3.1.3. Azaphilones

Azaphilones or azaphilonoids are a structurally variable family of fungal polyketide metabolites harboring a highly oxygenated pyranoquinone bicyclic core [47]. In recent years, about 31 azaphilones with unusual structures and remarkable bioactivities were reported from mangrove-associated fungi, including genera *Aspergillus*, *Diaporthe*, *Penicillium*, and *Talaromyces*.

Two new citrinin derivatives, penicitol A (**37**) and penicitol B (**38**) (Figure 12) were identified from *Penicillium chrysogenum* ML226 obtained from the rhizosphere soil of the mangrove plant *Acanthus ilicifolius* [48]. The citrinin derivatives are a family of azaphilones, with the first one, namely citrinin, isolated from a *P. citrinum* strain in 1931 [49]. Penicitol A (**37**) is the first reported citrinin derivative with an unusual tetracyclic skeleton, and **38** is the first citrinin dimer with a single oxygen bridging center. **37** and **38** exhibited potent cytotoxic activities against HeLa, BEL-7402, HEK-293, HCT-116, and A-549 cell lines with IC50 values of 4.6–10.5 and 3.4–9.6 *μ*M, respectively. In 2011, Hosokawa et al. reported the first total synthesis of penicitol A (**37**), achieved by acetalization [50].

**Figure 12.** Structures of compounds **37** and **38**.
