115(P52) 抗真菌活性天然物UK-2Aおよびその類縁体の合成と生理活性(ポスター発表の部)

概要

論文の詳細を見る
UK-2A which has recently been isolated from the mycelial cake of Streptomyces sp. 517-02, possesses nine-membered dilactone and a picolinic acid moiety. The plane structure of UK-2A has been elucidated by ^1H and ^<13>C NMR analyses and chemical degradation studies, but the relative and absolute configurations of the four chiral centers in UK-2A still remain to be determined. UK-2A has strongly inhibited the growth of various kinds of yeasts and filamentous fungi, but its cyctotoxic activities against several kinds of mammalian cells were very weak. The combination of its interesting molecular architecture and the potent antifungal activity prompted us to launch the total synthesis of UK-2A. The synthesis of UK-2A has been achieved through a 12-step sequence from 7 in 26% overall yield. The key strategy employed in this approach involves; (1) construction of the three consecutive chiral centers from C_2 to C_4 based upon the well-established Evans aldol reaction and (2) the nine-membered lactonization. Our synthetic route to UK-2A would permit a practical and reliable construction of UK-2A and a variety of its analogs. In order to define the selective cytotoxicities of UK-2A against yeasts and filamentous fungi, UK-2A and its analogs synthesized were subjected to the MIC evaluation and cytotoxic activity examination compared with the reference compounds, amphotericin B and fluconazole. As summarized in Table 1, UK-2A has a broad antifungal spectrum, while its cytotoxicities was considerably weak compared to other substrates. The results of the UK-2A analogs suggested that the basicity of the picolinic acid moiety in UK-2A was essential for the antifungal activities and that the feature of the nine-membered dilactone contributed to the selective cytotoxicities.
1998-08-31

115(P52) 抗真菌活性天然物UK-2Aおよびその類縁体の合成と生理活性(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク