.1 [M + K]+. C46H53NO16 (876.0): C
63.06, H 6.11, N 1.59; found C 62.84, H 6.15, N 1.61.
Trichloroacetimidate 20: A mixture of 19 (0.77 g, 1.9 mmol) and
trichloroacetonitrile (1.5 mL, 15.0 mmol, 2.16 g) in dry dichloro-
methane (7.0 mL) was treated with DBU (0.1 mL, 0.66 mmol) and
stirred at room temp. overnight. The solvent was evaporated in
vacuo and the residue purified by flash chromatography (petroleum
ether/ethyl acetate, 1:2 + 1% Et3N) to yield 20 (0.843 g, 80%) as a
pale yellow foam. TLC (petroleum ether/ethyl acetate, 1:2 + 1%
Et3N): Rf = 0.53. 1H NMR (250 MHz, CDCl3): δ = 1.99, 2.06, 2.11
(3 s, 9 H, 3 CH3CO), 4.02 (m, 1 H, 5-H), 4.11–4.39 (m, 6 H, 2 -
CH2-,6Ј-H, 6-H), 5.05 (dd, J1,2 = 8.7, J2,3 = 10.5 Hz, 1 H, 2-H),
5.27 (dd, J3,4 = 8.9, J4,5 = 10.2 Hz, 1 H, 4-H), 5.84 (dd, J2,3 = 10.5,
J3,4 = 8.9 Hz, 1 H, 3-H), 6.64 (d, J1,2 = 8.7 Hz, 1 H, 1-H), 8.74 (s,
1 H, NH) ppm. C18H21Cl3N2O11 (547.8).
Thexyldimethylsilyl 3,4,6-Tri-O-acetyl-2-deoxy-2-diglycolylimido-β-
D
-glucopyranosyl-(1Ǟ4)-2-azido-3,6-di-O-benzyl-2-deoxy-β-D-
glucopyranoside (21f): The residue was purified by flash chromatog-
raphy (petroleum ether/ethyl acetate, 2:1) to afford 21f (86%) as a
colourless foam. TLC (petroleum ether/ethyl acetate, 2:1): Rf =
0.16. [α]D = +12.0 (c = 0.15, CHCl3). 1H NMR (600 MHz, CDCl3):
δ = 0.05–0.08 [2 s 6 H, Si(CH3)2], 0.66, 0.67, 0.70, 0.72 (4 s, 12 H,
4 CH3), 1.45 (m, 1 H, CH), 1.94, 1.95, 1.96, 1.99 (4 s, 12 H, 4
CH3CO), 3.44 (m, 1 H, 5a-H), 3.51 (m, 1 H, 5b-H), 3.56 (dd, J6,6Ј
General Procedure for the Synthesis of Compounds 21a,d,f,g: A mix-
ture of 20 (0.53 mmol) and the appropriate acceptor (4a,[26] 4d,[33]
and 4f[34]) or 1,3,5-trimethoxybenzene (0.348 mmol) in dry dichlo-
romethane (1 mL) was stirred under argon at room temp. while
TMSOTf (0.01 m in CH2Cl2, 0.53 mL) was added dropwise. After
2 h the mixture was neutralized with Et3N and the solvents evapo-
rated in vacuo.
