An easy route to 2-amino-β-C-glycosides by conjugate addition to 2-nitroglycals

Article abstract of DOI:10.1002/1099-0690(200205)2002:9<1479::AID-EJOC1479>3.0.CO;2-P

2-Nitroglycals were found to undergo conjugate addition with a variety of stabilized soft carbanions. The Michael adducts from galactal derivatives were converted into bicyclic lactams. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200205)2002:9<1479::AID-EJOC1479>3.0.CO;2-P

FULL PAPER
An Easy Route to 2-Amino-β-C-Glycosides by Conjugate Addition to
2-Nitroglycals
Kandasamy Pachamuthu,[a] Anuradha Gupta,[a] Jagattaran Das,[b] Richard R. Schmidt,*[b]
and Yashwant D. Vankar*[a]
Keywords: Glycosides / Cyclization / Michael addition / Nitroglycals / Nitro group
2-Nitroglycals were found to undergo conjugate addition
with a variety of stabilized soft carbanions. The Michael ad-
ducts from galactal derivatives were converted into bicyclic
lactams.
(
Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
The synthesis of C-glycosides, which in general have con-
formations similar to those of the parent O-glycosides,[1,2]
has gained wide attention owing to their biological signific-
ance[3] and their synthetic utility,[4] mainly because of their
stability towards enzymes, acids or bases. 2-Amino sugars
such as N-acetylglucosamine (GlcNAc) and N-acetylgalac-
tosamine (GalNAc) are major components of a number of
important compounds and are attractive targets for the de-
sign of C-linked mimetics.[5,6] C-Glycosyl derivatives of 2-
amino sugars have been regarded as among the most diffi-
cult to prepare by common C-glycosylation strategies,[7Ϫ13]
due to the incompatibility of neighbouring nitrogen-based
functional groups (i.e., amides, carbamates and azides).
Therefore, not many methods for the synthesis of α-linked
2-amino-C-glycosides are reported in the literature,[14Ϫ24]
while methods for the synthesis of β-linked 2-amino-C-
glycosides[25Ϫ34] are also limited. It is thus desirable to in-
troduce new and stereoselective approaches for the syn-
thesis of 2-amino-2-deoxy-C-glycosides.
Recently, Michael-type addition to 3,4,6-tri-O-benzyl-2-
nitro--galactal (1) (Scheme 1) was shown to be a conveni-
ent method for the synthesis of α- and β-O-glycosides[35]
and β-nucleosides[36] of glactosamine, and this methodology
was also extended to the synthesis of α-GalNAc-Ser and -
Thr building blocks[37] for glycopeptide synthesis. Here we
now report the synthesis of 2-deoxy-2-nitro-β-C-glycosides
by Michael addition of carbon nucleophiles to 3,4,6-tri-O-
benzyl-2-nitro--glycals 1 and 2.
Scheme 1. Addition of dimethyl malonate to 2-nitrogalactal 1
Results and Discussion
Initial experiments were carried out with 3,4,6-tri-O-
benzyl-2-nitro--galactal (1) and dimethyl malonate in the
presence of different bases such as NaH, DBU, tBuOK, Na-
OCH3, KHMDS and NaHMDS, to afford 3α and 3β
(Scheme 1, Table 1). Of the bases used, the best was found
to be tBuOK, in terms both of yield and of anomeric select-
ivity. Investigations with various solvents, such as CH3CN,
CH2Cl2, DMF and THF, showed the best results for THF,
and we therefore pursued further studies with tBuOK in
THF as solvent. Thus, addition of dimethyl malonate to
galactal derivative 1 gave only the β-C-glycoside 3β, in 80%
yield. In its 1H NMR spectrum, the anomeric hydrogen sig-
nal appeared at δ ϭ 4.4 as a dd with J1Ј,2 ϭ 4.6 Hz and
J1Ј,2Ј ϭ 10.2 Hz. Similarly, the 2Ј-H signal appeared as an
overlapping dd (like a triplet) at δ ϭ 5.22 with ϭ 10.2 Hz.
