ASYMMETRIC SYNTHESIS OF ANTITUMOR AGENTS

抗肿瘤剂的不对称合成

• 批准号: 2501135
• 负责人: JAMES S. PANEK
• 金额: $ 22.5万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-13 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2501135
• 关键词: antineoplastic antibiotics; biological products; carbene; catalyst; chemical synthesis; drug design /synthesis /production; hydrogen bond; intermolecular interaction; ligands; metals; phosphatase inhibitor; silanes; stereochemistry; stereoisomer

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.

描述：（主要研究者）本研究提案反映了我们的 在新的反应过程和试剂的开发兴趣， 不对称催化和无环立体控制领域。 目标 我们打算追求的重点是发展和应用 手性硅烷试剂，虽然在方法学上具有很强的活性， 发展超出了这个计划的范围。 我们的短期 目标是获得一个关于 少量官能化手性烯丙基硅烷的合成用途 而不是大量的硅烷试剂， 它们在合成中的用途。 预算期间将追求的新方向 这一建议将集中在改善现有的反应期 关于催化不对称卡宾插入到 杂原子氢键 我们还将继续发展双 立体分化反应及其在合成 来自陆地和海洋的抗肿瘤抗生素 源 我们的目标是鉴定和开发用于手性金属催化剂， 催化的不对称分子间卡宾插入反应 杂原子-氢键（X-H）。 虽然一个深入的机械 评估超出了本计划的范围，这是我们的短期目标。 目的是开发一些有用的合成转换使用此 方法论 作为这项技术的新方向，我们将开发新的 介绍了合成新型手性硅烷试剂D或 L-α-氨基酸、α-羟基酸和α-硫代酸。 我们打算继续努力， 除草霉素A合成我们的一贯目标是完成 真菌三烯素-I和三烯霉素的不对称合成。 我们的目标是完成乌拉内酯A的不对称合成。 我们还打算开始合成和立体化学归属的 相关天然产物卡比胺C。 我们的目标是进行磷酸酶的不对称合成 抑制剂nodularin和motuporin。