= 11.6, J5,6 = 3.3 Hz, 1 H, 6a-H), 3.61 (dd, J6,6Ј = 11.6, J5,6Ј
=
1.1 Hz, 1 H, 6Јa-H), 3.85 (dd, J1,2 = 10.7 Hz, 1 H, 2a-H), 3.90 (dd,
J6,6Ј = 12.3, J5,6 = 2.0 Hz, 1 H, 6b-H), 4.04–4.08 (m, 2 H, 0.5
-CH2-, 4a-H), 4.13–4.17 (m, 2 H, 6Јb-H, 3a-H), 4.23–4.26 (m, 2 H,
-CH2-), 4.33 (d, Jgem = 16.4 Hz, 1 H, 0.5 -CH2-), 4.60–4.67 (2 d,
Jgem = 11.4 Hz, 2 H, CH2Ph), 4.74 (dd, J1,2 = 8.2, J2,3 = 10.5 Hz,
1 H, 2b-H), 4.43, 4.83 (2 d, Jgem = 12.7 Hz, 2 H, CH2Ph), 5.09 (d,
J1,2 = 8.2 Hz, 1 H, 1a-H), 5.10 (dd, J3,4 = 8.9, J4,5 = 10.0 Hz, 1 H,
4b-H), 5.61 (d, J1,2 = 8.2 Hz, 1 H, 1b-H), 5.67 (dd, J2,3 = 10.5, J3,4
= 8.9 Hz, 1 H, 3b-H), 7.14–7.39 (m, 10 H, 2 Ph) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = –3.89, –1.91 [Si(CH3)2], 3.16 (SiC), 8.14
(C-thexyl), 18.37–20.66 (4 CH3, 3 CH3CO), 24.49 (CH), 33.94 (2
CH3), 55.59 (C-2b), 57.52 (C-2a), 61.60 (C-6b), 67.41, 68.05 (2 -
CH2-), 68.23 (C-6a), 68.65 (C-4b), 70.56 (C-3b), 71.41 (C-5b),
73.46, 73.80 (2 CH2Ph), 74.76 (C-5a), 76.60 (C-4a), 77.59 (C-3a),
93.29 (C-1a), 97.54 (C-1b), 122.13–139.10 (2 Ph), 169.37, 169.57,
170.09, 170.66, 170.72 (5 CO) ppm. MALDI MS (positive ion
mode, DHB/THF matrix): m/z = 936.0 [M + Na]+, 952.0 [M + K]
+. C44H62N4O15Si (913.2): C 57.86, H 6.63, N 6.13; found C 57.45,
H 6.71, N 6.11.
Methyl 3,4,6-Tri-O-acetyl-2-deoxy-2-diglycolylimido-β-
D-glucopyr-
anosyl-(1Ǟ6)-2,3,4-tri-O-benzyl-α- -glucopyranoside (21a): The
D
residue was purified by flash chromatography or MPLC (petroleum
ether/ethyl acetate, 1.5:1) to afford 21a (quant.) as a colourless
foam. TLC (petroleum ether/ethyl acetate, 1.5:1): Rf = 0.12. [α]D
=
+2.8 (c = 0.25, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 0.93,
0.98 (2 s, 6 H, CH3), 1.94, 2.02, 2.06 (3 s, 9 H, 3 CH3CO), 3.33 (s,
3 H, -OCH3), 3.37 (dd, J3,4 = J4,5 = 9.5 Hz, 1 H, 4a-H), 3.50 (dd,
J1,2 = 3.4, J2,3 = 9.6 Hz, 1 H, 2a-H), 3.68 (dd, J5,6 = 1.1, J6,6Ј
10.5 Hz, 1 H, 6a-H), 3.74–3.79 (m, 2 H, 5b-H, 5a-H), 3.94–3.97
(m, 2 H, 3a-H, 0.5 -CH2-), 4.06 (dd, J5,6Ј Ͻ 1.0, J6,6Ј = 10.5 Hz, 1
H, 6Јa-H), 4.12–4.21 (m, 4 H, 1.5 -CH2-, 6b-H), 4.27 (dd, J5,6Ј
=
=
4.7, J6,6Ј = 12.2 Hz, 1 H, 6Јb-H), 4.43 (d, Jgem = 10.7, 1 H, 0.5
CH2Ph), 4.55 (d, J1,2 = 3.4 Hz, 1 H, 1a-H), 4.63 (d, Jgem = 12.1 Hz,
1 H, 0.5 CH2Ph), 4.76–4.82 (m, 4 H, 2b-H, 1.5 CH2Ph), 4.95 (d,
Jgem = 10.8 Hz, 1 H, 0.5 CH2Ph), 5.16 (dd, J3,4 = 9.1, J4,5 = 9.7 Hz,
1 H, 4b-H), 5.44 (d, J1,2 = 8.3 Hz, 1 H, 1b-H), 5.68 (dd, J2,3 = 10.3,
J3,4 = 9.1 Hz, 1 H, 3b-H), 7.24–7.35 (m, 15 H, 3 Ph) ppm. 13C
NMR (600 MHz, CDCl3): δ = 20.51, 20.63, 20.74 (3 CH3CO),
54.94 (C-2b), 55.14 (-OCH3), 62.04 (C-6b), 67.98, 67.31 (2 -CH2-),
69.49 (C-6a), 68.80 (C-4b), 69.17 (C-5a), 70.74 (C-3b), 71.76 (C-
5b), 73.39, 74.81, 75.82 (3 CH2Ph), 77.69 (C-4a), 81.82 (C-3a),
97.75 (C-2a), 97.99 (C-1a), 98.45 (C-1b), 127.61–138.57 (3 Ph),
169.13, 169.30, 169.96, 170.72, 170.86 (5 CO) ppm. MALDI MS
(positive ion mode, DHB/THF matrix): m/z = 870.1 [M + Na]+,
886.0 [M + K]+. C44H51NO16 (850.0): C 62.17, H 6.06, N 1.64;
found C 61.71, H 6.04, N 1.64.