This clearly indicated trans relationships between 1Ј-H and
2Ј-H and between 2Ј-H and 3Ј-H. For the α anomer, the 1Ј-
H signal appeared at δ ϭ 5.09 as a dd with J1Ј,2Ј ϭ 4.9 Hz,
[a]
Department of Chemistry, Indian Institute of Technology,
Kanpur 208 016, India
[b]
Fachbereich Chemie, Universität Konstanz, M 725,
78457 Konstanz, Germany
Eur. J. Org. Chem. 2002, 1479Ϫ1483
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0509Ϫ1479 $ 20.00ϩ.50/0
1479

K. Pachamuthu, A. Gupta, J. Das, R. R. Schmidt, Y. D. Vankar
FULL PAPER
Table 1. Influence of the base on the addition of dimethyl malonate to 1
Entry
Base
Time [h]
Temperature
Anomer (3α/3β)
Yield[a] (%)
1
2
3
4
5
6
NaH
1
48
5
3
3
0 °C
Ϫ
Ϫ
NaOMe
NaHMDS
tBuOK
KHMDS
DBU
Ϫ40 °C to room temp.
Ϫ40 °C to room temp.
0 °C to room temp.
Ϫ78 °C
1:2.8
1:1.4
β
1:15.2
β
48
52
80
81
62
3
0 °C to room temp.
[a]
All reactions were carried out in THF.
and the 2Ј-H signal appeared at δ ϭ 5.27 with J2Ј,3Ј
ϭ
8.0 Hz, thus indicating an axial-equatorial relationship be-
4
tween 1Ј-H and 2Ј-H and a C1 conformation for 3α.
The anions derived from methyl phenylsulfonylacetate,
methyl acetoacetate and methyl nitroacetate also added
across the conjugated nitro olefin 1 to yield only the β ano-
mers 4, 5 and 6 (Scheme 2), respectively, although a mixture
of two diastereomers was, as would be expected, formed in
each case. This was apparent in each case from the appear-
ance of the 2Ј-H signal as two triplets in the 1H NMR spec-
trum, in a ratio of approximately 35:65. Thus, for example,
in compound 4, the 2Ј-H signal appeared at δ ϭ 5.07 and
5.37 with J ϭ 11.5 Hz, while in compound 5 this proton
signal appeared at δ ϭ 4.94 and 5.19 with J ϭ 10.4 Hz. In
compound 6, on the other hand, the 2Ј-H signal appeared
at δ ϭ 5.26 and 5.30 as two triplets with J ϭ 9.3 Hz. In
addition, the methoxy group signal also appeared as two
singlets in each case.
Scheme 3. Addition of dimethyl malonate to 2-nitroglucal 2
J1Ј,2Ј ϭ 7.0 Hz, indicating an axial/equatorial arrangement
for 1Ј-H and 2Ј-H, while the 2Ј-H signal appeared at δ ϭ
5.18 with J2Ј,3Ј ϭ 4.9 Hz, indicating diequatorial arrange-
ments for 2Ј-H and 3Ј-H as well as for all the other ring
1
protons and thus supporting a preferential C4 conforma-
tion for 7α.[17,38] This structural assignment was also sup-
ported by NOE experiments, which indicated strong inter-
action between 1Ј-H/2Ј-H and 1Ј-H/6Ј-H but no interaction
between 2Ј-H/3Ј-H, thus also ruling out formation of
manno-configured products.
The presence of a nitro group at C-2Ј has several advant-
ages, especially since the C-glycosides formed are β at the
anomeric centre. For example, radical-mediated[39] reduc-
tion of the nitro group could result in 2-deoxy-β-C-glycos-
ides. Similarly, it might also be expected that use of the
Nef[40] reaction should result in the formation of a carbonyl
group at C-2Ј, which could be reduced to form either an
axial or an equatorial hydroxy group, depending on the re-
action conditions. This would provide flexibility in ob-
taining different β-C-glycosides. In this study, our efforts
were concentrated on the formation of 2-amino-2-deoxy-
C-glycosides.
