Expedient Synthesis of C-Aryl Carbohydrates by Consecutive Biocatalytic Benzoin and Aldol Reactions

• Published in: Chemistry : a European journal Vol. 21; no. 8; pp. 3335 - 3346
• Main Authors: Hernández, Karel, Parella, Teodor, Joglar, Jesús, Bujons, Jordi, Pohl, Martina, Clapés, Pere
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16-02-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Aldehyde-Lyases - chemistry; Aldehyde-Lyases - metabolism; Aldehydes; Aldehydes - chemistry; Aldolase; aldolases; Aromatic compounds; Benzaldehyde; benzaldehyde lyase; Benzoin; Benzoin - chemistry; Biocatalysis; Carbohydrates; Carbohydrates - chemical synthesis; Carbohydrates - chemistry; Chemical reactions; Chemical synthesis; Chemistry; CC bond formation; Derivatives; Dihydroxyacetone; Dihydroxyacetone - chemistry; Dihydroxyacetone phosphate; enzyme catalysis; Escherichia coli - chemistry; Escherichia coli - metabolism; Fructose; Fructosephosphates - chemical synthesis; Fructosephosphates - chemistry; Glycolaldehyde; Methodology; Molecular Structure; Phosphates; Pseudomonas fluorescens; Sorbose; Substrates; Xylose; carbohydrates; enzyme catalysis; benzaldehyde lyase; aldolases; CC bond formation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201406156

The introduction of aromatic residues connected by a CC bond into the non‐reducing end of carbohydrates is highly significant for the development of innovative structures with improved binding affinity and selectivity (e.g., Caril‐sLex). In this work, an expedient asymmetric “de novo” synthetic route to new aryl carbohydrate derivatives based on two sequential stereoselectively biocatalytic carboligation reactions is presented. First, the benzoin reaction of aromatic aldehydes to dimethoxyacetaldehyde is conducted, catalyzed by benzaldehyde lyase from Pseudomonas fluorescens biovar I. Then, the α‐hydroxyketones formed are reduced by using NaBH4 yielding the anti diol. After acetal hydrolysis, the aldol addition of dihydroxyacetone, hydroxyacetone, or glycolaldehyde catalyzed by the stereocomplementary D‐fructose‐6‐phosphate aldolase and L‐rhamnulose‐1‐phosphate aldolase is performed. Both aldolases accept unphosphorylated donor substrates, avoiding the need of handling the phosphate group that the dihydroxyacetone phosphate‐dependent aldolases require. In this way, 6‐C‐aryl‐L‐sorbose, 6‐C‐aryl–L‐fructose, 6‐C‐aryl–L‐tagatose, and 5‐C‐aryl‐L‐xylose derivatives are prepared by using this methodology.
Bottom‐up sugars: C‐Aryl carbohydrates on the non‐reducing end exhibit interesting biological activities. These molecules have been prepared in four synthetic steps combining cross‐benzoin and aldol addition reactions with simple chemical transformation. By using this methodology, C‐aryl carbohydrate analogues of L‐sorbose, L‐xylose, L‐fructose, and L‐tagatose are prepared (see figure).