## 3 Chemistry and Biological Activities of Selected Meroterpenoids
Compound **245** was then deprotected, followed by biomimetic cationic cyclization of epoxide mediated by Lewis acid, Iron (III) to generate the advanced meroterpenoid derivative **247** in good enantioselective excess. **Scheme 18. Total synthesis of (+)-Hongoqercin A. **As shown in Scheme 19, compound **247** was deprotected to yield the corresponding acid, followed by selective acetylation of the secondary hydroxyl group to provide natural product **153**. Furthermore, halocyclization of farnesyl rescorylate **233** or geranyl-substituted analogue **239** (Scheme 18) in the presence of halogenating reagents **256** (Bromodiethylsulfonium bromopentachloroantimonate V) or **257** (iodonium reagent), provided halogenated meroterpenoid **254**/**255**, or **252**/**253** respectively in good yields [85]. These important intermediates will allow the generation of several derivatives that can further provide insight into the biological mode of action of these natural products. An interesting meroterpenoid derivative of hongoquercin was generated geranyl-substituted rescorylate **239**. This was protected with a silyl group followed by regioselective asymmetric epoxidation with Shi chiral ketone to generate epoxide **249**. The resultant system was deprotected under basic conditions to yield epoxide **250**, which underwent cationic polyene cyclization reaction mediated by boron trifluoride etherate to provide the advanced meroterpenoid derivative **251**. This compound should serve as a chemical tool to interrogate the biological properties of these natural products. A modular synthetic approach to the tetracyclic meroterpenoids was recently reported [86] and it is as illustrated in Scheme 20. The synthesis featuring sterically demanding sp\({}^{2}\)-sp\({}^{3}\) cross-coupling and acid mediated cyclization/isomerization for installation of the required _cis_ or _trans_-decalin stereochemistry of the tetracyclic meroterpenoid scaffold is highlighted. The total synthesis commenced with a solvent-free Alder-Rickert reaction between the dimedone-derived bis-trimethylsilyl enol ether **258** and dimethyl 2-butynedioate (DMAD) provided rescorinol, followed by mono-methylation yielded phenol, which upon thermal treatment in the presence of 3,4-dimethoxybenzylamine (DMBNH\({}_{2}\)) yielded imide **259**. Regioselective halogenation of imide **259** generated intermediate **259a**, which upon regioselective imide reduction provided key isoinodinone **260**. Next diene **263** was generated from \(\beta\)-hydroxyketone **261** via three step protocol, involving the formation of benzyl-protected ketone, subsequent vinyltriflate formation, followed by Stille coupling with vinyl(\(n\)Bu\({}_{3}\))Sn mediated by Pd(PPh\({}_{3}\))\({}_{4}\). Then, a Lewis acid catalyzed Diels-Alder [4+2] cycloaddition reaction between diene **263** and dienophile **264** provided intermediate **265** as the major product due to the shown transition state. Compound **265**, following a two-step sequential reduction reaction, generated alcohol via thioester intermediate **266**, and it was converted to iodide **267** via two linear steps (mesylation of the alcohol followed by \(\text{S}_{\text{N}}2\) reaction). Then, the key step was conducted, namely sp\({}^{2}\)-sp\({}^{3}\) Negishi coupling of isoindolinone **260** with iodide **267** to provided 5,6-dehydrodecalin intermediate **268**. Next compound **268** underwent deprotection, intramolecular cation trapping of the phenol group, followed by hydrogenation to yield the cyclized product **272**. This established the required merotterpenoid scaffold. Lastly, global deprotection of intermediate **272** provided the natural product (+)-stachyflin (**162**). Next as shown in Scheme 21, thioester **273** was reduced to the corresponding aldehyde **274** via Pd(II) in the presence of triethylsilane hydride in good yields. Then, aldehyde was coupled with the anion of arena **275** or **277**, followed by 2-step Barton-McCombie deoxygenation to produce intermediate **276** or **278** respectively.