Study On Synthesis And Activity Of Micromide Analogues

For its good biological activities,such as anti-cancer,anti-bacterial,anti-inflammatory,anti-viral,anti-microbial,insecticidal,and immune system suppression,peptide compounds has been gradually become an important source for the development of new drugs-lead compound.Micromide,extracted from marine cyanobacteria in the peptide chain pentapeptide,have a selective inhibitory effect with multi-drug resistant tumor cells.Thus,It is of great significance to improve its anti-tumor activity by total synthesis of Micromide and structural transformation.In order to change Micromide’s activity,we should make it as template by modifying the structure and the transformation,retain their basic skeleton,using the structure principle of split in the drug synthesis,and changing the substituents and the nitrogen terminals of the peptide chain of amino acids.This paper aimed to the total synthesis and structural transformation of Micromine.And the details are as follows:Based on 2-thiazole formaldehyde,L-dopa,natural amino acid,diethanolamine and other raw materials,we can intermediate synthesized 2-(N-methylaminomethyl)thiazole,Phenylalanine containing crown ether,N-methyl amino acids,aza-15-crown-5,etc.Meanwhile,their structures have been characterized by 1HNMR and MS.With ethyl butyrylacetate as raw material,we synthesize hydrogenation ethyl(3R)-3-hydroxyhexanoate by asymmetric hydrogenation reaction,and check the effects of reaction temperature as well as substrate/catalyst molar ratio influence on the reaction.The peptide fragments and natural product micromide were synthesized by two experimental methods--natural amino acids and N-methyl amino acid coupling--used interchangeably.Four micromide analogues,one of which is micromide analogue possessing crown ether ring,were designed and synthesized.The purpose of my paper is to determinate the anti-tumor activity of natural products micromide and its several analogues,meanwhile,to study the change rule of the activity and structure for the preliminary discussion on the structure-activity relationship.