Convenient synthesis of nucleosides of 2-deoxy-2-nitro-D-galactose and N-acetyl-D-galactosamine

Article abstract of DOI:10.1002/1099-0690(200009)2000:17<3047::AID-EJOC3047>3.0.CO;2-6

A new method for the construction of nucleosides of 2-deoxy-2-nitro-D-galactose and of N-acetyl-D-galactosamine based on addition reactions to 3,4,6-tri-O-benzyl-2-nitro-D-galactal (1) is presented. The reaction of imidazole, benzimidazole, purine, N

Full text of DOI:10.1002/1099-0690(200009)2000:17<3047::AID-EJOC3047>3.0.CO;2-6

FULL PAPER
Convenient Synthesis of Nucleosides of 2-Deoxy-2-nitro-
N-Acetyl- -galactosamine
D
-galactose and
D
Gottfried A. Winterfeld,[a] Jagattaran Das,[a] and Richard R. Schmidt*[a]
Keywords: Carbohydrates / Nucleosides / Glycosylations / Michael additions / Nitroglycals
A new method for the construction of nucleosides of 2-deoxy-
2-nitro- -galactose and of N-acetyl- -galactosamine based
on addition reactions to 3,4,6-tri-O-benzyl-2-nitro- -galactal
(1) is presented. The reaction of imidazole, benzimidazole,
purine, N6-benzyladenine, indazole, benzotriazole, and pyri-
done with 1 under base activation afforded the correspond-
ing β-glycosides with a high degree of stereo- and regiose-
lectivity. Reduction of the 2-deoxy-2-nitro-nucleosides 3 and
4 gave, after N-acetylation, the corresponding 2-acetamido-
2-deoxy-nucleosides 9 and 10. Complete deprotection of 9
was achieved with H2 in the presence of Pd(OH)2/C and THF
as solvent.
D
D
D
Introduction
Nucleosides of 2-nitrogen-substituted pyranoses espe-
cially galactopyranoses have not been well studied, and only
few syntheses for this class of compounds are reported in
literature.[1Ϫ4] The preparation of purine and pyrimidine
nucleosides of N-acetyl--galactosamine succeeded with
haloses and trifluoroacetyl protection for the amino func-
tion at C-2; however, rather harsh conditions are needed for
coupling (fusion method), and chloromercurated or silyl-
ated bases are required.[2,3] Yields as well as stereoselectivit-
ies in the formation of purine nucleosides remained unsatis-
factory.[2] Recently, we have introduced the concept of
Michael-type addition to 3,4,6-tri-O-benzyl-2-nitro--gal-
actal (1) as a powerful tool in the synthesis of O-glycosides
of galactosamine.[5,6] Here, a versatile and efficient ap-
proach to the synthesis of nucleosides of 2-deoxy-2-nitro--
galactose and of N-acetyl--galactosamine is presented,
thus widening the scope of the strategy of addition reac-
tions to 2-nitro--galactal to the formation of N-glycosides.
Scheme 1. Nucleoside formation by Michael addition reactions
In all these cases, addition of a second base with reduced
nucleophilicity was required to obtain a good rate of reac-
tion and high yields. A combination of 1.2 equiv. of N-
methylimidazole and catalytic amounts of DBU proved to
be very efficient. All reactions proceeded smoothly at room
temperature and completed within 6Ϫ48 h. Uniformly, in
all cases studied β-glycosides were isolated in good to excel-
lent yields varying between 60% for the pyridone glycoside
8 and 91% for the purine glycoside 4. Thus, under the con-
ditions favoring β-glycoside formation with O-nucleo-
philes,[5] with nitrogen heterocycles as N-nucleophiles, the
β-glycosides were obtained exclusively. This is presumably
Results and Discussion
In a test case we treated our previously established glyco-
syl donor 3,4,6-tri-O-benzyl-2-nitro--galactal (1)[5,6] with
imidazole as nucleophile (Scheme 1). In THF as solvent,
glycoside formation was complete within 6 h at room tem-
perature, and we observed the exclusive formation of the
corresponding N-(3,4,6-tri-O-benzyl-2-deoxy-2-nitro-β--
galactopyranosyl)imidazole (2), which was isolated in 88%
yield. We then moved to other heterocyclic nitrogen nucleo-
philes to generalize the methodology. Among the nucleob-
ases studied were benzimidazole, purine, N-benzyladenine,
indazole, benzotriazole, and pyridone (Scheme 1).