2,4,6-Trimethoxyphenyl 3,4,6-Tri-O-acetyl-1,2-dideoxy-2-diglycolyl-
imido-β-D-glucopyranoside (21g): The residue was purified by flash
chromatography (petroleum ether/ethyl acetate, 1.5:1) to yield 21g
(86%) as a colourless foam. TLC (petroleum ether/ethyl acetate,
1.5:1): Rf = 0.2. [α]D = –21.2 (c = 0.25, CHCl3). 1H NMR
(600 MHz, CDCl3): δ = 1.97, 2.06, 2.07 (3 s, 9 H, 3 CH3CO), 3.74,
3.77, 3.83 (3 s, 9 H, 3 OCH3), 3.90 (m, 1 H, 5-H), 4.01–4.19 (m, 5
H, 6-H, 2 -CH2-), 4.29 (dd, J6,6Ј = 12.3, J5,6Ј = 4.4 Hz, 1 H, 6Ј-H),
5.27 (dd, J3,4 = 9.4, J4,5 = 9.7 Hz, 1 H, 4-H), 5.70 (dd, J1,2 = 10.4,
J2,3 = 10.3 Hz, 1 H, 2-H), 5.87 (d, J1,2 = 10.4 Hz, 1 H, 1-H), 5.98
(dd, J2,3 = 10.3, J3,4 = 9.4 Hz, 1 H, 3-H), 6.02, 6.07 (2 d, J = 2.1 Hz,
2 H, Ar) ppm. 13C NMR (150.9 MHz, CDCl3): δ = 20.72, 20.76,
20.82 (3 CH3CO), 52.67 (C-2), 55.19, 55.78, 56.02 (3 OCH3), 62.65
Allyl 3,4,6-tri-O-acetyl-2-deoxy-2-diglycolylimido-β-
D-glucopyrano-
syl-(1Ǟ2)-3,4,6-tri-O-benzyl-α- -mannopyranoside (21d): The resi-
D
due was purified by flash chromatography (petroleum ether/ethyl
acetate, 2:1) to afford 21d (94%) as a colourless foam. TLC (petro-
leum ether/ethyl acetate, 2:1): Rf = 0.17. [α]D = +6.0 (c = 0.2, (C-6), 67.29, 68.11 (2 -CH2-), 69.48 (C-4), 69.65 (C-1), 72.40 (C-3),
1
CHCl3). H NMR (600 MHz, CDCl3): δ = 1.96, 2.03, 2.04 (3 s, 9
75.68 (C-5), 90.39, 91.70 (2 C-Ar), 104.45 (C-Ar), 159.70–170.89 (5
H, 3 CH3CO), 3.62–3.73 (m, 4 H, 4a-H, 5a-H, 6Јa-H, 6a-H), 3.82 CO, 3 C-Ar) ppm. MALDI MS (positive ion mode, DHB/THF
4390
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4382–4392

New Diacylamino Protecting Groups for Glucosamine
FULL PAPER
matrix): m/z = 575.9 [M + Na]+, 591.9 [M + K]+. C25H31NO13
(553.9): C 54.23, H 5.65, N 2.53; found C 53.92, H 5.85; N 2.64.
