Stereochemical studies on sphinxolide: Advances in the J-based NMR determination of the relative configuration of flexible systems

An improved Version of the J-based NMR configurational analysis of flexible organic molecules, that relies on extensive use of HSQC-TOCSY spectra, was applied to the stereochemical study of sphinxolide, a potent anti-tumor ma rine macrolide acting on cell microfilaments that has lately proven to circ umvent multi-drug-resistance (MDR) in cancer cells. NMR data allowed stereo chemical assignment of all molecular segments except the C18-C19 unit, whos e configuration had to be addressed by a chemical/degradative approach.