A convenient synthesis of methyl N-acetyl-α-D-lividosaminide from D-glucal

Article abstract of DOI:10.1016/S0040-4039(03)01044-X

Methyl N-acetyl-α-D-lividosaminide has been synthesised starting from 4,6-di-O-benzyl-D-glucal via a new nitro glucal derivative in six steps.

Full text of DOI:10.1016/S0040-4039(03)01044-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4765–4767
A convenient synthesis of methyl N-acetyl-a-
from
-glucalꢀ
D-lividosaminide
D
B. Gopal Reddy and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology Kanpur 208016, India
Received 6 January 2003; revised 8 April 2003; accepted 17 April 2003
This paper is respectfully dedicated to Professor Dr. Richard R. Schmidt on the occasion of his 68th birthday
Abstract—Methyl N-acetyl-a-
D-lividosaminide has been synthesised starting from 4,6-di-O-benzyl-D-glucal via a new nitro glucal
derivative in six steps. © 2003 Elsevier Science Ltd. All rights reserved.
2-Aminosugars are integral components of several
glycolipids2 and glycoproteins.3 Apart from this, they
are used4 as important building blocks in the synthesis
few antibiotics such as lividomycins and 3%-deoxy-
kanamycin. Also, it has been used6 in the synthesis
of thienamycin, an important penem antibiotic. In
of useful natural products.
D
-Lividosamine 1 (Scheme
view of this, many routes to
D-lividosamine or its
1), a 2-aminosugar, is found5 as a component of a
derivatives have been reported in the literature, some
Scheme 1. Reagents and conditions: (i) Ac2O, HNO3, −33°C, 0.5 h; (ii) Et3N, CH2Cl2, 0°C, 0.5 h, 72%; (iii) 0.1 M NaOMe in
methanol, rt, 1 h, 85%; (iv) Raney-Ni (T4)/H2, EtOH, overnight; (v) Ac2O/pyridine, 4 h, 65% (two steps); (vi) 20% Pd(OH)2/C–H2/
THF, overnight; (vii) Ac2O/pyridine, 4 h, 77% (two steps).
ꢀ Transformations in carbohydrate chemistry, Part 6. For Part 5, see Ref. 1.
* Corresponding author. Tel.: +91-512-2597169; fax: +91-512-2590007; e-mail: vankar@iitk.ac.in
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01044-X

4766
B. G. Reddy, Y. D. Vankar / Tetrahedron Letters 44 (2003) 4765–4767
from carbohydrate7 and some from non-carbohydrate
precursors.8 The amino functionality in lividosamine
and its derivatives has been introduced by reducing
functional groups such as an oxime7a,c and by replacing
a leaving group by an amine equivalent such as azide8c
or via a Michael reaction.7d Besides this, some synthetic
methods have been developed7b for reductive removal
of the oxygen functionality at C-3 while maintaining
the amino or its equivalent functionality at C-2.
(SP/S1/G-29/2001). We would also like to thank the
referee for useful suggestions in identifying the minor
isomer.
References
1. Rani, S.; Vankar, Y. D. Tetrahedron Lett. 2003, 44, 907.
2. (a) Banoub, J.; Boullanger, P.; Lafont, D. Chem. Rev.
1992, 92, 1167; (b) Deshpande, P. P.; Danishefsky, S. J.
Nature 1997, 387, 164; (c) Vankar, Y. D.; Schmidt, R. R.
Chem. Soc. Rev. 2000, 29, 201; (d) Wei, A.; Haudrechy,
A.; Audin, C.; Jun, H.-S.; Haudrechy-Bretel, N.; Kishi,
Y. J. Org. Chem. 1995, 60, 2160.
3. (a) Herzner, H.; Reipen, T.; Schultz, M.; Kunz, H. Chem.
Rev. 2000, 100, 4495; (b) Wang, Z.-G.; Zhang, X. F.;
Live, D.; Danishefsky, S. J. Angew. Chem., Int. Ed. Engl.
2000, 39, 3652; (c) Davis, B. Chem. Rev. 2002, 102, 579;
(d) Burkhart, F.; Hoffmann, M.; Kessler, H. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1191.