In some cases (3β, 6 and 7β) the nitro group was reduced
with Raney nickel T4/H2,[41] followed by treatment with
Et3N, resulting in immediate cyclization to the correspond-
ing lactams 9, 10 and 11 (Scheme 4), respectively, in good
Scheme 2. Addition of unsymmetrical CH-acidic compounds to
2-nitrogalactal 1
Surprisingly, however, the 2-nitro--glucal derivative 2 yields; amine 8 was only obtained as a crude intermediate.
gave a mixture of two anomers 7β and 7α (Scheme 3) in a Formation of the lactam was also found to occur even with-
2:1 ratio when treated with dimethyl malonate in THF as out treatment with Et3N, albeit in lower yields. Further-
solvent and in the presence of tBuOK as base. The struc- more, if the reaction mixture was filtered to remove Raney
tures of these glycosides were confirmed by 1H NMR spec- nickel and the solvent was evaporated at higher temperature
troscopic data (cf. Exp. Sect.). Compound 2 also yielded a (ca. 55Ϫ60 °C), the amount of cyclized products increased.
mixture of α/β-C-glycosides with other bases. For the α an- This indicated that the lactam formation was also depend-
omer, the 1Ј-H signal appeared at δ ϭ 4.99 as a dd with ent on the temperature. However, treatment with Et3N gave
1480
Eur. J. Org. Chem. 2002, 1479Ϫ1483

An Easy Route to 2-Amino-β-C-Glycosides
FULL PAPER
Conclusion
CH-acidic compounds can readily be added to 2-nitrogly-
cals. In the case of 2-nitrogalactal only the β-product could
be obtained, and this was readily transformed into the cor-
responding galactosamine derivatives.
Experimental Section
General: Infrared spectra were recorded with Bruker FT/IR Vector
22 spectrometers. 1H and 13C NMR spectra were recorded withn a
Jeol LA-400 NMR spectrometer in CDCl3 solutions with tetra-
methylsilane as the internal standard. FAB mass spectra were ob-
tained with a Jeol SX 102/DA-6000 spectrometer. Elemental ana-
lyses were carried out in a Coleman automatic CHN analyser. 2-
Nitroglucal 1 and 2-nitrogalactal 2 were prepared according to lit-
erature procedures.[35]
Dimethyl (3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galacto-
pyranosyl)malonate (3β): tBuOK (112 mg, 1 mmol) was added at 0
°C to a stirred solution of 2-nitrogalactal 1 (461 mg, 1 mmol) and
dimethyl malonate (132 mg, 1 mmol) in THF (4 mL). The reaction
mixture was then brought to room temperature and stirred for 3 h.
It was quenched with saturated NH4Cl solution and extracted with
ethyl acetate, washed with water and brine, and dried with Na2SO4.
Evaporation of the solvent and purification by column chromato-
graphy yielded the pure compound. Yield 474 mg, 80%. Rf ϭ 0.5
(hexane/ethyl acetate, 8:2). [α]2D5 ϭ ϩ7 (c ϭ 0.85, CH2Cl2). IR
Ϫ1
(CH2Cl2): ν ϭ 1557, 1749 cm
.
1H NMR: δ ϭ 3.55 (br. d, J ϭ
˜
Scheme 4. Synthesis of bicyclic lactams 9؊11
6.7 Hz, 2 H, 6-H, 6Ј-H), 3.62 (s, 3 H, ϪOCH3), 3.64 (d, J ϭ 4.7 Hz,
1 H, 2-H), 3.69 (s, 3 H, OCH3), 3.7Ϫ3.74 (m, 1 H, 5Ј-H), 4.04 (d,
J ϭ 2.1 Hz, 1 H, 4Ј-H), 4.16 (dd, J ϭ 10.2, 2.4 Hz, 1 H, 3Ј-H), 4.40
(dd, J ϭ 10.0, 4.6 Hz, 1 H, 1Ј-H), 4.39Ϫ4.84 (m, 6 H, 3 ϫ
OCH2Ph), 5.22 (t, J ϭ 10.1 Hz, 1 H, 2Ј-H), 7.23Ϫ7.36 (m, 15 H).
13C NMR: δ ϭ 52.6, 52.8, 53.7, 67.8, 71.8, 72.4, 73.4, 74.6, 74.7,
77.3, 80.0, 85.5, 127.7Ϫ138 (18 C), 165.7, 166.3. MS (FAB): m/z
(%) ϭ 594 (50) [Mϩ ϩ 1], 593 (100) [Mϩ]. C32H35NO10 (593.62):
calcd. C 64.75, H 5.94, N 2.36; found C 64.80, H 6.12, N 2.15.
the best yield of the cyclized products. The trans fusion of
bicyclic lactams 9؊11 could be deduced from the 1H NMR
spectroscopic data (J2,3 ഠ 9 Hz). Surprisingly, treatment of
9 with strong base (for instance, DBU) resulted in decom-
position rather than anomerisation to the cis-fused lactam.
