1532
D. Prosperi et al.
LETTER
(6) (a) Ichikawa, Y.; Nishiyama, T.; Isobe, M. Synlett 2000,
1253. (b) Nishiyama, T.; Ichikawa, Y.; Isobe, M. Synlett
2003, 47.
(7) Prosperi, D.; Ronchi, S.; Lay, L.; Rencurosi, A.; Russo, G.
Eur. J. Org. Chem. 2004, 395.
In summary, we have described a simple and versatile
route for the synthesis of a new class of pseudodisaccha-
rides, involving the stereoselective isocyanide approach.
The carbamate bridge demonstrated to be a useful tool for
an easy conjugation with other therapeutically important
molecules. Work is in progress to extend this strategy to
the preparation of stabilized oligosaccharide analogs of
biological interest.
(8) Toth, G.; Pintér, I.; Kovács, J.; Haessner, R. Magn. Reson.
Chem. 1997, 37, 203.
(9) Selected data for compound 1a. Mp 63–65 °C; [a]D23 +14.1
(c 1.00, CHCl3). 1H NMR (200 MHz, CDCl3): d = 1.94 (3 H,
s, OAc), 2.01 (3 H, s, OAc), 2.02 (3 H, s, OAc), 2.07 (3 H, s,
OAc), 3.35 (3 H, s, OMe), 3.41 (1 H, dd, J = 9.6, 1.5 Hz,
H-6a), 3.51 (1 H, dd, J = 9.6, 3.4 Hz, H-6b), 3.72–3.86 (2 H,
m, H-5, H-5¢), 3.99 (1 H, t, J = 9.2 Hz, H-3), 4.07 (1 H, dd,
J = 12.6, 1.1 Hz, H-6a¢), 4.19–4.37 (2 H, m, H-4, H-6b¢),
4.48–5.13 (9 H, m, H-1, H-2¢, H-4¢, 3 CH2Ph), 5.01 (1 H, d,
J = 8.9 Hz, H-1¢), 5.29 (1 H, t, J = 9.3 Hz, H-3¢), 5.63 (1 H,
br d, J = 9.5 Hz, NH), 7.20–7.41 (15 H, m, Ph). 13C NMR (50
MHz, CDCl3): d = 20.5, 55.2, 61.5, 64.4, 68.0, 68.6, 70.2,
72.7, 73.2, 73.4, 75.0, 75.7, 77.6, 79.8, 80.7, 81.8, 97.9,
127.6, 127.9, 128.1, 128.4, 137.8, 137.9, 138.5, 155.2,
169.5, 169.9, 170.5.
Preparation of 2,3,4,6-Tetra-O-acetyl-a-D-mannopyranosyl Iso-
cyanide (7).
A mixture of potassium isothiocyanate (2.0 g, 20 mmol) and tet-
rabutylammonium iodide (3.7 g, 10 mmol) was dissolved in dry
MeCN (250 mL) under nitrogen at r.t. Finely powdered 4 Å molec-
ular sieves (15 g) and 5 (4.1 g, 10 mmol) were added successively
and the mixture was refluxed for 3 h under stirring. When the reac-
tion was complete, the mixture was filtered over celite, the crude
product was concentrated and purified by flash chromatography
(EtOAc–hexane 3:7) furnishing mannosyl isothiocyanate 6 in 82%
yield as a pale yellow solid. Compound 6 (1.0 g, 2.57 mmol) was
dissolved in dry Et2O (10 mL) under nitrogen. Tributyltin hydride
(680 mL, 2.57 mmol) was added and stirring continued at r.t. for 2
h. The solvent was evaporated and the resulting brown foam was
passed through a silica gel column affording 860 mg of pure isocy-
anide 7 (94%) as a white solid.
(10) Petrakova, E.; Glaudemans, C. P. J. Carbohydr. Res. 1995,
279, 133.
(11) Toepfer, A.; Schmidt, R. R. J. Carbohydr. Chem. 1993, 12,
809.
(12) (a) Procedure for the Deprotection of 1a: Compound 1a
(90 mg, 0.11 mmol) was hydrogenated in MeOH (2 mL) in
the presence of a catalytic amount of Pd/C; the crude product
was deacetylated in methanolic NaOMe (0.02 mmol), giving
44 mg of 4a, with a 100% overall yield. (b) Deprotection
of 1d: To a solution of compound 1d (109 mg, 0.13 mmol)
in CH2Cl2 (2 mL), 90% aq TFA (620 mL) was added; after
1.5 h, the mixture was diluted with CH2Cl2 (15 mL) and
washed with a sat. solution of NaHCO3 (10 mL). The
organic layer was dried over Na2SO4 and the solvent was
evaporated. The crude product was dissolved in dry MeOH
(4 mL) and 70 mL of a 1 M solution of NaOMe (0.07 mmol)
were added, furnishing 60 mg of 4d (92%) as a white solid
after flash chromatography.
General Procedure for the Preparation of the Glycosyl Car-
bamates 1a–f.
To a mixture of glycosyl isocyanide 3a–c (0.40 mmol) and pow-
dered 3 Å molecular sieves (300 mg) in dry MeCN (5 mL), were
added pyridine N-oxide (115 mg, 1.2 mmol) dissolved in dry MeCN
(0.5 mL) and iodine (8 mg, 0.03 mmol) under nitrogen. After 10
min, a solution of alcohol 2a–e (0.40 mmol) dissolved in dry MeCN
(1 mL) was added under stirring. The reaction was monitored by
TLC (EtOAc–hexane 3:7). The mixture was quenched with a sat.
solution of NaHSO3 (5 mL), extracted with CH2Cl2 (20 mL) and
washed with brine (20 mL). After drying over anhyd Na2SO4 and
evaporation of the solvent, the crude product was purified by flash
chromatography (EtOAc–hexane 3:7), affording glycosyl carbam-
ate 1a–f (yields reported in Table 1).
(13) Chaxiraxi, N.; Vazquéz, J. T. Tetrahedron: Asymmetry
2003, 14, 2793.
(14) García Fernández, J. M.; Ortiz Mellet, C. Sulfur Rep. 1996,
19, 61.
(15) Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F.-G.;
Barth, R. F.; Codogni, I. M.; Wilson, J. G. Chem. Rev. 1998,
98, 1515.
(16) (a) Locher, G. L. Am. J. Roentgenol. 1936, 36, 1.
(b) Hawthorne, M. F. Angew. Chem., Int. Ed. Engl. 1993, 32,
950.
Acknowledgment
This work was supported by Regione Lombardia – Assessorato
alla Sanità and Istituto di Scienze e Tecnologie Molecolari of the
National Council of Research (CNR).
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(20) Selected data for Compound 11: [a]D21 +40.1 (c 1.00,
MeOH). 1H NMR (300 MHz, CD3OD): d = 1.11–3.16 (10 H,
m, BH), 3.45 (1 H, ddd, J = 9.0, 4.8, 3.1 Hz, H-5), 3.66 (1 H,
t, J = 9.0 Hz, H-4), 3.70–3.77 (3 H, m, H-3, H-6a, H-6b),
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carboranyl CH), 4.63 (2 H, s, CH2), 5.26 (1 H, d, J = 1.8 Hz,
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Synlett 2004, No. 9, 1529–1532 © Thieme Stuttgart · New York