Lonza Inc.

Pharma Mar, S.a.

Judit Tulla-Puche

Fernando Albericio

Maria Del Carmen Cuevas Marchante

María Del Carmen Cuevas Marchante

Matthieu Giraud

Núria Bayó-Puxan

Michèle Cristau

Miriam Gongora Benitez

Eleonora Marcucci

The invention relates to a method for homogeneous solution phase peptide synthesis (HSPPS) of a N-terminal peptide fragment PEP-N and a C-terminal peptide fragment C-PEP, with C-PEP carrying a specific diketopiperazine (DKP) comprising C-terminal protecting group, which contains a handle group HG, with HG being connected to the C-terminus of the peptide fragment; thereby this specific DKP comprising C-terminal protecting group can be selectively cleaved from the peptide as a conventionally used C-terminal protecting group. By the use of this DKP and HG comprising C-terminal protecting group, certain process steps in convergent peptide synthesis based on a combination of HSPPS and solid phase peptide synthesis (SPPS) can be avoided. The invention relates further to a method for the preparation of such specifically protected fragment C-PEP by SPPS by using a linker comprising a specific dipeptide and HG for connecting the growing peptide chain to the resin, which linker forms said DKP group, when the peptide fragment C-PEP is cleaved from the supporting resin; and further to the intermediates of the preparation method.

Diketopiperazine forming dipeptidyl linker

Antitumoral compounds of Formula I, and pharmaceutically acceptable salts, derivatives, tautomers, prodrugs or stereoisomers thereof useful as antitumour agents.

Antitumoral compounds

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Judit Tulla-Puche