CAREER: Chemical and Biological Studies on Natural Modulators of Cell Signaling

本研究的重点是两类天然产物：紫素和绿素的全合成。通过电化学环闭合构建关键中间体将在这两种情况下进行研究。青紫素已被证明可以上调神经生长因子的合成，而病毒素是磷脂酰肌醇3-激酶的抑制剂，磷脂酰肌醇3-激酶是与细胞生长和癌症相关的关键信号酶。Wright教授的合作者将设计和合成这两类天然产物的类似物，并对其生物活性进行评估。Wright教授将他的本科有机化学课组织成5-8人的“学习社区”。这些小组每周将在讲座之外举行一小时的问题解决研讨会。进一步的创新将是让学生小组设计一种潜在候选药物的短合成（3-5步），然后为赖特教授的研究小组进行。有了这个职业奖，有机合成项目支持佛罗里达大学化学系的丹尼斯·赖特教授的研究。赖特教授的研究方向是两类天然产物的合成，即紫素和绿素。青紫素（可能是它们的类似物）刺激神经生长因子（NGF）的合成，可能用于替代外源性NGF的给药。病毒蛋白（可能还有它们的类似物）抑制一种与细胞生长相关的酶，可能被用作抗肿瘤药物。该项目的教育部分将在本科有机化学课程中引入解决问题和综合设计课程。

The proposed research focusses on the total synthesis of two classes of natural products, the cyathins and the viridins. Construction of key intermediates via an electrochemical ring closure will be investigated in both cases. The cyathins have been shown to upregulate the synthesis of nerve growth factor while the viridins are inhibitors of phosphatidylinositol 3-kinase, a key signaling enzyme linked to cell growth and cancer. The design and synthesis of analogs of both classes of natural product will be carried out and their biological activity will be evaluated by collaborators of Professor Wright. Professor Wright will organize his undergraduate organic chemistry class into "learning communities" of 5-8 students. These groups will meet for one hour per week outside of lecture for problem-solving workshops. A further innovation will be to have the student groups design a short (3-5 step) synthesis of a potential drug candidate that would then be carried out for Professor Wright's research group. With this CAREER award, the Organic Synthesis program is supporting the research of Professor Dennis Wright of the Department of Chemistry at the University of Florida. Professor Wright's studies are directed towards the synthesis of two classes of natural products, the cyathins and the viridins. The cyathins (and possibly their analogs) stimulate nerve growth factor (NGF) synthesis and could potentially be used in place of exogenous NGF administration. The viridins (and possibly their analogs) inhibit an enzyme associated with cell growth and could potentially be used as antitumor agents. The education component of the project will introduce problem-solving and synthesis design sessions into the undergraduate organic chemistry course.