Alstiphyllanines E–H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

Three new picraline-type alkaloids, alstiphyllanines E–G ( 1– 3) and a new ajmaline-type alkaloid, alstiphyllanine H ( 4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids ( 5– 20). Structures and stereochemistry of 1– 4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F ( 1 and 2) showed moderate Na +-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A series of a hydroxy substituted derivatives 21– 28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity. 10-Methoxy- N(1)-methylburnamine-17- O-veratrate ( 6) exhibited potent inhibitory activity, suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity. Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.