Formose reaction

The formation of sugars from the reaction of formaldehyde under alkaline conditions was discovered in 1861 and is known as the formose reaction , although it is not understood fully (Figure 8.7). It requires the presence of suitable inorganic catalysts such as Ca(OH)2 or CaCOr, either of which may be found on a prebiotic Earth. The reaction is autocatalytic and produces over 40 different types of sugars, some rings, some long chains. 

The formose reaction leads to the production of many sugars with the exception of ribose, which occurs in very low concentrations and it is hard to see how this could be increased. A variation on the formose reaction starting at the phospho-rylated glycoaldehyde intermediate, with the addition of base or in the presence of mineral substrate, produced a surprisingly large amount of ribose but this still... 

Endogenous organic synthesis Urey-Miller experiments as a source of prebiotic molecules via the Strecker synthesis for amino acids, HCN polymerisation for purines and pyrimidines and the formose reaction for sugars... 

Formose reaction A prebiotic reaction producing sugars but little ribose. 

Ribose The sugar that attaches to the DNA bases to form part of the DNA backbone helical structure. The sugar is not made in the formose reaction process. 

Figure 3.6 The formose reaction. (Adapted from Miller, 1998.)...

Are there other types of self-replication in nature, possibly based on a quite different mechanism There are not many, but there is a famous case the formose reaction, described in 1861, and based on a reaction cycle of formaldehyde. This reaction has already been mentioned in Chapter 3, on the subject of prebiotic... 

Figure 7.4 Schemae of the formose reaction (a) spontaneous, slow formation of glycolaldehyde from formaldehyde (b) after one cycle, one new molecule of glycolaldehyde is produced. The structural isomers of sugars are specified by the carbon skeleton and by the position of the carbonyl group (open circle). (Adapted, with some modifications, from Maynard Smith and SzathmSry, 1995.)...

We have also learned that self-replication is not a prerogative only of nucleic acids, but it can be shared by different kinds of chemical families see the formose reaction, the self-replicating peptides, and the self-reproducing micelles and vesicles. The list should include the cellular automata and the corresponding devices of artificial life. Self-reproduction of vesicles and liposomes is important because it represents a model for cell reproduction. 

Additional advantages of the formamide condensation protocol were observed performing the reaction in the presence of catalysts which decompose formamide to formaldehyde. Formaldeyde is the most important pre-biotic precursor of sugars through a series of enolization and aldol-like condensation processes catalyzed under acidic or basic conditions, known as the formose reaction [100]. When formamide was heated at 160 °C in the presence of titanium dioxide (a catalyst able to degrade amides to aldehydes) [101] a complex mixture of nucleobase derivatives was obtained including adenine 1, purine 12, cytosine 17, N9-formylpurine 28, N9, N6-diformyladenine 29, 5-hydroxymethyluracil 30, thymine 31 and three novel... 

Intermediates of the formose reaction can yield amino acids in the presence of ammonia and thiols [61,62] through a process that will be examined in more details in subsequent sections (see Sect. 3.4.2) since amino-thioesters are activated peptide precursors. 

Weber [61,62] has developed in the context of prebiotic chemistry an original pathway for a-aminothioester synthesis [180], which can start from hydroxyaldehydes 30 intermediates in the formose reaction (a likely prebiotic pathway to carbohydrates). Obviously, thioesters themselves are not observed as products because of their fast hydrolysis in the medium, but they could be converted into peptide bonds in the presence of amino acids or peptide free amino groups, and into mixed anhydride with phosphoric acid in the presence of inorganic phosphate. The reaction involves two key-steps the condensation of ammonia and of the mercaptan on a-keto aldehyde 31... 

One experimental approach would be to generate heterogeneous vesicles in broths containing the constituents of the formose reaction, initially limiting the concentration of formaldehyde. After leaving the system for a while, formaldehyde would be added to the solution. Those vesicles that grew and divided fastest would be selected for. There may be rare conditions under which the constituents of the formose reaction are permeable to the membrane. They enter the vesicle and become trapped as soon as those conditions change. Formaldehyde could then enter the vesicles and allow the autocatalytic cycle to run. 

See, for example, Breslow R., 1959, On the mechanism of the formose reaction, Tetrahedron Lett. 21 22-26 Butlerow, A., 1861, Bildung einer zuckerartigen Substanz durch Synthese. Annalen 120 295-298 and Ricardo, A., Carrigan, M.A., Olcott, A.N., and Benner, S.A., 2004, Borate minerals stabilize ribose, Science 303 196. 

Solutions of that type are improbable. In exchange for a simplification mixture of the formose reaction, we must specify the presence of glycolaldehyde, glyceraldehyde, and borate minerals (and the absence of many potentially interfering substances, such as cyanide) and a route by which the protective borate will be removed so that the route to oligonucleotide formation remains open. Ribose is only one of the six components present in RNA. An extended number of steps involving the synthesis, purification, transportation, and highly specific... 

Although there are a number of inefficient steps in most proposed prebiotic syntheses of ribotides, the major objection to RNA as the primogenitor of life has been the relatively small yield of ribose in the formose reaction, a simple condensation of glycoaldehyde. Muller et a/.,18 however, have discovered a variation of the formose reaction that produces a limited mix of pentose diphosphates in which the ribose forms predominate (52 14 23 11, ribose arabinose lyxose xylose). Although many critical chemical roadblocks remain (such as the extremely low yield of pyrimidine nucleosides following the condensation of ribose and free bases), this advance belies the previously held view that products of the formose reaction are necessarily so chemically diverse that they are the carbohydrate analog of petroleum. 19... 

First, the question of where nucleotide monomers may have come from is critical. Given that the formose reaction is the most likely candidate for the synthesis of prebiotic ribose, but yields very little pure material, the role of stereoselective catalysts (clays, amino acids, or lipid aggregates) in directing the reaction should be fully explored. In this respect, Wachters-hauser16 has advanced a scheme for nucleotide synthesis based on pyrite catalysis than can be readily tested. 

Under UV irradiation, aqueous solutions of formaldehyde and ammonium salts produce imidazoles (Scheme 85). It is conceivable that the irradiation has catalyzed a formose reaction, yielding trioses and glycolaldehyde, and that reaction of these species with ammonia could account for the products isolated. Such a reaction might be classed as a primitive-life synthesis, as might the observation that hydrogen cyanide and liquid ammonia react to form 4,5-dicyanoimidazole and adenine (70AHC(12)103). 

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