THE SYNTHESIS OF SOME COMPLEX CYTOTOXIC COMPOUNDS

我们打算实现以下综合目标 在申请资助的时间范围内 首先，我们打算完成vertisporin问题，它应该 只需要一个研究生一年的时间。 我们已经投资 花了很多时间，但我们现在知道怎么做了 正常 这个问题的一个主要组成部分， 学习新的化学，涉及一些应用 有机锡试剂与糖衍生的酮反应。 这些 反应产生的立体化学是相反的更多 用这种类型的酮观察到的常见立体化学。 因此，在本发明中， 沿着完成vertisporin的合成，我们打算 研究有机锡烷试剂的立体化学， 与许多糖衍生的酮反应。 第二，我们打算开展一项相当雄心勃勃的计划， 冈田酸的全合成。 这种分子是一种复合物 细胞毒性离子载体，其结构要求许多有趣的 立体化学问题。 在过去的一年里，我们开发了， 通过考虑离子载体一般，新的方法，基于 乙烯基吡咯烷酮的化学性质， 这些天然产物所带来的复杂的立体化学问题 产品. 冈田酸在其结构框架内具有 大多数立体化学问题由离子载体提出。 由于分子具有作为已知分子的额外优点， 抗肿瘤物质，而且由于冈田酸的结构 酸提出了立体化学问题的当前意义，我们 我打算用这种天然产品来证明和进一步 开发我们新方法的功效

It is our intention to accomplish the following synthetic goals within the time frame requested for this grant application. Firstly, we intend to finish the vertisporin problem, which should only take a year of one graduate student's time. We have invested a lot of time in this problem, but we now know how to do it properly. A major component of this problem, in terms of learning new chemistry, concerns the application of some organotin reagents to reaction with sugar-derived ketones. These reactions yield stereochemistry that is the reverse of the more usual stereochemistry observed with ketones of this type. Thus, along with finishing the synthesis of vertisporin, we intend to examine the stereochemistry of organostannane reagents in reaction with a number of sugar-derived ketones. Secondly, we intend to embark on a rather ambitious project, the total synthesis of okadaic acid. This molecule is a complex cytotoxic ionophore, the structure of which asks many interesting stereochemical questions. Over the past year, we have developed, via a consideration of ionophores in general, new methods, based on the chemistry of vinylogous urethanes, to deal with the intricate stereochemical problems presented by these natural products. Okadaic acid holds within its structural framework a majority of the stereochemical problems presented by ionophores. Since the molecule has the additional virtue of being a known anti-tumor substance, and further since the structure of okadaic acid presents stereochemical problems of current significance, we intend to use this natural product to demonstrate and further develop the efficacy of our new methods.