6 Alstonia pneumatophoraおよびA. angustiloba由来の新規多環性インドールアルカロイドの構造研究(口頭発表の部)

抄録

Alstonia pneumatophora and A. angustiloba are members of the Apocynaceae family growing in Malaysia and Indonesia. Traditionally, their leaves have been used for the treatment of periodic fever and malaria. Alstonia species so far have been shown to produce various skeletal alkaloids, including scholaricine-type alkaloids such as echitamidine, uleine-type alkaloids such as undulifoline, and bisindole alkaloids such as villalstonine. In the search for structurally and biogenetically interesting alkaloids from tropical plants found in Malaysia, the alkaloid components of the leaves of A. pneumatophora and A. angustiloba were investigated. As a result, alsmaphorazines A and B, novel indole alkaloids with an unprecedented polycyclic skeleton possessing an oxyamine moiety, alsmaphorazines C - E, novel indole alkaloids with an unprecedented pentacyclic skeleton fused octahydropyrrolo[2,3-b]pyrrole and azabicyclo[3.3.1]nonane moiety, and alpneumines A-H were isolated from A. pneumatophore, and alstilobanines A - E were isolated from A. angustiloba. The structures of alsmaphorazines A - E were determined by 1D & 2D-NMR data (^1H-^1H COSY, HSQC, HMBC, NOESY) and the absolute configuration of alsmaphorazines B and C was assigned by CD spectral analysis and the modified Mosher's method. Biogenetically, alsmaphorazines A - E may be derived from preakuammicine and plausible biogenetic route of alsmaphorazines A - E from preakuammicine is proposed. Indole alkaloids isolated in this research were evaluated for inhibition of the NO production, vasorelaxant effect, and anti-melanogenesis activity. Alsmaphorazine A was found to dose-dependently inhibit the NO production in LPS-stimulated J774.1 cell line without affecting the cell viability, alstilobanine A showed a moderate vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta and alpneumine G showed anti-melanogenesis activity in B16 mouse melanoma cells.