Organocatalysis is a powerful approach to extend and (enantio‐) selectively modify molecular structures. Adapting this concept to the Early Earth scenario offers a promising solution to explain their evolution into a complex homochiral world. Herein, we present a class of imidazolidine‐4‐thione organocatalysts, easily accessible from simple molecules available on an Early Earth under highly plausible prebiotic reaction conditions. These imidazolidine‐4‐thiones are readily formed from mixtures of aldehydes or ketones in presence of ammonia, cyanides and hydrogen sulfide in high selectivity and distinct preference for individual compounds of the resulting catalyst library. These organocatalysts enable the enantioselective α‐alkylation of aldehydes under prebiotic conditions and show activities that correlate with the selectivity of their formation. Furthermore, the crystallization of single catalysts as conglomerates opens the pathway for symmetry breaking.

All evolutionary biological processes lead to a change in heritable traits over successive generations. The responsible genetic information encoded in DNA is altered, selected, and inherited by mutation of the base sequence. While this is well known at the biological level, an evolutionary change at the molecular level of small organic molecules is unknown but represents an important prerequisite for the emergence of life. Here, we present a class of prebiotic imidazolidine-4-thione organocatalysts able to dynamically change their constitution and potentially capable to form an evolutionary system. These catalysts functionalize their building blocks and dynamically adapt to their (selfmodified) environment by mutation of their own structure. Depending on the surrounding conditions, they show pronounced and opposing selectivity in their formation. Remarkably, the preferentially formed species can be associated with different catalytic properties, which enable multiple pathways for the transition from abiotic matter to functional biomolecules.

Nucleotides play a fundamental role in organisms, from adenosine triphosphate (ATP), the body‘s main source of energy, to cofactors of enzymatic reactions (e. g. coenzyme A), to nucleoside monophosphates as essential building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Although nucleotides play such an elemental role, there is no pathway to date for the selective formation of nucleoside 5′‐monophosphates. Here, we demonstrate a selective reaction pathway for 5’ mono‐phosphorylation for all canonical purine and pyrimidine bases under exceptionally mild prebiotic relevant conditions in water and without using a condensing agent. The pivotal reaction step involves activated imidazolidine‐4‐thione phosphates. The selective formation of non‐cyclic mono‐phosphorylated nucleosides represents a novel and unique route to nucleotides and opens exciting perspectives in the study of the origins of life.

Alle evolutionsbiologischen Prozesse führen zu einer Veränderung der vererbbaren Merkmale über nachfolgende Generationen hinweg. Die in der DNA kodierte genetische Information wird durch Mutation der Basensequenz verändert, selektiert und vererbt. Während dies auf der biologischen Ebene gut verstanden wird, ist eine evolutionäre Veränderung auf der molekularen Ebene kleiner organischer Moleküle unbekannt, stellt aber eine wichtige Voraussetzung für die Entstehung von Leben dar. In dieser Arbeit stellen wir eine Klasse von präbiotischen Imidazolidin-4-thion-Organokatalysatoren vor, die ihre Zusammensetzung dynamisch ändern können und möglicherweise in der Lage sind, ein evolutionäres System zu bilden. Diese Katalysatoren funktionalisieren ihre Bausteine und passen sich durch Mutation ihrer eigenen Struktur dynamisch an ihre (selbst modifizierte) Umgebung an. Abhängig von den Umgebungsbedingungen zeigen sie eine ausgeprägte und gegensätzliche Selektivität bei ihrer Bildung. Bemerkenswerterweise können die bevorzugt gebildeten Spezies mit unterschiedlichen katalytischen Eigenschaften verbunden sein, die mehrere Wege für den Übergang von abiotischer Materie zu funktionellen Biomolekülen ermöglichen.

Nucleotides play a fundamental role in organisms, from adenosine triphosphate (ATP), the body's main source of energy, to cofactors of enzymatic reactions (e.g. coenzyme A), to nucleoside monophosphates as essential building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Although nucleotides play such an elemental role, there is no pathway to date for the selective formation of nucleoside 5'-monophosphates. Here we demonstrate a selective reaction pathway for 5’ mono-phosphorylation for all canonical purine and pyrimidine bases under exceptionally mild prebiotic relevant conditions in water and without using a condensing agent. The pivotal reaction step involves activated imidazolidine-4-thione phosphates. The selective formation of non-cyclic mono-phosphorylated nucleosides represents a novel and unique route to nucleotides and opens exciting perspectives in the study of the origins of life.