Solid-phase peptide synthesis (SPPS) enables routine synthesis of virtually any type of peptide sequence and is the preferred method for peptide synthesis in academia and the pharmaceutical industry alike. Still,...

The first enantioselective total synthesis of the complex tricarbocyclic sesquiterpenoid periconianone A based on a postulated biogenesis is reported. Key elements of the synthetic route include the use of an isopropenyl group as a removable directing group for stereoselective synthesis, a sequence featuring a Rh-mediated O-H insertion/[3,3]-sigmatropic rearrangement and subsequent α-ketol rearrangement, and a late stage aldol reaction to furnish the complex cage-like framework.

The exploration of different routes leading to the stereoselective synthesis of the neuritogenic steroid withanolide A is reported in full detail. Notable features of the synthesis include a Corey-Seebach homologation, a vinylogous aldol reaction, a singlet oxygen Schenck-ene reaction, and finally, a latestage Wharton transposition. Semi-synthetic elaboration of the natural product resulted in 15 derivatives allowing a better understanding of its inherent reactivity pattern as well as its biological properties related to neuronal differentiation and neurite outgrowth.

Synthetic studies toward highly oxygenated seco-prezizaane sesquiterpenes are reported, which culminated in a formal total synthesis of the neurotrophic agent (−)-jiadifenolide. For the construction of the tricyclic core structure, an unusual intramolecular and diastereoselective Nozaki-Hiyama-Kishi reaction involving a ketone as electrophilic coupling partner was developed. In addition, synthetic approaches toward the related natural product (2R)-hydroxy-norneomajucin, featuring a Mn-mediated radical cyclization for the tricycle assembly and a regioselective OH-directed C-H activation are presented. TOC Graphic AbstractSynthetic studies towards highly oxygenated seco-prezizaane sesquiterpenes are reported, which culminated in a formal total synthesis of the neurotrophic agent (-)-jiadifenolide.For the construction of the tricyclic core structure, an unusual intramolecular and diastereoselective Nozaki-Hiyama-Kishi reaction involving a ketone as electrophilic coupling partner was developed. In addition, synthetic approaches towards the related natural product (2R)-hydroxynorneomajucin, featuring a Mn-mediated radical cyclization for the tricycle assembly and a regioselective OH-directed C-H activation are presented.