A flow
chart figure indicates the general method of solution phase synthesis.
It should be noted that peptides are normally synthesised in a carboxyl
to amino terminal direction. This allows the racemisation resistant urethane
protected amino acid to be activated in preference to the racemisation
prone carboxyl terminal of the peptide.
Care
has to be taken in selection of protecting groups so that they can be removed with
appropriate selectivity. Side chain and carboxyl protecting groups need to be selected so
as not to be labile under the conditions required to deprotect the amino group. If a long peptide is to be made then it is common
to synthesise it in smaller sections, which are later coupled to form the overall peptide
- a process called fragment condensation. If a fragment condensation technique is being
adopted then the carboxyl terming must also be deprotected without loss of side chain
protection.
There
are two ways of achieving this selective deprotection:
1.
Chose
protecting groups that are deprotected with completely different reagents (refered to as
orthogonal protection)
e.g. tert butyl (acid), fluorenyl methyl (base),
benzyl (catalytic hydrogenolysis).
2.
Chose
protecting groups that are deprotected with the same type of reagent but under different
conditions.
e.g. tert butyl and benzyl which require
increasingly strong acids for deprotection.
