Structure elucidation of (+)-amphidinolide a by total synthesis and NMR chemical shift analysis.
The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. Using the reported structure as a starting point, a number of diastereomers of amphidinolide A were prepared. The deviations of the chemical shifts of key protons in each isomer relative to the values reported for the isolated material were used to determine the locations of the errors in relative stereochemistry. The spectroscopic data for our proposed structure of (+)-amphidinolide A and the isolated material are in excellent agreement. The key step, a [Cp*Ru(MeCN)3]PF6-catalyzed alkene-alkyne coupling, was used to form the 20-membered ring in the final step of the synthesis.
Trost
Barry M
BM
Department of Chemistry, Stanford University, California 93405-5080, USA. bmtrost@stanford.edu
Harrington
Paul E
PE
D000818:Animals; D002384:Catalysis; D003500:Cyclization; D004141:Dinoflagellida / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism; D000097442:Amphidinolides
D004852:Epoxy Compounds; D007783:Lactones; D018942:Macrolides; D012428:Ruthenium; C469329:amphidinolide A; D000097442:Amphidinolides