12 新規IV型コラゲナーゼ阻害剤、matlystatin類に関する研究(口頭発表の部)

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TypeIV collagenases are metalloproteinases which degrade typeIV collagen, one of the major components of basement membranes. These enzymes are thought to play an important role in tumor cell invasion. Many studies to date indicate a correlation between the amounts of these enzymes secreted and metastatic potential of tumor cells. During the course of screening for inhibitors of these enzymes, matlystatin A (1), B (2a), D (3), E (4) and F (5) were isolated from Actinomadura atramentaria. The structures of both compounds were deduced on the basis of spectroscopic analysis including several types of 2D NMR and FAB-MS/MS. In connection with our interests in the biological activities of matlystatins and our desire to determine their absolute configurations unambiguously, we planned the syntheses of matlystatins. The total synthesis of matlystatin B was accomplished by coupling 4 protected subunits: 7,9,13 and O-benzylhydroxylamine. Matlystatin A was synthesized using the carboxylic acid 15 and the amine 19 as key intermediates. Since spectral properties of 1 and 2a were identical with those of the corresponding natural products, the absolute configuration of 1 and 2a were unambiguously determined. In the next stage, the relationships between stereochemistry and inhibitory activity were studied for ten stereoisomers of matlystatin B. The structure activity relationships revealed that C2' stereochemistly plays an important role in the inhibition of typeIV collagenases.
天然有機化合物討論会の論文
1993-09-10

12 新規IV型コラゲナーゼ阻害剤、matlystatin類に関する研究(口頭発表の部)

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