Synthesis of a Novel Pentagastrin-Drug Conjugate for a Targeted Tumor Therapy

✍ Scribed by Lutz F. Tietze; Olaf Panknin; Felix Major; Birgit Krewer

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 335 KB
• Volume: 14
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200701521

✦ Synopsis

Abstract

The synthesis of the novel pentagastrin seco‐CBI conjugate 3, which is based on the highly cytotoxic antitumor antibiotic (+)‐duocarmycin SA (1), is reported. A key step in the synthesis is the palladium‐catalyzed carbonylation of aryl bromide 7 to give the benzyl ester 16, which is transformed into the new seco‐CBI derivative 21 bearing a carboxylic acid ester moiety. Subsequent transformation of 21 into an activated ester followed by the introduction of β‐alanine and tetragastrin led to the new pentagastrin drug 3 that contains a peptide moiety for targeting cancer cells expressing CCK‐B/gastrin receptors.