オキサソール環の構築、開裂反応を基盤とする生理活性物質の合成研究

我们已经公开了4-烷氧基羰基恶唑可以通过使用叠氮磷酸二苯酯由羧酸和异氰基乙酸烷基酯有效地制备。4-烷氧基羰基恶唑可用作-羟基- -氨基酸配体。作为恶唑合成的一个应用，我们研究了从短小芽孢杆菌（Bacillus pumilus）AI-77中分离的胃保护物质AI-77-B的合成，其中包括两个关键片段，二氢异香豆素部分和羟基氨基酸部分。二氢异香豆素部分由6-甲基水杨酸衍生物和N-保护的亮氨酸一步制备。羟基氨基酸部分是通过从甘油酸衍生物和异氰基乙酸乙酯的相应恶唑立体选择性地制备。或者，以立体选择性方式从D-焦谷氨酸乙酯构建羟基氨基酸。在对每个部分进行适当的脱保护后，通过使用氰基磷酸二乙酯进行两个关键片段的偶联，得到具有腈官能团的AI-77-B衍生物。腈部分最终转化为羧酸部分，得到与天然产物相同的AI-77-B。

We have already disclosed that 4-alkoxycarbonyloxazoles can be efficiently prepared by use of diphenyl phosphorazidate from carboxylic acid and alkyl isocyanoacetate. 4-Alkoxycarbonyloxazoles can be utilized as -hydroxy- -amino acid synthons. As an application of the oxazole synthesis, a synthesis of AI-77-B, a gastroprotective substance isolated from Bacillus pumilus AI-77, has been investgated by a convergent approach involving the two key fragments, the dihydroisocoumarin part and the hydroxy amino acid one. The dihydroisocoumarin part was prepared from the 6-methylsalicylic acid derivative and N-protected leucinal in one step. The hydroxy amino acid moiety was stereoselectively prepared via the corresponding oxazole from the glyceric acid derivative and ethyl isocyanoacetate. Alternatively, the hydroxy amino acid was constructed from ethyl D-pyroglutamate in a stereoselective manner. After proper deprotection of each part, coupling of the two key fragment was carried out by use of diethyl phosphorocyanidate to give the AI-77-B derivative with the nitrile function. final transformation of the nitrile part to the carboxylic acid one furnished AI-77-B which was identical with the natural product.