Synthese von 3'-Aminonukleosiden (English shop)

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Chemical modification of nucleosides offers new opportunities for synthesizing functionalized DNA structures and investigating nonenzymatic replication processes.
Ralf Eisenhuth’s dissertation investigates the synthesis of 3’-amino-2’,3’-dideoxynucleosides and their application in preparing amino-modified oligonucleotides.
The research begins with naturally occurring deoxynucleosides containing the four canonical nucleobases adenine, cytosine, guanine, and thymine.
Efficient synthetic routes consisting of five to six reaction steps are developed to obtain the corresponding aminonucleosides.
For pyrimidine derivatives, amino functionality is introduced through anhydronucleoside intermediates followed by azide reduction.
Purine derivatives are prepared through oxidation and reduction reactions combined with substitution under Mitsunobu conditions.
The resulting aminonucleosides are protected and subsequently immobilized on Controlled Pore Glass supports for solid-phase DNA synthesis.
A hexafluoroglutaric acid linker proves particularly suitable for enabling reliable oligonucleotide chain elongation.
Automated DNA synthesis is then employed to produce oligonucleotides containing a terminal 3’-amino group.
These 3’-amino primers successfully undergo rapid and complete chemical primer extension reactions.
Another major research focus involves synthesizing 3’-amino-2’,3’-dideoxynucleoside 5’-monophosphates derived from adenosine, thymidine, and cytidine.
The resulting aminophosphates serve as precursors for preparing fluorescently labeled monomers used in chemical primer extension.
Overall, the dissertation establishes important synthetic foundations for developing amino-modified DNA systems and nonenzymatic methods for analyzing genetic information.