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Synthesis 2005(5): 675-702  
DOI: 10.1055/s-2005-861848
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Aza-C-disaccharides (Dideoxyimino-alditols C-Linked to Monosaccharides) and Analogues

Inmaculada Robinaa, Pierre Vogel*b
a Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 553, 41071 Sevilla, Spain
b Laboratoire de glycochimie et de synthèse asymétrique, Ecole Polytechnique Fédérale de Lausanne (EPFL), BCH, 1015 Lausanne, Switzerland
Fax: +41(21)6939475; e-Mail: pierre.vogel@epfl.ch;
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Publication History

Received 11 October 2004
Publication Date:
10 March 2005 (online)

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Abstract

The first aza-C-disaccharide (D-azaMan-β-CH2-(1→6)-d-Man-α-OMe) that mimicks α-d-Manp-(1→6)-α-d-ManOMe was made in 1994 by Johnson and coworkers. Several synthetic approaches to these disaccharide mimetics have been proposed. These are reviewed and compared. Several strategies rely on C-C bond forming reactions such as the Miyaura-Suzuki cross-coupling, the SmI2 Barbier reaction, the addition of acetylides to aldonolactones, the cross-aldol reaction or the Michael addition of 7-oxabicy­clo[2.2.1]heptanone derivatives (‘naked sugars’), with subsequent formation of the iminoalditol moieties. Other approaches use nitrogen-containing systems such as sugar-derived nitrones or iminoaldoses that are coupled by either Wittig olefinations, cross-aldol reactions or Takai-Oshima-Nozaki-Kishi reactions. When available, the conformational analysis of the aza-C-disaccharides, as well as their inhibitory activities toward glycosidases, will be summarized.

  • 1 Introduction

  • 2 Synthesis of Linear Aza-C-disaccharides

  • 2.1 Miyaura-Suzuki Coupling

  • 2.2 Samarium Diiodide Barbier Reaction

  • 2.3 Acetylide Addition to Aldonolactones

  • 2.4 Intramolecular Oxyalkylation

  • 2.5 Wittig Olefination

  • 2.6 Cycloaddition Reactions of Functionalized Nitrones

  • 3 Synthesis of Branched Aza-C-disaccharides

  • 3.1 Cross-Aldol Reaction with ‘Naked Sugar’-Derived Ketones

  • 3.2 Michael Condensation of ‘Naked Sugar’-Derived Enone and Urunolactone

  • 3.3 Cross-Aldol Reactions with Isolevoglucosenone Derivatives and 2,5-Dideoxy-2,5-iminopentoses

  • 3.4 Takai-Oshima-Nozaki-Kishi Couplings

  • 3.5 Miyaura-Suzuki Couplings

  • 3.6 Dipolar Cycloadditions of Chiral Nitrones

  • 3.7 Intramolecular Oxyalkylations

  • 4 Synthesis of Pseudo-aza-C-disaccharides

  • 5 Synthesis of Homo-aza-C-(1→3)-disaccharides

  • 6 Conformations of Aza-C-disaccharides

  • 7 Glycosidase Inhibitory Activities

  • 8 Conclusion

Key words

aza-C-disaccharides - conformational analysis - cross-glycosidase inhibitors - naked sugars - homo-aza-C-disaccharides - pseudo-aza-C-disaccharides