Research On Synthesis Of Analogs Of Largamide B

Early 20th century, chemical synthesis of dipeptide marked the birth of peptide science.Throughout thehundred years, scientists have achieved great accomplishment. Cyclic peptides are still a growing research area even in the 21st century. They mainly were isolated from marine organisms and terrestrial microorganisms.Cyclic peptides and depsipeptides have been show a wide spectrum of biological activity. They are therefore sought after as promising lead compounds for drug discovery.Thus the limits of the quantity affect the determination of precise structure as well as the clarification of detailed biological activities. In fact, the total synthesis is still playing a final means for the structure determination. Furthermore, the structure of activity relationship (SAR) will offer an opportunity to investigate their biological activities in detail.Largamides A-C have been isolated from the marine cyanobacterium Lyngbya confervoides collected from southeastern Florida. Our systematic chemical investigations of the active fractions of Lyngbya confervoides previously yielded the potent elastase, chymotrypsin and trypsin inhibitor. Elastase is associated with tissue destruction and inflammation characteristic of chronic obstructive pulmonary disease (ARDS) such as emphysema. Because of the critical role of elastase in inflammatory processes, elastase inhibitors might be of importance in the treatment of inflammation related syndromes.According to the isostere principles of drug design a series of new Sansalvamide A cyclic peptide were designed. In three of designed molecules the hydrogen of benzene in Sansalvamide A peptide was substituted by Br and methoxyl respectively. And in other two new cyclic pentadepsipeptides the hydrophobic hydroxy acid was replaced with serine. These synthetic cyclic depsipeptide analogues keep the basic structure of Sansalvamide A peptide.In this paper the preparation of amino acid and the synthesis of RGD chain peptide and cyclic depsipeptide had been studied. The linear peptide and the cyclic depsipeptide were purified by recrystallization and chromato graphic. The structure of the intermediates and the target molecules were determined by 1H-NMR and 13H-NMR.