title: Total synthesis of (+)-amphidinolide A. Structure elucidation and completion of the synthesis.
abstract: 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.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
authors.forename: Barry M
authors.initials: BM
authors.lastname: Trost
authors.forename: Paul E
authors.initials: PE
authors.lastname: Harrington
authors.forename: John D
authors.initials: JD
authors.lastname: Chisholm
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Wrobleski
mesh_terms: D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D000097442:Amphidinolides
chemical_list: D007783:Lactones; D018942:Macrolides; C469329:amphidinolide A; D000097442:Amphidinolides