## 3 Chemistry and Biological Activities of Selected Meroterpenoids
In parallel, other similar synthetic strategies to this family of meroterpenoids with alkaloid features have been reported [94]. The total synthesis of (+)-kopsihainanine A (**187**) is shown in Scheme 29 and begins with \(\beta\)-amidoester **337**, which was generated via sequential double \(\alpha\)-C-alkylation of dihydropyrido[1,2-a]indolone **330**, using allyl cyanoordinate in the presence of LiHMDS. This was followed by treatment with methyl acrylate **331** under basic conditions. Further decarboxylulative asymmetric allylation of compound **337** in the presence of Pd\({}_{2}\)(pmdba)\({}_{3}\) with a chiral ligand provided an intermediate with the \(\alpha\)-quaternary all-carbon stereocenter, which underwent Rh-catalyzed hydrocarbon to yield alcohol **338**. Compound **338** was mesylated and displaced by the azide group to generate compound **339**, followed by Staudinger reduction mediated by polymer-bond PPh\({}_{3}\) with concomitant translactamization, which provided \(\delta\)-lactam **340**. Subsequent Bischler-Napieralski cyclization of \(\delta\)-lactam **340** furnished _trans_-fused tetracycle **341**. This was subjected to intramolecular lactamization between the piperidine nitrogen, and the pendant methyl ester group mediated by bicyclic guanidine base triazabicyclodecene (TBD) and generated pentacycle **342**. Upon \(\alpha\)-hydroxylation mediated by lithium dimethylamide (LDMA) in the presence of HMPA, using bis(trimethylsilyl) peroxide as the oxidant successfully afforded the natural product (+)-kopsihainanine A (**187**). The overall synthetic maneuvers maximize the chemical yields, and a distinctive feature of this concise synthetic endeavors is the use of palladium-catalyzed reactions to form all the carbon-carbon bonds in the transformation of simple precursors to highly elaborate natural products with promising biological properties. The total synthesis of cytosolic, an oxidized derivative of strictosidine with an unprecedented hexacyclic skeleton which includes a double bridge linking the indole and the monoterpene moieties was isolated from the leaves of _Chimarrhis cynose_ and provides a fertile ground for organic chemists as shown in Scheme 30. The total synthesis of cytosolic (**188**) via biomimetic oxidative cyclization was reported [95]. The synthesis commenced with Knoevenagel condensation reaction between aldehyde **345** and 3-formyl-1,1,1-trichloroacetone **346** which generated enone intermediate, which upon inverse-demand hetero-Diels-Alder (HDA) reaction with enol ether **347** furnished cyclic intermediate **348** together with other diastereoisomers. Upon methanolysis and sulfoxide elimination, intermediate **348** was further converted to olefin intermediate, followed by deprotection furnished Tietze secologanin aglycon **349**. Subsequent Pictet-Spengler reaction between the secologanin aglycon **349** and tryptamine **356**, followed by protection of the secondary amine furnished the mixture of the protected strictosidine aglycon ethyl ether **350a** and its epimer **350b**. The biomimetic cascade reaction sequence of oxidation with oxaziridine **351** and acid catalyzed cyclization reaction of strictosidine aglycon ethyl ether **350a** furnished the complete framework **352** of cytosolic via intermediate **352a**, **352b**, and **352c**, which was deprotected to generate ethyl ether aglycon **353** of cytosolic. Hydrolysis of acetal **352** provided hemiacetal **354**, which upon Schmit glycosylation with glycosyl trichloroacetimide, generated glycosylated product **355a** with its diastereoisomer, together with glycosylated product **355b**. Global deprotection of intermediate **355a** furnished the natural product cytosolic **188**, global deprotection of compound **355b** provided product **188a** as the diastereoisomer of cytosolic **188**. **Scheme 29. Total synthesis of (+)-kopishaiananine A. **  
**Scheme 30. Total synthesis of cytosolic via biomimetic oxidative cyclization strategy. **