The Furan Shuffling Hypothesis: A Biogenetic Proposal for Eremophilane Sesquiterpenoids.

Based on the structural similarities of the recently isolated eremophilane-type sesquiterpenoids microsphaeropsisin B and C and the iso-eremophilane periconianone C, a revised biogenetic hypothesis for C8-C11-connected iso-eremophilanes is presented and corroborated by strong experimental evidence. The first enantioselective total syntheses of microsphaeropsisin B and C were achieved starting from a known intermediate, whose synthesis was elaborated previously in the total synthesis of periconianone A, and in a total of 15 steps starting from γ-hydroxy carvone. Mild reaction conditions for the subsequent α-ketol rearrangement not only resulted in the herein proposed conversion of microsphaeropsisin B into periconianone C, but also in the conversion of microsphaeropsisin C into 4-epi-periconianone C.

Metal-Free Regioselective Chloroazidation of Internal Alkynes.

A metal-free, room temperature protocol for the regioselective chloroazidation of internal alkynes is disclosed. The reactions of internal alkynes with trimethylsilyl azide (TMSN3 ) in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) afforded the corresponding chloroazidoalkenes in good yields. This reaction has good functional group tolerance and is operationally simple.

Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis.

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.

Mapping Out Biogenetic Hypotheses by Chemical Synthesis.

Synthesis of natural products via their postulated or established biosynthetic intermediates ('biomimetic synthesis' or 'bio-inspired synthesis') has the power to identify both yet undiscovered intermediates and undiscovered mechanistic pathways for their formation. In this account, we report on our recent studies on unusual hypotheses for biosynthetic transformations, such as a late-stage aldol reaction (periconianone A), benzilic acid rearrangement (taiwaniaquinone H), a redox-neutral light-driven C-H activation (taiwaniaquinol A and cyclocoulterone), a hetero Diels-Alder reaction (obtusinones), aziridinium chemistry (Securinega alkaloids), and a [3+2] nitrone olefin cycloaddition (virosaine A). All these studies provided evidence on the molecular level for the feasibility of these transformations, and suggest that further studies investigating the relevance of these hypotheses in biological systems are warranted.

Formal Total Synthesis of (-)-Jiadifenolide and Synthetic Studies toward seco-Prezizaane-Type Sesquiterpenes.

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.

Caged retinoids as photoinducible activators: implications for cell differentiation and neurite outgrowth.

Aiming to control neurite formation and navigate the axonal growth by an extrinsic guidance, we report on the design, synthesis and biological evaluation of caged retinoids. Agonists of RARß have been temporarily blocked either by the [(α-methyl-2-nitropiperonyl)oxy]carbonyl (MeNPOC) group or by immobilization using nitrocatechol linkers on TiO2 particles. Release on demand has been achieved by release under UV irradiation, leading to the biologically active compounds, which have been shown to induce neuronal differentiation and neurite outgrowth.