*Article* **Cytosporin Derivatives from Arctic-Derived Fungus** *Eutypella* **sp. D-1 via the OSMAC Approach**

**Hao-Bing Yu 1,†, Zhe Ning 1,†, Bo Hu 1, Yu-Ping Zhu 2, Xiao-Ling Lu 3, Ying He 1, Bing-Hua Jiao <sup>3</sup> and Xiao-Yu Liu 1,\***


**Abstract:** A chemical investigation of the Arctic-derived fungus *Eutypella* sp. D-1 based on the OS-MAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds **1**–**3** and **11**–**12**) from rice medium and eight cytosporins (compounds **2** and **4**–**11**) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (**1**), cytosporin Y (**2**), cytosporin Z (**3**), cytosporin Y1 (**4**), cytosporin Y2 (**5**), cytosporin Y3 (**6**), and cytosporin E1 (**7**), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (**4**) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound **1** contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (**12**) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds **6** and **7** was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from *Eutypella* sp. D-1 were evaluated. Unfortunately, only compounds **3**, **6**, **8**, and **10**–**11** displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 μg/mL.

**Keywords:** cytosporin; arctic fungus; *Eutypella* sp.; immunosuppressive activity
