Total synthesis of (+)-amphidinolide A. Structure elucidation and completion of the synthesis.
The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. The 20-membered ring of amphidinolide A was formed by a ruthenium-catalyzed alkene-alkyne coupling to forge the C15-C16 bond. Using the reported structure 1 as a starting point, a number of diastereomers of amphidinolide A were prepared. Deviations of the chemical shift of key protons in each isomer relative to the natural material were used as a guide to determine the locations of the errors in the relative stereochemistry. The spectroscopic data for the synthetic and natural material are in excellent agreement.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Harrington
Paul E
PE
Chisholm
John D
JD
Wrobleski
Stephen T
ST
D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D000097442:Amphidinolides
D007783:Lactones; D018942:Macrolides; C469329:amphidinolide A; D000097442:Amphidinolides