Asymmetric Total Synthesis and Revision of Absolute Stereochemistry for (+)-Taumycin A: An Approach that Exploits Orthogonally Protected Quasienantiomers.

The first asymmetric total synthesis of C(9)--(+)-taumycin A is now reported using an approach that targeted both C(9) diastereomers concurrently. To facilitate this work, we called upon the symmetrical nature of a C(5)-C(13) side-chain intermediate and exploited orthogonal protecting groups as a tactic to access both stereoisomers from a single chiral, nonracemic intermediate. In addition to our successful approach, several minor detours that helped refine our strategy and a detailed analysis of H NMR data will be discussed.

Detailed analysis of (-)-palmyrolide a and some synthetic derivatives as voltage-gated sodium channel antagonists.

A small library of synthetic (-)-palmyrolide A diastereomers, analogues, and acyclic precursors have been examined with respect to their interaction with voltage-gated sodium channels (VGSCs). Toward this goal, the ability of (-)-palmyrolide A and analogues to antagonize veratridine-stimulated Na(+) influx in primary cultures of mouse cerebrocortical neurons was assessed. We found that synthetic (-)-palmyrolide A and its enantiomer functioned as VGSC antagonists to block veratridine-induced sodium influx.

Evolution of a protecting-group-free total synthesis: studies en route to the neuroactive marine macrolide (-)-palmyrolide A.

A full account of our synthetic work toward the first total synthesis of the neuroactive marine macrolide (-)-palmyrolide A is described. Our first-generation approach aimed to unlock the unknown C(5)-C(7) stereochemical relationship via the synthesis of four diastereomers of palmyrolide A aldehyde, a known degradation product. When these efforts provided inconclusive results, recourse to synthesizing all possible stereocombinations of the 15-membered macrolide was undertaken.