Chemical synthesis of 13C-labeled isopentenyl pyrophosphate

Isopentenyl pyrophosphate (IPP) is a key precursor in the biosynthesis of terpenoids, the largest class of natural products. ¹³C isotope incorporation into the terpenoid scaffolds has been proved to be a powerful chemical probe to track the elusive cyclization mechanism of distinct terpene synthases which are the driving force for the tremendous chemical diversities seen in terpenoid natural products. Here, we present synthetic routes for the preparation of C1 to C5 individually ¹³C labeled IPP starting from ¹³C-labeled acetic acid and iodomethane, resulting in five distinct labeled substrates. The ¹³C labeled IPP will be served as useful chemical probes to elucidate the new cyclization mechanisms catalyzed by those cryptic terpene synthases.