5
due to kinetically favored β-side addition to the H4 con-
former of 1.[5] The β-selectivity could be also due to hydro-
gen bond interaction of the N-nucleophiles with O-4 of the
4
sterically favored H5 conformer of 1.[5,7] The anomeric di-
astereocontrol is particularly worth mentioning because it
adds further value to this convenient N-glycoside bond
formation.
[a]
Fakultät für Chemie, Universität Konstanz,
Fach M 725, D-78457 Konstanz, Germany
Eur. J. Org. Chem. 2000, 3047Ϫ3050
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0917Ϫ3047 $ 17.50ϩ.50/0
3047

G. A. Winterfeld, J. Das, R. R. Schmidt
FULL PAPER
In the glycosylation of purine, the protected adenine de-
rivative, indazole, benzotriazole, and pyridone, more than
one regioisomer can form, for at least two or more nucleo-
philic centers are present in the heterocyclic base. In all
cases, only one single considerable product was observed
and characterized. The regiochemical outcome for all reac-
tions is shown in Scheme 1. The purine heterocycles formed
N-9 nucleosides 4 and 5; benzotriazole and indazole were
glycosylated at N-1, leading to nucleosides 6 and 7. Nucleo-
philic attack of the pyridone occurred via the nitrogen
atom, leading to glycoside 8. Hence, in all experiments, a
remarkable degree of stereo- as well as regioselectivity was
observed.
Conclusion
In conclusion, a new and versatile approach to the syn-
thesis of nucleosides of 2-deoxy-2-nitro--galactose and N-
acetyl--galactosamine was established. The high degree of
stereo- and regioselectivity, the use of unmodified hetero-
cyclic bases in nucleoside synthesis, as well as the conveni-
ent experimental conditions underline the efficiency of this
approach.
Experimental Section
General: Solvents were removed under reduced pressure while
maintaining the water bath temperature below 40 °C. Ϫ Chromato-
graphy was done on silica gel for flash chromatography 40 µm (J.
T. Baker) at 3 bar pressure. Ϫ For thin-layer chromatography TLC
plastic sheets, silica gel 60 F254, were used and the compounds visu-
alized by illumination under UV light at 254 nm and by treatment
with 5% (NH4)2MoO4, 0.1% Ce(SO4)2 in 10% H2SO4 and heating
to 160 °C. Ϫ Optical rotations were measured at 25 °C with a
PerkinϪElmer polarimeter 241/MS using the sodium D line. Ϫ
NMR: Bruker AC 250 Cryospec, Bruker DR 600, TMS or the solv-
The regiochemical outcome of glycosylation was unequi-
1
vocally determined using the three-bond H-13C spin-spin
long-range coupling between the anomeric proton of the
carbohydrate moiety and the α-carbon atoms of the hetero-
cycle next to the glycosylation site. In the purine nucleoside
4, for instance, C-4, C-5, and C-8 were first assigned by
1
means of their H-13C long-range coupling to either 2-H,
6-H, and 8-H (C-4) or 8-H only (C-5), or a lack thereof (C-
8). The anomeric proton in glycoside 4 shows a 1H-13C
long-range coupling to C-4 and C-8 proving attachment of
the glycosyl residue at N-9. Structures 5 and 7 were deter-
mined the same way; structure 6 was ascertained by a
NOE experiment.
In order to show that this route is suitable for the syn-
thesis of 2-amino-2-deoxynucleosides, the benzimidazole
nucleoside 3 and the purine nucleoside 4 were exemplarily
reduced to the corresponding amines, which were isolated
after N-acetylation (Scheme 2).
3
ent residual peak were used as internal standard. JC,4 couplings
were observed in gradient-selected heteronuclear multi-bond cor-
relations (HMBC). Ϫ MALDI-MS: Kratos Kompact Maldi 1, 2,5-
dihydroxybenzoic acid was used as matrix. Ϫ FAB-MS: Finnigan
MAT 312/AMD 5000, 790 eV, 70 °C. Ϫ Yields are calculated based
on consumed 1 where its recovery is stated.
