Synthesis of pyranoid δ-sugar amino acids and their oligomers from per-benzylated β-C-vinyl glucoside

Article abstract of DOI:10.1016/j.tetlet.2003.12.032

Two pyranoid δ-sugar amino acids were prepared from the common per-benzylated β-C-vinyl glucoside and easily oligomerised using solution-phase coupling methodology.

Full text of DOI:10.1016/j.tetlet.2003.12.032

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1477–1479
Synthesis of pyranoid d-sugar amino acids and their oligomers
from per-benzylated b-C-vinyl glucoside
*
ꢀ
Francois Durrat, Juan Xie and Jean-Marc Valery
ß
Synthꢁese, Structure et Fonction des Molꢀecules Bioactives, CNRS UMR 7613, Equipe Chimie des Glucides,
Universitꢀe Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France
Received 30 October 2003; revised 2 December 2003; accepted 8 December 2003
Abstract—Two pyranoid d-sugar amino acids were prepared from the common per-benzylated b-C-vinyl glucoside and easily
oligomerised using solution-phase coupling methodology.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Recently, sugar amino acids (SAAs) have found wide
applications in the creation of diverse novel structures
with unique properties.1 For example, the pyranoid
d-SAAs 12 and 23 (Fig. 1) have been used in the synthesis
of sulfated b-1,6-linked oligosaccharide mimetics with
potent inhibitory activity towards HIV replication2 or in
the preparation of cyclic homooligomers as potential
host molecules.3 Compound 1 was prepared in several
benzylated b-C-vinyl glucoside 36 and their use in the
synthesis of several oligomers.
Scheme 1 summarises the synthesis of SAA 4 and its
octamer 5. Starting with the b-C-vinyl glucoside 3,
selective acetolysis of the 6-benzyloxy group7 afforded
8
ꢀ
the alcohol 6 after Zemplen deacetylation. Oxidation of
the primary hydroxyl function with PCC in the presence
t
steps from methyl 2,6-anhydro-
D
-glycero-
D
-gulo-hep-
turonate, by introducing the 6-amino groupafter selec-
of BuOH and Ac2O9 gave the tert-butyl ester 7 in 58%
yield. Oxidative cleavage followed by reduction trans-
formed the vinyl function into alcohol 8, which was
converted into azide 910 by displacement of the mesylate.
The ester groupof 9 was hydrolysed with TFA to give
10, which was used for the next coupling reaction
without purification. Finally the amino ester 4 was
obtained after reduction of the azido function by a
Staudinger reaction. The coupling of 4 with 10 was
carried out with diethylphosphoryl cyanide (DEPC)/
Et3N11 to give the dimer 11 in 77% yield. Repetition of
tive protection.2 On the other hand, the SAA 2 was
synthesised from D-glucose using a nucleophilic aldol
reaction to introduce a nitromethylene groupat the
anomeric position as an aminomethylene equivalent,
followed by selective oxidation of the primary hydroxyl
3;4
groupto a carboxylic acid.
As part of our ongoing
efforts in the synthesis of SAAs,5 we report herein an
alternative approach to pyranoid d-SAAs from the per-
t
the same synthetic manipulation: (i) removal of the Bu
group, (ii) reduction of the azido function and (iii)
coupling furnished readily the tetramer 1412 and the
octamer 5.12
NHBoc
δ
HO2C
β
γ
β
α
O
δ
O
BnO
BnO
HO
CO2H
γ
NHFmoc
Alternatively, transformation of the primary hydroxyl
function of 6 into the azide 17 gave access to an ana-
logue of SAA 1 (Scheme 2). However, direct oxidation
of the olefin 17 failed to furnish the anomerically pure
b-acid 19. Furthermore, ozonolysis of 17 followed by
treatment with an excess of H2O2 did not furnish the
desired acid 19 either: the intermediate ozonide
remaining unchanged under the reaction conditions. We
then decided to reduce the ozonide into alcohol 18,
HO
α
OBn
OH
1
2
Figure 1. Structure of pyranoid d-sugar amino acids.
Keywords: d-Sugar amino acid; C-Glucoside; Oligomer.
* Corresponding author. Tel.: +33-1-44275893; fax: +33-1-44275513;
e-mail: xie@ccr.jussieu.fr
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.032

