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Synthetic Studies toward Surveying Biologically Active Compounds from Solubility

从溶解度调查生物活性化合物的综合研究

基本信息

批准号：
10672088
负责人：
TANAKA Tetsuaki
金额：
$ 2.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Macrocarpals exhibiting interesting biological activities such as inhibitory activity of HIV RTase is a coupling at C11 position of the hydrophobic sesquiterpene aromadendrane skeleton and at the benzylic position of the hydrophilic isopentyl phloroglucinol dialdehyde. Totally, they are water-soluble. The key step of the synthesis is the coupling reaction of a cyclic dienol ether corresponding to the aromadendrane part with a hexasubstituted benzene chromium complex as a chiral benzyl cation equivalent. The reaction proceeded with an extremely high stereoselective manner. The synthetic method developed here would be applicable to various compounds bearing different alkyl group from isobutyl group, and furthermore, demethylation procedure could control the deprotection step.On the way of the total synthesis of macrocarpal C, we found a new radical ipso-substitution reaction of an aromatic methoxy group. This new C-C bond formation reaction would have great possibilities in the filed of synthetic studies. Therefore, the scope and limitations were investigated with model compounds. In this reaction, the distance of the radical and the aromatic ring was found to be crucial. The limitation could be overcome by the chelation control with Sm (II) iodide. Namely, SmIィイD22ィエD2 generates a ketyl radical, and then is chelating intramolecularly to the oxygen atom of the methoxyl group. Therefore, the radical is easily approaching to the aromatic ring, thereby causing C-C bond formation. From these results, it was found that this new reaction takes place by making the radical close to the methoxy group on an aromatic ring.

具有HIV逆转录酶抑制活性等生物活性的大心形化合物是疏水倍半萜芳烃骨架的C11位和亲水的异戊基间苯三酚二醛的苯基位置的偶联产物。总而言之，它们是水溶性的。合成的关键步骤是以六取代苯铬络合物作为手性的苯基阳离子当量，与对应于芳烃部分的环状二烯醇醚发生偶联反应。反应以极高的立体选择性进行。该合成方法适用于含有不同烷基和异丁基的各种化合物，而且脱甲基化过程可以控制脱保护步骤。在全合成大腕C的方法上，我们发现了一个新的芳香族甲氧基的同位取代反应。这种新的C-C成键反应在合成研究领域具有很大的可能性。因此，用模型化合物研究了模型化合物的范围和局限性。在该反应中，自由基和芳香环的距离被发现是关键。这一局限性可以通过Sm(II)碘化物的络合控制来克服。也就是说，SmiィイD22ィエD2产生一个酮基自由基，然后在分子内与甲氧基的氧原子进行螯合。因此，自由基很容易接近芳环，从而导致C-C键的形成。从这些结果中发现，这个新的反应是通过使自由基接近芳环上的甲氧基而发生的。