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

拟开展的研究主要集中在两类天然产物的全合成上，即氰草素类化合物和绿豆素类化合物。在这两种情况下，都将研究通过电化学环闭合来构建关键中间体。苏铁菌素被证明能上调神经生长因子的合成，而绿色素类则是磷脂酰肌醇3-激酶的抑制剂，磷脂酰肌醇3-激酶是一种与细胞生长和癌症有关的关键信号酶。这两类天然产物的类似物将进行设计和合成，其生物活性将由赖特教授的合作者进行评估。赖特教授将把他的本科生有机化学班级组织成5-8名学生的“学习社区”。这些小组将在讲座之外每周聚会一小时，以解决问题。进一步的创新将是让学生小组设计一个潜在候选药物的简短(3-5步)合成，然后为赖特教授的研究小组进行。有了这个职业奖，有机合成项目将支持佛罗里达大学化学系的丹尼斯·赖特教授的研究。赖特教授的研究针对的是两类天然产物的合成，氰尿嘧啶和青霉素类。苏铁蛋白(及其类似物)可刺激神经生长因子(NGF)的合成，有可能取代外源性NGF的应用。这种绿色素类化合物(可能还有它们的类似物)抑制了一种与细胞生长相关的酶，有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问题解决和综合设计课程。

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.