<p>In this thesis oxidative coupling of H-phosphonate and H phosphonothioate diesters with different alcohols and amines are presented. Since the reactions with alcohols previously have been particularly unfavourable due to competing side reactions, a modified protocol leading to high coupling yields of structurally diverse hydroxylic components was developed. The phosphorylation reaction was studied using <sup>31</sup>P NMR spectroscopy and for the first time the previously only postulated reactive intermediate involved in these reactions was observed. </p><p>The use of iodine in combination with a bulky chlorosilane in pyridine was found to have a profound effect on both the suppression of side reactions and the rate of the oxidative couplings, and led to a clean formation of phosphorylated products in high yields. This synthetic protocol was then extended to include coupling reactions with bis-functional reagents containing hexamethylene linkers to provide handles for derivatisations of oligonucleotides.</p><p>A synthetic protocol consisting of the stereospecific oxidative coupling of amines with H-phosphonate diesters to produce phosphoroamidates was designed in such a way that it permitted control of the stereochemical outcome of the reactions.</p><p>Based on a silylation-mediated reaction utilising phenyl H phosphonothioate monoester as a thiophosphonyl transferring agent, a method was developed and used for the preparation of H-phosphonothioate building blocks for the synthesis of DNA analogues.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:su-203 |
| Date | January 2004 |
| Creators | Nilsson, Johan |
| Publisher | Stockholm University, Department of Organic Chemistry, Stockholm : Institutionen för organisk kemi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
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