*3.3. Anti-HIV Activity*

From *Paraconiothyrium brasiliense*, new tricyclic sesquiterpenoids, brasilamides A–D (**45**–**48**) and the formerly reported pinthunamide (**44**), were separated from the culture's EtOAc extract utilizing SiO2/Sephadex LH-20 CC and HPLC. Their structures were established using NMR and X-ray analyses (Figure 5). Compounds **45** and **46** are rare metabolites having a 4-oxatricyclo[3.3.1.02,7]nonane moiety with a tetrahydro-2*H*-pyrone or a tetrahydro-2*H*-pyran linked with bicyclo[3.1.1]heptane ring at C-5 and C-2, whereas compounds **47** and **48** are analogs of **44**, possessing an unprecedented 9-oxatricyclo[4.3.0.04,7] nonane core.

The differences of the above-mentioned compounds from **44** were the existence of a tetrahydrofuran moiety connected to the bicycle[3.1.1]heptane unit instead of γ-lactone ring, as well as different C-10 substituents. Compounds **45**–**48** demonstrated inhibitory effectiveness (EC50s of 108.8, 57.4, and 48.3 μM, respectively) versus HIV-1 replication in C8166 cells compared with indinavir sulfate (EC50 of 8.2 nM) [43]. Biogenetically, they were derived from the mevalonate/*trans*-*cis*-farnesol/bisabolene/bergamotane pathway (Scheme 2).

**Figure 5.** Structures of tricyclic bergamotane sesquiterpenoids (**44**–**55**)**.**
