著者

室伏 良信 木村 美佐子 桑野 晴光 飯島 康輝 山崎 光郎 金子 正勝

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.10, pp.3760-3769, 1988-10-25

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Addition reactions of the C^<4′>-C^<5′> double bond of griseolic acid were investigated. C^<4′>-C^<5′>Dihydrogrisiolic acid was obtained by reduction of the adduct having halogen at the 4′-position.The ring juncture of the two five-membered rings of the C^<4′>-C^<5′> dihydro derivaticves was of all-"cis"configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1′-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C^<4′>-C^<5′> cis dihydrogriseolic acid derivative was weaker than that of griseolic acid.The uracil derivative of C^<4′>-C^<5′> cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3′, 5′-cyclic monophosphate (cAMP) and guanosine 3′, 5′-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C^<4′>-C^<5′>trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.