N-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galactopyranosyl)-
imidazole (2): Nitrogalactal 1[5,6] (150 mg, 0.325 mmol) and imida-
zole (27 mg, 0.390 mmol) in THF (2 mL) were stirred at room tem-
perature for 6 h. The solvent was evaporated and the crude product
purified by flash chromatography with toluene/ethyl acetate (1:1)
as eluent to yield 2 (152 mg, 88%). Ϫ Rf ϭ 0.45 (toluene/ethyl acet-
ate, 1:3); [α]2D5 ϭ ϩ19.1 (c ϭ 1, CHCl3). Ϫ 1H NMR (250 MHz,
CDCl3): δ ϭ 3.59Ϫ3.62 (m, 2 H, 6aЈ- and 6bЈ-H), 3.85 (t, 1 H,
3J ϭ 7.1 Hz, 5Ј-H), 4.31 (d, 1 H, 3J ϭ 1.9 Hz, 4Ј-H), 4.20 (dd, 1
3
3
H, J2,3 ϭ 10.3 Hz, J3,4 ϭ 2.6 Hz, 3Ј-H), 4.42Ϫ4.83 (m, 6 H,
3
3
benzyl H), 5.20 (t, 1 H, J ϭ 10.0 Hz, 2Ј-H), 5.57 (d, 1 H, J1,2
ϭ
Scheme 2. Reduction of 2-nitro nucleosides to 2-amino nucleosides;
reagents: i) Raney nickel T4 (Pt), H2, EtOH; ii) Ac2O, pyridine
9.3 Hz, 1Ј-H), 7.05Ϫ7.07 (m, 2 H, im-H), 7.23Ϫ7.39 (m, 15 H,
arom. H), 7.58 (s, 1 H, im-H). Ϫ MS (FAB): calcd. 529 ϩ 1 (H) ϭ
530, 529 ϩ 23 (Na) ϭ 552; found 530 [M ϩ H]ϩ, 552 [M ϩ Na]ϩ.
For the hydrogenation reaction we used platinized Raney
nickel T4,[8] a catalyst, which had proven to work very effi-
General Procedure for the Preparation of Nucleosides 3؊8: Nitroga-
lactal 1 (1.0 equiv.) and the nitrogen heterocycle (1.2 equiv.) were
ciently in a related problem.[6] After reduction with the sys- dissolved in dry THF (75Ϫ150 equiv.). The reaction was activated
by addition of N-methylimidazole (1.2 equiv.) and a catalytic
amount of DBU (0.2Ϫ0.3 equiv.) to the stirred solution at room
temperature. The reaction mixture was stirred for 6Ϫ48 h at that
temperature before the solvent was evaporated and the residue
purified by flash chromatography to yield products 3؊8.
tem Raney nickel T4 (Pt)/H2 in ethanol as solvent, and sub-
sequent N-acetylation, the 2-acetamido nucleosides 9 and
10 were obtained in 54% and 51% yield, respectively. The
benzyl protection remains intact during the reduction of the
nitro group. Complete deprotection is possible using H2/
Pearlman’s catalyst in THF, as shown for the deprotection
of 9 to give 11 in 66% yield (Scheme 3).
