Determination of the absolute configuration of Xylopiacin by Mosher ester methodology and molecular modeling studies

Xylopiacin 1, a cytotoxic mono-tetrahydrofuran Annonaceous acetogenin, has been isolated from the seeds of Xylopia aromatica (Lam.) Mart. (Annonaceae). The absolute configuration of this compound was determined by its Mosher ester derivatives. The stereogenic carbinol centers of xylopiacin S-MTPA 2 and xylopiacin R-MTPA 3 have been determined by (1)H-NMR and 2D-NMR experiments utilizing Mosher esters. The preferred conformation of xylopiacin 1 and its derivatives 2 and 3 were determined using molecular mechanics and molecular dynamics calculations.