Protecting group

A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments. Then, these parts, or groups, must be protected. For example, lithium aluminium hydride is a highly reactive but useful reagent capable of reducing esters to alcohols. It will always react with carbonyl groups, and this cannot be discouraged by any means. When a reduction of an ester is required in the presence of a carbonyl, the attack of the hydride on the carbonyl has to be prevented. For example, the carbonyl is converted into an acetal, which does not react with hydrides. The acetal is then called a protecting group for the carbonyl. After the step involving the hydride is complete, the acetal is removed (by reacting it with an aqueous acid), giving back the original carbonyl. This step is called deprotection. Protecting groups are more commonly used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to the process. However, the availability of a cheap chiral building block can overcome these additional costs (e.g. shikimic acid for oseltamivir). Protection of alcohols: Acetyl (Ac) – Removed by acid or base (see Acetoxy group). Benzoyl (Bz) – Removed by acid or base, more stable than Ac group. Benzyl (Bn) – Removed by hydrogenolysis. Bn group is widely used in sugar and nucleoside chemistry. Methoxyethoxymethyl ether (MEM) – Removed by acid. Dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl] (DMT) – Removed by weak acid. DMT group is widely used for protection of 5'-hydroxy group in nucleosides, particularly in oligonucleotide synthesis. Methoxymethyl ether (MOM) – Removed by acid.