Fluorous Mixture Synthesis (FMS) of Four Isomers of 4,8,12,-Trimethylnonadecanol and the Development of an NMR-based Method for Determining the Configurations of Polyisoprenoid Structures

The chiral polyisoprenoid motif has been identified in various natural products such as vitamin E, chlorophyll-d, and beta-mannosyl phosphomycoketide. This motif features stereocenters bearing branched methyl groups at every fourth carbon of a long alkyl chain. Due to the lack of function group, assigning the configurations of these structures is difficult.\ud Herein, we describe the fluorous mixture synthesis (FMS) of the 4S,8S,12S-, 4S,8R,12S-, 4R,8S,12S-, and 4R,8R,12S-trimethylnonadecanol isomers. The FMS features a new family of ultra-light fluorous O-phenyl thionocarbonate tags and employees the most efficient fluorous tagging strategy to date. The analyses of these four isomers were found to exhibit small but reliable differences in 1H and 13C NMR spectra. Furthermore, these chemical shifts of the branched methyl groups were diagnostic of relative configurations. By deducing the relative relationship between configuration and chemical shift, we developed predictions of 4,8,12,16-tetramethyltricoanol, and 4,8,12,16,20-pentamethyl-heptacosanol