## 3 Chemistry and Biological Activities of Selected Meroterpenoids
At this point in the synthesis compound **53** was treated with lithium tetramethylpiperidineidle (LTMP), and TsCl to introduce the \(\alpha\)-vinylgous chlorine to generate compound **54**, followed by acylation to introduce the congested quaternary center leading to compound **55**. Various types of alkylation reactions are feasible for such compound, but alkylation with borane prenyl system mediated by [Pd(allyl)Cl2], and catalytic CPhos ligand under basic conditions introduce the prenyl group and remove the silyl protecting group to provide garsubellin A (**104**), as well as compound **56**, which could be treated with acid or base to yield garsubellin A (**104**). The polycyclic fused ring meroterpenes such as berkeleyone A have displayed anti-inflammatory activity [74], while preandiloid A has shown antimicrobial properties. As-perterpene A was identified as a potent BACE-1 inhibitor with an IC\({}_{50}\) value of 78 nM against this enzyme, out preforming commercial BACE-1 inhibitors. Furthermore, in vivo animal model studies were congruent with the in vitro efficacy studies of this natural product [74]. These findings indicate that these compounds require further studies and synthetic strategies to access them in large quantities. A successful approach to these natural products involves the use of a cyclization reaction to set up the tricyclic system in a single step as shown in Scheme 7 [73]. The synthesis began with farnesyl bromide being subjected to alkylation with the anion of propionitrile, followed by one-pot bromohydrin formation/cyclization reaction sequence to generate epoxide **57**, which upon reductive epoxide-opening radical cyclization furnished tricyclic ketone **58**. Then, ketone intermediate **58** was subjected to annulation reaction with \(\beta\)-lactone diketene to produce diketone **59**, which was O-methylated, followed by oxidative ring expansion mediated by PhI(OAc)\({}_{2}\) under basic conditions to furnish bicyclo[3.3.1]nonane ring system **60**. The newly formed tetracyclic **60** was exposed to [PERSON] olefination and subsequent chlorination reaction to yield halogenated polycyclic compound **61**. Upon further three-step \(\alpha\)-alkylative methyl ester functionalization, methylation via Suzuki coupling reaction of the vinyl chloride with MeB(OH)\({}_{2}\), and acid mediated depprotection yielded advanced intermediate **62**. Then, compound **62** was subjected to the final chloride-mediated demethylation, leading to the DMOA-derived metabolite, protoausti-noid A (**175**). Compound **175** was further oxidized with _m_CPBA to provide berkeley-one A (**174**). In addition, advanced polycyclic compound **62** was treated with pyridinium chlorochrome (PCC) to generate compound **63**, which was subjected to [PERSON]'s cobalt(II)-catalyzed hydroalkoxylation reaction leading to polycyclic intermediate **68**. Finally, this compound was treated with LiCl to free the trapped enolate system, yielding the natural product andrastic D (**158**) in racemic form. Furthermore, as shown in Scheme 8, the tetracyclic compound **63** was subjected to [PERSON]'s alkene hydroxlofination conditions to provide the polycyclic compound **69** via hydrogen-atom-transfer (HAT) process involving radical intermediate **66**. Subsequent demethylation of polycyclic compound **69** mediated by LiCl yielded the natural product preterenoid (**159**), which underwent stereoselective \(\alpha\)-oxidation mediated by magnesium monoperoxyphthalate (MMPP) to afford terpenoid (**160**). Upon ring-expansion via retro-Claisen/esterification cascade reaction under basic conditions, compound **160** was converted to racemic terretonin L (**161**). This synthetic strategy is efficient at enabling the generation of multiple members of this metorterpene family in good overall chemical yields [73]. This approach is not asymmetric, however, there are multiple opportunities to introduce asymmetry.