Shiina macrolactonization

Simultaneously, residual aromatic carboxylic acid salt, which is derived from the MA, acts as a deprotonation agent, causing the cyclization to progress and produce the desired lactone.

Then, the nucleophilic catalyst acts selectively on a carbonyl group derived from the seco acid in MA to again produce activated acyl carboxylate.

The hydroxyl group in the seco acid attacks its host molecule through intramolecular nucleophilic substitution, and at the same time, carboxylate anion, derived from 2-methyl-6-nitrobenzoic acid, acts as a deprotonation agent, promoting the progression of the cyclization and producing the desired lactone.

Because the nucleophilic catalyst is reproduced at the end of the reaction, only small stoichiometric quantities are required.

All of the processes of Shiina macrolactonization consist of reversible reactions, with the exception of the last cyclization step.