N-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galactopyranosyl)-
benzimidazole (3): Flash chromatography using toluene/ethyl acet-
ate (4:1) as eluent afforded 85% of pure 3. Ϫ Rf ϭ 0.49 (toluene/
ethyl acetate, 1:1); [α]2D5 ϭ Ϫ1.9 (c ϭ 1, CHCl3). Ϫ 1H NMR
(250 MHz, CDCl3): δ ϭ 3.58Ϫ3.71 (m, 2 H, 6aЈ- and 6bЈ-H), 3.95
3
3
(t, 1 H, J ϭ 6.5 Hz, 5Ј-H), 4.19 (d, 1 H, J ϭ 2.2 Hz, 4Ј-H), 4.29
3
3
(dd, 1 H, J2,3 ϭ 10.3 Hz, J3,4 ϭ 2.5 Hz, 3Ј-H), 4.40Ϫ5.02 (m, 6
H, benzyl H), 5.60 (t, 1 H, 3J ϭ 10.0 Hz, 2Ј-H), 5.90 (d, 1 H, 3J1,2 ϭ
9.3 Hz, 1Ј-H), 7.13Ϫ7.40 (m, 17 H, arom. H), 7.50 (d, 1 H, 3J ϭ
3
Scheme 3. Deprotection of a 2-acetamido nucleoside
3048
8.4 Hz, benzim H), 7.77 (d, 1 H, J ϭ 8.0 Hz, benzim H), 7.90 (s,
Eur. J. Org. Chem. 2000, 3047Ϫ3050

Convenient Synthesis of Nucleosides
1 H, benzim H). Ϫ MS (FAB): calcd. 579 ϩ 1 (H) ϭ 580, 579 ϩ 1Ј-H), 7.25Ϫ7.38 (m, 17 H, arom. H), 7.62, 8.06 (2 d, 2 H, benzotri-
FULL PAPER
23 (Na) ϭ 602; found 580 [M ϩ H]ϩ, 602 [M ϩ Na]ϩ.
azole H). Ϫ 13C NMR (150 MHz, CDCl3): δ ϭ 67.5, 71.3, 72.6,
73.7, 75.0, 76.4, 79.5, 85.0, 85.3, 110.6, 120.5, 124.7, 128 (m), 131.4
(C-7a), 136.3, 137.3, 137.6, 146.5. Ϫ MS (EI): calcd. 580; found
580 [M]ϩ, 489, 308, 264, 197, 91.
9-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β- -galactopyranosyl)purine
D
(4): Flash chromatography using toluene/ethyl acetate (3:2) as elu-
ent afforded 91% of pure 4 along with 40% of recovered 1. Ϫ Rf ϭ
0.31 (toluene/ethyl acetate, 1:1); [α]2D5 ϭ ϩ20.3 (c ϭ 2, CHCl3). Ϫ
1H NMR (600 MHz, CDCl3): δ ϭ 3.57Ϫ3.62 (m, 2 H, 6aЈ- and
N-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galactopyranosyl)-
pyridone (8): Flash chromatography using toluene/ethyl acetate
(9:1) as eluent afforded 60% of pure 8 along with 42% of recovered
1. Ϫ Rf ϭ 0.23 (toluene/ethyl acetate, 3:1); [α]2D5 ϭ ϩ65.0 (c ϭ 1,
3
3
6bЈ-H), 3.97 (t, 1 H, J ϭ 6.6 Hz, 5Ј-H), 4.15 (d, 1 H, J ϭ 2.4 Hz,
3
3
4Ј-H), 4.35 (dd, 1 H, J2,3 ϭ 10.3 Hz, J3,4 ϭ 2.6 Hz, 3Ј-H),
4.40Ϫ4.95 (m, 6 H, benzyl H), 5.68 (t, 1 H, 3J ϭ 10.0 Hz, 2Ј-H),
6.20 (d, 1 H, J1,2 ϭ 9.6 Hz, 1Ј-H), 7.24Ϫ7.37 (m, 15 H, arom. H),
1
CHCl3). Ϫ H NMR (600 MHz, CDCl3): δ ϭ 3.56Ϫ3.63 (m, 2 H,
6aЈ- and 6bЈ-H), 3.92 (t, 1 H, 3J ϭ 6.8 Hz, 5Ј-H), 4.10 (d, 1 H,
3
3
3
3J ϭ 2.4 Hz, 4Ј-H), 4.37 (dd, 1 H, J2,3 ϭ 10.3 Hz, J3,4 ϭ 2.6 Hz,
3Ј-H), 4.41Ϫ4.85 (m, 6 H, benzyl H), 5.05 (t, 1 H, 3J ϭ 10.0 Hz,
2Ј-H), 6.21 (t, 1 H, 3J ϭ 6.8 Hz, pyridone H), 6.46 (d, 1 H, 3J ϭ
9.3 Hz, pyridone H), 6.53 (d, 1 H, 3J1,2 ϭ 9.5 Hz, 1Ј-H), 7.24Ϫ7.36
(m, 17 H, arom. H). Ϫ 13C NMR (150 MHz, CDCl3): δ ϭ 67.4,
71.8, 72.8, 73.5, 75.0, 76.3, 78.9, 79.3, 86.5, 106.9, 120.9, 128 (m),
132.0, 137.0 (t), 139.9, 161.3. Ϫ MS (FAB): calcd. 556 ϩ 1 (H) ϭ
557; found 557 [M ϩ H]ϩ.
