Synthesis and carbohydrate binding studies of fluorescent alpha-amidoboronic acids and the corresponding bisboronic acids

Abstract

Fluorescent boronic acids are very useful for the design and synthesis of carbohydrate sensors. In an earlier communication, we first described the effort of developing water soluble fluorescent alpha-amidoboronic acids, which change fluorescence upon sugar binding. In this report, we describe a general method of functionalizing such boronic acids and their applications in the preparation of bis-alpha-amidoboronic acids with significantly enhanced binding for oligosaccharides as compared to their monoboronic acid counterparts. The advantages of good water solubility, easy modification to generate diversity, and modularity in synthesis will make alpha-amidoboronic acids very useful building blocks for future synthesis of boronic acid-based fluorescent sensors.

Figure 1

Enantiomeric pairs of α-amidoboronic acids 1 and the corresponding bisboronic acids 2.

Figure 2

(A) Fluorescent spectral changes of boronic acid D-2 (5 × 10⁻⁶ M) upon addition of D-fructose (0.5 mM to 20 mM) in phosphate buffer (0.1 M) at pH 7.4: λ_ex = 280 nm, λ_em = 334 nm; (B) fluorescent spectral changes of D-2 (5 × 10⁻⁶ M) upon addition of D-maltose (7 mM to 100 mM) in phosphate buffer (0.1 M) at pH 7.4: λ_ex = 280 nm, λ_em = 334 nm; (C) fluorescent spectral changes of D-2 (5 × 10⁻⁶ M) upon addition of Neocarratetraose-41-O-sulphate (Na⁺) (T1) (0.02 mM to 0.25 mM) in phosphate buffer (0.1 M) at pH 7.4: λ_ex = 280 nm, λ_em = 334 nm; (D) binding curve of D-2 upon addition of D-fructose; (E) binding curve of D-2 upon addition of D-maltose; (F) binding curve of D-2 upon addition of T1;

Figure 3

The DFT optimized structures for L-2. Hydrogen atoms are not shown for clear depiction. The distances between the boronic acid pairs are labelled as angstrom (Å)

Figure 4

Structures of the saccharides that were used for binding studies with α-amidoboronic acids 1 and the corresponding bisboronic acids 2.

Scheme 1

Synthesis route of D-1 and D-2