1478
F. Durrat et al. / Tetrahedron Letters 45 (2004) 1477–1479
CO2tBu
OBn
O
OBn
OH
O
OBn
CO2tBu
CO2tBu
CO2H
N3
OH
O
OBn
N3
O
OBn
O
OBn
O
OBn
d
b
c
a
e
BnO
BnO
BnO
BnO
BnO
BnO
OBn
OBn
OBn
OBn
OBn
OBn
3
6
8
9
10
7
f
CO2tBu
CO2R
NHCO
NHCO
O
O
CO2tBu
OBn
OBn
NH2
N3
NH2
f
O
OBn
O
OBn
O
OBn
g
BnO
BnO
e
BnO
BnO
BnO
12
BnO
BnO
OBn
OBn
OBn
11: R = tBu
13: R = H
4
h
CO2R
CO2tBu
NHCO
NHCO
O
O
OBn
i
OBn
NHCO
NHCO
O
OBn
O
OBn
R'
N3
O
OBn
O
OBn
BnO
BnO
BnO
e
BnO
BnO
BnO
BnO
BnO
BnO
BnO
2
6
OBn
OBn
5
14: R = tBu, R' = N3
15: R = tBu, R' = NH2
16: R = H, R' = N3
f
Scheme 1. Reagents and conditions: (a) (i) 1 equiv TMSOTf, 53 equiv Ac2O, CH2Cl2, )40 ꢁC, 1 h, 80%; (ii) 1 equiv NaOMe (1 M), MeOH, rt, 20 h,
t
66%; (b) 2 equiv PCC, 10 equiv Ac2O, 20 equiv BuOH, CH2Cl2, rt, 48 h, 58%; (c) (i) O3, CH2Cl2, )78 ꢁC, 30 min; (ii) 1.5 equiv NaBH4, MeOH, rt,
20 h, 71% overall; (d) (i) 1.5 equiv MsCl, 2 equiv Et3N, CH2Cl2, rt, 20 h; (ii) 5 equiv NaN3, DMF, 90 ꢁC, 20 h, 74% overall; (e) 20 equiv TFA, CH2Cl2,
rt, 20 h, 100%; (f) 1.1 equiv PPh3, 12 equiv H2O, THF, rt, 20 h, 89% for 4, 79% for 12 and 46% for 15; (g) 1.1 equiv 10, 1.5 equiv DEPC, 3 equiv Et3N,
DMF, rt, 72 h, 77%; (h) 1.2 equiv 13, 1.5 equiv DEPC, 3 equiv Et3N, DMF, rt, 72 h, 99%; (i) 1.12 equiv 16, 1.5 equiv DEPC, 3 equiv Et3N, DMF, rt,
72 h, 65%.
N3
O
OBn
N3
N3
O
OBn
CO2H
OH
O
OBn
c
b
a
6
BnO
BnO
BnO
OBn
OBn
OBn
N3
17
19
18
CONH
BnO
CO2R
O
d
f
O
OBn
OBn
N3
H2N
BnO
BnO
CO2tBu
CO2tBu
BnO
O
O
e
OBn
OBn
OBn
22: R = tBu
23: R = H
g
BnO
OBn
OBn
20
21
e
N3
H2N
BnO
CONH
CONH
O
O
CONH
CO2tBu
h
CO2tBu
O
O
OBn
OBn
O
OBn
OBn
OBn
BnO
BnO
BnO
OBn
BnO
24
BnO
OBn
25
OBn
2
OBn
Scheme 2. Reagents and conditions: (a) (i) 1.5 equiv MsCl, 2 equiv Et3N, CH2Cl2, rt, 20 h; (ii) 5 equiv NaN3, DMF, 90 ꢁC, 20 h, 82% overall; (b) (i)
O3, CH2Cl2, )78 ꢁC, 30 min; (ii) 3 equiv NaBH4, MeOH, rt, 20 h, 62% overall; (c) 1.1 equiv TEMPO, 12 equiv NaOCl, 0.1 equiv KBr, NaHCO3,
acetone, rt, 1 h, 100%; (d) 2 equiv PCC, 10 equiv Ac2O, 20 equiv tBuOH, CH2Cl2, rt, 48 h, 62%; (e) 1.1 equiv PPh3, 12 equiv H2O, THF, rt, 20 h, 89%
for 21, 77% for 24; (f) 1.5 equiv DEPC, 3 equiv Et3N, DMF, rt, 72 h, 72%; (g) 20 equiv TFA, CH2Cl2, rt, 20 h, 100%; (h) 1.1 equiv 23, 1.5 equiv DEPC,
3 equiv Et3N, DMF, rt, 72 h, 79%.
which was oxidised quantitatively to acid 19 with
TEMPO. Treatment of 18 with PCC/Ac2O/tBuOH
afforded the ester 2010 in 62% yield, which was reduced
to amino ester 21 with PPh3. Finally, coupling of 21 with
19 catalysed by DEPC gave the dimer 22 in 72% yield.
Repetitive coupling as described before produced the
tetramer 25.12
In summary, we have demonstrated alternative synthe-
ses of two pyranoid d-SAAs from per-benzylated b-C-

