*3.6. Pancreatic Lipase Inhibition*

Purpurolides B (**83**) and C (**84**) are new 6/4/5/5-tetracyclic sesquiterpenoids that were separated from *Penicillium purpurogenum* IMM003 cultures by SiO2/RP-18/preparative HPLC analysis. The structures and configurations of compounds **83** and **84** were established using spectral and X-ray analyses as well as ECD and GIAO NMR data calculations (Figure 9).

**Figure 9.** Structures of tetracyclic bergamotane sesquiterpenoids (**80**–**93**).

Compounds **83** and **84** demonstrated potent pancreatic lipase inhibition (IC50s of 5.45 and 6.63 μM, respectively), compared with kaempferol (IC50 of 1.50 μM) [47]. These compounds were possibly biosynthesized via numerous the cyclization and enzyme-catalyzed oxidation of FPP (farnesyl pyrophosphate), leading to four- and six-membered rings and the formation of two five-membered heterocyclic rings (Scheme 3) [47].

**Scheme 2.** Biosynthetic pathways of brasilamides A–D (**45**–**48**) [43].

Xia et al. separated from *Penicillium purpurogenum* IMM003 purpurolides D–F (**85**–**87**), which are new polyoxygenated 6/4/5/5-tetracyclic bergamotanes, using SiO2/Sephadex-LH-20/RP-18 CC and preparative HPLC processing [48]. Their elucidation was accomplished using spectral 13C NMR calculations coupled with DP4+ probability and ECD analyses. Compound **87** had potent pancreatic lipase inhibition potential (IC50 of 1.22 μM) compared with kaempferol (IC50 of 1.50 μM) and orlistat (IC50 of 0.75 μM), whereas compounds **85** and **86** (IC50s of 6.50 and 7.88 μM, respectively) were five or six-fold less powerful than **87**, revealing that the C-14 hydroxylated decanoic acid moiety increased the potency [48]. Therefore, polyoxygenated bergamotanes could be viable candidates as pancreatic lipase inhibitors for further clinical development [48].