Moreover, it was also found that ethyl esters invariably
underwent transformation into the cyclized products more
readily than the corresponding methyl esters did.
Dimethyl (3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-α-D-galactopyranosyl)-
In an attempt to acetylate the amino compound 8 with
acetic anhydride in the presence of Et3N and DMAP (cat.),
formation of the bicyclic compound 12 (Scheme 5) was ob-
served. However, treatment of 8 with acetyl chloride in
dichloromethane gave N,N-diacetylated product 13, and no
cyclized product was obtained under the reaction condition.
malonate (3α): The same procedure was applied as for compound
3β, but NaOMe was used instead of tBuOK and the reaction took
48 h for completion. Under these reaction condition, two anomers
(3α and 3β) were formed and were separated by column chromato-
graphy. Rf ϭ 0.6 (hexane/ethyl acetate, 8:2). [α]2D5 ϭ ϩ38 (c ϭ 1,
Ϫ1
˜
CH2Cl2). IR (CH2Cl2): ν ϭ 1557, 1749 cm
.
1H NMR: δ ϭ
3.55Ϫ3.62 (m, 2 H, 6Ј-H, 6ЈЈ-H), 3.65, 3.72 (2 s, 6 H, 2 ϫ OCH3),
3.78 (d, J ϭ 11.2 Hz, 1 H, 2-H), 4.08Ϫ4.13 (m, 2 H, 5Ј-H, 4Ј-H),
4.34 (dd, J ϭ 7.8, 2.4 Hz, 1 H, 3Ј-H), 4.4Ϫ4.82 (m, 6 H, 3 ϫ
OCH2Ph), 5.09 (dd, J ϭ 11.0, 4.9 Hz, 1 H, 1Ј-H), 5.27 (dd, J ϭ
8.0, 4.9 Hz, 1 H, 2Ј-H), 7.24Ϫ7.37 (m, 15 H, aromatic). 13C NMR:
δ ϭ 52.9, 53, 53.2, 67.1, 69.6, 72.3, 72.7, 73.4, 74.4, 75.1, 86.3, 95.7,
127.8Ϫ137.7(18 C), 166.1, 166.5. MS (FAB): m/z (%) ϭ 594 (55)
[Mϩ ϩ 1], 593 (100) [Mϩ]. C32H35NO10 (593.62): calcd. C 64.75,
H 5.94, N 2.36; found C 64.85, H 6.22, N 2.10. The same experi-
mental procedure as for compound 3β was applied, but methyl
nitroacetate, methyl (phenylsulfonyl)acetate and methyl acetoacet-
ate were employed instead of dimethyl malonate to obtain 4, 5 and
6, respectively.
Methyl 2-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-O-galactopyrano-
syl)-2-nitroacetate (4): Yield 429 mg, 74%. Rf ϭ 0.2 (hexane/ethyl
acetate, 8:2). [α]2D5 ϭ ϩ7.2 (c ϭ 1.25, CH2Cl2). IR (CH2Cl2): ν ϭ
˜
Scheme 5. Acetylation of 2-amino-2-deoxy-C-glucopyranoside 8
Eur. J. Org. Chem. 2002, 1479Ϫ1483
1481

K. Pachamuthu, A. Gupta, J. Das, R. R. Schmidt, Y. D. Vankar
FULL PAPER
1
1563, 1762 cmϪ1. H NMR: δ ϭ 3.49Ϫ3.81 (m, 3 H, 5Ј-H, 6Ј-H, stirred solution of freshly prepared Raney nickel T4 (Pt)[13] catalyst
6ЈЈ-H), 3.63, 3.75 (2 s, 3 H, OCH3), 4.05 (dd, 11.5, 2.8 Hz, 1 H, 3Ј- (1 g) in EtOH, and the reaction mixture was stirred under hydrogen
H), 4.13, 4.17 (2 dd, J ϭ 10.2, 2.8 Hz, 1 H, 4Ј-H), 4.39Ϫ4.85 (m, for 8 h at room temperature. After the completion of reaction (TLC
7 H, 1Ј-H, 3 ϫ OCH2Ph), 5.07, 5.37 (2 t, J ϭ 11.5 Hz, 1 H, 2Ј-H), monitoring), the reaction mixture was filtered and the solvent was
5.18 (2d, J ϭ 6.0 Hz, 1 H, 2-H), 7.21Ϫ7.34 (m, 15 H, aromatic). evaporated under vacuum to give the crude amine 8. This amine
13C NMR: δ ϭ 53.6, 67.4, 71.5, 72.4, 73.6, 74.1, 74.7, 79.7, 83.8,
was dissolved in CH2Cl2 (2 mL), and Et3N (0.15 mmol) was added.
