Synthesis of Benzaldehyde‐Functionalized Glycans: A Novel Approach Towards Glyco‐SAMs as a Tool for Surface Plasmon Resonance Studies

Abstract

In recent years the interest in tools for investigating carbohydrate-protein (CPI) and carbohydrate-carbohydrate interactions (CCI) has increased significantly. For the investigation of CPI and CCI, several techniques employing different linking methods are available. Surface plasmon resonance (SPR) imaging is a most appropriate tool for analyzing the formation of self-assembled monolayers (SAM) of carbohydrate derivatives, which can mimic the glycocalyx. In contrast to the SPR imaging methods used previously to analyze CPI and CCI, the novel approach reported herein allows a facile and rapid synthesis of linker spacers and carbohydrate derivatives and enhances the binding event by controlling the amount and orientation of ligand. For immobilization on biorepulsive amino-functionalized SPR chips by reductive amination, diverse aldehyde-functionalized glycan structures (glucose, galactose, mannose, glucosamine, cellobiose, lactose, and lactosamine) have been synthesized in several facile steps that include olefin metathesis. Effective immobilization and the first binding studies are presented for the lectin concanavalin A.

Short Synthetic Route to Benzaldehyde‐Functionalized Idose and Talose Derivatives by Acetoxonium Ion Rearrangements

“…Application of a previously established procedure realized the benzaldehyde functionalization of allyl glycopyranosides 7 and 12 by olefin cross metathesis with para ‐allyloxybenzaldehyde dimethyl acetal and Grubbs–Hoveyda 2nd generation catalyst 24. After reaction in anhydrous dichloromethane at 40 °C for 6 h, butenyl derivatives 13 and 14 were obtained in 66 and 82 % yields, respectively (Scheme ).…”

“…Recently, we reported the immobilization of benzaldehyde‐functionalized glycosides onto amino‐SAMs (SAM = self‐assembled monolayer) on surface plasmon resonance sensors by reduction after imine formation in an overall reductive amination process 24. Combined with SAM formation on gold nanoparticles,25 this approach allows a detailed study of the basic mechanisms of Ca 2+ ‐dependent carbohydrate–carbohydrate recognition, in which the complexation of metal ions, the subject of Angyal's postulate, plays a crucial role.…”

Carbohydrate‐Modified Gold Nanoparticles

“…Mannose [73], galactose [73,74], maltose [74] galactose [76,77], glucose [76,78,79], mannose [76,80], N-acetylglucosamine [76,77], N-acetylgalactosamine [78], sialic acid [77,81], lactose [60,76], N-acetyl-lactosamine [79,81], mannobiose [79], heparin decasaccharide [76], globo H [82], complex carbohydrates [76,[80][81][82][83][84] (p) Mannose, galactose, glucose [87] (s) Mannose, galactose, glucose, glucosamine, cellobiose, lactose, lactosamine [88] (t) glucose [94][95][96][97], sulfonated glucose [95], mannose [97,98], galactose [97] (z) cyclooctyne group on azide-terminated surfaces [58]. The main disadvantage of the sPAAC reaction is the more challenging synthesis of carbohydrate derivatives con taining cyclooctynes when compared with the ones containing linear terminal alkynes.…”

“…The formation of an imine bond can also be used to attach aldehyde-functionalized carbohydrates on amine-terminated surfaces. The imine bond can then be reduced with mild reducing agents such as sodium cyanoborohydride to obtain irreversible immobilization (Table 1.3; entry s) [88]. The reaction between amines and isocyanate or isothiocyanate groups (Table 1.3; entries t and u) has also been used to immobilize carbohydrate derivatives on surfaces.…”

New synthesis and reactions of phosphonates

“…The bis-t-butyldimethylsilyl protected compound 118 106 19,146,147 Interest in HWE olefination applications towards the total synthesis of schweinfurthin analogues led to studies of the zinc methodology for phosphonate synthesis on some heteroaromatic substrates provided by Dr. John Kodet (Figure 31).…”