International Research Fellowship Program: Enantioselective Synthesis of Spiro[Pyrrolidine and- Pyrrolidinone-Oxindoles and Indolines: The Total Synthesis of - Pauciflorine A

[00:50 . 09]沃尔特曼国际研究奖学金计划使美国科学家和工程师能够在国外进行三到二十四个月的研究。该计划的奖励为联合研究提供了机会，并利用独特或互补的设施、专业知识和国外的实验条件。该奖项将支持Andrew W. Waltman博士与Erick M. Carreira博士在瑞士苏黎世的瑞士联邦理工学院（ETH）进行为期22个月的研究。传统上，许多候选药物是由天然来源的化合物衍生或启发的有机化合物。这些天然产物的复杂性和挑战性促使人们发现了构建它们的新方法。由于大多数先进的有机化合物都是手性的，这意味着它们在空间中具有两种被称为对映体的原子镜像取向，这一事实使这种努力变得更加复杂。通常，安全有效药物的合成要求有机化合物仅作为这些镜像中的一种。不幸的是，选择性地形成两种可能的对映体中的一种通常并不容易。现代合成有机研究的一个主要组成部分是对映选择性反应的发展，这意味着它们选择性地只形成单一的对映体。吲哚类生物碱是一类非常大的有机化合物，它为合成提供了特别有前途的目标。在吲哚类生物碱中，有一大类化合物具有一种称为螺旋[吡咯烷]单元的分子结构，这种结构特别难以形成。最近，在宿主实验室中开发了一种有效的方法来研究这些分子。利用这种技术，已经实现了几种非常复杂的有机分子的非对映选择性合成。这个项目将涉及对先前发现的反应进行修饰，使其具有对映选择性。一旦这一目标实现，第二个任务将是将这种方法应用于复杂有机分子Pauciflorine a的对体选择性合成。Pauciflorine a或与其相关的化合物，可能有一天会作为皮肤癌的治疗方法，因为它已经被观察到可以抑制黑色素细胞中的生物合成。除此之外，螺旋[吡咯烷]单元的对映选择性形成可能有助于大量吲哚生物碱的合成，从而扩大了有机化学家可以获得的化合物的范围。其中许多可能具有新的药用价值。卡雷拉教授的实验室处于有机合成研究的前沿。

0502009WaltmanThe International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-two-month research fellowship by Dr. Andrew W. Waltman to work with Dr. Erick M. Carreira at the Swiss Federal Institute of Technology (ETH), in Zurich, Switzerland.Traditionally, many drug candidates are organic compounds derived from, or inspired by compounds obtained from, natural sources. The complexity and challenge of these natural products has driven the discovery of new methods of constructing them. Such endeavors are further complicated by the fact that most advanced organic compounds are chiral, meaning that they have two mirror-image orientations of atoms in space, called enantiomers. Often, the synthesis of safe and effective drugs requires that organic compounds are made as only one of these mirror images. Unfortunately, it is not often easy to selectively form only one of two potential enantiomers. A major component of modern synthetic organic research is the development of reactions that are enantioselective, meaning that they selectively form only a single enantiomer (enantiomers). One very large class of organic compounds, the indole alkaloids, offers especially promising targets for synthesis. Among the indole alkaloids, there is a large class of compounds that feature a molecular architecture called a spiro[pyrrolidine] unit, which is particularly difficult to form. Recently, an efficient approach to these molecules has been developed in the host laboratory. Using this technique, several non-enantioselective syntheses of very complicated organic molecules have been achieved. This project will involve the modification of the previously discovered reaction to render it enantioselective. Once this goal has been met, the second task will be to apply this approach in the enantioselective synthesis of a complicated organic molecule, Pauciflorine A. Pauciflorine A, or compounds related to it, may one day serve as skin cancer therapies, since it has been observed to inhibit melanin biosynthesis in melanoma cells. Beyond this, the enantioselective formation of the spiro[pyrrolidine] unit may aid in the synthesis of a large number of indole alkaloids, thereby expanding the scope of compounds attainable by organic chemists. Many of these may possess novel medicinal value of their own. The laboratory of Prof. Carreira is at the forefront of synthetic organic research.