α-Glucosyl triazoles have rarely been tested as α-glucosidase inhibitors, partly due to inefficient synthesis of their precursor α-d-glucosylazide (αGA1). Glycosynthase enzymes, made by nucleophile mutations of retaining β-glucosidases, produce αGA1 in chemical rescue experiments. Thermoanaerobacterium xylanolyticus glucosyl hydrolase 116 β-glucosidase (TxGH116) E441G nucleophile mutant catalyzed synthesis of αGA1 from sodium azide and pNP-β-d-glucoside (pNPGlc) or cellobiose in aqueous medium at 45 °C. The pNPGlc and azide reaction product was purified by Sephadex LH-20 column chromatography to yield 280 mg of pure αGA1 (68% yield). αGA1 was successfully conjugated with alkynes attached to different functional groups, including aryl, ether, amine, amide, ester, alcohol, and flavone via copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry reactions. These reactions afforded the 1,4-substituted 1,2,3-triazole-α-d-glucoside derivatives AGT2-14 without protection and deprotection. Several of these glucosyl triazoles exhibited strong inhibition of human lysosomal α-glucosidase, with IC50 values for AGT4 and AGT14 more than 60-fold lower than that of the commercial α-glucosidase inhibitor acarbose.

In the present study, we derivatized several hydroxycinnamic and hydroxybenzoic acids to phenolic amides (PAMs) via one step BOP mediated amide coupling reactions. Fifteen PAMs were synthesized in >40% yields and were screened for their cytotoxic activities against four cancer cell lines: THP-1 (leukemia), HeLa (cervical), HepG2 (liver), and MCF-7 (breast), in comparison to 5-flurouracil (5-FU). Four amides showed IC50 ranging from 5 to 55 µM against all four cell lines. In contrast, tetradecyl-gallic-amide (13) affected only THP-1 leukemia cells with IC50 of 3.08 µM. The activities of these compounds support the promise of phenolic amides as anticancer agents.

Fatty acyl group utilized as both protection and migratory group for the synthesis of ceramides and glucosylceramides.