| Peptide compounds are widely distributed in nature,peptides and its analogues show diverse biological functions,including hormones,antibiotics,toxins,antitoxins,anticancer and antiviral et.al.Investigations of total synthesis and structure modification of the active natural peptides receive extensive attentionMicromide,chain of five peptides with anti-tumor activity,is extraced from Symploca green bacteria which is a cytotoxic alkaloids.It inhibits selectively solid tumor cell lines,especially on KB cells that IC50 is 260 n M.Therefore,total synthesis and structure modification of Micromide have great significance to improve its anti-tumor activity.This topic aims to total synthesis and structural modification of the chain pentapeptide Micromide Details are as follows:Racemic 3-hydroxy ethyl hexanoate was chiral resolution by active enzyme to obtain D-3-hydroxy hexanoic acid.Synthesis methods of 3-methoxy-hexanoic acid were investigated by changing different methylation reagents,solvents,catalysts,the best synthetic route was selected.2-(N-methylaminomethyl)thiazole was prepared from 2-thiazolyl formaldehyde by nucleophilic addition and reduction reaction.Phenylalanine containing crown ether was synthesized by coupling reaction of protective L-Dopa and four glycol tosylate.Synthesis methods of N-methylation amino acid were explored.A series of the Boc-and Cbz-protected N-methyl amino acids and peptide fragments containing N-methylation amino acid were synthesized.Micromide was obtained by coupling of peptide fragments using liquid phase synthesis method.Taking Micromide for template,based on retain their basic skeleton,its structure was carried out modification and transformation by changed substituents and peptide-chain amino acids in order to change its activity.We synthesised 9 N-methylation amino acid,1 amino acid containing crown ether,6 peptides containing N-methylation amino acid,including 10 new compounds in this topic.All compounds are characterized by ~1HNMR and MS. |
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