Posaconazole: Application of HSQC-ADEQUATE from General Indirect Covariance Processing

Abstract

Posaconazole is a structurally complex triazole antifungal agent that, by virtue of its structural complexity, provides a good test molecule for the evaluation of NMR structure elucidation methodologies. Although GHMBC and related long-range 1H–13C heteronuclear shift correlation techniques are extremely powerful, at the same time, when dealing with unknowns, they can be problematic in that there is no way to readily differentiate adjacent (2 JCH) correlations from longer range correlations, e.g., 3JCH and nJCH, n > 3. The 1,1-ADEQUATE experiment, in contrast, provides unequivocal experimental access to adjacent carbon–carbon correlation information, albeit with a sensitivity penalty, as the experiment involves an adjacent 13C–13C out-and-back magnetization transfer. In part, the sensitivity penalty can be overcome by using unsymmetrical indirect covariance or general indirect covariance processing methods. The application of these methods through the coprocessing of multiplicity-edited GHSQC and 1,1-ADEQUATE data to generate an HSQC-ADEQUATE correlation plot is demonstrated for posaconazole.