Peptide synthesis has become one of the most reliable and predictable fi elds of practical organic chemistry, principally because of the effectiveness of the protecting groups it employs. For this reason, peptides are one of the few classes of complex organic molecules that can routinely be made by machines, such as the one on the right, in which much of the chemistry we are about to talk about takes place without any human intervention. Biology makes peptides and proteins by selectively coupling together members of a pool of 20 or so amino acids. To do the same in the laboratory, we need to overcome a number of challenges. For example, we’ll start by thinking about how to react two amino acids together, to make a dipeptide—leucine and glycine, for example. If we want the NH₂ group of glycine to react with the CO₂H group of leucine we will first have to activate the carboxylic acid towards nucleophilic substitution—by making the acyl chloride, say, or a particularly reactive ester, which we will represent as RCOX.

The main problem, though, is that there is another free CO₂H, which could react with the COX group to form an anhydride, and two different free amines, either of which might react, giving both LeuLeu (which we don’t want) and LeuGly (which we do). For this reason, we need to protect both the NH₂ group of leucine and the CO₂H group of glycine. What sort of protecting groups do they need to be? We will need to be able to take them off again once they have done their job, so there is no point using, say, an amide to protect the amine since we would have great difficulty hydrolysing the amide in the presence of the amide bond we are trying to form. Not only do we want the protecting groups to be removable under mild conditions, but we want two groups (one for each of NH₂ and CO₂H) which we can take off under different conditions. We then have the opportunity to modify either end of the dipeptide at will.

A good choice for a pair of conditions might be acid and base—we might protect the NH₂ group with a protecting group we can remove only in base, and the CO₂H group with protection we can remove only in acid.

مواضيع ذات صلة

The Boc protecting group—gastrin and aspartame

The Cbz protecting group—oxytocin

A survey of protecting groups

How to react the less reactive group (II): protecting groups

Chemoselectivity in the reactions of dianions

How to react the less reactive group (I): react both then ‘unreact’ one

Competing reactivity: choosing which group reacts

How to oxidize primary alcohols to aldehydes

How to oxidize secondary alcohols to ketones

Birch reduction of arenes

Dissolving metal reductions

Getting rid of functional groups