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. 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.
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico 88003, USA.
Rodolfo
R
Tello-Aburto
Tara D
TD
Newar
William A
WA
Maio
D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D018942:Macrolides; C572829:palmyrolide A