ASYMMETRIC SYNTHESIS OF ANTITUMOR AGENTS

描述：(首席调查者)这项研究建议反映了我们的 对开发新的反应工艺和试剂感兴趣 不对称催化和非环立体控制领域。目标 我们打算追求的将专注于开发和应用 手性硅烷试剂，尽管方法学上的活性很高 开发不在本计划的范围之内。我们的短期计划 目标(S)是为了获得一个完善的数据库，关于 少量手性手性烯丙基硅烷的合成应用 而不是大量的硅烷试剂，而不是更少的信息 它们在合成中的应用。预算期间要追求的新方向 这项建议的期限将集中在改善现有的反应上 催化不对称卡宾插入的方法学 杂原子-氢键。我们也将继续发展双赢 立体区分反应及其在合成中的应用 来源于陆地和海洋来源的抗肿瘤抗生素 消息来源。 我们的目标是识别和开发手性金属催化剂，用于 催化的不对称分子间卡宾插入反应 杂原子-氢(X-H)键。尽管一个深入的机械论 评估不在本计划的范围内，这是我们的短期计划 目的开发一系列有用的合成变换。 方法论。作为这项技术的新方向，我们将开发新的 新型手性硅烷试剂D或 L--α-氨基酸、α-羟基酸和α-硫代酸。 我们打算继续努力，以期完成不对称 合成除草霉素A是我们一直以来的目标 霉菌素-I和三环素的不对称合成。 我们的目标是完成乌拉帕里德A的不对称合成。 我们还打算启动合成和立体化学指定 相关天然产物卡比拉胺C. 我们的目标是追求磷酸酶的不对称合成 抑制剂根瘤菌素和莫托普林。

DESCRIPTION: (Principal Investigator's) This research proposal reflects our interest in the development of new reaction processes and reagents in the areas of asymmetric catalysis and acyclic stereocontrol. The objectives that we intend to pursue will focus on the development and application of chiral silane reagents, although intensive activity in methodology development is outside the scope of this program. Our short term objective(s) is to obtain a well-developed data base concerning the synthetic utility of a small number of functionalized chiral allylsilanes rather than a larger number of silane reagents with less information on their use in synthesis. A new direction to be pursued during the budget period of this proposal will focus on the improvement of existing reaction methodology concerning catalytic asymmetric carbene insertions into heteroatom-hydrogen bonds. We will also continue the development of double stereodifferentiating reactions and applications to the synthesis of antitumor antibiotics derived from terrestrial sources as well as marine sources. It is our aim to identify and develop chiral metal catalysts for the catalyzed asymmetric intermolecular carbene insertion reactions into heteroatom-hydrogen (X-H) bonds. Although an in-depth mechanistic evaluation is outside the scope of this program, it is our short term objective to develop a number of useful synthetic transformations using this methodology. As a new direction for this technology we will develop novel approaches to the synthesis of new chiral silane reagents, D or L-alpha-amino acids, alpha-hydroxy acids and alpha-thio acids. We intend to continue our efforts aimed at the completion of the asymmetric synthesis of herbimycin A. It is our continuing objective to complete the asymmetric syntheses of mycotrienin-I and trienomycin. It is our objective to complete the asymmetric synthesis of ulapualides A. We also intend to initiate the synthesis and stereochemical assignment of the related natural product kabiramide C. It is our objective to pursue the asymmetric synthesis of the phosphatase inhibitors nodularin and motuporin.