Synthesis of Waixenicin A: Exploring Strategies for Nine-Membered Ring Formation.

We present a comprehensive account on our efforts behind the recently published synthesis of waixenicin A. Our approach for constructing the dihydropyran ring relied on an Achmatowicz rearrangement. For the assembly of the nine-membered ring, four distinct strategies were investigated.

Total Syntheses of (+)-Waixenicin A, (+)-9-Deacetoxy-14,15-deepoxyxeniculin, and (-)-Xeniafaraunol A.

The first asymmetric total synthesis of the diterpenoid waixenicin A, a potent and highly selective TRPM7 inhibitor, is reported. The characteristic -fused oxabicyclo[7.4.

9-Membered Carbocycles: Strategies and Tactics for their Synthesis.

Many natural products comprising a nine-membered carbocyclic core structure exhibit interesting biological effects. However, only a minority have succumbed to their synthesis in the past. The synthesis of functionalized nine-membered carbocycles still remains a challenging goal for synthetic chemists, mainly due to their high ring strain.

Development of a β-C-H Bromination Approach toward the Synthesis of Jerantinine E.

The development of an asymmetric and highly convergent three-component synthesis of the functionalized ABC ring system of the Aspidosperma alkaloid jerantinine E is reported. The presented synthetic strategy relies on our recently developed method for the one-pot β-C-H bromination of enones, which allows for rapid construction of the tricyclic tetrahydrocarbazolone core via a palladium-catalyzed amination and oxidative indole formation. Moreover, a secondary amine building block that contains all carbon atoms of the D and E ring of the natural product could be installed in three additional steps.

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms.

This review describes strategies for the chemical synthesis of xenicane diterpenoids and structurally related metabolites. Selected members from the four different subclasses of the Xenia diterpenoid family, the xenicins, xeniolides, xeniaphyllanes and xeniaethers, are presented. The synthetic strategies are discussed with an emphasis on the individual key reactions for the construction of the uncommon nine-membered carbocycle which is the characteristic structural feature of these natural products.

Experimental Studies on the Selective β-C-H Halogenation of Enones.

Here we describe the realization of a one-pot protocol for the β-C-H halogenation of cyclic enones via umpolung of the β-carbon. The developed method includes hydrazone formation and selective β-halogenation (bromination, chlorination) with N-bromosuccinimide and Palau'chlor (2-chloro-1,3-bis(methoxycarbonyl)guanidine) followed by hydrolysis of the hydrazone moiety. Using the optimized conditions, we were able to effectively β-brominate and β-chlorinate for the first time cyclic enones with different substitution patterns and various functional groups in one flask, whereas previous methods for this transformation required several steps.

Rhodium(III)-catalyzed alkenyl C-H bond functionalization: convergent synthesis of furans and pyrroles.

Ring in the new: a new annulation for the efficient synthesis of substituted furans and pyrroles is reported. The Rh(III) -catalyzed reaction of O-methyl α,β-unsaturated oximes with aldehydes and N-tosyl imines affords secondary alcohol and amine intermediates, respectively. Cyclization and aromatization occurs under the reaction conditions to provide access to biologically relevant furans and pyrroles in good yields.