<p>In this thesis, mechanistic and synthetic studies on transformations of H-phosphonates into DNA analogues containing P-S or P-C bonds are described. </p><p>Configurational stability of dinucleoside H-phosphonates and the stereochemical course of their sulfurisation in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were investigated. In light of these studies, the reported stereoselective sulfurisation of dinucleoside H-phosphonates and benzoylphosphonates in the presence of DBU was proved to be incorrect.</p><p>Efficient protocols for the synthesis of new nucleotide analogues with non-ionic C-phosphonate internucleotide linkages were developed. The synthesis of dinucleoside 2-pyridylphosphonates was successfully performed by a DBU-promoted reaction of H-phosphonate diesters with <i>N</i>-methoxypyridinium salts. The thio analogues, 2-pyridyl- and 4-pyridyl phosphono<i>thio</i>ate diesters, could be obtained by modifying the reactions developed for their oxo counterparts. Dinucleoside 3-pyridylphosphonates were prepared <i>via</i> a palladium(0)-catalysed cross coupling strategy that could be extended also to the synthesis of nucleotide analogues with metal-complexing properties, <i>i.e</i>. terpyridyl- and bipyridylphosphonate derivatives.</p><p>Oligonucleotides modified with pyridylphosphonate internucleotide linkages have been prepared and preliminary studies on their hybridisation properties and resistance towards enzymatic degradation were performed.</p><p>Finally, nucleotidic units for the incorporation of pyridylphosphonate groups at the 5’-terminus of oligonucleotides were designed. Condensations of such units with a suitably protected nucleoside afforded after oxidation the expected dinucleoside (3’-5’)-phosphates with pyridylphosphonate monoester functions at the 5’-ends.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:su-202 |
| Date | January 2004 |
| Creators | Johansson, Tommy |
| 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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