Study On Synthesis And Activity Of Glycosyl Modified Pentadepsipeptide

Sansalvamide A is a cyclic depsipeptide isolated from Fusarium(Ocean genus).Two leucines,one valine,one phenylalanine and one a-hydroxy isocaproic acid were included in its structure.Related studies show that sansalvamide A has many physiological activities,including antitumour,topoismerase inhibition etc.At present they attract more and more attention as prospective leading compounds in drug discovery.The separation,synthesis and optimizing of cyclic peptides turn into a popular research field.Carbohydrates are widely distributed in nature and structurally diverse class of biomolecules.They are essential to most forms of life and play key roles in varied cellular processes.Glycopeptides are glycosylated peptide compounds.The glycosyl moieties of the glycopeptide are closely related with cell identification,immune and metabolic regulation,fertilization,ontogenesis,cancer,aging,organ transplantation etc.According to principles of drug design,this text takes an antitumor activity of marine natural product Sansalvamide A as lead compound.On the one hand,the chain-like cyclopentadepsipeptide is prepared by replacing a-hydroxy isocaproic acid with serine and replacing one of leucine with proline,respectively.On the other hand,using Sansalvamide A as a templet,ring expanding Sansalvamide A is obtained by replacing a-hydroxy isocaproic acid with serine or threonine.And then,replacing phenylalanine with para-F,-Cl,-Br,-OMe phenylalanine and naphthalene respectively.Unnatural amino acids are used in synthesis of these target compounds.On the basis of the above work,glycosyl is introduced in its side chain to give glycopeptide easter.The anticancer activities of all compounds are estimated,and the bioactivity differences between cyclic depsipeptide and chain-like cyclic depsipeptide are investigated,and that we have preliminary discussion of glycosyl introduced influence on cyclic peptide biological activity.