Structure elucidation of plumerubradins A–C: Correlations between 1H NMR signal patterns and structural information of [2+2]-type cyclobutane derivatives

Abstract

[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures. However, the structure elucidation of the cyclobutane ring, including its connection mode and stereochemistry, presents a significant challenge. Plumerubradins A–C (–), three novel iridoid glycoside [2+2] dimers featuring a highly functionalized cyclobutane core and multiple stereogenic centers, were isolated from the flowers of Plumeria rubra. Through biomimetic semisynthesis and chemical degradation of compounds –, synthesis of phenylpropanoid-derived [2+2] dimers –, combined with extensive spectroscopic analysis, single-crystal X-ray crystallography, and microcrystal electron diffraction experiments, the structures with absolute configurations of – were unequivocally elucidated. Furthermore, quantum mechanics-based H NMR iterative full spin analysis successfully established the correlations between the signal patterns of cyclobutane protons and the structural information of the cyclobutane ring in phenylpropanoid-derived [2+2] dimers, providing a diagnostic tool for the rapid structural elucidation of [2+2]-type cyclobutane derivatives.