Differentiation of HMBC two- and three-bond correlations: A method to simplify the structure determination of natural products

Abstract

The structure elucidation of natural products, today, relies heavily on the application of proton-detected heteronuclear NMR experiments. Perhaps the most useful of these methods is the HMBC experiment, which provides correlations between protons and carbons over two and three bonds. The application of the HMBC method for the direct translation of H,C correlations to yield bonding information is limited, however, by the fact that it does not distinguish between 2 J CH and 3 J CH correlations. Reported here is an application of the recently described 1,1-ADEQUATE experiment that yields only two bond H,C connectivities in HCC moieties and therefore allows the differentiation of HMBC two- and three-bond correlations. The method is demonstrated on a 14 mg sample of a new marine natural product, 5,6-dihydro lamellarin H ( 1). An NMR methodology is presented which allows the differentiation of two- and three-bond correlation in HMBC spectra. The ω 1-refocused 1,1-ADEQUATE is used to obtain exclusively two-bond correlations which thereby facilitates the assignment of the constitution of complex structures. The method is demonstrated on a new polycyclic marine natural product, 5,6-dihydro lamellarin H.