Synthesis of non-natural carbohydrates from glycerol and aldehydes in a one-pot four-enzyme cascade reaction

A simple procedure has been developed for the synthesis of enantio- and diastereomerically pure carbohydrate analogues from glycerol and a variety of aldehydes in one pot using a four-enzyme cascade reaction. As a proof of concept of the usefulness of this enzymatic catalytic cascade the naturally occurring azasugarD-fagomine was synthesized. This work highlights the potential value of using enzymes in cascade reactions to selectively form complex products that by previous traditional organic chemistry could only be obtained via repeated isolation and purification of intermediates.

[1]  Chi‐Huey Wong,et al.  Synthesis of complex carbohydrates and glycoconjugates: enzyme-based and programmable one-pot strategies. , 2000, Chemical reviews.

[2]  Y. Igarashi,et al.  1-N-Iminosugars: Potent and Selective Inhibitors of β-Glycosidases , 1998 .

[3]  W. Fessner,et al.  Synthesis of Dihydroxyacetone Phosphate (and Isosteric Analogues) by Enzymatic Oxidation; Sugars from Glycerol** , 1994 .

[4]  G. Sprenger,et al.  Fructose-6-phosphate aldolase in organic synthesis: preparation of D-fagomine, N-alkylated derivatives, and preliminary biological assays. , 2006, Organic letters.

[5]  Alle Bruggink,et al.  Concepts of Nature in Organic Synthesis: Cascade Catalysis and Multistep Conversions in Concert , 2003 .

[6]  Chi‐Huey Wong,et al.  Asymmetric Aldol Reactions Using Aldolases , 2003 .

[7]  H. Schoemaker,et al.  Simple enzymatic in situ generation of dihydroxyacetone phosphate and its use in a cascade reaction for the production of carbohydrates: increased efficiency by phosphate cycling. , 2006, The Journal of organic chemistry.

[8]  A. Hartog,et al.  Regioselective phosphorylation of carbohydrates and various alcohols by bacterial acid phosphatases; probing the substrate specificity of the enzyme from Shigella flexneri , 2005 .

[9]  E. García-Junceda Multi-Step Enzyme Catalysis: Biotransformations and Chemoenzymatic Synthesis , 2008 .

[10]  A. Hartog,et al.  Phosphorylation and dephosphorylation of polyhydroxy compounds by class A bacterial acid phosphatases. , 2003, Organic & biomolecular chemistry.

[11]  Roger A Sheldon,et al.  E factors, green chemistry and catalysis: an odyssey. , 2008, Chemical communications.

[12]  J. Kennedy,et al.  Biotransformations in Organic Chemistry, 5th ed., Kurt Faber. Springer, Heidelberg, Germany (2004), (xi+454 pp., £27.00, ISBN 3-540-20097-5) , 2006 .

[13]  Wolf-Dieter Fessner,et al.  Recent progress in stereoselective synthesis with aldolases. , 2010, Current opinion in chemical biology.

[14]  Chi‐Huey Wong,et al.  Sequential Three- and Four-Substrate Aldol Reactions Catalyzed by Aldolases , 1995 .

[15]  E. Jacobsen,et al.  The Simplest "Enzyme" , 2002, Science.

[16]  N. Asano Sugar-mimicking glycosidase inhibitors: bioactivity and application , 2009, Cellular and Molecular Life Sciences.

[17]  J. McMurray,et al.  Pd-C-induced catalytic transfer hydrogenation with triethylsilane. , 2007, The Journal of organic chemistry.

[18]  Chi-Huey Wong,et al.  Recent advances in aldolase-catalyzed asymmetric synthesis , 2007 .

[19]  G. Whitesides,et al.  Glycerol kinase: synthesis of dihydroxyacetone phosphate, sn-glycerol-3-phosphate, and chiral analogs , 1985 .

[20]  H. Waldmann,et al.  Rabbit muscle aldolase as a catalyst in organic synthesis , 1989 .

[21]  Adam Nelson,et al.  Directed evolution of aldolases for exploitation in synthetic organic chemistry , 2008, Archives of biochemistry and biophysics.

[22]  S. Masamune,et al.  Total Synthesis of the L-Hexoses , 1983, Science.

[23]  R. Sheldon,et al.  A four-step enzymatic cascade for the one-pot synthesis of non-natural carbohydrates from glycerol. , 2000, The Journal of organic chemistry.

[24]  Sven Panke,et al.  Chemical and enzymatic routes to dihydroxyacetone phosphate , 2007, Applied Microbiology and Biotechnology.

[25]  G. Whitesides,et al.  Synthesis of sugars by aldolase-catalyzed condensation reactions , 1983 .

[26]  Chi‐Huey Wong,et al.  D-Fructose-6-phosphate aldolase-catalyzed one-pot synthesis of iminocyclitols. , 2007, Journal of the American Chemical Society.

[27]  W. Fessner,et al.  Facile enzymic de novo synthesis and NMR spectroscopic characterization of d-tagatose 1,6-bisphosphate , 1993 .

[28]  D. MacMillan,et al.  Two-Step Synthesis of Carbohydrates by Selective Aldol Reactions , 2004, Science.

[29]  K. Matsui,et al.  Fagomine isomers and glycosides from Xanthocercis zambesiaca. , 1997, Journal of natural products.