Biological polymers such as nucleic acids and proteins are constructed of only one-the D or L-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the D enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers.carbonaceous meteorites | sugar acids | enantiomer excesses | aldonic acids | polyols T he organic phase of carbonaceous meteorites comprises an insoluble "macromolecular" material (1-3), a complex mixture of largely uncharacterized solvent-extractable compounds (4), as well as discrete (identified) soluble organic compounds such as amino acids (3, 5) nucleobases (6, 7), and sugar derivatives (8). Analyses of this prebiotic organic carbon have been important in understanding its early Solar System synthesis and history: Characteristics of the organic phase suggest that it consists of both products and survivors of interstellar/presolar grain irradiation (9) and subsequent encapsulation and aqueous reactions (10, 11) in asteroids "parent bodies."Several identified meteoritic organic compounds are chiral: They can exist as two nonsuperimposable mirror image compounds called enantiomers, commonly designated D and L. To date, most chiral meteoritic compounds are reported to be racemic mixtures, i.e., their D and L enantiomers are equal in abundance (3). Racemic compounds are expected in nature because typical abiotic synthetic processes are (historically) thought to occur in the absence of asymmetric influences. Racemic mixtures are equated with pristine/uncontaminated abiotic samples when discussing meteoritic compounds. However, some meteoritic amino acids that are rare on Earth, i.e., they are not constituents of proteins and therefore less likely to be contaminants, have been confirmed to contain L enantiomer excesses (EE) (3, 12, 13). The origins of such excesses are unknown.Sugars, aldehydes, or ketones that contain multiple carbon hydroxyl (carbon alcohol) groups, are also chiral and were likely necessary for the origin of life. In the majority of extant biological sugars and derivatives ("polyols"), the D enantiomers are significantly more abundant than the L enantiomers (we will note exceptions in Results and Natural Occurrence of Relevant Sugar Derivatives and Enantiomers)...

The native bases of RNA and DNA are prominent examples of the narrow selection of organic molecules upon which life is based. How did nature “decide” upon these specific heterocycles? Evidence suggests that many types of heterocycles could have been present on the early Earth. It is therefore likely that the contemporary composition of nucleobases is a result of multiple selection pressures that operated during early chemical and biological evolution. The persistence of the fittest heterocycles in the prebiotic environment towards, for example, hydrolytic and photochemical assaults, may have given some nucleobases a selective advantage for incorporation into the first informational polymers. The prebiotic formation of polymeric nucleic acids employing the native bases remains, however, a challenging problem to reconcile. Hypotheses have proposed that the emerging RNA world may have included many types of nucleobases. This is supported by the extensive utilization of non-canonical nucleobases in extant RNA and the resemblance of many of the modified bases to heterocycles generated in simulated prebiotic chemistry experiments. Selection pressures in the RNA world could have therefore narrowed the composition of the nucleic acid bases. Two such selection pressures may have been related to genetic fidelity and duplex stability. Considering these possible selection criteria, the native bases along with other related heterocycles seem to exhibit a certain level of fitness. We end by discussing the strength of the N-glycosidic bond as a potential fitness parameter in the early DNA world, which may have played a part in the refinement of the alphabetic bases.

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The synthesis and photophysical properties of four fluorescent nucleoside analogs, related to pyrrolo-C (PyC) and pyrrolo-dC (PydC) through the conjugation or fusion of a thiophene moiety, are described. A thorough photophysical analysis of the nucleosides, in comparison to PyC, is reported.

