Concise total synthesis of (±)-actinophyllic acid.

A concise total synthesis of the complex indole alkaloid (±)-actinophyllic acid was accomplished by a sequence of reactions requiring only 10 steps from readily-available, known starting materials. The approach featured a Lewis acid-catalyzed cascade of reactions involving stabilized carbocations that delivered the tetracyclic core of the natural product in a single chemical operation. Optimal conversion of this key intermediate into (±)-actinophyllic acid required judicious selection of a protecting group strategy.

Identification of inhibitors of PvdQ, an enzyme involved in the synthesis of the siderophore pyoverdine.

Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe(3+) ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings.

Synthesis of (±)-actinophyllic acid and analogs: applications of cascade reactions and diverted total synthesis.

Actinophyllic acid is a biologically active indole alkaloid with a unique structural framework that incorporates five contiguous stereocenters. A total synthesis of (±)-actinophyllic acid has been completed that proceeds in only 10 steps from readily available, known compounds and with the isolation of nine intermediates. The synthesis features a novel cascade of reactions of N-stabilized carbocations with π-nucleophiles to create the tetracyclic core of actinophyllic acid in a single chemical operation.

Iminium Ion Cascade Reactions: Stereoselective Synthesis of Quinolizidines and Indolizidines.

A novel iminium ion cascade reaction has been developed that allows for the stereoselective synthesis of a variety of substituted aza-fused bicycles. The combination of amino allylsilanes and aldehydes (or ketones) was used to synthesize a number of quinolizidines and indolizidines in an one-pot reaction sequence. This technology has been used to effect the facile syntheses of several indolizidine and quinolizidine natural products including, (±)-epilupinine, (±)-tashiromine, and (-)-epimyrtine.