Question

Eudesmol is a sesquiterpene found in eucalyptus. Propose a mechanism for its biosynthesis.

Short answer

Formation of farnesyl pyrophosphate

Resonance delocalization.

Attack of the terminal alkene on the electrophilic carbocation

Biosynthesis of eudesmol

Step-by-step solution

Step-by-step-solutionStep 1: Terpenes

Terpenes are a diverse class of compounds that contain 10, 15, 20, 25, 30, or 40 carbons. More than 20,000 terpenes are known. Many are found in oils extracted from fragrant plants. Terpenes can be hydrocarbons, or they can contain oxygen and be alcohols, ketones, or aldehydes. Oxygen-containing terpenes are sometimes called terpenoids.

Biosynthesis of Eudesmol

• Sesquiterpenes are a sub-class of terpenes that consists of three isoprene units. A common intermediate in the HMG-CoA reductase pathway is the compound named farnesyl pyrophosphate. Farnesyl pyrophosphate can be prepared from isopentenyl pyrophosphate (via a geranyl pyrophosphate intermediate).

Formation of farnesyl pyrophosphate

• Pyrophosphate is a great leaving group, as the resulting negative charge can be stabilized via resonance delocalization. The resulting cation is allylic, and can also be catabolized using resonance delocalization.

  
  

Resonance delocalization.

• Attack of the terminal alkene on the electrophilic carbocation closes a ten-membered ring, leaving a tertiary carbocation that is stabilized via hyperconjugation effects from the three alkyl substituents. An attack of water at this position followed by proton abstraction from the positively charged oxygen places the necessary alcohol group on the geminal dimethyl carbon.

Attack of the terminal alkene on the electrophilic carbocation

• From here, the top alkene can attack the freshly- formed acidic species, which produces another tertiary carbocation intermediate. This positively charged carbon is a tempting target for the alkene located nearby; an attack of the pi electrons from the alkene on the positively charged carbon forms two fused six-membered rings. The resulting positively charged tertiary carbocation is stabilized by the hyperconjugation effects of the three alkyl substituents. To finish the synthesis, a basic species can abstract a proton from the methyl group alpha to the carbocation. This forms an alkene and completes the biosynthesis of eudesmol.

Biosynthesis of eudesmol