Nature’s selection of the contemporary nucleobases in RNA and DNA continues to intrigue the origin of life community. While the prebiotic synthesis of the N-glycosyl bond has historically been a central area of investigation, variations in hydrolytic stabilities among the N-glycosyl bonds may have presented an additional selection pressure that contributed to nucleobase and nucleoside evolution. To experimentally probe this hypothesis, a systematic kinetic analysis of the hydrolytic deglycosylation reactions of modified, alternative and native nucleosides was undertaken. Rate constants were measured as a function of temperature (at pH 1) to produce Arrhenius and Eyring plots for extrapolation to 37°C and determination of thermodynamic activation parameters. Rate enhancements based on the differences in reaction rates of deoxyribo- and ribo-glycosidic bonds were found to vary under the same conditions. Rate constants of deoxynucleosides were also measured across the pH range of 1 – 3 (at 50°C), which highlighted how simple changes to the heterocycle alone can lead to significant variation in deglycosylation rates. The contemporary nucleosides exhibited the slowest deglycosylation rates in comparison to the non-native/alternative nucleosides, which we suggest as experimental support for nature’s selection of the fittest N-glycosyl bonds.

A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission spectra of the highly conjugated quinoxalenediynes were red-shifted approximately 100-200 nm relative to those of 1,2-diethynylbenzene. Strong exotherms indicative of enediyne cyclization were observed by differential scanning calorimetry, while solution cyclizations in the presence of 1,4-cyclohexadiene confirmed C(1)-C(6) Bergman cyclization. To provide further insight into Bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier, reaction enthalpy, and barrier of retro-Bergman ring-opening. Extension of benzannelation from 1,2-diethynylbenzene to either 2,3-diethynylnaphthalene or the 6,7-diethynylquinoxalines had a minimal effect on the cyclization barrier. In comparison, the enthalpies of cyclization were increased upon linearly extended benzannelation, which resulted in reduced barriers to retro-Bergman ring-opening. In addition, the orientation of extended benzannelation was found to have a significant effect on the cyclization endothermicity. In particular, 5,6-diethynylquinoxaline exhibited a 6.9 kcal/mol decrease in cyclization enthalpy compared to 6,7-diethynylquinoxaline due to increased aromatic stabilization energy in the respective angularly versus linearly fused azaacene cyclized products.

The homoaldol condensation product of pyruvate, 2-methyl-4-oxopent-2-enedioic acid (OMPD), has been recently implicated as a catabolic intermediate in the bacterial degradation of lignin and previously identified from other biological sources in reports ranging over 60 years. Yet, while a preparation of the pyruvate homoaldol product precursor, 4-hydroxy-4-methyl-2-oxoglutaric acid (HMOG/Parapyruvate), was first reported in 1901, there has not been a complete published synthesis of OMPD. Analyses of reaction mixtures have helped identify zymonic acid, the lactone of HMOG, as the direct precursor to OMPD. The reaction appears to proceed through an acid- or base-mediated ring opening that does not involve formal lactone hydrolysis. In addition to a preparative protocol, we provide a proposed mechanism for the formation of methylsuccinic acid that arises from the nonoxidative decarboxylation of OMPD. Finally, we calculated the relative stability of the isomers of OMPD and found Z-OMPD to be the lowest in energy. These computations also support our observations that Z-OMPD is the most abundant isomer across a range of pH values.

Carbonaceous meteorites provide the best glimpse into the solar system’s earliest physical and chemical processes. These ancient objects, ~4.56 billion years old, contain evidence of phenomena ranging from solar system formation to the synthesis of organic compounds by aqueous and (likely) low-temperature photolytic reactions. Collectively, chemical reactions resulted in an insoluble kerogen-like carbon phase and a complex mixture of discrete soluble compounds including amino acids, nucleobases, and monosaccharide (or “sugar”) derivatives. This review presents the documented search for sugars and their derivatives in carbonaceous meteorites. We examine early papers, published in the early 1960s, and note the analytical methods used for meteorite analysis as well as conclusions on the results. We then present the recent finding of sugar derivatives including sugar alcohols and several sugar acids: The latter compounds were found to possess unusual “d” enantiomeric (mirror-image) excesses. After discussions on the possible roles of interstellar grain chemistry and meteorite parent body aqueous activity in the synthesis of sugar derivatives, we present a scenario that suggests that most of Earth’s extraterrestrial sugar alcohols (e.g., glycerol) were synthesized by interstellar irradiation and/or cold grain chemistry and that the early solar disk was the location of the initial enantiomeric excesses in meteoritic sugar derivatives.