Revision of the Peniroquesine Biosynthetic Pathway by Retro-Biosynthetic Theoretical Analysis: Ring Strain Controls the Unique Carbocation Rearrangement Cascade.

ABSTRACT: Peniroquesine, a sesterterpenoid featuring a unique 5/6/5/6/5 fused pentacyclic ring system, has been known for a long time, but its biosynthetic pathway/mechanism remains elusive. Based on isotopic labeling experiments, a plausible biosynthetic pathway to peniroquesines A-C and their derivatives was recently proposed, in which the characteristic peniroquesine-type 5/6/5/6/5 pentacyclic skeleton is synthesized from geranyl-farnesyl pyrophosphate (GFPP) via a complex concerted A/B/C-ring formation, repeated reverse-Wagner-Meerwein alkyl shifts, three successive secondary (2°) carbocation intermediates, and a highly distorted trans-fused bicyclo[4.2.1]nonane intermediate. However, our density functional theory calculations do not support this mechanism. By applying a retro-biosyntheti

SUBMITTER: Matsuyama T 

PROVIDER: S-EPMC10301677 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature