Orsellinic acid, a common constituent of lichens, is...

Name: Problem 86, Chapter 17: Organic Chemistry
Uploaded: 2020-11-25T15:11:52-08:00
Duration: 10 min 54 s
Channel: Zubair Abdulla
Description: Orsellinic acid, a common constituent of lichens, is synthesized from the condensation of acetyl thioester and malonyl thioester. If a lichen is grown on a Propose a mechanism for the reaction and explain why the reaction does not occur if hydroxide ion is the base.

Orsellinic acid, a common constituent of lichens, is synthesized from the condensation of acetyl thioester and malonyl thioester. If a lichen is grown on a Propose a mechanism for the reaction and explain why the reaction does not occur if hydroxide ion is the base.

Key Concepts

Claisen Condensation

This reaction is a type of Claisen condensation, a carbon–carbon bond forming process where an enolate ion (generated from one ester or thioester) attacks a carbonyl carbon of another ester or thioester. In the context of polyketide synthesis, such as in the biosynthesis of orsellinic acid, the reaction involves the deprotonation of a malonyl thioester to form an enolate that then nucleophilically attacks an acetyl thioester, setting up the formation of a new carbon–carbon bond.

Thioester Reactivity

Thioesters are key functional groups in many biochemical reactions because they are more reactive than regular esters due to the reduced resonance stabilization offered by sulfur. Their reactivity makes them ideal for facilitating condensation reactions in biosynthetic pathways, allowing for efficient formation and rearrangement of carbon skeletons during the synthesis of complex molecules like orsellinic acid.

Enolate Formation

The formation of an enolate ion is central to many carbon–carbon bond forming reactions. In the synthesis mechanism, deprotonation at the alpha-carbon of the malonyl thioester creates an enolate intermediate that is stabilized by the electron-withdrawing carbonyl groups. This enolate then serves as a nucleophile that attacks the electrophilic carbonyl carbon of the acetyl thioester, driving the condensation reaction forward.

Base Selection and Reaction Conditions

The choice of base is crucial in such condensation reactions because it must effectively deprotonate the substrate to form the enolate without promoting unwanted side reactions. Hydroxide ion, although a strong base, is also a good nucleophile and can lead to hydrolysis of thioesters rather than the desired condensation. This underscores the importance of using milder, non-nucleophilic bases in order to maintain the integrity of the thioester groups and favor the proper progression of the reaction mechanism.

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