CAREER: Chemoselective Tools for Exploration of Natural Product Chemical Space

在美国国家科学基金会生命过程化学项目的CAREER奖的支持下，印第安纳大学的Erin Carlson教授将领导一个研究项目，该项目将专注于开发和应用化学选择方法来探索天然产物的化学空间。对天然产物的持续研究对于发现小分子来探测生物过程，作为治疗线索，以及为合成和生物合成研究确定新的分子结构至关重要。目前的分离策略促进富集基于一套有限的机制，依赖于物理性质，如溶解度或大小。产生一种通过独特和互补机制（如官能团组成）分离化合物的方法，将代表该领域的重大进步，也是拟议研究的主要目标。Carlson教授实验室的初步工作已经产生了一种用于富集含醇天然产物的标记策略，并证实了这种方法有助于检测低丰度物种的能力。该奖项将使更多功能基团类的标记策略得以实现，并将这些工具应用于探索无数天然产物来源，从而发现新的天然产物和新的化学支架。授予印第安纳大学卡尔森教授的终身成就奖将产生一系列更广泛的影响。将特别强调利用天然产物作为一个平台，以激发对化学的兴趣和欣赏，特别是在女孩和青年妇女中。女孩往往感觉不到与科学的联系——她们不了解科学对她们生活的用处或相关性，也无法与她们认为是科学家的人建立联系。需要培养和培养对科学的兴趣，以鼓励女孩继续接受科学教育。PI将开发名为“天然产品”和“点燃好奇之火”的外展项目，以激发当地小学和中学女生对科学的兴趣。本课程将向学生介绍天然产品，重点是植物产生的化合物。制作的外联材料将通过互联网广泛传播，使全世界的教师都能利用这些资源。到目前为止，这个计划已经与超过125名学生分享，现在已经成为印第安纳州南部女童子军的官方活动。天然产物也将被用作印第安纳大学实验室课程开发的灵感来源，使其更接近真实的研究经验。探究式模块将设计和包括在入门和高级有机实验室。

With the support of a CAREER award from the Chemistry of Life Processes Program at the National Science Foundation, Professor Erin Carlson of Indiana University will lead a research program that will focus on the development and application of chemoselective methods for the exploration of natural product chemical space. Continued investigation of natural products is essential for the discovery of small molecules to probe biological processes, as therapeutic leads, and to identify new molecular architectures for synthetic and biosynthetic studies. Current isolation strategies facilitate enrichment based on a restricted set of mechanisms that are dependent upon physical properties such as solubility or size. Generation of a method that separates compounds by a unique and complementary mechanism, such as functional group composition, would represent a major advance in the field and is a major goal of the proposed research. Preliminary work in Professor Carlson's lab has resulted in the generation of a tagging strategy for the enrichment of alcohol-containing natural products and confirmed the ability of this method to facilitate detection of low abundance species. This award will enable pursuit of tagging strategies for additional functional group classes and application of these tools to the exploration of myriad natural products sources resulting in the discovery of new natural products and novel chemical scaffolds.This CAREER award to Professor Carlson of Indiana University will result in a number of broader impacts. Of particular emphasis will be the utilization of natural products as a platform to ignite an interest in and appreciation for chemistry, especially in girls and young women. Girls often do not feel a connection with science - they lack an understanding of how it is useful or relevant to their lives and cannot relate to the people they perceive as being scientists. Interest in science needs to be generated and nurtured to encourage girls to continue with science education. The PI will develop an outreach program called Natural Products and Lighting the Fire of Curiosity to ignite an interest in science in local elementary and middle school aged girls. This program will introduce students to natural products, focusing on compounds produced by plants. The outreach materials generated will be broadly disseminated via the internet to enable teachers worldwide to utilize these resources. To date, this program has been shared with over 125 students and is now published as an official activity available to Girl Scout troops throughout southern Indiana. Natural products will also be used as inspiration for the development of laboratory curriculum at Indiana University that more closely resemble genuine research experiences. Inquiry-based modules will be devised and included in both introductory and advanced organic laboratories.