4. (a) Giannis, A. Kontakte 1994, 37 and references cited
therein; (b) Nicolaou, K. C.; Mitchell, H. J. Angew.
Chem., Int. Ed. Engl. 2001, 40, 1577.
5. (a) Mori, T.; Ichyansi, T.; Kondo, H.; Tokkunasa, T.;
Oda, T.; Munakata, T. J. Antibiot. Ser. A 1971, 24, 339;
(b) Konstantinova, N. V.; Lavrova, M. F.; Nesterova, T.
P.; Potapova, N. P.; Ponomarenko, V. I.; Rozynov, B.
V.; Brazhnikova, M. G.; Lapchinskaya, O. A.; Sinyagina,
O. P. Antibiot. Med. Biotekhnol. 1985, 30, 729. (Chem.
Abs. 104, 17418f).
In recent years nitro sugars have been utilised9 as
important synthons in the synthesis of a variety of
useful carbohydrate analogues. In particular, pioneer-
ing work by Schmidt et al.10 has led to the synthesis of
2-amino-O- and C-glycosides and glycopeptides from
2-nitro-glycals. Since the nitro group is an excellent
source of an amino functionality it is possible to start
with an appropriately substituted glucal and synthesise
a lividosamine derivative.
In this communication we wish to report a short syn-
thesis of methyl N-acetyl-a-
D-lividosaminide starting
from
D
-glucal as shown in Scheme 1. Thus, nitration10a
of 4,6-di-O-benzyl-glucal 2, obtained from tri-O-acetyl
glucal,11 using acetic anhydride/nitric acid followed by
Et3N led to the formation of nitroglucal 3 in 72% yield
whose glycosidation with MeOH in the presence of a
catalytic amount of NaOMe yielded a mixture of two
isomers 4 and 5 in a 2.5:1 ratio as revealed by 1H NMR
spectroscopic analysis.12 For the major isomer, the
anomeric proton appeared as a doublet at l 5.23 with
J=3.6 Hz whereas for the minor isomer it appeared as
a broad singlet at l 5.30. At this stage the two isomers
were chromatographically inseparable and hence the
6. Miyashita, M.; Chida, N.; Yoshikoshi, A. J. Chem. Soc.,
Chem. Commun. 1982, 1354.
7. (a) Brewer, C. L.; Guthrie, R. D. J. Chem. Soc., Perkin
Trans. 1 1974, 657; (b) Hanessian, S.; Vatele, J.-M.
Tetrahedron Lett. 1981, 22, 3579; (c) Rosenthal, A.; Cat-
soulacos, P. Can. J. Chem. 1969, 47, 2748; (d) Ravindran,
B.; Deshpande, S. G.; Pathak, T. Tetrahedron 2001, 57,
1093 and references cited therein.
8. (a) de Guchteneere, E.; Fattori, D.; Vogel, P. Tetrahedron
1992, 48, 10603; (b) Jager, V.; Schohe, R. Tetrahedron
1984, 40, 2199; (c) Fattori, D.; de Guchteneere, E.; Vogel,
P. Tetrahedron Lett. 1989, 30, 7415.
9. (a) Holzapfel, C. W.; van der Merwe, T. L. Tetrahedron
Lett. 1996, 37, 2307; (b) Nitro Compounds; Feuer, H.;
Nielsen, A. T., Eds.; VCH: Weinheim, 1990; (c) Scheffler,
G.; Justus, M.; Vasella, A.; Wessel, H. P. Tetrahedron
Lett. 1999, 40, 5845; (d) Sakakibara, T.; Tokuda, K.;
Hayakawa, T.; Seta, A. Carbohydr. Res. 2000, 327, 489.
10. (a) Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 1998,
1609; (b) Winterfeldt, G. A.; Ito, Y.; Ogawa, T.; Schmidt,
R. R. Eur. J. Org. Chem. 1999, 1167; (c) Winterfeldt, G.
A.; Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 2000,
3047; (d) Pachamuthu, K.; Gupta, A.; Das, J.; Schmidt,
R. R.; Vankar, Y. D. Eur. J. Org. Chem. 2002, 1479–
1483; (e) Winterfeldt, G. A.; Schmidt, R. R. Angew.