tralized with Et3N, the solvent evaporated in vacuo, and the residue
purified by flash chromatography (toluene/acetone, 3:1) to yield 23
(0.458 g, 55%) as colourless foam. TLC (toluene/acetone, 3:1): Rf
= 0.24. Compound 23 was stirred with TBDMS-Cl (0.18 g,
1.2 mmol) and imidazole (0.17 g, 2.5 mmol) in dry dichlorometh-
ane (5 mL) at room temp. After 75 min the mixture was diluted
with H2O (10 mL) and dichloromethane (50 mL), then the organic
layer was separated, dried with MgSO4, and the solvent evaporated
in vacuo. The residue was purified by flash chromatography (petro-
leum ether/ethyl acetate, 2:1) to yield 24 (0.475 g, 79%) as a colour-
less amorphous mass. TLC (petroleum ether/ethyl acetate, 2:1): Rf
= 0.18. [α]D = –4.5 (c = 0.3, CHCl3). 1H NMR (250 MHz, CDCl3):
δ = 0.02, 0.07 [2 s, 6 H, Si(CH3)3], 0.82 [s, 9 H, C(CH3)3], 2.64 (br.
s, 1 H, OH), 3.51, 3.77 (2 m, 3 H, 4-H, 6-H, 5-H), 4.20–4.36 (m, 5
General Procedure for the Synthesis of Compounds 6a,[12] 6d,[17]
6g,[37] and 22.[35,36] Method A: A mixture of the appropriate glyco-
side 16 or 21a, 21d, and 21f (0.17 mmol) and KOH (1.2 g) in EtOH
(96% v/v, 5 mL) was refluxed for 4 h and then the solvent was
evaporated until dryness in vacuo. The residue was stirred with
pyridine (12 mL) in an ice/water bath and then treated with Ac2O
(6 mL). The cooling bath was removed after 2 h and the mixture
stirred at room temp. overnight and then coevaporated with toluene
in vacuo. The residue was taken up in H2O (20 mL) and dichloro-
methane (100 mL), the organic layer was separated, dried with
MgSO4, and the solvents evaporated in vacuo. The physical data
obtained for 6a[12] and 6d[17] are identical to those given in the
literature.
H, 2 -CH2-, 6Ј-H), 4.55–4.64 (m, 2 H, 2-H, 3-H), 5.45 (d, J1,2
=
7.2 Hz, 1 H, 1-H), 5.51 (s, 1 H, CHPh), 7.32–7.48 (m, 5 H,
Ph) ppm. MALDI MS (positive ion mode, DHB/THF matrix):
m/z = 502.5 [M + Na]+, 516.6 [M + K]+. C23H33NO8Si (479.7): C
57.58, H 6.94, N 2.92; found C 57.11, H 7.17; N 2.91.
2,4,6-Trimethoxyphenyl 2-Acetamido-3,4,6-tri-O-acetyl-1,2-dide-
oxy-β-D-glucopyranoside (6g): The residue was purified by flash
chromatography (toluene/acetone, 1.5:1) to yield 6g[37] (76%) as a
1
yellowish foam. TLC (toluene/acetone, 1.5:1): Rf = 0.26. H NMR
tert-Butyldimethylsilyl 2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl-
(600 MHz, [D6]DMSO, 100 °C): δ = 1.53, 1.91, 1.97, 1.98 (4 s, 12
