Formaldehyde as a Catalyst: Investigations on the Role of Formaldehyde as a Potential Prebiotic Catalyst and Desymmetrization Agent

Title: Formaldehyde as a Catalyst: Investigations on the Role of Formaldehyde as a Potential Prebiotic Catalyst and Desymmetrization Agent
Authors: Jamshidi, Mohammad
Date: 2017
Abstract: Life, as we know it, has emerged from the association of simple building blocks (e.g. HCN, NH3, aldehydes, etc). The reactions required to form the complex subunits of life face a great entropic barrier due to the intermolecular nature of their reactivity. Intermolecular reactions are slow at low concentrations, and therefore, the assembly of complex subunits requires the presence of a concentration mechanism. Formaldehyde, which was present in concentrations as high as 0.02 M, may have been used as a concentration mechanism on early Earth. By tethering two molecules together, formaldehyde allows catalysis via temporary intramolecularity. Moreover, formaldehyde has been shown to act as a hydrolase / hydratase mimic, allowing important rate accelerations in hydration and hydrolysis reactions which are of fundamental importance to prebiotic chemistry. Herein, the efficiency of formaldehyde as a catalyst, operating via temporary intramolecularity is demonstrated for a hydroamination reaction that occurs in dilute aqueous conditions. First, using soluble N-methylallylamine and Nmethylhydroxylamine, formaldehyde allowed catalytic turnover at prebiotically relevant formaldehyde concentrations (0.02 M) for a model hydroamination reaction. The efficiency of formaldehyde was compared to other prebiotic aldehydes, demonstrating that although other prebiotic aldehydes are capable of inducing temporary intramolecularity, they were inferior.A second small molecule which may have played a role in the origin of life is D-glyceraldehyde. Since life’s molecules are homochiral, there is a need to explain how this homochirality arose. There have been many breakthroughs by the scientific community when it comes to addressing this challenge, however there is still no general consensus on the origins of homochirality from a prebiotic perspective. Herein, we demonstrate that D-glyceraldehyde is capable of templating a challenging intermolecular reaction while also transmitting some of its chirality to the product. Though the enantiomeric excess produced was generally low (usually around 20 %), there is a significance behind these results due to prebiotically relevant amplification procedures. Lastly, formaldehyde is examined as a possible desymmetrizing agent; coupled with Brønsted acids, the possibility of formaldehyde to induce desymmetrization of alpha-amino or alpha-hydroxy diesters to produce azlactones, and oxalactones, respectively will be established. Moreover, the use of a chiral Brønsted acid would introduce the ability to achieve this transformation in an enantioselective manner. The resulting azlactones / oxalactones are valuable for two reasons: 1) the lactones are present in bioactive molecules, and 2) the lactones can be hydrolyzed to produce chiral alpha-amino / alpha-hydroxy acids. Therefore, we began a systematic study of the conditions required to allow this transformation to occur. This study indicates that the desymmetrization of an alpha-amino diester is possible, producing moderate yields of the resulting azlactone. The desymmetrization of alpha-hydroxy diesters however proved more challenging, and no conversion was observed. Further investigation is required to the increase efficiency of the desymmetrizations, and experimentation with chiral Brønsted acids is required in order to discover enantioselective transformations.
CollectionThèses, 2011 - // Theses, 2011 -