Diastereoselective Synthesis, Glycosidase Inhibition, and Docking Study of C-7-Fluorinated Casuarine and Australine Derivatives

Abstract

C-7-fluorinated derivatives of two important polyhydroxylated pyrrolizidines, casuarine and australine, were synthesized with organocatalytic stereoselective α-fluorination of aldehydes as the key step. The strategy is extensively applicable to some synthetically challenging fluorinated iminosugars and carbohydrates. The docking studies indicated that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are due to the interaction modes dominated by fluorine atoms in these iminosugars with the amino acids' residues of the corresponding enzymes. Steady interactions were established between the C-7 fluoride and a hydrophobic pocket in amyloglucosidase by untypical anion−π interactions. These unexpected docking modes and related structure−activity relationship studies emphasize the value of fluorination in the design of polyhydroxylated pyrrolizidine glycosidase inhibitors.

Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

“…14 With these properties, many studies have been conducted on the effects of pyrrole and its derivatives on many enzyme activities and they attract the attention of more and more researchers day by day. [15][16][17] For this reason, N-methylpyrrole (1a), 2-acetylpyrrole (1b), 3-acetylpyrrole (1c), 2,4-dimethylpyrrole (1d), 2,5-dimethylpyrrole (1e), 3-acetyl-2,4-dimethylpyrrole (1f), 2-acetyl-1-methylpyrrole (1g), 3-acetyl-1-methylpyrrole (1h) pyrrole the biological activities of G6PD and 6PGD enzymes of derivatives were investigated in vitro (Figure 1). 2 | MATERIALS AND METHODS…”

“…In addition, many anticancer drugs with pyrrole structure have the potential to treat breast cancer, pancreatic cancer, lung cancer, and many other types of cancer 14 . With these properties, many studies have been conducted on the effects of pyrrole and its derivatives on many enzyme activities and they attract the attention of more and more researchers day by day 15–17 …”