Chemoenzymatic Synthesis of a New Germacrene Derivative Named Germacrene F

Abstract

The new farnesyl pyrophosphate (FPP) derivative with a shifted olefinic double bond from C6‐C7 to C7‐C8 is accepted and converted by the sesquiterpene cyclases protoilludene synthase (Omp7) as well as viridiflorene synthase (Tps32). In both cases, a so far unknown germacrene derivative was found to be formed, which we name "germacrene F". Both cases are examples in which a modification around the central olefinic double bond in FPP leads to a change in the mode of initial cyclization (from 1→11 to 1→10). For Omp7 a rationale for this behaviour was found by carrying out molecular docking studies. Temperature‐dependent NMR experiments, accompanied by NOE studies, show that germacrene F adopts a preferred mirror‐symmetric conformation with both methyl groups oriented in the same directions in the cyclodecane ring.

Telescoping a Prenyltransferase and a Diterpene Synthase to Transform Unnatural FPP Derivatives to Diterpenoids

“…While the syntheses of FPP ether derivative 6 ( 17 ) as well as FPP derivative 8 ( 22 ) with a shifted central olefinic double bond have been reported before, the nor- FPP derivative 7 is a so far unknown substrate. Its synthesis commenced from ( E )-hex-3-enedioic acid ( 10 ; Scheme 2 ).…”