Novel Efficient Routes to Indoxyl Glycosides for Monitoring Glycosidase Activities

Abstract

A new efficient synthesis for broad access to indoxyl glycosides was developed. Indoxylic acid allyl ester linked to a sugar structure served as the key intermediate in this route. Selective ester cleavage and mild decarboxylation led to the corresponding indoxyl glycosides in good yields. This synthesis was applied for preparation of indoxyl glycosides of fucose, sialic acid, and 6'-sialyl lactose.

Indoxylic Acid Esters as Convenient Intermediates Towards Indoxyl Glycosides

“…In this paper, we wish to report an improved synthesis of indoxyl glycosides based on indoxylic acid esters as key intermediates 10. Indoxylic acid allyl and methyl esters were obtained in good yields using a scalable pathway.…”

“…For the decarboxylation step, a modification of a recently published method was used 18. Instead of NMP ( N ‐methylpyrrolidone) or DMF, acetic anhydride was used as the solvent, in combination with AgOAc and K 2 CO 3 10. Under these conditions, decarboxylations could take place at lower temperatures between 90–110 °C, and the reaction times required were shorter (20–40 min).…”

“…HRMS (ESI) spectra were recorded with a Thermo Finnigan MAT 95XL mass spectrometer. The preparation and characterization of compounds 1a ,10 3a – 8a ,10 3b 19 were carried out as reported previously.…”

“…General Procedure 5b. Opening of Isatoic Anhydrides; Formation of Allyl Ester: 10 The following reaction was carried out under an argon atmosphere using dry solvents. A mixture of the starting material (1.0 mmol) and allyl alcohol (4.0 mL) was treated portionwise with sodium hydride (0.3 equiv.).…”

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

“…Glycosylation in acetone/ sodium hydroxide, following deprotection and decarboxylation (160 °C, acetic anhydride, 1 hr) and finally deacetylation yielded Indicane and 5-bromo-indicane. Based on this concept we developed an improved synthesis of indoxyl glycosides, employing indoxylic acid allyl esters as acceptors [17][18][19] . The acceptor synthesis starts with the respective substituted aniline derivative (5) (Figure 2).…”