F. Durrat et al. / Tetrahedron Letters 45 (2004) 1477–1479
1479
ꢀ
€
8. Wang, W.; Zhang, Y.; Zhou, H.; Bleriot, Y.; Sinay, P. Eur.
J. Org. Chem. 2001, 1053–1059.
vinyl glucoside. These monomeric SAAs can be easily
oligomerised using a solution-phase coupling procedure.
9. Kramer, S.; Nolting, B.; Ott, A.-J.; Vogel, C. J. Carbo-
hydr. Chem. 2000, 19, 891–921.
10. Selected physical data. tert-Butyl 2,6-anhydro-7-azido-
3,4,5-tri-O-benzyl-7-deoxy-L-glycero-L-gluco-hepturonate
9: 1H NMR (250 MHz, CDCl3) d 7.29–7.16 (m, 15H, Ph),
4.87–4.78 (m, 3H, OCH2Ph), 4.74 (d, 1H, J ¼ 10:8 Hz,
OCH2Ph), 4.62 (d, 1H, J ¼ 10:8 Hz, OCH2Ph), 4.52 (d,
1H, J ¼ 11 Hz, OCH2Ph), 3.82–3.61 (m, 3H), 3.48–3.36
References and notes
1. For reviews on sugar amino acids, see: (a) Gruner, S. A.
W.; Locardi, E.; Lohof, E.; Kessler, H. Chem. Rev. 2002,
102, 491–514; (b) Schweizer, F. Angew. Chem., Int. Ed.
2002, 41, 230–253; (c) Chakraborty, T. K.; Ghosh, S.;
Jayaprakash, S. Curr. Med. Chem. 2002, 9, 421–435; (d)
Gervay-Hague, J.; Weathers, T. M., Jr. J. Carbohydr.
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2. (a) Suhara, Y.; Ichikawa, M.; Hildreth, J. E. K.; Ichikawa,
Y. Tetrahedron Lett. 1996, 37, 2549–2552; (b) Suhara, Y.;
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M.; Hildreth, J. E. K.; Shimada, I.; Ichikawa, Y. Bioorg.
Med. Chem. 2002, 10, 1999–2013.
t
(m, 3H), 3.24–3.21 (m, 1H, H-7), 1.41 (s, 9H, Bu); 13C
t
NMR (62.5 MHz, CDCl3) d 168.0 (CO2 Bu), 138.4, 137.6
(Cipso), 128.6–127.8 (CH-Ph), 86.1 (CH), 82.4 (Cq tBu),
79.9, 79.3, 79.0, 78.3 (4 · CH), 75.7, 75.3, 75.1
(3 · OCH2Ph), 51.0 (C-7), 27.9 (CH3 tBu). tert-Butyl 2,6-
anhydro-7-azido-3,4,5-tri-O-benzyl-7-deoxy-D-glycero-D-
gulo-hepturonate 20: 1H NMR (250 MHz, CDCl3) d 7.27–
7.12 (m, 15H, Ph), 4.85–4.76 (m, 3H, OCH2Ph), 4.73 (d,
1H, J ¼ 10:5 Hz, OCH2Ph), 4.61 (d, 1H, J ¼ 10:5 Hz,
OCH2Ph), 4.50 (d, 1H, J ¼ 11 Hz, OCH2Ph), 3.85–3.59
(m, 3H), 3.49–3.33 (m, 3H), 3.23–3.15 (m, 1H, H-7), 1.39 (s,
€
3. Locardi, E.; Stockle, M.; Gruner, S.; Kessler, H. J. Am.
Chem. Soc. 2001, 123, 8189–8916.
9H, tBu); 13C NMR (62.5 MHz, CDCl3) d 167.8 (CO2 Bu),
t
4. (a) Graf von Roedern, E.; Kessler, H. Angew. Chem., Int.
Ed. 1994, 33, 687–689; (b) Graf von Roedern, E.; Kessler,
H. Angew. Chem., Int. Ed. 1994, 33, 684–686.
5. Xie, J. Eur. J. Org. Chem. 2002, 3411–3418.
138.3, 137.9, 137.7 (Cipso), 128.6–127.8 (CH-Ph), 86.1 (CH),
82.4 (Cq tBu), 79.9, 79.3, 79.1, 78.3 (4 · CH), 75.7, 75.3,
75.1 (3 · OCH2Ph), 51.0 (C-7), 27.9 (CH3 tBu).
11. Hayashi, K.; Hamada, Y.; Shioiri, T. Tetrahedron Lett.
1992, 33, 5075–5076.
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Chem. 1996, 61, 1894–1897.
12. The structures of the oligomers have been confirmed by
1H, 13C NMR data and fast atom bombardment mass
spectroscopy.