Evolution of a protecting-group-free total synthesis: studies en route to the neuroactive marine macrolide (-)-palmyrolide A
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Updated: May 21, 2026

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Rodolfo Tello-Aburto1, Tara D Newar, William A Maio
1Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico 88003, USA.
Abstract:
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. These studies were critical in confirming the absolute stereochemistry, yielding the first total synthesis of (+)-ent-palmyrolide A. Subsequent to this work, the first protecting-group-free total synthesis of natural (-)-palmyrolide A is also reported.
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