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Total Synthesis of Thymosin β 4 by Fragment Condensation
Author(s) -
Kapurniotu Afroditi,
Link Peter,
Voelter W.
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1993199301188
Subject(s) - chemistry , yield (engineering) , thymosin , fragment (logic) , peptide , chromatography , amino acid , peptide synthesis , total synthesis , combinatorial chemistry , stereochemistry , biochemistry , materials science , computer science , metallurgy , programming language
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.