Total Synthesis of Bicyclic Bioactive Diterpenoids

这项赠款申请的长期目标集中在以下几个方面： 具有良好生物活性的天然产物及其合成新产品的开发 方法：研究方法。新的合成方法的发展是简单、高效和 一般的范围仍然是一项基本的科学追求。这样的方法服务于 基础科学的许多需求，使新药物和新药物的开发成为可能 其他必需的化学结构。天然产品极大地影响了公众 通过作为新药的来源或主导结构，过去六十年来的健康。 目前使用的大部分抗生素和癌症治疗药物都是天然的。 天然产品或天然产品的衍生品。这份提案描述了设计 并对几种天然产物二萜类化合物执行高效的合成蓝图 具有独特和有前途的生物作用模式。这些合成的蓝图将 提供独特的天然产品混合结构的集合。这些 否则，无法访问的复合集合将有助于解开并揭示 生物学意义这些天然产物的结构特征中的每一个都发挥了作用， 预计将是进一步发展和应用的关键。网络的效率 此处详细说明的拟议合成路线是通过战略性地使用 不发达的氧化脱芳烃方案。它的机制和范围 将严格评估强大的氧化脱芳烃协议，以 支持非对称变体的开发，并为未来提供蓝图 申请。使用这种方法产生的合成子的反应性将是 在授权期内设立。这项拨款申请的目标是完成三个不同类别的完全合成 双环天然产物。在所有建议的合成方法中，完全适合 脱芳烃议定书，我们计划在授权期内研究和推进， 作为基石。我们高效的合成路线将被用来创造独特的 天然产品混合收藏，将被证明在解码这些天然的 产品的分子机制，这反过来又应该有助于推动它们的发展。 建议的新合成方法将使学术界和学术界的化学家受益。 医药行业因此直接或间接地影响着发现、研究、 新药的开发和生产。

The long term objectives of this grant application are focused on the total syntheses of natural products with promising biological profiles and the development of new synthetic methods. The development of new synthetic methods that are simple, efficient and general in scope continues to be an essential scientific pursuit. Such methods serve many needs of basic science and enable the development of new pharmaceuticals and other essential chemical structures. Natural products have greatly impacted public health over the last sixty years by serving as the source or lead structures for new drugs. A large percentage of currently used antibiotics and cancer therapeutics are natural products or derivatives of natural products. This proposal describes efforts to design and execute efficient synthetic blueprints towards several natural product diterpenoids with unique and promising biological modes of action. These synthetic blueprints will provide access to collections of unique natural product hybrid structures. These otherwise inaccessible compound collections will help unravel and shed light on the biological significance each one of these natural product structural features play, which is expected to be critical for further advancement and applications. The efficiency of the proposed synthetic routes detailed herein are enabled by strategic use of an underdeveloped oxidative dearomatization protocol. The mecahnism and scope of this powerful oxidative dearomatization protocol will be rigorously evaluated in order to enable development of asymmetric variants as well as to provide a blueprint for future applications. The reactivity of the synthons generated using this method will be established during the grant period. The goal of this grant application is to complete total syntheses of three different classes of bicyclic natural products. In all proposed synthetic approaches a perfectly suited dearomatization protocol, which we plan to study and advance during the grant period, serves as the cornerstone. Our efficient synthetic routes will be used to create unique natural product hybrid collections that will prove invaluable in decoding these natural products molecular mechanisms, which in turn should help advance their development. The new synthetic method proposed will benefit chemists both in academia and the pharmaceutical industry thus directly or indirectly impacting the discovery, study, development and production of new drugs.