| 摘要 |
The synthesis of useful peptides presents a promising approach to new therapeutic agents. The Dolastatins, a series of linear and cyclic antineoplastic and/or cytostatic peptides isolated from Indian Ocean sea hare Dolabella auricularia represent excellent leads for synthetic modification. In the present invention, the corresponding amine was allowed to react with Boc-L-phenylalanine. Synthesis of amides led to excellent yields; The protecting group of amides was removed with hydrogen chloride in acetic acid to afford the hydrochloride salt, The correspondent deprotected N-tert-butyloxycarbonyl-L-phenylalanineamide was coupled with dolaproine in the presence of diethyl phosphorocyanidate and triethylamine thereby yielding dipeptideamides. The protecting groups of amides was removed with trifluoroacetic acid to afford the trifluoroacetate salt. Diethyl phosphorocyanidate was used again with excellent results for coupling tripeptide trifluoroacetate with each of the amide salts to yield Dolastatin 10 structural modifications. The extraordinary inhibition of cell growth shown by the Pentapeptideamides against six major types of human cancer has been presented. The intermediates of these reaction also show anticancer activity against the murine P388 lymphocytic leukemia cell line. |
