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The selectivity of simplicity - prebiotic investigations on Deoxyribonucleosides
The selectivity of simplicity - prebiotic investigations on Deoxyribonucleosides
This doctoral thesis presents the prebiotic synthesis of ribonucleosides (RNA) and deoxyribonucleosides. In search of prebiotic access to deoxyribonucleosides (DNA), a new approach to disconnect ribonucleosides was discovered. This new sugar-forming reaction improves the so far applied practice leading to ribonucleosides. Utilising this novel pathway, synthetic access to all canonical deoxyribonucleosides was achieved in one pot. The reactions are mild and highly prebiotically plausible. The implementation of multiple steps was avoided as well as the need for pure deoxyribose. By this approach, exclusive \bet-stereo- and furano-regioselectivity was achieved. Given its outstanding selectivity, the presented pathway to deoxyribonucleosides is considered the most plausible. By changing the sugar-precursors, nucleoside predecessors were discovered. A possible direct progenitor of DNA-nucleosides named deoxyapionucleosides (DApiNA) was discovered. For verification, a conventional synthetic method to DApiNA-nucleosides is presented, which might be relevant in fields apart from prebiotic interest. Another variation of the DNA-yielding pathway lead to a rational pathway to ribonucleosides, lacking impracticable and drastic variations of the synthetic conditions as previously applied. A concomitant DNA- and RNA-nucleoside synthesis was performed under the same conditions. Other than previously postulated, it is concluded that RNA- and DNA-nucleosides developed at the same stage of molecular evolution. Employing a cut-set of starting materials facilitated a simple, one-step formation of cytosine and adenine. Further, the application of this novel sugar-forming reaction to other heterocycles provided a rationale for the key-step in prebiotic riboflavin synthesis. The simple, but effective design of our novel sugar-forming reaction lead to the discovery of DNA- and RNA-nucleosides, its DApiNA-progenitor and synthetic access to riboflavin and is thus considered as highly prebiotically plausible.
prebiotic chemistry, DNA nucleoside synthesis, RNA nucleoside synthesis, cofactor synthesis, prebiotic building blocks
Kruse, Florian Michael
2021
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Kruse, Florian Michael (2021): The selectivity of simplicity - prebiotic investigations on Deoxyribonucleosides = Die Selektivität der Einfachheit - Präbiotische Betrachtungen zur Synthese von Desoxyribonukleosiden. Dissertation, LMU München: Faculty of Chemistry and Pharmacy
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Abstract

This doctoral thesis presents the prebiotic synthesis of ribonucleosides (RNA) and deoxyribonucleosides. In search of prebiotic access to deoxyribonucleosides (DNA), a new approach to disconnect ribonucleosides was discovered. This new sugar-forming reaction improves the so far applied practice leading to ribonucleosides. Utilising this novel pathway, synthetic access to all canonical deoxyribonucleosides was achieved in one pot. The reactions are mild and highly prebiotically plausible. The implementation of multiple steps was avoided as well as the need for pure deoxyribose. By this approach, exclusive \bet-stereo- and furano-regioselectivity was achieved. Given its outstanding selectivity, the presented pathway to deoxyribonucleosides is considered the most plausible. By changing the sugar-precursors, nucleoside predecessors were discovered. A possible direct progenitor of DNA-nucleosides named deoxyapionucleosides (DApiNA) was discovered. For verification, a conventional synthetic method to DApiNA-nucleosides is presented, which might be relevant in fields apart from prebiotic interest. Another variation of the DNA-yielding pathway lead to a rational pathway to ribonucleosides, lacking impracticable and drastic variations of the synthetic conditions as previously applied. A concomitant DNA- and RNA-nucleoside synthesis was performed under the same conditions. Other than previously postulated, it is concluded that RNA- and DNA-nucleosides developed at the same stage of molecular evolution. Employing a cut-set of starting materials facilitated a simple, one-step formation of cytosine and adenine. Further, the application of this novel sugar-forming reaction to other heterocycles provided a rationale for the key-step in prebiotic riboflavin synthesis. The simple, but effective design of our novel sugar-forming reaction lead to the discovery of DNA- and RNA-nucleosides, its DApiNA-progenitor and synthetic access to riboflavin and is thus considered as highly prebiotically plausible.