85.7, 87.6, 127.9Ϫ137.9 (18 C), 161.3. MS (FAB): m/z (%) ϭ 581 After 3 h of stirring at room temperature, the solvent was evapor-
(38) [Mϩ ϩ 1], 580 (100) [Mϩ]. C30H32N2O10 (580.58): calcd. C ated and the crude product was purified by column chromato-
62.06, H 5.56, N 4.83; found C 61.91, H 5.62, N 5.01.
Methyl 2-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β- -galactopyrano-
graphy.
D
Bicyclic Lactam 9: Yield 345 mg, 65%. Rf ϭ 0.5 (hexane/ethyl acet-
ate, 3:7). [α]2D5 ϭ ϩ42 (c ϭ 1.55, CH2Cl2). IR (CH2Cl2): ν˜ ϭ 1730,
syl)-2-acetylacetate (5): Yield 462 mg, 80%. Rf ϭ 0.3 (hexane/ethyl
acetate, 8:2). [α]2D5 ϭ ϩ6.0 (c ϭ 1.25, CH2Cl2). IR (CH2Cl2): 1555,
1750 cmϪ1 1H NMR: δ ϭ 3.57 (d, J ϭ 11.2 Hz, 1 H, 2-H),
.
1731, 1743 cmϪ1 1H NMR: δ ϭ 2.21, 2.23, (2 s, 3 H, COCH3),
.
3.60Ϫ3.71 (m, 3 H, 3Ј-H, 6Ј-H, 6ЈЈ-H), 3.74 (s, 3 H, OCH3),
3.80Ϫ3.86 (m, 2 H, 2ЈЈ-H, 5Ј-H), 3.95 (dd, J ϭ 11, 8.8 Hz, 1 H, 1Ј-
H), 4.1 (br. s, 1 H, 4Ј-H), 4.43Ϫ4.9 (m, 6 H, 3 ϫ OCH2Ph), 6.54
(s, 1 H, NH), 7.23Ϫ7.37 (m, 15 H, aromatic). 13C NMR: δ ϭ 52.7,
53.8, 55.1, 69.0, 71.3, 73.0, 73.6, 75.4, 79.8, 80.1, 81.4, 127.7Ϫ138.1
(18 C), 168.3, 169.7. MS (FAB): m/z (%) ϭ 532 (12) [Mϩ ϩ 1], 531
(100) [Mϩ]. C31H33NO7 (531.60): calcd. C 70.05, H 6.26, N 2.63;
found C 69.01, H 6.32, N 2.82.
3.49Ϫ3.73 (m, 4 H, H-2, 6Ј-H, 6ЈЈ-H, 5Ј-H), 3.61, 3.68 (2 s, 3 H,
ϪOCH3), 4.02Ϫ4.18 (m, 2 H, 4Ј-H, 3Ј-H), 4.35Ϫ4.84 (m, 7 H, 1Ј-
H, 3 ϫ OCH2Ph), 4.94, 5.19, (2 t, J ϭ 10.4 Hz, 1 H, 2Ј-H),
7.22Ϫ7.33 (m, 15 H, aromatic). 13C NMR: δ ϭ 29.4, 60.4, 61.4,
67.8, 72.0, 72.4, 73.4, 74.1, 74.6, 75.4, 79.8, 80.5, 127.4Ϫ138.3 (18
C), 166.3, 198.9. MS (FAB): m/z (%) ϭ 578 (40) [Mϩ ϩ 1], 577
(100) [Mϩ]. C32H35NO9 (577.62): calcd. C 66.54, H 6.11, N 2.43;
found C 66.58, H 6.02, N 2.48.
