Amiaspochalasins A–H, Undescribed Aspochalasins with a C‑21 Ester Carbonyl from Aspergillus micronesiensis

Amiaspochalasins
A–H (1–8), eight undescribed
aspochalasins, and trichalasin D (9), a known analogue,
were isolated from the solid culture of Aspergillus
micronesiensis. Compounds 1–9 are aspochalasins with a C-21 ester carbonyl,
and their structures were determined by spectroscopic data, X-ray
crystallographic analyses, electronic circular dichroism calculations,
and chemical methods. The CH3-25 in compound 1 is located at C-16 rather than C-14 in the previously reported aspochalasins,
endowing 1 with an unexpected carbon skeleton. Compounds 2 and 3 are the first examples of aspochalasins
with an unprecedented 5/6/6/8 tetracyclic ring system. Compounds 4 and 5 are diastereomers of aspochalasins I
and J, respectively. Compounds 6 and 7 are
the first aspochalasins featuring a long open-chain system, and their
absolute configurations were discussed by comparing the NMR data of
the hydrolysis and methyl esterification products of 4 and 5. Compound 8 is an isomeride of 9. The cytotoxic and antimicrobial effects of 1–9 were tested.

从密克罗尼西亚曲霉（Aspergillus micronesiensis）的固体发酵培养物中，分离得到8个未报道的阿波菌素类（aspochalasins）新化合物——Amiaspochalasins A–H（编号1–8），以及1个已知类似物毛壳菌素D（trichalasin D，编号9）。编号1至9的化合物均为带有C-21酯羰基的阿波菌素类化合物，其结构通过波谱数据、X射线单晶衍射分析、电子圆二色性（electronic circular dichroism）计算及化学方法得以确定。化合物1中的CH3-25位点位于C-16，而非此前已报道的阿波菌素类化合物中的C-14，这赋予化合物1一种前所未有的碳骨架。化合物2与3是首批拥有5/6/6/8四环环系的阿波菌素类化合物。化合物4与5分别为阿波菌素I与阿波菌素J的非对映异构体。化合物6与7是首批具备长链开环体系的阿波菌素类化合物，其绝对构型通过对比化合物4与5的水解产物及甲酯化产物的核磁共振（Nuclear Magnetic Resonance，NMR）数据得以阐明。化合物8为化合物9的同分异构体。本研究对编号1至9的化合物进行了细胞毒性与抗菌活性测试。