Innovative Approaches to Macrocyclic Natural Products

化学部化学合成计划支持里奇·G·卡特教授的这一项目。卡特教授和他的合作研究员张教授都是俄勒冈州立大学化学系的教员。他的团队正在探索一系列令人兴奋的新聚酮类天然产品的化学成分，这些产品被称为扁桃内酯和马德罗内酯。这项提议的总体目标是为这些天然产物的构建开发创新的方法，从而在反应和战略开发方面推动该领域的发展。这些化合物显示出良好的细胞毒性和抗真菌活性。该项目汇集了实验(卡特教授)和计算(张教授)有机化学方面的专业知识。卡特教授的团队处于有利地位，可以为科学界代表性不足的学生提供最高水平的教育和培训。参与该项目的学生的职业发展努力被整合到该计划中。此外，还计划开展外联活动，让更广泛的社区了解化学的重要性。复杂天然产物的全合成已被证明是开发新的合成策略以及验证新的化学方法的重要试验台。杏仁内酯A-B和马兜铃内酯A的拟议合成突破了现代有机合成的极限。一种新的方法是开发一种可靠的顺式烯烃不对称双羟基化快速获得反式二醇的方法，这是这些项目不可或缺的。此外，建议的合成展示了银催化的炔丙基苯甲酸酯的环化反应。该教育计划包括通过俄勒冈州立大学的NSF研究生研究培训基金(NRT IGE)拨款为研究生提供专业发展培训，以及通过在俄勒冈州内另外一到两所学校开展外联活动让社区参与进来。

The Chemical Synthesis Program of the Chemistry Division supports this project by Professor Rich G. Carter. Professor Carter and his co-investigator, Professor Cheong, are both a faculty members in the Department of Chemistry at Oregon State University. His group is exploring the chemistry of an exciting new series of polyketide natural products called the mandelalides and madeirolides. The overarching goal of this proposal is to develop innovative methods for the construction of these natural products, which advance the field in both reaction and strategy development. These compounds have shown promising cytotoxic and antifungal activities. The project brings together expertise in both experimental (Professor Carter) and computational (Professor Cheung) organic chemistry. Professor Carter's group is well positioned to provide the highest level of education and training for students underrepresented in science. Professional development efforts for students participating in this project are integrated into the program. In addition, outreach activities to engage the broader community on the importance of chemistry are planned. The total synthesis of complex natural products has proven to be an important test bed for the development of new synthetic strategy as well as for the validation of novel chemical methodologies. The proposed syntheses of mandelalides A-B and madeirolide A push the limits of modern organic synthesis. One new methods is the development of a reliable asymmetric dihydroxylation of cis-alkenes to rapidly access trans diols, which is integral to these projects. In addition, the proposed syntheses showcase silver-catalyzed cyclizations of propargylic benzoates. The educational plan includes professional development training for graduate students through an NSF Graduate Research Trainingship Innovation in Graduate Education (NRT IGE) grant at Oregon State University and community engagement through outreach activities at one or two additional schools within the State of Oregon.