Scholarisines HeO, novel indole alkaloid derivatives from long-term stored Alstonia scholaris Xing-Wei Yang a, b , Xiao-Dong Luo a, * , Paul K. Lunga a , Yun-Li Zhao a , Xu-Jie Qin a, b , Ying-Ying Chen a, b , Lu Liu a, b , Xiao-Nian Li a , Ya-Ping Liu a, * a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China b University of Chinese Academy of Sciences, Beijing 100049, PR China article info Article history: Received 8 July 2014 Received in revised form 16 September 2014 Accepted 17 September 2014 Available online xxx Keywords: Indole alkaloid Alstonia scholaris Scholarisines HeO abstract Eight new monoterpenoid indole and quinoline alkaloids, scholarisines HeO(1e8), together with six known analogues, were isolated from seven-year stored leaves of Alstonia scholaris. Their structures were elucidated on the basis of comprehensive spectroscopic data and X-ray diffraction. The obtained com- pounds were presumably derived from the known precursors by mild oxidation during the post-harvest storage. Ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Alstonia plants (Apocynaceae) are known to be rich sources of monoterpenoid indole alkaloids (MIAs) with diverse structures and significant bioactivities, some of which have attracted attention as new drug leads as well as challenging targets for total synthesis. 1 Alstonia scholaris is extensively used as traditional medicine for the treatment of various diseases in different countries of Asia. Different organs of this plant can be used as medicine of both codified and non-codified drug system of India for the treatment of malaria, jaundice, gastrointestinal troubles, cancer, etc. Its medici- nal importance has been recorded in the ancient Ayurvedic text ‘Bhavaprakasha’ in India. 2 The leaves of A. scholaris have been his- torically used in ‘dai’ ethnopharmacy to treat chronic respiratory diseases in Yunnan province, China. 3 Our previous chemical study on A. scholaris led to the isolation of a series of MIAs from different parts of this plant, 4 of which (E/Z)-alstoscholarine, scholarisine A, and picrinine have been synthesized elaborately by other out- standing chemists after we reported the structures. 5 Moreover, a defined mixture of alkaloids from A. scholaris leaf, 6 registered as investigational new botanical drug (No. 2011L01436) has been ap- proved for clinical trials (phase I and II) by China Food and Drug Administration (CFDA). Interestingly, during our quality control of this medicinal plant, more compounds appeared in the HPLC fingerprint profile of the seven-year stored leaves of A. scholaris. Furthermore, the extracted total alkaloids exhibited antimicrobial activities, which motivated us to trace the antimicrobial MIAs from it. As a result, eight new indole and quinoline alkaloids, scholarisines HeO(1e8, Fig. 1), to- gether with six known analogues: nareline (9); 7 19E-vallesamine; 8 picrinine; 9 strictamine; 10 5a-methoxylstrictamine; 11 and 16- formyl-5a-methoxylstrictamine, 12 were isolated. Their structures were elucidated on the basis of comprehensive spectroscopic data and X-ray diffraction, and compounds 1e3 possessed rare cage carbon skeletons. The new MIAs might be derived from the known precursors by N-methylation and/or mild oxidation during the storage, and they showed weak antibacterial activities against five bacterial strains. 2. Results and discussions Scholarisine H (1) was obtained as colorless gum. Its molecular formula C 21 H 22 N 2 O 3 was established by 13 C NMR and HR-EIMS data (m/z 350.1636, [M] þ ) indicating 12 indices of hydrogen deficiency. The UV spectrum showed the characteristic maximal absorptions of indolenine alkaloids at 212 and 258 nm, 4b while the FTIR spectrum exhibited absorption bands due to lactone group (1738 cm 1 ) and aromatic ring (1631, 1439 cm 1 ). The 1 H and 13 C NMR data of 1 indicated an ortho-disubstituted phenyl ring (Tables 1 and 2). * Corresponding authors. Tel.: þ86 871 65223177; e-mail addresses: xdluo@mail. kib.ac.cn (X.-D. Luo), liuyaping@mail.kib.ac.cn (Y.-P. Liu). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet http://dx.doi.org/10.1016/j.tet.2014.09.052 0040-4020/Ó 2014 Elsevier Ltd. All rights reserved. Tetrahedron xxx (2014) 1e5 Please cite this article inpress as: Yang, X.-W.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.09.052