Bicyclic Lactam 10: Yield 435 mg, 71%. Rf ϭ 0.4 (hexane/ethyl
acetate, 3:7). H NMR: δ ϭ 3.22 (dd, J ϭ 9.0, 5.1 Hz, 1 H, 5Ј-H),
Methyl 2-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-galactopyrano-
1
syl)-2-phenylsulfonylacetate (6): Yield 460 mg, 68%. Rf ϭ 0.3 (hex-
3.46 (t, J ϭ 8.8 Hz, 1 H, 6Ј-H), 3.52 (dd, J ϭ 10.2, 2.4 Hz, 1 H,
3Ј-H), 3.62Ϫ3.64 (m, 1 H, 6ЈЈ-H), 3.7 (t, J ϭ 10.5 Hz, 1 H, 2Ј-H),
3.90 (dd, J ϭ 10.5, 8.8 Hz, 1 H, 1Ј-H), 3.99 (br. s, 1 H, 4Ј-H), 4.12
(d, J ϭ 11.0 Hz, 1 H, 2-H), 4.33Ϫ4.78 (m, 6 H, 3 ϫ OCH2Ph), 5.9
(s, 1 H, NH), 7.17Ϫ7.88 (m, 20 H, aromatic). 13C NMR: δ ϭ 54.3,
67.3, 68.0, 71.4, 72.7, 73.4, 75.5, 77.6, 80.2, 81.2, 127.7Ϫ138.4
(24C), 165.2. MS (FAB): m/z (%) ϭ 614 (40) [Mϩ ϩ 1], 613 (100)
[Mϩ]. C35H35NO7S (613.72): calcd. C 72.27, H 6.06, N 2.41; found
C 72.21, H 6.20, N 2.62.
ane/ethyl acetate, 6:4). [α]2D5 ϭ ϩ5.0 (c ϭ 0.8, CH2Cl2). IR
1
(CH2Cl2): ν˜ ϭ 1554, 1752 cmϪ1. H NMR: δ ϭ 2.9 (dd, J ϭ 9.0,
5.9 Hz, 1 H, 5Ј-H), 3.29 (dd, J ϭ 15.1, 5.9 Hz, 2 H, 6Ј-H, 6ЈЈ-H),
3.51, 3.65 (2 s, 3 H, OCH3), 3.90Ϫ4.85 (m, 10 H, 2-H, 1Ј-H, 3Ј-H,
4Ј-H, 3 ϫ OCH2Ph) 5.26, 5.30 (2 t, J ϭ 9.3 Hz, 1 H, 2Ј-H),
7.15Ϫ7.97 (m, 20 H, aromatic). 13C NMR: δ ϭ 66.5, 69.8, 71.4,
71.9, 72.3, 73.3, 73.9, 74.6, 74.9, 79.7, 84.8, 127.6Ϫ137.9 (24 C),
162.4. MS (FAB): m/z (%) ϭ 676 (23) [Mϩ ϩ 1], 677 (52) [Mϩ].
C36H37NO10S (675.75): calcd. C 63.99, H 5.52, N 2.07; found C
64.12, H 5.48, N 2.20.
Bicyclic Lactam 11: Yield 430 mg, 81%. [α]2D5 ϭ ϩ22.8 (c ϭ 1.05,
CH2Cl2). IR (CH2Cl2): ν ϭ 1730, 1750 cmϪ1. H NMR: δ ϭ 3.20
1
˜
Dimethyl 2-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-β-D-glucopyranosyl)-
(t, J ϭ 9.5 Hz, 1 H, 2Ј-H), 3.58 (d, J ϭ 11.2 Hz, 1 H, 2-H),
3.63Ϫ3.81 (m, 5 H, 3Ј-H, 4Ј-H, 5Ј-H, 6Ј-H, 6ЈЈ-H), 3.73 (s, 3 H,
OCH3), 4.01 (dd, J ϭ 11.2, 9.5 Hz, 1 H, 1Ј-H), 4.45Ϫ4.85 (m, 6 H,
3 ϫ OCH2Ph), 6.23 (s, 1 H, NH), 7.16Ϫ7.36 (m, 15 H, aromatic).
