Isolation and structural determination of natural products bearing tetrahydrogenated isoprenoid side-chains at their ω-termini†

Hydrogenated isoprenoids are found in a range of biologically important natural products, such as isoprenoid quinones, chlorophyll, vitamin E, and dolichol. In this study, a new method was developed for determining the chirality of the tetrahydrogenated isoprenoid (THI) structures of two natural products, namely heptaprenylcycli-14E,18E-diene and (22R,5E,9E,13E,17E)-6,10,14,18,22,26-hexamethylheptacosa-5,9,13,17-tetraen-2-one, for which the chiral carbon centres have never been elucidated. Our research group previously isolated the former sesquarterpene from Mycobacterium chlorophenolicum, while the latter was isolated as a new polyprenyl acetone from Conexibacter woesei in the current study. To determine their chiralities, these two THI-containing terpenoids were subjected to ozonolysis to produce (R)-6,10-dimethyl-2-undecanones. The optically active (S)-6,10-dimethyl-2-undecanone was prepared as an authentic chiral sample by the reduction of (S,E)-6,10-dimethylundeca-3,9-dien-2-one. Chiral high-performance liquid chromatographic analysis of the ozonolysis products and of authentic (S)- and racemic 6,10-dimethyl-2-undecanone samples unambiguously assigned the THI chiral carbon centres of both compounds as R. This new method could be a useful tool for determining the chiralities of other THIs. It is also expected to contribute to our understanding of the biosynthetic mechanisms and biological roles of THIs.