动物共生真菌作为一种新型的微生物资源,因其高度的生物多样性及所产生的代谢物质的天然来源,具有广阔的应用前景。虫生真菌是指寄生或共生于昆虫及其他节肢动物体内或体表的一类真菌，其生存环境受宿主的生理状态、代谢过程及免疫机制等多方面因素影响。因此，该类真菌在适应特殊生态位的过程中，往往能够代谢出具有独特结构和显著生物活性的次级代谢产物。

为了发现新颖结构活性化合物，我们对从蜜蜂中分离得到的一株共生真菌链格孢菌（Alternaria alternata），活性筛选结果表明链格孢菌的提取物具有较强的抑制醛糖还原酶的活性。进一步以抑制醛糖还原酶活性为导向，并聚焦聚酮和杂萜类化合物，采用正、反相（ODS）硅胶柱色谱、凝胶柱色谱等各种色谱分离技术对活性组分中的化合物进行系统分离。共从Alternaria alternata 的活性组分中分离得到33个化合物（1^**–33）。通过分析核磁共振波谱和高分辨质谱确定化合物的平面结构。通过NMR核磁计算、DP4+分析、单晶X射线衍射实验、圆二色谱（CD）及计算ECD确定了化合物的立体构型。共鉴定出6个新化合物，分别为聚酮类化合物alternoxadeca（1^**）、rhizopycnolide D（2^*）、alternatain E（3^*）与杂萜类化合物tricycloalternarenes Z1–Z3（4^*–6^*）。其中，化合物1^**含有一种罕见的1-氧杂螺[4.5]癸烷-2,6-二酮骨架。化合物6^*是首次报道的在A/B/C三环稠环骨架上具有两个羰基的三环链烷烯（TCA）杂萜类化合物。

药理活性研究表明，化合物2^*、9、10、14、26、30、32、33对醛糖还原酶具有较好的抑制作用，抑制率分别为51.8%，52.0%，61.0%，72.2%，53.7%，57.0%，59.7%和53.3%（10 μM）。化合物24对醛糖还原酶具有显著的抑制作用，其IC₅₀值为6.1 μM。同时，对分离得到的单体化合物系统的开展其他活性研究，其中tricycloalternarenes Z1（4^*）对LPS诱导的NO产生有明显的抑制活性，其IC₅₀值为为0.93 μM。

Symbiotic fungi, as a new type of microbial resources, have broad application prospects because of their high biodiversity and the natural origin of the metabolites they produce. Entomogenous fungi refer to a type of fungi that parasitize or coexist within or on the surface of insects and other arthropods. Their survival environment is influenced by various factors of the host, including physiological state, metabolic processes, and immune mechanisms. Therefore, during the process of adapting to specific ecological niches, this type of fungi is often capable of capabling secondary metabolites with unique structures and significant biological activities.

In order to discover novel structurally active compounds, we studied a symbiotic fungal strain, Alternaria alternata, isolated from Apis mellifera. The results showed that the extract of Alternaria alternata exhibited a strong inhibitory effect on aldose reductase activity. Further, inhibiting aldose reductase activity oriented, and focusing on polyketides and meroterpenoids, a variety of chromatographic separation technologies including ODS column chromatography, gel column chromatography, silica gel column chromatography, and other methods were used comprehensively to systematically separate the compounds in the active fractions. A total of 33 compounds (1^**–33) were isolated from Alternaria alternata. The planar structures of the isolated compounds were identified by NMR spectroscopy and high-resolution electrospray ionization mass spectra. Their absolute configurations were elucidated via NMR calculations, DP4+ probability analyses, single crystal X-ray diffraction, computational and experimental electronic circular dichroism spectroscopy. Six novel compounds were identified, including alternoxadeca (1^**), rhizopycnolide D (2^*), alternatain E (3^*) and tricycloalternarenes Z1–Z3 (4^*–6^*). Specifically, alternoxadeca (1^**) contains a rare 1-Oxaspiro[4.5]decane-2,6-dione skeleton. Tricycloalternarene Z3 (6^*) was tricyclic alkene (TCA) heteriterpenoid compound with two carbonyl groups on the A/B/C tricyclic thick ring skeleton.

The pharmacological activity studies indicate that compounds 2^*, 9, 10, 14, 26, 30, 32, and 33 exhibited good inhibitory effects on aldose reductase, with inhibition rates of 51.8%, 52.0%, 61.0%, 72.2%, 53.7%, 57.0%, 59.7%, and 53.3% (10 μM), respectively. Compound 24 exhibits significant inhibitory activity against aldose reductase with IC₅₀ of 6.1 μM. Meanwhile, systematic studies on other activities of the isolated monomer compounds were carried out, tricycloalternarenes Z1 (4^*) exhibit significant inhibitory activity against the LPS-inducted production of NO with IC₅₀ of 0.93 μM.