8.28, 8.98, 9.14 (3 s, 3 H, purine H). Ϫ 13C NMR (150 MHz,
CDCl3): δ ϭ 67.5, 71.4, 72.6, 73.6, 75.0, 79.4, 79.9, 85.9, 128 (m),
133.7, 136.0, 137.2, 137.5, 142.6 (C-8), 149.1, 150.9 (C-4), 153.2. Ϫ
MS (FAB): calcd. 581 ϩ 1 (H) ϭ 582; found 582 [M ϩ H]ϩ. Ϫ
C32H31N5O6 (581.6): calcd. C 66.08, H 5.37, N 12.04; found C
66.32, H 5.45, N 11.65.
N6-Benzyl 9-(3,4,6-tri-O-benzyl-2-deoxy-2-nitro-β-
D-galactopyra-
nosyl)adenine (5): Flash chromatography using toluene/ethyl acetate
(3:1) as eluent afforded 90% of pure 5 along with 25% of recovered
1. Ϫ Rf ϭ 0.61 (toluene/ethyl acetate, 1:1); [α]2D5 ϭ ϩ2.0 (c ϭ 0.5,
CHCl3). Ϫ H NMR (600 MHz, CDCl3): δ ϭ 3.56 (dd, 1 H, J ϭ
9.2 Hz, 3J ϭ 5.5 Hz, 6aЈ-H), 3.60 (dd, 1 H, 2J ϭ 9.2 Hz, 3J ϭ
N-(2-Acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-galactopyranosyl)-
benzimidazole (9): Compound 3 (100 mg, 0.173 mmol) was dis-
solved in EtOH (5 mL) and transferred to a hydrogenation vessel.
Platinized Raney nickel T4 catalyst was freshly prepared as de-
scribed in the literature[8] and the material obtained from 2 g of
Raney nickel/aluminum alloy was suspended in EtOH (15 mL).
From a homogenous suspension of this catalyst 5 mL was added
to the reaction vessel and the suspension shaken under H2 at room
temperature for 12 h. The catalyst was filtered off and all volatiles
were removed. The residue was dissolved in pyridine/acetic anhyd-
ride (2:1, 5 mL) and stirred for 3 h. Removal of the volatiles and
flash chromatography (toluene/acetone, 3:1Ǟ3:2) gave 9 (56 mg,
54%). Ϫ Rf ϭ 0.24 (toluene/acetone, 1:1); [α]2D5 ϭ Ϫ6.85 (c ϭ 2,
CHCl3). Ϫ 1H NMR (600 MHz, CDCl3): δ ϭ 1.73 (s, 3 H,
1
2
3
3
7.8 Hz, 6bЈ-H), 3.94 (t, 1 H, J ϭ 6.3 Hz, 5Ј-H), 4.13 (d, 1 H, J ϭ
3
3
2.7 Hz, 4Ј-H), 4.31 (dd, 1 H, J2,3 ϭ 10.3 Hz, J3,4 ϭ 2.7 Hz, 3Ј-
H), 4.40Ϫ4.90 (m, 8 H, benzyl H), 5.55 (t, 1 H, J ϭ 10.0 Hz, 2Ј-
H), 6.10 (d, 1 H, J1,2 ϭ 9.7 Hz, 1Ј-H), 6.70 (br. d, 1 H, NH),
3
3
7.19Ϫ7.36 (m, 20 H, arom. H), 7.63, 8.87 (2 br. s, 2 H, adenine H).
