Elsevier

Tetrahedron

Volume 68, Issue 5, 4 February 2012, Pages 1502-1506
Tetrahedron

Alsmaphorazines C–E, indole alkaloids from Alstonia pneumatophora

https://doi.org/10.1016/j.tet.2011.12.014Get rights and content

Abstract

Three novel indole alkaloids, alsmaphorazines C (1)–E (3), were isolated from the leaves of Alstonia pneumatophora (Apocynaceae) and their structures were determined on the basis of the 2D NMR and MS spectral analyses. The absolute configurations of 1 and 3 were elucidated by applying a modified Mosher’s method and CD spectral analysis. These alkaloids possessed novel ring skeletons containing an octahydropyrrolo[2,3-b]pyrrole unit.

Introduction

Alstonia plants (Apocynaceae) growing widely in the tropical regions of Africa and Asia, have traditionally been used as a remedy for defervescence, antitussive, and arrest of hemorrhage.1 They are also well-known as a rich source of unique heterocyclic alkaloids having a monoterpene indole skeleton. Some of these indole alkaloids, especially bisindole alkaloids villalstonine and macrocarpamine isolated from Alstonia macrophylla, have attracted great attention because they show biological activity, such as anticancer and antimalarial properties.2 In our previous paper,3 we have reported the isolation of two new indole alkaloids, alsmaphorazines A and B consisting of an 1,2-oxazinane and an isoxazolidine chromophore, and new anti-melanogenic indole alkaloids, alpneumines from the leaves of Alstonia pneumatophora Backer ex L.G. Den Berger collected in Malaysia. Further investigation on extracts of the leaves of A. pneumatophora resulted in the isolation of three alkaloids having novel skeletons, alsmaphorazines C (1)–E (3). This paper describes the isolation and structural elucidation of 13 mostly on the basis of their NMR and CD data.

Section snippets

Results and discussion

Alsmaphorazine C (1), {[α]D20 +38 (c 0.1, MeOH)} showed a pseudomolecular ion peak at m/z 415 (M+H)+ in the ESIMS, and the molecular formula was established to be C22H26N2O6 by the HRESIMS [m/z 415.1863, (M+H)+, Δ −0.1 mmu]. Its 13C NMR data (Table 1) revealed the presence of 22 carbons consisting of three sp2 quaternary, three sp2 methine, one ketone, one ester carbonyl, two sp3 quaternary, four sp3 methine, four sp3 methylene, one methyl, two methoxy, and one aldehyde carbon. Of them, two

General experimental methods

1H and 2D NMR spectra were recorded on a 600 MHz spectrometer, and chemical shifts were referenced to the residual solvent peaks (δH 3.31 and δC 49.0 for methanol-d4). Standard pulse sequences were employed for the 2D NMR experiments. 1H−1H COSY, and NOESY spectra were measured with spectral widths of both dimensions of 7200 Hz, and 32 scans with two dummy scans were accumulated into 2 K data points for each of 256 t1 increments. NOESY spectra in the phase-sensitive mode were measured with a

Acknowledgements

This work was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and a grant from the Open Research Center Project. We also acknowledge Takeda Science Foundation.

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