13C NMR: δ ϭ 52.8, 53.6, 58.6, 68.2, 73.6, 74.3, 75.4, 78.2, 78.8,
81.3, 83.9, 127.8Ϫ137.9 (18 C), 168.2, 169.8. MS (FAB): m/z (%) ϭ
532 (10) [Mϩ ϩ 1], 531 (100) [Mϩ]. C31H33NO7 (531.60): calcd. C
70.05, H 6.26, N 2.63; found C 70.21, H 6.42, N 2.72.
malonate (7β): The same procedure was adopted as for preparation
of compound 3, but 2-nitroglucal was employed instead of 2-nitro-
galactal. Yield 368 mg, 62%. Rf ϭ 0.5 (hexane/ethyl acetate, 8:2).
[α]2D5 ϭ Ϫ0.63 (c ϭ 3.15, CH2Cl2). IR (CH2Cl2): ν ϭ 1557, 1749
˜
1
cmϪ1. H NMR: δ ϭ 3.55Ϫ3.78 (m, 5 H, 6Ј-H, 6ЈЈ-H, 2-H, 4Ј-H,
5Ј-H), 3.70, 3.71 (2 s, 6 H, 2 ϫ OCH3), 4.33 (t, J ϭ 9.8 Hz, 1 H,
3Ј-H), 4.42 (dd, J ϭ 9.8, 4.4 Hz, 1 H, 1Ј-H), 4.46Ϫ4.82 (m, 6 H, 3
ϫ OCH2Ph), 4.94 (t, J ϭ 9.8 Hz, 1 H, 2Ј-H), 7.19Ϫ7.34 (m, 15 H,
aromatic). 13C NMR: δ ϭ 52.8, 52.8, 53.3, 67.9, 73.3, 74.5, 75.0,
75.8, 77.5, 79.8, 82.1, 87.6, 127.5Ϫ138.0 (18 C), 165.6, 166.3. MS
(FAB): m/z (%) ϭ 594 (25) [Mϩ ϩ 1], 593 (65) [Mϩ]. C32H35NO10
(593.62): calcd. C 64.75, H 5.94, N 2.36; found C 64.70, H 6.01,
N 2.25.
Bicyclic Enolacetate 12: Et3N (1 mL) was added to a stirred solu-
tion of crude amine 8 (563 mg, 1 mmol) in acetic anhydride (1 mL),
and stirring was continued for 6 h at room temperature. After com-
pletion of the reaction, the excess acetic anhydride and Et3N were
evaporated to give a crude product, which was purified by column
chromatography. Yield 345 mg, 56%. Rf ϭ 0.4 (hexane/ethyl acet-
Dimethyl 2-(3,4,6-Tri-O-benzyl-2-deoxy-2-nitro-α-D-glucopyranosyl)-
1
ate, 1:1). IR (CH2Cl2): ν ϭ 1720, 1600 cmϪ1. H NMR: δ ϭ 2.26,
˜
malonate (7α): Yield 178 mg, 30%. Rf ϭ 0.4 (hexane/ethyl acetate,
8:2). [α]2D5 ϭ ϩ3 (c ϭ 1, CH2Cl2). IR (CH2Cl2): ν ϭ 1557, 1750
2.48 (2 s, 6 H, 2 ϫ OCOCH3), 3.56Ϫ3.65 (m, 2 H, 6Ј-H, 6ЈЈ-H),
3.75Ϫ3.76 (m, 1 H, 2Ј-H), 3.84 (br. t, J ϭ 5.4 Hz, 1 H, 5Ј-H), 3.89
(s, 3 H, OCH3), 4.03 (br. s, 1 H, 4Ј-H), 4.19Ϫ4.26 (m, 2 H, 1Ј-H,
3Ј-H), 4.4Ϫ5.0 (m, 6 H, 2 ϫ OCH2Ph), 7.24Ϫ7.36 (m, 15 H, aro-
matic). 13C NMR: δ ϭ 26.7, 30.4, 53.7, 56.6, 68.1, 71.8, 72.6, 73.5,
73.7, 75.3, 77.8, 80.6, 82.7, 127.5Ϫ138.3 (18 C), 165.8, 167.1, 170.8,
198.3. MS (FAB): m/z (%) ϭ 617 (40) [Mϩ ϩ 1], 616 (100) [Mϩ].
C35H37NO9 (615.67): calcd. C 68.28, H 6.06, N 2.28; found C
68.32, H 6.26, N 2.49.
