Stereoselective Phosphorylation of Diols and Carbohydrates with N-Phosphoryl Oxazolidinones: Application to the Rapid Synthesis of Phosphoglycerides

自然界中的许多物质以两种不同的形式存在，称为对映体。这些分子具有相同的原子数量，并以相同的方式连接，只是有些原子的排列不同。你的两只手都是对映体--它们都是由相同的部位组成的(一个手掌、一个拇指和四个不同的手指)，并且都以相同的方式连接(拇指、食指、中指等等)。然而，连接的顺序不同，这导致你的左手和右手被关联为不可重叠的镜像。作为不可叠加镜像的物体或物质称为手性。自然界中的每一种手性物质和许多药物成分都具有不同的生物活性，因此人们致力于开发只能选择性地产生其中一种形式的化学反应。这些实验室的研究已经开发出一种通过形成磷酸酯来实现这种转化的全新方法。这样的反应是令人难以置信的有用的，因为这个反应形成的产物可以用作化学积木来构建其他更大的材料。该项目的目的是建立在这一新方法的基础上，并试图制造更复杂分子的磷酸酯，如碳水化合物、甘油酯和肌醇。这些反应的磷酸酯产物在生物学中是极其重要和有价值的材料，它们可以作为分子工具来研究细胞如何工作。我们方法的另一个优势是它可以选择性地、快速地在一个反应容器中进行，大大简化了制备这些物质所需的时间和精力。我们将通过构建几个具有生物活性的目标分子来证明这项工作的有效性，这些分子将用于谢菲尔大学基因组医学系的合作者。我们将研究为这个反应系统开发催化剂的方法，这将进一步简化程序，并进一步降低这些非常理想的产品的生产成本。

Many substances in Nature exist as two different forms called enantiomers. These molecules have the same number of atoms and are connected in the same way, except the arrangement of some of the atoms is different. Your hands are both enantiomers - both are made up of the same bits (a palm, one thumb and four different fingers) and all are connected in the same way (thumb, first finger, second finger and so on). However the order of connectivity is different which leads to your left and right hand being related as non-superimposable mirror images. Objects or substances that are non-superimposable mirror images are called chiral. Each of these chiral substances in Nature and many pharmaceutical ingredients have different biological activities and so much effort is devoted to developing chemical reactions that can selectively produce only one of these forms. Research from these laboratories has developed a completely new method for achieving such a transformation by formation of a phosphate ester. Such a reaction is incredibly useful since the products formed from this reaction can be used as chemical building blocks to construct other larger materials. The purpose of this project is to build upon this new methodology and to attempt to make phosphate esters of more complex molecules such as carbohydrates, glycerides and inositols. The phosphate ester products of these reactions are extremely important and valuable materials for use in biology where they can be used as molecular tools to investigate how cells work. The added advantage of our methodology is that it can be carried out selectivity, quickly and in one reaction vessel, significantly simplifying the time and effort required to prepare these substances.We will demonstrate the effectiveness of this work by constructing several biologically active target molecules that will be of use to collaborators in the Department of Genomic Medicine here at the University of Sheffield.We will investigate ways to develop a catalyst for this reaction system that will further simplify the procedure and reduce the cost of production of these highly desirable products even further.