Yunnanensine type indole and secostemmadenine-yunnanensine type bisindole alkaloids from the bark of Alstonia scholaris

Abstract

Two previously undescribed monoterpenoid indole alkaloids, N-formylyunnanensine (1) and scholaphylline (2), along with eight known alkaloids, namely, 19,20-E-vallesamine (3), 19,20-Z-vallesamine (4), 19,20-E-vallesamine N-oxide (5), 6,7-seco-19,20α-epoxyangustilobine B (6), 16R-19,20-E-isositsirikine (7), N-demethylalstogustine N-oxide (8), E-vallesiachotamine (9), and Z-vallesiachotamine (10), were isolated from the bark of Alstonia scholaris. Alkaloid 1 was determined to be the N-formyl derivative of the known alkaloid, yunnanensine, comprising a pair of inseparable E/Z-formamide rotamers, while scholaphylline (2) was identified as the first member of the secostemmadenine-yunnanensine type bisindole alkaloid. The structures of these alkaloids and their absolute configurations were established based on detailed analysis of the spectroscopic data in conjunction with the TDDFT-ECD method. A possible biogenetic pathway to 1 and 2, involving stemmadenine as the primary precursor, was proposed. Scholaphylline (2) showed modest cytotoxicity against Panc1 (IC₅₀ 27.7 ± 5.1 µM), MDA-MB-231 (IC₅₀ 32.0 ± 2.2 µM), and MDA-MB-468 (IC₅₀ 34.1 ± 3.3 µM) cancer cell lines, while N-formylyunnanensine (1) did not show appreciable cytotoxicity against any of the tested cell lines.