Chem., Int. Ed. Engl. 2001, 40, 2654.
13
mixture was reduced with platinised Raney-Ni(T4)/H2
and subsequently acetylated with acetic anhydride and
pyridine. The two isomers could then be separated at
this stage either by using a chromatotron or by recrys-
tallisation from ethyl acetate/hexane. The minor isomer
7, a viscous liquid isolated in 18% yield, showed a
broad singlet for the anomeric hydrogen at l 4.48 in its
1H NMR spectrum. The structure of 7 was assigned on
the basis of NOE experiments which indicated enhance-
ments of peaks corresponding to H-1 and H-3% (axial)
when H-2 was irradiated clearly establishing a cis-rela-
tionship between the three hydrogens. The major iso-
mer 6, a crystalline solid isolated in 47% yield, could be
readily debenzylated with Pd(OH)2/C-H2 in THF to
obtain methyl N-acetyl-lividosaminide 8, which was
characterised14 as methyl N-acetyl-4,6-di-O-acetyl-
D-
lividosaminide 9 obtained in a 77% yield over the two
steps.
In conclusion, nitro sugar based chemistry has been
readily utilised to prepare a
staring from -glucal. We expect this procedure to find
use in organic synthesis.
D-lividosamine derivative
D
11. Fraser-Reid, B.; Radatus, B. J. Am. Chem. Soc. 1970, 92,
6661.
Acknowledgements
12. 4,6-Di-O-benzyl-2,3-dideoxy-2-nitro-
+129.6 (c 2.3, CH2Cl2); IR (CH2Cl2): 1555 cm−1
NMR (400 MHz): l 2.70–2.73 (dd, J=16.3, 6.8 Hz, 1H,
D
-glucal 3: [h]2D6=
1H
.
We thank the Department of Science and Technology,
New Delhi for financial support through a project

B. G. Reddy, Y. D. Vankar / Tetrahedron Letters 44 (2003) 4765–4767
4767
H-3), 2.95–3.0 (br dd, J=16.3, 5.4 Hz, 1H, H-3%), 3.67–3.71
(dd, J=10.7, 3.7 Hz, 1H, H-6), 3.72–3.76 (dd, J=10.7, 4.6
Hz, 1H, H-6%), 3.90–3.94 (m, 1H, H-4), 4.15–4.20 (m, 1H,
H-5), 4.52–4.70 (m, 4H, 2× -OCH2Ph), 7.24–7.40 (m, 10H,
aromatic), 8.16 (s, 1H, H-1); 13C NMR (100 MHz): l 25.8,
67.6, 67.7, 71.3, 73.6, 78.4, 127.7–137.3 (m, aromatic),
129.1, 153.4. MSES+: 373.3 [M+NH4]+. Anal. calcd for
C20H21NO5 (355.38): C, 67.59; H, 5.95; N, 3.94; found: C,
67.71; H, 5.98; N, 3.80%.
J=11.5 Hz, 1H, H-3), 1.97 (s, 3H, -NHAc), 2.31–2.36 (dt,
J=11.4, 4.6 Hz, 1H, H-3%), 3.40 (s, 3H, -OCH3), 3.57–3.63
(m, 1H, H-4), 3.67–3.71 (m, 3H, H-5, H-6, H-6%), 4.14–4.21
(ddd, J=13.0, 8.8, 4.2 Hz, 1H, H-2), 4.34–4.64 (m, 5H, 2×
-OCH2Ph and H-1), 5.71–5.74 (d, J=9.0 Hz, 1H, -NHAc),
7.18–7.34 (m, 10H, aromatic). 13C NMR (100 MHz): l
23.3, 30.8, 47.0, 54.6, 68.7, 70.7, 70.8, 71.5, 73.3, 97.1,
127.4–128.2 (m, aromatic), 137.9, 138.1, 169.3. Anal. calcd
for C23H29NO5 (399.48): C, 69.15; H, 7.31; N, 3.50; found:
C, 69.20; H, 7.35; N, 3.57%. MSES+: 422 [M+Na]+.
