## 3 Chemistry and Biological Activities of Selected Meroterpenoids
Forging complicated carbon-carbon bonds in complex natural products represents a challenge that requires groundbreaking synthetic endeavors or engaging in biomimetic synthesis, the process of imitating nature's way to make molecules. Biomimetic synthesis of the psiguadial merotterpenoids featuring the key cationic cyclization reaction using terpene (+)-bicyclogermacrene **70** as the platform has been reported [75] and it is depicted in Scheme 9. The synthesis commenced with the generation of ketone-aldehyde **72**, which was generated from (+)-2-caren (**71**) upon treatment with KMnO4 to mediate the dihydroxylation, and subsequent oxidative diol cleavage reaction. Compound **72** was further treated with Wittig reagent **A** under basic reaction conditions to provide compound **73**, which wasoprotected, and cyclized under samarium mediation to provide the 10-membered cyclic system **75**, which was then converted to (+)-bicyclogermacrene **70** with the required _E_-olefin geometry using a modified Corey-Winter protocol. Compound **70** was then converted to 2-ledene (**105**) via acid facilitated intramolecular cationic cyclization. The natural product **105** was transformed to (+)-viridiflorl (**106**) upon treatment with hydrocarbon/hydroxylation conditions. Alternatively, compound **105** was subjected to [PERSON]'s cobalt-catalyzed phenylsilane/O2 hydration conditions to provide natural product (-)-palustrol **107**. Finally, epoxidation of compound **70** was facilitated upon treatment with _m_CPBA, followed by intramolecular cyclization provided (+)-spathulenol (**108**). As highlighted in Scheme 10, biomimetic approaches allow for flexible synthesis of various members of the same natural product family [75]. Thus, compound **70** was treated with intermediate _o_-QM **77** to enable the hetero-Diels-Alder (HDA) reaction, in order to yield the natural product psiguadial D (**112**). The compound _o_-QM **77** was synthesized in situ as the Knoevenagel-type condensation reaction product between bisformylated phloroglucinol **76** and phenyl aldehyde. Furthermore, **112** was converted to psiguadial C (**111**) via epoxidation reaction. Under the similar reaction conditions, the _o_-QM **77** was unified with compound **4** via sequential cationic intermolecular coupling reaction followed by intramolecular cyclization cascade reactions. Briefly, intermediate **77** under acidic conditions generated the benzylic carbocation, which was able to react with compound **70** via addition reaction to yield intermediate **79**. Compound **79** underwent an intramolecular cyclization, and a 1,2-hydride shift to establish the most stable cation **81**. Finally, intramolecular cyclization from the phenolic system facilitated the installation of the last 7-member ring system of the natural product pisguadal A (**110**). The sesquiterpene-tropolones belong to a class of structurally distinctive meroter-penoids characterized as sesquiterpene mono- and bistropolones, which includes pycnidione and eupenifeldin, featuring a unique polycyclic ring system with rich stereochemistry. These compounds are isolated from _Neosetophoma_ sp. a species of fungi. These compounds were tested against a series of cancer cell lines: human breast cancer (MDA-MB-231), two human ovarian cancer cell lines (OVCAR-3 and OVCAR-8), human mesothelioma (MSTO-211H), and human lung cancer (A549) to determine their IC\({}_{50}\) values; the most potent compound, euperinfeldin (**133**, Scheme 11) had IC\({}_{50}\) values of 2.83, 0.33, 0.02, 0.08, 1.33 \(\upmu\)M for the above listed cell lines respectively [76]. To further evaluate the cytotoxicity of these compounds towards healthy tissues a mitochondrial toxicity assay was conducted for compounds **129**, **131** and **133** (Figure 5). The results of this experiment showed no cytotoxicity up until a maximum dose of 12.5 \(\upmu\)M, which was well above the majority of the IC\({}_{50}\) values for the compounds tested [76]. Further study of this natural product was conducted by [PERSON] et al.