H, 4 CH3CO), 3.70 (m, 1 H, 5-H), 3.75 (br. s, 9 H, 3 OCH3), 4.06
(1Ǟ3)-4,6-di-O-benzylidene-2-deoxy-2-diglycolylimido-β-
D-glucopy-
ranoside (26): A mixture of 25[38,39] (0.3 g, 0.6 mmol) and 24 (0.2 g,
0.41 mmol) in dry dichloromethane (1 mL) was stirred under argon
at room temp. while TMSOTf (0.01 m in CH2Cl2, 0.6 mL) was
added dropwise. After 45 min the mixture was neutralized with
Et3N and the solvent evaporated in vacuo. The residue was purified
by flash chromatography (petroleum ether/ethyl acetate, 2:1) and
then stirred with Pyr (4 mL) and Ac2O (2 mL). After 4 h the mix-
ture was coevaporated with toluene in vacuo and the residue was
purified by MPLC (petroleum ether/ethyl acetate, 2:1) to yield 26
(0.308 g, 91%) as a colourless foam. TLC (petroleum ether/ethyl
acetate, 2:1): Rf = 0.18. [α]D = –4.8 (c = 1.85, CHCl3). 1H NMR
(600 MHz, CDCl3): δ = 0.03, 0.08 [2 s, 6 H, Si(CH3)2], 0.84 [s, 9
H, SiC(CH3)3], 1.93, 1.94, 1.99, 2.12 (4 s, 12 H, 4 CH3CO), 3.43
(m, 1 H, 5b-H), 3.58 (m, 1 H, 5a-H), 3.81–3.88 (m, 3 H, 6b-H, 6a-
H, 4a-H), 4.03 (dd, J6,6Ј = 11.0, J5,6Ј = 8.0 Hz, 1 H, 6Јb-H), 4.28–
4.31 (m, 2 H, 0.5 -CH2-, 6Јa-H), 4.36 (m, 2 H, -CH2-), 4.47 (d, Jgem
= 16.1 Hz, 1 H, 0.5 -CH2-), 4.65 (d, J1,2 = 7.9 Hz, 1 H, 1b-H),
4.72–4.73 (m, 2 H, 2a-H, 3a-H), 4.85 (dd, J2,3 = 10.2, J3,4 = 3.0 Hz,
1 H, 3b-H), 4.98 (dd, J1,2 = 7.3, J2,3 = 10.2 Hz, 1 H, 2b-H), 5.23
(d, J3,4 = J4,5 = 3.0 Hz, 1 H, 3b-H), 5.36 (d, J1,2 = 7.3 Hz, 1 H, 1a-
H), 5.53 (s, 1 H, CHPh), 7.38–7.47 (m, 5 H, Ph) ppm. 13C NMR
(600 MHz, CDCl3): δ = –5.47, –4.22 [Si(CH3)2], 17.62 (Si-C), 20.54,
20.57, 20.70, 20.80 (4 CH3CO), 25.39 [C(CH3)3], 57.17 (C-2a),
60.97 (C-6b), 66.28 (C-5a), 66.60 (C-4b), 67.48, 68.15 (2 -CH2-),
68.83 (C-6a), 69.84 (C-2b), 70.23 (C-5b), 70.93 (C-3b), 75.11 (C-
3a), 81.90 (C-4a), 93.39 (C-1a), 100.07 (C-1b), 101.63 (CHPh),
126.00, 128.46, 129.40, 136.99 (Ph), 169.54, 170.02, 170.09, 170.32
(6 CO) ppm. FAB MS (positive ion mode, NBOH/NaI matrix): m/
z = 832.0 [M + Na]+. C37H51NO17Si (810.0): C 54.86, H 6.35, N
1.72; found C 55.01, H 6.39; N 1.77.
(m, 2 H, 6Ј-H, 6-H), 4.70 (m, 1 H, 2-H), 4.88 (dd, J3,4 = J4,5
9.6 Hz, 1 H, 4-H), 4.96 (d, J1,2 = 10.3 Hz, 1 H, 1-H), 5.19 (dd, J2,3
=
= J3,4 = 9.6 Hz, 1 H, 3-H), 6.17 (s, 2 H, Ar), 7.12 (d, J2,NH
=
6.9 Hz, 1 H, NH) ppm. 13C NMR (150.9 MHz, CDCl3): δ = 19.74,
21.84 (4 CH3CO), 50.46 (C-2), 54.71, 55.88 (3 OCH3), 62.27 (C-6),
69.43 (C-4), 71.55 (C-1), 74.55 (C-3, C-5), 92.04 (Ar) ppm.
