Synlett 2004(9): 1529-1532  
DOI: 10.1055/s-2004-829074
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Novel Pseudodisaccharides and Neoglycoconjugates Containing an N-Glycosyl Carbamate Backbone

Davide Prosperi*a,b, Silvia Ronchi, Luigi Panza, Anna Rencurosia, Giovanni Russob
a Istituto di Scienze e Tecnologie Molecolari (ISTM) - CNR, via Golgi 19, 20133 Milano, Italy
b Dipartimento di Chimica Organica e Industriale, Centro Interdisciplinare Studi Bio-molecolari e Applicazioni Industriali (CISI), Università degli Studi di Milano, via Venezian 21, 20133 Milano, Italy
Fax: +39(02503)14061; e-Mail: davide.prosperi@unimi.it;
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Publikationsverlauf

Received 17 March 2004
Publikationsdatum:
29. Juni 2004 (online)

Abstract

A new class of pseudodisaccharides is presented in which a N-glycosyl carbamate is connected to a monosaccharide unit, using a mild and stereo-controlled isocyanide approach. The methodology was extended to the case of neoglycoconjugates ­useful as synthons for the construction of molecules with potential therapeutic interest.

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  • 12a

    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.

  • 12b

    Deprotection of 1d: To a solution of compound 1d (109 mg, 0.13 mmol) in CH2Cl2 (2 mL), 90% aq TFA (620 µL) 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 µL 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.

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9

Selected data for compound 1a. Mp 63-65 °C; [α]D 23 +14.1 (c 1.00, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 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): δ = 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.

20

Selected data for Compound 11: [α]D 21 +40.1 (c 1.00, MeOH). 1H NMR (300 MHz, CD3OD): δ = 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), 3.80, (1 H, dd, J = 2.8, 1.8 Hz, H-2), 4.58 (1 H, br s, carboranyl CH), 4.63 (2 H, s, CH2), 5.26 (1 H, d, J = 1.8 Hz, H-1). 13C NMR (75 MHz, CD3OD): δ = 63.0, 66.4, 69.0, 72.0, 72.5, 76.1, 82.6, 156.8.