Total Synthesis of Thymosin β4 by Fragment Condensation

✍ Scribed by Kapurniotu, Afroditi ;Link, Peter ;Voelter, W.

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 750 KB
• Volume: 1993
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.1993199301188

✦ Synopsis

Abstract

The total synthesis of thymosin β~4~ by means of classical methods using three protected fragments is described. For their syntheses the Z/__t__Bu strategy and temporary phenyl ester protection of the C‐terminal carboxyl were used. Various coupling procedures were applied in order to optimize the yields of the synthesis. The BOP/HOBt method proved to be very efficient for the coupling of larger fragments. The fragment condensation for the synthesis of protected thymosin β~4~ was performed by two different strategies. The deprotected thymosin β~4~ was purified by prep. HPLC on a RP‐18 column. Applying the first synthetic strategy the 43‐peptide was obtained in 12% overall yield for the final steps of the synthesis, including two fragment condensations, two hydrogenations, deprotection, and purification. The second synthetic strategy afforded thymosin β~4~ in 4% overall yield (based on the final synthetic steps: two fragment condensations, two hydrogenations, deprotection, and purification). The purified products of both synthetic pathways were shown to be identical with the natural thymosin β~4~, isolated from calf thymus tissue, according to HPLC, capillary zone electrophoresis, SDS‐PAGE, ion‐spray mass spectrometry, and amino acid analysis.