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

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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.