Benzyl 2-Acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-glucose (22):
The residue was purified by flash chromatography (petroleum
ether/ethyl acetate, 1:1) to yield 22[36] (94 mg, 82%) as amorphous
mass. TLC (petroleum ether/ethyl acetate, 1:1): Rf = 0.31. 1H NMR
(250 MHz, CDCl3): δ = 1.81 (s, 3 H, CH3CO), 3.53–3.80 (m, 5 H),
4.04 (dd, J = 8.5, 10.0 Hz, 1 H), 4.55–4.85 (m, 8 H, 3.5 CH2Ph, 1-
H), 4.89 (d, Jgem = 11.5 Hz, 1 H, CHHPh), 5.53 (d, J8,6 = Hz, 1
H, NH), 7.18–7.38 (m, 20 H, 4 Ph) ppm. MALDI MS (positive
ion mode, DHB/THF matrix): m/z = 582.3 [M + H]+, 604.2 [M +
Na]+ , 620.2 [M + K]+. C36H39NO6 (581.76).
Method B: Compound 16 (0.268 g, 0.42 mmol) in NaOBu (1.0 m,
10 mL) was gently refluxed for 20 h. The reaction mixture was then
treated with Pyr/Ac2O and worked up as described in method A.
The residue was purified by flash chromatography (petroleum
ether/ethyl acetate, 1:1) to yield 22 (0.169 g, 69%).
Method C: A mixture of 16 (0.22 g, 0.34 mmol) and hydrazine hy-
drate (3 mL) was heated at 120–130 °C for 14 h and then stirred
with Pyr (16 mL) and Ac2O (12 mL) in an ice bath. After 1 h the
mixture was diluted with ethyl acetate (20 mL), filtered at a vacuum
pump, and coevaporated with toluene in vacuo. The residue was
taken up in ethyl acetate (100 mL), washed with 5 % HCl
(5×20 mL), H2O (20 mL), and sat. Na2CO3 (20 mL), dried with
MgSO4, evaporated in vacuo, and purified as described before to
yield 22 (76.0 mg, 38%).
Acknowledgments
Method D: A mixture of 16 (0.174 g, 0.27 mmol) and hydrazine
hydrate (0.5 mL, 10.2 mmol) in dry EtOH (5 mL) was refluxed
overnight, then evaporated in vacuo, and dried well. The residue
was treated with Ac2O/Pyr and purified as described in method B
to yield 22 (6.0 mg, 3%).
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie.
[1] R. R. Schmidt, W. Kinzy, Adv. Carbohydr. Chem. Biochem.
1994, 50, 21–123; and references cited therein.
[2] H. G. Garg, K. von dem Bruch, H. Kunz, Adv. Carbohydr.
Chem. Biochem. 1994, 50, 227–310 and references cited therein.
[3] R. U. Lemieux, T. Takeda, B. Y. Chung, ACS Symp. Ser. 1976,
39, 90–115.
tert-Butyldimethylsilyl 4,6-Di-O-benzylidene-2-deoxy-2-diglycolyli-
mido-β-D-glucopyranoside (24): A mixture of 17 (0.626 g,
2.2 mmol), benzaldehyde dimethylacetal (0.7 mL, 4.6 mmol), and
pTsOH (0.04 g, 0.2 mmol) in a mixture of CH3CN/DMF (2:1,
15 mL) was stirred at room temp. overnight. The mixture was neu-
Eur. J. Org. Chem. 2005, 4382–4392
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4391

M. R. E. Aly, R. R. Schmidt
FULL PAPER
[4]
[22] R. R. Schmidt, M. Behrendt, A. Toepfer, Synlett 1990, 694–
697.
[23] M. R. E. Aly, E. I. Ibrahim, E. H. El Ashry, R. R. Schmidt,
Eur. J. Org. Chem. 2000, 319–326.
[24] S. Jonke, PhD Dissertation, University of Konstanz, 2005.
[25] U. Zehavi, J. Org. Chem. 1977, 42, 2819–2821.
[26] 4a: A. Liptak, I. Jodal, P. Nonasi, Carbohydr. Res. 1975, 44, 1–
11.
S. S. Debenham, R. Rodebough, B. Fraser-Reid, Liebigs Ann./
Recueil 1997, 791–802 and references cited therein.