˜
1
cmϪ1. H NMR: δ ϭ 3.62Ϫ3.70 (m, 2 H, 6Ј-H, 6ЈЈ-H), 3.64, 3.67
(2 s, 6 H, 2 ϫ OCH3), 3.77 (d, J ϭ 6.7 Hz, 1 H, 2-H), 3.90 (t, J ϭ
4.9 Hz, 1 H, 4Ј-H), 3.95 (dd, J ϭ 10.2, 4.9 Hz, 1 H, 5Ј-H), 4.14
(dd, J ϭ 4.9 Hz, 1 H, 3Ј-H), 4.40Ϫ4.53 (m, 6 H, OCH2Ph), 4.99
(dd, J ϭ 7.0, 7.0 Hz, 1 H, 1Ј-H), 5.18 (dd, J ϭ 7.0, 4.9 Hz, 1 H,
2Ј-H), 7.09Ϫ7.27 (m, 15 H, aromatic). 13C NMR: δ ϭ 52.8, 52.8,
53.1, 67.8, 67.9, 72.1, 72.8, 73.2, 73.3, 74.5, 76.2, 82.0, 127.6Ϫ138.0
(18 C), 166.4, 166.9. MS (FAB): m/z (%) ϭ 594 (20) [Mϩ ϩ 1], 593
(72) [Mϩ]. C32H35NO10 (593.62): calcd. C 64.75, H 5.94, N 2.36;
found C 64.50, H 5.81, N 2.45.
Dimethyl 2-[3,4,6-Tri-O-benzyl-2-deoxy-2-(N,N-diacetylamino)-β-D-
galactopyranosyl]malonate (13): Acetyl chloride (195 mg, 2.5 mmol)
General Procedure for the Preparation of Bicyclic Lactams 9, 10 and
and Et3N (252 mg, 2.5 mmol) were added to a stirred solution of
11: The nitro compound 3β, 6 or 7β (1 mmol) was added to a crude amine 8 (563 mg, 1 mmol) in dichloromethane, and stirring
1482 Eur. J. Org. Chem. 2002, 1479Ϫ1483

An Easy Route to 2-Amino-β-C-Glycosides
FULL PAPER
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was continued at room temperature for 3 h. The reaction mixture
was extracted with ethyl acetate, washed with water and dried with
Na2SO4. The solvent was evaporated under reduced pressure to
yield a crude product, which was purified by column chromato-
graphy. Yield 466 mg, 72%. IR (CH2Cl2): ν ϭ 1720, 1710 cmϪ1. 1H
˜
NMR: δ ϭ 2.27, 2.41 (2 s, 6 H, 2 ϫ OCOCH3), 3.53Ϫ3.61 (m, 3
H, 2-H, 6Ј-H, 6ЈЈ-H), 3.65, 3.68 (2 s, 6 H, 2 ϫ OCH3), 3.75 (t, J ϭ
6.6 Hz, 1 H, 5Ј-H), 4.07 (d, J ϭ 2.2 Hz, 1 H, 4Ј-H), 4.36Ϫ4.85 (m,
8 H, 3Ј-H, 2Ј-H, 3 ϫ OCH2Ph), 4.98 (dd, J ϭ 9.3, 4.9 Hz, 1 H, 1Ј-
H), 7.15Ϫ7.34 (m, 15 H, aromatic). 13C NMR: δ ϭ 25.1, 27.9,
52.5, 52.6, 53.6, 57.6, 68.3, 71.9, 73.3, 73.3, 74.3, 74.5, 77.2, 77.5,
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calcd. C 66.76, H 6.38, N 2.16; found C 66.82, H 6.45, N 2.01.
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Acknowledgments
We thank the Department of Science & Technology, New Delhi,
for financial assistance through a project (DST/SP/S1/G-07/1997).
K. P thanks the Council of Scientific and Industrial Research, New
Delhi, for senior research fellowship. Financial support from the
Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
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von Humboldt Foundation for a Fellowship.
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