SYNTHESIS OF ANTHRACYCLINONES

提出了一种通用的合成策略，用于合成几个 基于卡宾铬配合物与邻苯二甲酸二异氰酸酯的反应 乙炔。合成靶点包括柔红霉素的苷元 和阿霉素是治疗癌症的重要化疗药物 治疗多种人类癌症。该战略可以灵活地 允许合成11-氧基和11-脱氧基 我们建议从它发展出第一个收敛的 合成这两类主要的蒽环己酮类化合物。11-脱氧 由于这一发现，人们最近对蒽环己酮类药物感兴趣 这一类中的一些成员具有与阿霉素类似的活性 但心脏毒性水平有所降低。有人建议合成一种 这一类的六个成员的苷元，其中包括阿拉维酮( 阿克拉霉素的苷元)和7-酮-O-甲基橙花酚，半合成 诺加拉霉素的衍生物，不久将进入人类临床 审判。初步结果表明，该策略具有足够的灵活性。 为几种非天然单核苷酸的区域选择性合成提供了条件 阿拉维酮的氟衍生物。

A general synthetic strategy is presented for the synthesis of several anthracyclinones based on the reactions of chromium carbene complexes with acetylenes. The synthetic targets include the aglycones of daunorubicin and adriamycin which are important chemotherapeutic agents for the treatment of a broad range of human cancers. The strategy is flexible to allow for the synthesis of both the 11-oxy and the 11-deoxy anthracyclinones and we propose to develop from it the first convergent synthesis for these two major classes of anthracyclinones. The 11-deoxy anthracyclinones have been of more recent interest due to the finding that some memberrs of this class have comparable activity to that of adriamycin but with a reduced level of cardiotoxicity. It is proposed to synthesize the aglycones of six members of this class which include aklavinone (the aglycone of aclacinomycin) and 7-con-o-methylnogarol, a semi-synthetic derivative of nogalamycin, which will shortly go into human clinical trials. Preliminary results indicate that this strategy is flexible enough to provide for the regioselective synthesis of several unnatural mono fluoro derivatives of aklavinone.