Development of Novel Antiinflammatory Drugs Based on Nonproteinaceous Signal Molecules

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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.