Ϫ
13C NMR (150 MHz, CDCl3): δ ϭ 67.4, 71.5, 72.5, 73.6, 75.0,
76.6, 79.5, 79.7, 86.0, 119.2, 128 (m), 136.2, 137.1, 137.2, 137.6,
138.3 (C-8), 148.8 (C-4), 153.8, 154.7. Ϫ MS (FAB): calcd. 686 ϩ
1 (H) ϭ 687; found 687 [M ϩ H]ϩ.
1-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galactopyrano-
NHCOCH3), 3.62Ϫ3.69 (m, 2 H, 6aЈ- and 6bЈ-H), 4.01 (t, 1 H,
3
3J ϭ 6.3 Hz, 5Ј-H), 4.13 (s, 1 H, 4Ј-H), 4.33 (br. d, 1 H, J2,3
ϭ
syl)indazole (6): Flash chromatography using toluene/ethyl acetate
(98:2) as eluent afforded 64% of pure 6 along with 29% of recovered
1. Ϫ Rf ϭ 0.45 (toluene/ethyl acetate, 9:1); [α]2D5 ϭ ϩ4.6 (c ϭ 2,
10.1 Hz, 3Ј-H), 4.45 (d, 1 H, 2J ϭ 11.9, benzyl H), 4.50 (d, 1 H,
2J ϭ 11.9, benzyl H), 4.57 (br. d, 1 H, 3J ϭ 9.8, 2Ј-H), 4.63 (d, 1
1
2
2
2
CHCl3). Ϫ H NMR (600 MHz, CDCl3): δ ϭ 3.58 (dd, 1 H, J ϭ
9.5 Hz, 3J ϭ 5.5 Hz, 6aЈ-H), 3.72 (dd, 1 H, 2J ϭ 9.5 Hz, 3J ϭ
H, J ϭ 11.0, benzyl H), 4.64 (d, 1 H, J ϭ 11.7, benzyl H), 4.75
2
2
(d, 1 H, J ϭ 11.7, benzyl H), 5.03 (d, 1 H, J ϭ 11.0, benzyl H),
6.33 (d, 1 H, 3J1,2 ϭ 9.5 Hz, 1Ј-H), 6.75 (br. s, 1 H, NH), 7.22Ϫ7.36
(m, 17 H, arom. H), 7.74, 7.86 (2 d, 2 H, J ϭ 8.1 Hz, benzim H),
3
3
7.8 Hz, 6bЈ-H), 3.93 (t, 1 H, J ϭ 7.8 Hz, 5Ј-H), 4.19 (d, 1 H, J ϭ
2.7 Hz, 4Ј-H), 4.31 (dd, 1 H, J2,3 ϭ 10.5 Hz, J3,4 ϭ 2.7 Hz, 3Ј-
3
3
3
3
8.90 (br. s, 1 H, benzim H). Ϫ 13C NMR (150 MHz, CDCl3): δ ϭ
23.2, 68.3, 72.6, 73.5, 74.8, 76.1, 78.5, 128 (m), 137.6, 137.8, 138.4,
171.4. Ϫ MS (FAB): calcd. 591 ϩ 23 (Na) ϭ 614; found 614 [M ϩ
Na]ϩ. Ϫ C36H37N3O5 · 0.5 H2O (600.7): calcd. C 71.98, H 6.38, N
6.99; found C 71.93, H 6.24, N 6.72.
H), 4.35Ϫ4.95 (m, 6 H, benzyl H), 5.92 (t, 1 H, J ϭ 10.0 Hz, 2Ј-
H, NOE with 7-H, no NOE with 3-H), 6.11 (d, 1 H, 3J1,2 ϭ 9.3 Hz,
1Ј-H, NOE with 7-H, no NOE with 3-H), 7.18 (t, 1 H, 3J ϭ 7.6 Hz,
indazole H), 7.23Ϫ7.34 (m, 15 H, arom. H), 7.50 (d, 1 H, 3J ϭ
3
8.4 Hz, 7-H), 7.69 (d, 1 H, J ϭ 8.0 Hz, indazole H), 8.05 (s, 1 H,
3-H). Ϫ 13C NMR (150 MHz, CDCl3): δ ϭ 67.7, 71.3, 72.3, 73.6,
74.8, 76.0, 80.0, 84.9, 85.1, 119.7, 121.3, 121.9, 125.1, 128 (m),
135.9, 136.5, 137.4, 137.8, 139.4. Ϫ MS (EI): calcd. 579; found 579
[M]ϩ, 488, 209, 118, 91. Ϫ C34H33N3O6 (579.7): calcd. C 70.45, H
5.74, N 7.25; found C 70.38, H 5.81, N 7.10.
