Synthesis of Trisaccharides by Hetero-Diels-Alder Welding of Two Monosaccharide Units

• Published in: European journal of organic chemistry Vol. 2012; no. 20; pp. 3765 - 3780
• Main Authors: Himanen, Jatta A., Pihko, Petri M.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-07-2012; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Carbohydrates; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Catalysis; Catalysts: preparations and properties; Chemistry; Chromium; Cycloaddition; Exact sciences and technology; General and physical chemistry; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Synthetic methods; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Configuration; Chiral compound; NMR spectrometry; Selectivity; Glucose; Modeling; Disaccharide; Monosaccharides; Schiff base; Stereoselectivity; Danishefsky synthesis; Chromium Complexes; Chromium complex; Functionalization; Benzylic compound; Glycoside; Synthetic methods; Chemical synthesis; Protection; Trisaccharide; Carbohydrates; Catalytic reaction; Aldose; Oside; Transition metal; Transition metal Complexes; Imine; Aldehyde; Dienic compound; Cycloaddition; Chromium; Hetero Diels Alder reaction; Galactose; Catalyst
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200277

A new strategy for the synthesis of di‐ and trisaccharides based on the de novo synthesis of the linking saccharide unit is presented. In this strategy, functionalized monosaccharide building blocks already incorporating the glycosidic linkages are welded together using a metal‐catalyzed hetero‐Diels–Alder (HDA) reaction to generate a new monosaccharide unit between them. The highest yields and selectivities in the HDA reaction were obtained by using chiral Schiff base chromium complexes. Disaccharide products were accessible by reaction of Danishefsky's diene with acetyl‐ and benzyl‐protected galactoside aldehydes. For the synthesis of trisaccharide products, acetyl‐protected glucose or galactose‐derived dienes were fused with monosaccharide‐derived aldehydes using chromium catalysts for the HDA reaction. The desired trisaccharide products were obtained in moderate to good yields with excellent stereoselectivity. The central pyranulose‐ring generated in the process possessed an L‐cis‐enulose configuration according to NMR spectroscopy and modeling studies.
1 + 1 equals 3! The hetero‐Diels–Alder union of two functionalized monosaccharide building blocks – one bearing an aldehyde and the other a readily accessible diene moiety – affords functionalized trisaccharide structures in moderate to good yields and excellent stereoselectivities when β‐anomers of the aldehydes are used.