Methyl 4,6-di-O-benzyl-2,3-dideoxy-2-nitro-D-glucopyran-
oside 4: [h]2D6=+87.4 (c 1.9, CH2Cl2); IR (CH2Cl2): 1552
Methyl 2-(acetylamino)-2,3-dideoxy-4,6-di-O-benzyl-b-D-
1
cm−1. H NMR (400 MHz): l (mixture of isomers: 2.5:1),
arabino-hexopyranoside 7: [h]2D6=+93.9 (c 1.15, CH2Cl2).
IR (CH2Cl2): 1653 cm−1. 1H NMR (400 MHz): l 1.86–1.91
(m, 1H, H-3), 1.95 (s, 3H, -NHAc), 2.17–2.22 (dt, J=13.0,
4.4 Hz, 1H, H-3%), 3.36 (s, 3H, -OCH3), 3.62–3.68 (m, 1H,
H-4), 3.71–3.83 (m, 3H, H-5, H-6, H-6%), 4.20–4.25 (br dt,
J=8.6, 4.9 Hz, 1H, H-2), 4.33–4.65 (m, 4H, 2× -OCH2Ph),
4.48 (br s, 1H, H-1), 6.14–6.16 (d, J=8.8 Hz, 1H, -NHAc),
7.20–7.34 (m, 10H, aromatic). 13C NMR (100 MHz): l
23.2, 29.0, 47.8, 54.7, 68.7, 70.7, 70.8, 73.5, 99.2, 127.6–
128.3 (m, aromatic), 137.8, 137.9, 169.4. Anal. calcd for
C23H29NO5 (399.48): C, 69.15; H, 7.31; N, 3.50; found: C,
69.27; H, 7.33; N, 3.53%.
l 2.02–2.14 (m, 1H, H-3, for minor isomer), 2.30–2.40 (q,
J=12.0 Hz, 1H, H-3, for h-isomer), 2.57–2.62 (m, 1H,
H-3%, for h-isomer), 2.70–2.80 (m, 1H, H-3%, for minor
isomer), 3.40 (s, 3H, -OCH3, for h-isomer), 3.43 (s, 3H,
-OCH3, for minor isomer), 3.62–3.86 (m, 4H, H-4, H-5,
H-6, and H-6%, for both isomers), 4.40–4.80 (m, 5H, H-2
and 2× -OCH2Ph, for both isomers), 5.23–5.24 (d, J=3.6
Hz, 1H, H-1, for h-isomer), 5.30 (br s, 1, H-1, for minor
isomer), 7.21–7.33 (m, 10H, aromatic, for both isomers);
13C NMR (100 MHz) (for both isomers): l 27.1, 27.4, 55.2,
55.4, 68.0, 68.7, 68.9, 70.7, 70.8, 71.2, 71.3, 71.5, 73.3, 73.5,
80.3, 82.5, 96.1, 96.9, 127.5–128.4 (m, aromatic), 137.5,
137.7, 137.8, 138.1. MSES+: 405 [M+NH4]+. Anal. calcd for
C21H25NO6 (387.42): C, 65.10; H, 6.50; N, 3.61; found: C,
64.97; H, 6.80; N, 3.55%.
13. For the preparation of Raney-nickel, see: Org. Synth. 1955,
Coll. Vol. 3, 181.
14. The spectral data of this compound, mp 133–134°C (lit.8a
133–134°C, lit.8b 139°C) and [h]D26=+99.1 (c 1.15, CH2Cl2)
[lit.8a [h]D25=+90.0 (c 0.17, MeOH), lit.8b [h]2D6=+90.2 (c 0.6,
MeOH)] were comparable with the literature8a,b values.
Methyl 2-(acetylamino)-2,3-dideoxy-4,6-di-O-benzyl-a-D-
ribo-hexopyranoside 6: [h]2D6=+90.3 (c 1.75, CH2Cl2); IR
(CH2Cl2): 1653 cm−1. 1H NMR (400 MHz): l 1.55–1.64 (q,