Combinatorial carbohydrate chemistry.

Modern organic/medicinal chemistry is undergoing a “cultural revolution” in the way new drugs are discovered and developed. Instead of discrete synthess and biological screening of individual compounds, which often takes years to identify and optimize leads, the currently developing technology called “combinatorial chemistry” can rapidly provide large numbers of chemicals (libraries) in a short time. In conjunction with these new synthetic methods, high-throughput screening (HTS) can rapidly screen the libraries produced, and in so doing, can provide information for optimizing lead compounds. This is going to lighten the increasing burden traditional drug development places on the pharmaceutical industry. For this reason, the generation of chemical libraries through combinatorial chemistry, including parallel synthesis, is making explosive progress both in academic and industrial areas in the last two years, especially for creating peptide, nucleotide and small molecule libraries. A number of excellent reviews1 on this field have appeared.

[1]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. , 1994, Journal of medicinal chemistry.

[2]  A strategy for a convergent synthesis of N-linked glycopeptides on a solid support. , 1995 .

[3]  T. Norberg,et al.  Solid-phase synthesis of a fragment of the capsular polysaccharide of Haemophilus influenzae type B using H-phosphonate intermediates , 1992 .

[4]  G. Schmid,et al.  Saccharide–Peptide Hybrids as Novel Oligosaccharide Mimetics† , 1996 .

[5]  J. Krepinsky,et al.  Polymer-supported syntheses of oligosaccharides: Using dibutylboron triflate to promote glycosylations with glycosyl trichloroacetimidates , 1996 .

[6]  Yukishige Ito,et al.  Orthogonal Glycosylation Strategy for Rapid Assembly of Oligosaccharides on a Polymer Support , 1996 .

[7]  D. Whitfield,et al.  Polymer-Supported Solution Synthesis of Oligosaccharides Using a Novel Versatile Linker for the Synthesis of D-Mannopentaose, a Structural Unit of D-Mannans of Pathogenic Yeasts , 1995 .

[8]  M. Postema Recent developments in the synthesis of C-glycosides , 1992 .

[9]  W. C. Still,et al.  Parallel Synthesis and Screening of a Solid Phase Carbohydrate Library , 1996, Science.

[10]  B. Ernst,et al.  A Strategy of “Random Glycosylation” for the Production of Oligosaccharide Libraries , 1996 .

[11]  D. Kahne,et al.  Glycosylation on the Merrifield Resin Using Anomeric Sulfoxides , 1994 .

[12]  R. Hughes,et al.  Generation of C-Glycoside Peptide Ligands for Cell Surface Carbohydrate Receptors Using a Four-Component Condensation on Solid Support. , 1996, The Journal of organic chemistry.

[13]  G. Boons,et al.  Vinyl Glycosides in Oligosaccharide Synthesis: A Strategy for the Preparation of Trisaccharide Libraries Based on Latent‐Active Glycosylation , 1996 .

[14]  The use of insoluble polymer supports in general organic synthesis , 1978 .

[15]  I. Ugi From Isocyanides via Four-Component Condensations to Antibiotic Syntheses†‡ , 1982 .

[16]  S. P. Fodor,et al.  Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. , 1994, Journal of medicinal chemistry.

[17]  Chi‐Huey Wong,et al.  Rapid Combinatorial Synthesis of Aminoglycoside Antibiotic Mimetics: Use of a Polyethylene Glycol-Linked Amine and a Neamine-Derived Aldehyde in Multiple Component Condensation as a Strategy for the Discovery of New Inhibitors of the HIV RNA Rev Responsive Element , 1996 .

[18]  P. Lansbury,et al.  Glycosamino Acids: New Building Blocks for Combinatorial Synthesis , 1996 .

[19]  J. Randolph,et al.  Major Simplifications in Oligosaccharide Syntheses Arising from a Solid-Phase Based Method: An Application to the Synthesis of the Lewis b Antigen , 1995 .

[20]  W. Roush,et al.  Solid-Phase Synthesis of 6-Deoxyoligosaccharides , 1996 .

[21]  C. Zechel,et al.  Combinatorial Synthesis of Small Organic Molecules , 1996 .

[22]  Osamu Kanie,et al.  Towards oligosaccharide libraries: a study of the random galactosylation of unprotected N-acetylglucosamine. , 1996, Bioorganic & medicinal chemistry.

[23]  J. Randolph,et al.  A strategy for the solid-phase synthesis of oligosaccharides. , 1993, Science.

[24]  K. Nicolaou,et al.  A General and Highly Efficient Solid Phase Synthesis of Oligosaccharides. Total Synthesis of a Heptasaccharide Phytoalexin Elicitor (HPE) , 1997 .

[25]  H. Kessler,et al.  A Sugar Amino Acid as a Novel Peptidomimetic , 1994 .

[26]  J. H. Boom,et al.  Solid-phase synthesis of a naturally occurring β-(1→5)-linked d-galactofuranosyl heptamer containing the artificial linkage arm L-homoserine , 1987 .

[27]  Jonathan A. Ellman,et al.  Synthesis and Applications of Small Molecule Libraries. , 1996, Chemical reviews.

[28]  J. Rademann,et al.  A NEW METHOD FOR THE SOLID PHASE SYNTHESIS OF OLIGOSACCHARIDES , 1996 .

[29]  Chi‐Huey Wong,et al.  Solid-Phase Chemical-Enzymic Synthesis of Glycopeptides and Oligosaccharides , 1994 .

[30]  Harry C. J. Ottenheijm,et al.  Solid-phase organic reactions: A review of the recent literature , 1996 .

[31]  K. Tatsuta,et al.  Recent progress in O-glycosylation methods and its application to natural products synthesis , 1993 .