Stereoselective Phosphorylation of Diols and Carbohydrates with N-Phosphoryl Oxazolidinones: Application to the Rapid Synthesis of Phosphoglycerides
Lead Research Organisation:
University of Sheffield
Department Name: Chemistry
Abstract
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.
Organisations
People |
ORCID iD |
Simon Jones (Principal Investigator) |
Description | The purpose of this project was to develop a strategy 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 approach would be that it can be carried out selectivity, quickly and in one reaction vessel, significantly simplifying the time and effort required to prepare these substances. The work conducted aimed to investigate the fundamental chemical processes that occur during the key reaction in this strategy. New mechanistic models to account for the processes occuring were proposed and tested through experiment. Although significant progress was made, and important new concepts in terms of stereocontrol in phosphoryl transfer developed, further experimentation is required to substantiate these hypotheses. |
Exploitation Route | In its present form, this work still requires further development. A long term goal would be to produce methodology that would be simple enough for researchers not trained in synthetic organic chemistry to be able to conduct these transformations to prepare the target biological molecules, specifically phospholipids and glycerides. If successful in the future, this strategy will provide a simple method for the rapid preparation of biological molecules such as phospholipids and glycerides. This methodology may be of benefit to researchers working in chemical or biochemical research laboratories. |
Sectors | Chemicals |
URL | http://simon-jones.staff.shef.ac.uk |
Description | We were recently able to further investigate the chemistry described in this proposal and have established further scientific insight into the reasons why perhaps some of the transformations attempted were not successful. See dx.doi.org/10.1016/j.tetasy.2014.08.003 |
Sector | Chemicals |
Description | Selective Phosphorylation with N-Phosphoryl Oxazolidinones |
Amount | £80,464 (GBP) |
Funding ID | Voucher no: 05000328 |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 09/2005 |
End | 08/2009 |