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Synlett 2008(7): 1027-1030  
DOI: 10.1055/s-2008-1072649
LETTER
© Georg Thieme Verlag Stuttgart · New York

Ferrier Glycosylation Reaction Catalyzed by Bi(OTf)3-Montmorillonite K-10: Efficient Synthesis of 3,4-Unsaturated Sialic Acid Derivatives

Kiyoshi Ikeda*, Yayoi Ueno, Satoru Kitani, Reiko Nishino, Masayuki Sato
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan
Fax: +81(54)2645108; e-Mail: ikeda@ys2.u-shizuoka-ken.ac.jp;
Further Information

Publication History

Received 7 December 2007
Publication Date:
28 March 2008 (online)

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Abstract

The reaction of the 4,5-oxazoline derivative of sialic acid with various alcohols was effectively promoted by a catalytic amount of montmorillonite K-10 clay supported Bi(OTf)3 to produce a variety of 3,4-unsaturated sialic acids via the Ferrier glycosylation reaction in moderate yields.

Key words

Ferrier glycosylation reaction - 3,4-unsaturated sialic acid - Bi(OTf)3-montmorillonite K-10 - 4,5-oxazoline derivative of sialic acid - sialidase inhibitor

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The α-methyl ketoside of 5-acetamido-3,4,5-trideoxy-d-manno-non-3-en-2-ulosonic acid (4a), and its β-epimer were synthesized from 3-acetamido-4,5,6,7-tetra-O-acetyl-2,3-dideoxy-d-manno-heptose, and methyl 2-methoxy-2-dimethylphosphono acetate in 29% yield over five steps. [18]

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Typical Procedure
To a stirred mixture of 5 (50 mg, 0.12 mmol) and MeOH (0.1 mL) in MeCN (1.0 mL) was added 40% w/w Bi(OTf)3-montmorillonite K-10 loading of 20% w/w of Bi(OTf)3 (15 mg) at ambient temperature. The mixture was stirred for
20 h at r.t. The reaction suspension was filtered and the filtrate was evaporated under vacuum. The residue was purified by column chromatography on silica gel with CH2Cl2-MeOH (10:1) to give 4a (51 mg, 95%).
Compound 4a-α: 1H NMR (500 MHz, CDCl3): δ = 1.99 (s, 3 H, CH3CONH), 2.05, 2.12, 2.14 (s, each 3 H, CH3CO), 3.34 (s, 3 H, CH3O), 3.78 (s, 3 H, CH3COO), 4.24 (dd, 1 H, J 9a,9b = 12.4 Hz, J 8,9a = 5.9 Hz, H-9a), 4.26 (dd, 1 H, J 5,6 = 9.8 Hz, J 6,7 = 2.1 Hz, H-6), 4.48 (dd, 1 H, J 8,9b = 2.4 Hz, H-9b), 4.52 (dddd, J 5,NH = 9.2 Hz, J 4,5 = 2.6 Hz, J 3,5 = 1.9 Hz, H-5), 5.35 (dd, 1 H, J 7,8 = 6.1 Hz, H-7), 5.44 (ddd, 1 H, H-8), 5.59 (d, 1 H, CH3CONH), 5.78 (dd, 1 H, J 3,4 = 10.1 Hz, H-4), 6.07 (dd, 1 H, H-3). MS-FAB (NBA): m/z = 446 [M + H]+, 468 [M + Na]+. HRMS-FAB: m/z calcd for C19H28NO11: 446.1662; found: 446.1613.
Compound 4a-β: 1H NMR (500 MHz, CDCl3): δ = 1.99 (s, 3 H, CH3CONH), 2.04, 2.10, 2.16 (s, each 3 H, CH3CO), 3.29 (s, 3 H, CH3O), 3.82 (s, 3 H, CH3COO), 4.05 (dd, 1 H, J 5,6 = 10.2 Hz, J 6,7 = 2.3 Hz, H-6), 4.24 (dd, 1 H, J 9a,9b = 12.5 Hz, J 9a,8 = 6.3 Hz, H-9a), 4.63 (dd, 1 H, J 8,9b = 2.3 Hz, H-9b), 4.64 (m, 1 H, H-5), 5.35 (ddd, 1 H, J 7,8 = 5.6 Hz, H-8), 5.40 (dd, 1 H, H-7), 5.51 (d, 1 H, CH3CONH), 5.91 (s, 2 H, H-3 and H-4).