Process for the synthesis of peptides containing a 4-hydroxy-proline substructure
The present invention relates to processes for preparing peptides and to intermediates involved in such processes, e.g. a process for preparing a compound of formula VIII wherein R 12 and R 13 are as defined herein.
1. A process for preparing a compound of formula VIII
wherein R 12 and R 13 are each a removable protecting group and R 12 and R 13 are different;
comprising reacting a compound of formula IX
with a suitable R 12 donor compound.
2. A process according to claim 1 , wherein the compound of formula IX is prepared by
(i) hydrolysing a compound of formula X
wherein R 13 is as defined in claim 1 ,
R 14 is a removable protecting group and R 14 is different to R 12 and R 13 , and
R 15 is a blocking group removable by hydrolysis or hydrogenolysis,
to obtain the corresponding carboxylic acid, and
(ii) removing the protecting group R 14 in the resulting carboxylic acid.
3. A process for producing a compound of formula VIII as defined in claim 1 , wherein R 12 is fluorenylmethoxycarbonyl and R 13 is a removable protecting group other than fluorenylmethoxycarbonyl, comprising reacting a compound of formula IX with a fluorenylmethoxycarbonyl donor compound.