Enzymatic Synthesis of Diterpenoids from iso‐GGPP III: A Geranylgeranyl Diphosphate Analog with a Shifted Double Bond

Abstract

AbstractThe analog of the diterpene precursor geranylgeranyl diphosphate with a double bond shifted from C14=C15 to C15=C16 (named iso‐GGPP III) has been synthesized and enzymatically converted with six bacterial diterpene synthases; this allowed the isolation of nine unnatural diterpenes. For some of the enzyme‐substrate combinations, the different reactivity implemented in the substrate analog iso‐GGPP III opened reaction pathways that are not observed with natural GGPP, resulting in the formation of diterpenes with novel skeletons. A stereoselective deuteration strategy was used to assign the absolute configurations of the isolated diterpenes.