Carbamate Linker Strategy in Solid‐Phase Synthesis of Amino‐Functionalized Glycoconjugates for Attachment to Solid Surfaces and Investigation of Protein‐Carbohydrate Interactions

Abstract

Amino‐functionalized serine‐based galactose and glucose neoglycolipids were prepared by solid‐phase synthesis using a carbamate strategy for anchoring amino functionalities to a (2‐fluoro‐4‐hydroxymethylphenoxy)acetic acid linker resin. Key synthetic steps were monitored with gel‐phase 19F NMR spectroscopy. Cleavage from the solid support was performed with trifluoroacetic acid. The terminal amine of the neoglycolipids was conjugated with didecyl squarate and then immobilized in amino‐functionalized microtiter plates and the glycoconjugates were successfully probed with a galactose‐binding lectin.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Synthesis and Application of a 2-[(4-Fluorophenyl)-sulfonyl]ethoxy Carbonyl(Fsec) Protected Glycosyl Donor in Carbohydrate Chemistry

“…Since the Fsec protecting group met our requirements concerning stability and cleavage conditions we decided to apply it for O -protection of a glycosyl donor. The Fsec protected glycosyl donor 8 was synthesized in two steps from the fully protected galactose donor 6 [ 20 ] ( Scheme 3 ). Compound 6 was treated with trimethylaminoborane and aluminium chloride [ 21 ] to open the acetal ring and give 7 with a free 4-OH in 85% yield.…”

“…The benzoyl protecting groups in 13 were removed with sodium methoxide in methanol and the remaining protecting groups were removed with palladium on charcoal in acetic acid producing the target compound 15 in 45% yield over two steps ( Scheme 3 ). The amino group allows conjugation to a wide variety of carriers and surfaces including proteins and microwell plates [ 20 ].…”

“…4-Methylphenyl 2,3-di-O-(4-fluorobenzoyl)-6-O-benzyl-1-thio-β-D-galactopyranoside ( 7 ). Trimethyl-aminoborane (0.238 g, 3.26 mmol) was added to 6 [ 20 ] (0.500 g, 0.808 mmol) in distilled THF (25 mL) followed by aluminium chloride (0.639 g, 4.79 mmol). After dissolution of the reagents water (0.029 mL, 1.61 mmol) was added and the mixture was stirred at room temperature overnight.…”

Be squared: expanding the horizon of squaric acid-mediated conjugations

“…64 Elofsson and coworkers applied the squaric acid mediated coupling for the modification of amino-functionalized microtiter plate wells. 65 They synthesized serine-based galactose or glucose neoglycolipids via solid-phase synthesis, modified them with squaric acid didecyl ester and coupled them to the surface (Table 1, entries 13 and 14). 65 A model compound bearing a biotin moiety was also investigated.…”

“…65 They synthesized serine-based galactose or glucose neoglycolipids via solid-phase synthesis, modified them with squaric acid didecyl ester and coupled them to the surface (Table 1, entries 13 and 14). 65 A model compound bearing a biotin moiety was also investigated. The biotin plates were successfully probed with avidin labeled with both horseradish peroxidase and fluorescein isothiocyanate.…”