Synthesis of azatriquinacene ; and, Backbone modified DNA using transition metal catalysts
Azatriquinacene (10-Azatricyclo[18.104.22.168"10]deca-2,5,8-triene) and azatriquinadiene (10-Azatricyclo[5.2.1.01"0]deca-2,8-diene) have been synthesised in respectively eight and seven steps from pyrrole. 27 Woodward dimerisation4 of azatriquinacene has beenattempted although no evidence of diazadodecahedraneh as yet been found. A unique nonacyclic species (10-Azatricyclo[22.214.171.124''10]-2,9-bis[1-azatricyclo [5.2.1.01'10]decane]dec-l-eneh) as been obtained by trimerisation of an enamine.Its structure and extraordinarily high basicity (pKa 25.1) make it a new class of "proton sponge". During this study thirteen new substituted azatriquinanes and four new substituted azabicycles have been synthesised, and nine crystal structures have been solved, providing valuable insights into the chemistry and structure of this novel heterocyclic system. The synthesis of a DNA building block containing a linker with an amine has been accomplished and its capacity to accommodate interesting molecules in an internal position of an oligonucleotide was proved by the attachment of the amino acid arginine. The coupling of the above dinucleotide with bis(disopropylamino)cyanoethyl phosphite has been achieved with the aim of making this material suitable for solid support synthesis as used in automated DNA synthesisers. A new methodology for the synthesis of H-phosphonates has been developed based upon three nucleophilic substitutions onto phosphorus trichloride in one pot. We have developed an easy and efficient way to carry out the palladium catalysed cross-coupling reactions using sealed, thick walled reaction vials. A new method for the synthesis of alkynylphosphonates from 1,1-dibromo-l-alkenes has been developed and the synthesis of a new alkyne-containing thymidine dimer has been achieved. Vinylphosphonate-linked dinucleotides have been prepared using an olefin crossmetathesis reaction as a key step.