Structure elucidation of proton-deficient natural products by NMR spectroscopy

Abstract

There has been a long-standing general notion that highly proton-deficient molecular structures, i.e. those that fall under what has become known as the Crews Rule, may be difficult or even impossible to elucidate by conventional NMR experiments. However, with the latest generation of probe technology and new experiments this challenging task has become feasible. We demonstrate a successful structure elucidation of the highly proton-deficient model compound staurosporine, using a combination of 1.7 mm cryoprobe technology with a new NMR experiment LR-HSQMBC, which affords more 'very long range' n J CH correlations with higher sensitivity than standard HMBC experiments when both are optimized for very small heteronuclear coupling constants, e.g. 2 – 4 Hz. In addition, applying CMC-se for computer-assisted structure elucidation significantly speeds up the process of spectral interpretation and structure generation.