9-(2-Acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-D-galactopyranosyl)-
purine (10): Compound 7 (313 mg, 0.538 mmol) was treated as de-
scribed for the preparation of 9 to give 10 (162 mg, 51%) after flash
chromatographic purification with toluene/acetone (2:3Ǟ1:2). Ϫ
Rf ϭ 0.31 (toluene/acetone, 1:2); [α]2D5 ϭ ϩ20.71 (c ϭ 2, CHCl3).
1-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-
D
-galactopyranosyl)-
Ϫ
1H NMR (600 MHz, CDCl3): δ ϭ 1.57 (s, 3 H, NHCOCH3),
3
benzotriazole (7): Flash chromatography using toluene/ethyl acetate
(97:3) as eluent afforded 83% of pure 7. Ϫ Rf ϭ 0.47 (toluene/ethyl
acetate, 9:1); [α]2D5 ϭ Ϫ13.5 (c ϭ 1, CHCl3). Ϫ 1H NMR (600 MHz,
3.61Ϫ3.64 (m, 2 H, 6aЈ- and 6bЈ-H), 3.95 (t, 1 H, J ϭ 6.5 Hz, 5Ј-
H), 3.99 (dd, 1 H, J2,3 ϭ 10.6, J3,4 ϭ 2.6 Hz, 3Ј-H), 4.12 (d, 1 H,
3J3,4 ϭ 2.9 Hz, 4Ј-H), 4.43 (d, 1 H, J ϭ 11.8, benzyl H), 4.47 (d,
3
3
2
2
2
CDCl3): δ ϭ 3.60Ϫ3.62 (m, 1 H, 6aЈ-H), 3.67Ϫ3.70 (m, 1 H, 6bЈ- 1 H, J ϭ 11.8, benzyl H), 4.52 (d, 1 H, J ϭ 12.0, benzyl H), 4.66
3
3
2
2
H), 4.01 (t, 1 H, J ϭ 6.6 Hz, 5Ј-H), 4.19 (d, 1 H, J ϭ 2.6 Hz, 4Ј-
(d, 1 H, J ϭ 11.4, benzyl H), 4.77 (d, 1 H, J ϭ 12.0, benzyl H),
3
3
3
3
H), 4.38 (dd, 1 H, J2,3 ϭ 10.4 Hz, J3,4 ϭ 2.6 Hz, 3Ј-H), 4.43 (d,
1 H, J ϭ 11.8, benzyl H), 4.48 (d, 1 H, J ϭ 11.8, benzyl H), 4.58 11.4, benzyl H), 5.77 (br. s, 1 H, NH), 5.94 (d, 1 H, J1,2 ϭ 9.8 Hz,
(d, 1 H, J ϭ 11.5, benzyl H), 4.65 (d, 1 H, J ϭ 11.0, benzyl H),
4.81 (dd, 1 H, J1,2 ϭ 8.3, J2,3 ϭ 10.2, 2Ј-H), 4.98 (d, 1 H, 2J ϭ
2
2
3
2
2
1Ј-H), 7.26Ϫ7.39 (m, 15 H, arom. H), 8.52, 9.04, 9.10 (3 s, 3 H,
purine H). Ϫ 13C NMR (150 MHz, CDCl3): δ ϭ 22.9, 51.9, 68.3,
71.7, 71.9, 73.6, 74.8, 76.6, 78.6, 81.9, 128 (m), 133.7, 137.4, 137.5,
2
2
4.69 (d, 1 H, J ϭ 11.5, benzyl H), 4.99 (d, 1 H, J ϭ 11.0, benzyl
3
3
H), 5.76 (t, 1 H, J ϭ 10.0 Hz, 2Ј-H), 6.45 (d, 1 H, J1,2 ϭ 9.5 Hz,
Eur. J. Org. Chem. 2000, 3047Ϫ3050
3049

G. A. Winterfeld, J. Das, R. R. Schmidt
FULL PAPER
138.1, 146.0, 151.0, 152.1, 170.7. Ϫ MS (MALDI-TOF): calcd.