A. Toepfer, PhD Dissertation, University of Konstanz, 1992.
G. Blatter, J.-M. Beau, J.-C. Jacquinet, Carbohydr. Res. 1994,
260, 189–202.
A. Gerull, R. R. Schmidt, manuscript in preparation.
M. Imoto, H. Yoshimura, T. Shimamoto, N. Skaguchi, S. Susu-
moto, T. Shiba, Bull. Chem. Soc. Jpn. 1987, 60, 2205–2214.
H. Paulsen, C. Krogmann, Liebigs Ann. Chem. 1989, 1203–
1213.
[5]
[6]
[7]
[8]
[27] 4b: K.-H. Jung, M. Hoch, R. R. Schmidt, Liebigs Ann. Chem.
[9]
1989, 1099–1106.
[28] 4c: J.-M. Petit, S.-C. Jacquinet, P. Sinaÿ, Carbohydr. Res. 1980,
82, 130–134.
[10]
[11]
[12]
D. Qiu, R. R. Koganty, Tetrahedron Lett. 1997, 38, 45–48.
K. G. I. Nilson, Tetrahedron Lett. 1997, 38, 135–136.
W. Dullenkopf, J. C. Castro-Palomino, L. Manzoni, R. R.
[29] A. Sarkar, K. Rakesh, K. L. Matta, Carbohydr. Res. 1990, 203,
33–46.
Schmidt, Carbohydr. Res. 1996, 296, 135–147.
[13] J. C. Castro-Palomino, R. R. Schmidt, Tetrahedron Lett. 1995,
36, 6871–6874.
[30] T. C. Bruice, W. C. Bradbury, J. Am. Chem. Soc. 1965, 87,
4838–4845.
[31] M. Bergmann, L. Zervas, Ber. Dtsch. Chem. Ges. 1931, 64, 975–
[14] J. S. Debenham, R. Madsen, C. Roberts, B. Fraser-Reid, J. Am.
Chem. Soc. 1995, 117, 3302–3303.
981.
[32] T. E. Inch, H. G. Fletcher, J. Org. Chem. 1966, 31, 1810–1815.
[33] 4d: T. Ogawa, T. Nukuda, Carbohydr. Res. 1985, 136, 135–152.
[34] 4f: T. Eisele, H. Ishida, G. Hummel, R. R. Schmidt, Liebigs.
Ann. Chem. 1995, 2113–2121.
[35] R. Harrison, H. G. Fletcher, J. Org. Chem. 1965, 30, 2317–
2321.
[36] J. Liu, D. Y. Gin, J. Am. Chem. Soc. 2002, 124, 9789–9797.
[37] J. C. Castro-Palomino, R. R. Schmidt, Liebigs Ann. 1996,
1623–1626.
[15] J. C. Castro-Palomino, R. R. Schmidt, Tetrahedron Lett. 1995,
36, 5343–5346.
[16] E. Meinjohanns, M. Meldal, H. Paulsen, K. Bock, J. Chem.
Soc., Perkin Trans. 1 1995, 405–415.
[17] M. R. E. Aly, J. C. Castro-Palomino, E. I. Ibrahim, E. H.
El Ashry, R. R. Schmidt, Eur. J. Org. Chem. 1998, 2305–2316.
[18] J. C. Castro-Palomino, R. R. Schmidt, Tetrahedron Lett. 2000,
41, 629–632.
[19] R. U. Lemieux, R. M. Ratcliffe, Can. J. Chem. 1979, 57, 1244–
[38] P. H. Amvam-Zollo, P. Sinaÿ, Carbohydr. Res. 1986, 150, 199–
1251.
212.
[20] H. Paulsen, Angew. Chem. 1982, 94, 184–201; Angew. Chem.
Int. Ed. Engl. 1982, 21, 155–173.
[21] R. R. Schmidt, Angew. Chem. 1986, 98, 213–236; Angew. Chem.
Int. Ed. Engl. 1986, 25, 212–235 and references cited therein.
[39] R. R. Schmidt, J. Michel, M. Roos, Liebigs Ann. Chem. 1984,
1343–1357.
Received: February 9, 2005
Published Online: August 26, 2005
4392
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4382–4392