Development of Novel Antiinflammatory Drugs Based on Nonproteinaceous Signal Molecules

1993年，从紫丁香假单胞菌中分离出一种新的非蛋白性低分子量代谢产物丁香内酯1和2，具有引起大豆植物过敏反应的能力。番茄。并分离得到了相应的化合物-第二丁香苷1和第二丁香苷1和第二丁香苷。我们试图合成这些生物活性化合物及其衍生物，希望进一步开发出具有更强抗炎活性的有用化合物。因此，以d -酒石酸盐为原料，将其转化为四氢呋喃衍生物。然后将该化合物转化为相应的二恶斯匹罗化合物，从该化合物中首次合成了(+)-第二syins 1和2。二联素1和二联素的全合成明确地确立了它们的绝对立体化学性质。我们也可以开发出一种高效的替代方法来制备(+)-丁香苷1和2。基于目前得到的结果，我们正在尝试合成更复杂的丁香内酯1和2。

In 1993 syringolides 1 and 2, novel nonproteinaceous low molecular weight metabolites possessing the ability of eliciting a hypersensitive reaction in soybean plants, were isolated from Pseudomonas syringae pv. tomato. The related compounds, secosyrins 1 and 2, and syributins 1 and 2 have also been isolated. We tried to synthesize these bioactive compounds and several their derivatives hoping to develop the further useful compounds having stronger antiinflammatory activity. Thus, D-tartrate was taken as a starting material, which was converted to the tetrahydrofuran derivative. This compound was then transformed into the corresponding dioxaspiro one, from which the first total synthesis of (+)-secosyrins 1 and 2 was accomplished. This total synthesis of secosyrins 1 and 2 unambiguously established their absolute stereochemistry. We also could develop an efficient alternative way for the preparation of (+)-syributins 1 and 2. Based on the result so far obtained, we are now trying to synthesize more complex syringolides 1 and 2.