Imidazolidine-4-thiones as prebiotic organocatalysts and substrates

Ebeling, Marian Simon Rafael (2026): Imidazolidine-4-thiones as prebiotic organocatalysts and substrates: enantioselective cyclizations and emergence of compartmentalization on early earth. Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

After previous studies identified imidazolidine-4-thiones as versatile organocatalysts and the Trapp Group additionally classified them as prebiotically plausible, it was of great interest to investigate the properties of these structures as catalysts and substrates in more detail. In the first part of this thesis, the effectiveness of S- and N-alkylated imidazolidine-4-thiones, among others, as organocatalysts was investigated. For this purpose, a synthesis route based on the amino acid phenylalanine was developed that does not require the use of H2S gas or a cyanide source. In order to compare it with previously tested N3-methylated imidazolidine-4-thiones and related MacMillan catalysts, the synthesized catalyst library was evaluated in a previously extensively studied Diels-Alder reaction of cyclopentadiene with trans-cinnamaldehyde. The yield, enantiomeric excess, and diastereomeric ratio were determined using chiral GC. Analysis of side products identified hexahydro-1H-pyrrolo[1,2-c]imidazole as the core structure, which is formed by a reaction of the catalyst with two equivalents of cinnamaldehyde. The synthesis of the side product was optimized and the reaction mechanism and enantioselectivity of the reaction were investigated using DFT calculations. In the second part of this thesis, the organocatalyzed aldol oligomerization of acetaldehyde by prebiotically plausible imidazolidine-4-thiones was investigated. Due to the dynamic exchange of the catalyst carbonyl substituents, oligomerized aldehydes could also be incorporated into the catalyst. The distribution of these products was tracked over time using high-resolution mass spectrometry. Due to cloudiness in the reaction, it was examined for light-refracting macroscopic particles using (fluorescence) microscopy. Oil droplets and vesicles were identified, whose size and properties were characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM).

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: origin of life, molecular evolution, emergent compartmentalization, organocatalysis, cyclization
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date of oral examination: 12. May 2026
• 1. Referee: Trapp, Oliver
• Signature of the printed copy: 0001/UMC 32014