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

作者：Arai Hiroko; Hirasawa Yusuke; Rahman Abdul; Kusumawati Idha; Zaini Noor Cholies; Sato Seizo; Aoyama Chihiro; Takeo Jiro; Morita Hiroshi^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(6): 2152-2158.

DOI：10.1016/j.bmc.2010.01.077

• Indole alkaloids
• Alstonia macrophylla
• Alstiphyllanines E-H
• SGLT

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.

• 出版日期2010-3-15