Organic synthesis

The cleavage process depends on the stability of the medium ions.

Carboxylic acid linkers

The first linking group used for peptide synthesis bears the name of the father of solid phase synthesis. Merrifield resin is cross-linked polystyrene functionalised with a chloromethyl group. The carbonyl group is attached by the nucleophilic displacement of the chloride with a cesium carboxylate salt in DMF. Cleavage to regenerate the carboxylic acid is usually achieved by hydrogen fluoride.


The ion is produced when ester is reacted with HF



The second class of linker used for carboxylic acid is the Wang linker. This linker is generally attached to cross-linked polystyrene, TentaGel and polyacrylamide to form Wang resin. It was designed for the synthesis of peptide carboxylic acids using the Fmoc-protection strategy, and due to the activated benzyl alcohol design, the carboxylic acid product can be cleaved with TFA.

A more acid-labile form of the Wang resin has been developed. The SASRIN resin has the same structure as the Wang linker but with the addition of a methoxy group to stabilise the carbonium ion formed during acid catalysed cleavage.


Stratergies for synthesis of chiral compounds
1. Used chiral starting material (chiral pool: amino acids, carbonhydrates, alkanoids etc)
- 100 % guaranteed
- Economical by saving steps
- but often only one enantiomer exists (Pros) L, D form does not exist in nature.