Sugar in the primordial soup The formose reaction and the origin of life Content • Life from the Soup • Proteins versus RNA • Prebiotic syntheses of amino acids & nucleobases • Prebiotic synthesis of sugars • Sugar in space • Conclusion Life on Earth Now → ← 0.7×109 yrs ago – Multicellular organisms ← 1.2×109 yrs ago – Eukaryotic organisms ← 3.5×109 yrs ago – Prokaryotic organisms Prebiotic ← 4.6×109 yrs ago – Formation of Earth What started life? What compounds were present in the beginning? What compounds/reactions are required now? The primordial ”soup” N CH3CN 2 CH2OCH4 HCCCN CO2 CH2CHCN NH NCCN CO 3 H2O HCN SO2 Note: no photosynthesis - no O2! Natural products Steroids Purines Polyketides Lipids Terpenes Aminoacids Alkaloids Pyrimidines Carbohydrates Some are more important! Steroids Purines Polyketides Lipids Terpenes Aminoacids Alkaloids Pyrimidines Carbohydrates The essentials of (modern) life Proteins composed of amino acids catalyse reactions RNA composed of nucleobases, ribose and phosphate carry genetic information Which was first, RNA or proteins? Proteins – superior catalysts, simple building blocks, stable RNA – can be catalysts, complex building blocks, unstable but can replicate themselves OH O Protein HN O aminoacid NH O OH H2N Prebiotic amino acid syntheses alanine 1,7% glycine 2,1% S.L. Miller Science 117 (1952) 528-529 J. Am. Chem. Soc. 77 (1955) 2351-2361 RNA phosphodiester NH O 2 N O P O N O nucleobase N N O O OH ribose Prebiotic nucleobase syntheses J. Oró, Nature 191 (1961) 1193-1194 Common monosaccharides aldopentoses aldohexoses ketohexose ribose glucose CHO CHO H OH H OH H OH HO H H OH H OH fructose CH2OH H OH CH2OH CH2OH O HO H arabinose mannose H OH H OH CHO CHO CH2OH HO H HO H H OH HO H H OH H OH H OH CH2OH CH2OH Prebiotic carbohydrate synthesis: The Formose reaction OH CH2O (CH2O)n A. Butlerow, Liebigs Ann. Chem. 53 (1861) 295-298 O. Leow, J. prakt. Chem. 33 (1886) 321-351 Some of the reactions involved Cannizzaro de Bruyn-van Ekenstein Aldol condensation Retro-aldol Cannizzaro reaction O OH O H O OH HO O ϕ H + O H ϕ H ϕ H ϕ ϕ Cannizzaro, Ann. 88 (1853) 129- de Bruyn-van Ekenstein rearrangement D-Glucose 66% D-Mannose 3% HO OH O HO HO O HO OH HO HO OH OH OH OH O OH HO OH D-Fructose 31% de Bruyn, Rec. Trav. Chim. 14 (1895) 150- Evans, Chem. Rev. 31 (1942) 537-559 de Bruyn-van Ekenstein mechanism Glucose Mannose Fructose CHO CHO CH2OH H OH HO H O HO H HO H HO H H OH H OH H OH H OH H OH H OH CH2OH CH2OH CH2OH H OH OH HO H 1,2-Enediol H OH H OH CH2OH The first step... O HO O O H H H H + H H H O H OH formate methanol glycolaldehyde O O HO OH HO OH OH H H O H H H H H H H Aldol condensation O O O O OH H H OH OH H OH H H OH glyceraldehyde de Bruyn-van Ekenstein O OH OH OH OH H OH H OH OH OH OH O glyceraldehyde dihydroxyacetone C3+C1 → C2+C2 O O O HO H H HO OH OH OH OH OH H H H OH OH O O O OH very slow Autocatalytic C1 C1 cycle C2 C C2 1 fast C4 C3 C1 The result: Sugars in formose (55% total yield of sugars) Aldopentoses 7% (1.4% ribose) Ketopentoses 8% Aldohexoses 18% Ketohexoses 18% Open chain forms aldoses ketoses tetroses 11-16% 100% pentoses 0.1-0.2% 8-22% hexoses 0.002-0.1% 0.3-0.7% Tautomers of D-ribose Cyclic forms (99,9%) OH OH OH Acyclic forms (0,1%) O O OH HO OH HO OH HO OH O H α-furanose β-furanose H OH H OH H OH H OH O O H OH H OH HO HO OH CH2OH CH2OH OH OH OH OH OH hydrate aldehyde α-pyranose β-pyranose Problems Much more hexoses than pentoses Very little ribose Racemic mixture of sugars dihydroxyacetone CH2OH O CH2OH CH2OH CH2OH O O OH HO OH + HO OH OH OH O CH OH CH OH OH 2 2 CH2OH D-sorbose D-fructose D-glyceraldehyde 26% 34% H.O.L. Fischer & E. Baer, Helv. Chim. Acta 19 (1936) 519-532 Glycolaldehyde phosphate 1 CHO CHO CH2OPO3 CHOPO3 CHO CHOH CH2OPO3 CHOPO3 CHO CHOH CH OPO 2 3 CH2OPO3 Müller et al., Helv. Chim. Acta 73 (1990) 1410 Glycolaldehyde phosphate 2 CHO CHO CH2OPO3 CHOPO3 CHO CHOH CH2OPO3 CHOPO3 CH O 2 CH2OH Extraterrestial compounds Aminoacids 60 ppm Carbohydrates 60 Pyrimidines 0.06 Purines 1.2 Aminoacids Gly Glu Pro Ala Val Leu Asp +12 not found in proteins Carbohydrates Glucose Mannose Arabinose Xylose Dihydroxyacetone + aldonic acids & alditols Conclusion The basic building blocks of proteins and RNA can be prepared from compounds expected to be present on early Earth. The conditions to make them are incompatible, i.e. they can not be formed under the same reaction conditions and in the same place. The strongest proof that they could have been formed prebiotically is their presence in extraterrestrial matter..