Development of Novel Antiinflammatory Drugs Based on Nonproteinaceous Signal Molecules

基于非蛋白质信号分子的新型抗炎药物的开发

• 批准号: 09672277
• 负责人: MUKAI Chisato
• 金额: $ 2.37万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672277/
• 关键词: nonproteinaceous low molecular; elicitor; secosyrin; syributin; syringolide; total synthesis; テトラヒドロフラン環; Knoevenagel; エリサイタ-

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.

1993年，从大豆假单胞菌致病变种中分离到了一种新的非蛋白质低分子量代谢产物--大豆异黄酮内酯1和2。番茄相关的化合物，secocoacetins 1和2，和syributins 1和2也已被分离。我们尝试合成这些具有生物活性的化合物及其衍生物，希望能开发出具有更强抗肿瘤活性的化合物。因此，采用D-酒石酸盐作为起始材料，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氧杂螺酮，由此完成了（+）-开环甾体素1和2的首次全合成。开环皂苷1和2的这种全合成明确地建立了它们的绝对立体化学。我们还可以开发一种有效的替代方法来制备（+）-syributins 1和2。基于迄今为止所获得的结果，我们现在正试图合成更复杂的姜油内酯1和2。

项目成果

Chisato Mukai: "First Total Synthesis of (+)-Secosyrin 1." Tetrahedron Letters. 38. 2511-2512 (1997)

Chisato Mukai：“首次全合成 ( )-Secosyrin 1。”

Chisato Mukai: "Total Synthesis of (+)-Secosyrins 1 and 2 and (+)-syributins 1 and 2" J.Org.Chem.62. 8095-8103 (1997)

Chisato Mukai：“( )-Secosyrin 1 和 2 以及 ( )-syributins 1 和 2 的全合成”J.Org.Chem.62。

Chisato Mukai: "First Total Synthesis of (+)-Secosyrin 1" Tetrahedron Letters. 38. 2511-2512 (1997)

Chisato Mukai：“首次全合成 ( )-Secosyrin 1”四面体字母。

Chisato Mukai: "Total Syntheses of(+)-Secosyrins 1 and 2 and (+)-Syributins 1 and 2" J.Org.Chem.62. 8095-8103 (1997)

Chisato Mukai：“( )-Secosyrin 1 和 2 以及 ( )-Syributins 1 和 2 的全合成”J.Org.Chem.62。