Acknowledgments
593.3 ϩ 23.0 (Na) ϭ 616.3; found 616.7 [M ϩ Na]ϩ.
Ϫ
We thank Dr. A. Geyer for his contribution in elucidating the regi-
ochemistry of compounds 4؊8. This work was supported by the
Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
Industrie. J. D. is grateful for an Alexander von Humboldt Fellow-
ship.
C34H35N5O5 · 0.5 H2O (602.9): calcd. C 67.76, H 6.02, N 11.62;
found C 68.10, H 6.13, N 11.39.
N-(2-Acetamido-2-deoxy-β-D-galactopyranosyl)benzimidazole (11):
Compound 9 (30 mg, 0.051 mmol) was dissolved in dry THF
(2 mL) and stirred together with Pd(OH)2/C (20% Pd, 30 mg) un-
der H2 for 4 d. The catalyst was filtered off and washed carefully
with MeOH. The filtrate was concentrated and purified by flash
chromatography (chloroform/methanol, 2:1) to give 11 (11 mg,
66%). Ϫ Rf ϭ 0.58 (chloroform/methanol, 1:1); [α]2D5 ϭ ϩ3.56 (c ϭ
[1]
L. B. Townsend, G. R. Revenkar, Chem. Rev. 1970, 70,
389Ϫ438.
[2]
M. L. Wolfrom, P. J. Coniglaro, Carbohydr. Res. 1969, 11,
63Ϫ76.
M. L. Wolfrom, H. B. Bhat, P. J. Coniglaro, Carbohydr. Res.
1971, 20, 375Ϫ381.
Z. Smiatacz, R. Szweda, H. Myszka, Carbohydr. Res. 1986,
153, 33Ϫ43.
J. Das, R. R. Schmidt, Eur. J. Org. Chem. 1998, 1609Ϫ1613.
[3]
1
0.5, CHCl3). Ϫ H NMR (600 MHz, CD3OD): δ ϭ 1.65 (s, 3 H,
[4]
NHCOCH3), 3.77Ϫ3.85 (m, 3 H, 5Ј-, 6aЈ- and 6bЈ-H), 3.91 (dd, 1
3
3
3
H, J2,3 ϭ 10.5 Hz, J3,4 ϭ 3.1 Hz, 3Ј-H), 4.03 (d, 1 H, J4,3
ϭ
[5]
3
3
[6]
3.2 Hz, 4Ј-H), 4.60 (t, 1 H, J2,1 ϭ 10.1 Hz, J2,3 ϭ 10.1 Hz, 2Ј-H),
5.64 (d, 1 H, J1,2 ϭ 9.7 Hz, 1Ј-H), 7.25Ϫ7.32 (m, 2 H, benzim H),
7.63, 7.71 (2 d, 2 H, J ϭ 8.0 Hz, benzim H), 8.33 (s, 1 H, benzim
G. A. Winterfeld, Y. Ito, T. Ogawa, R. R. Schmidt, Eur. J. Org.
Chem. 1999, 1167Ϫ1171.
3
[7]
3
A similar explanation for the β-selectivity was given in a related
case: H. Kunz, J. Weißmüller, B. Müller, Tetrahedron Lett.
H). Ϫ 13C NMR (150 MHz, CD3OD): δ ϭ 22.5, 30.7, 53.4, 62.6,
69.8, 72.9, 79.8, 85.2, 97.2, 112.6, 120.1, 123.9, 124.5, 143.3, 173.7.
Ϫ MS (FAB): calcd. 321 ϩ 1 (H) ϭ 322, 321 ϩ 23 (Na) ϭ 344;
found 322 [M ϩ H]ϩ, 344 [M ϩ Na]ϩ.
1984, 25, 3571Ϫ3574.
[8]
S. Nishimura, Bull. Chem. Soc. Jpn. 1959, 32, 61Ϫ64.
Received March 1, 2000
[O00099]
3050
Eur. J. Org. Chem. 2000, 3047Ϫ3050