The synthesis of sugars from formaldehyde under alkaline conditions was discovered long ago (Butlerow 1861). However, the Butlerow synthesis, or “formose reaction,” is very complex. It depends on the presence of a suitable inorganic catalyst, with calcium hydroxide or calcium carbonate being the most commonly used. In the absence of such mineral catalysts, little or no sugar is obtained. The reaction is autocatalytic and proceeds in a series of stages through glycolaldehyde, glyceraldehyde, and dihydroxyacetone, four-carbon sugars, and five-carbon sugars, to give finally hexoses, or six-carbon sugars, including the biologically important sugars glucose and fructose. There are two problems with the formose reaction as a source of sugars on the primitive Earth. The first is that the formose reaction gives a wide variety of sugars, both straight chain and branched. Indeed, more than 40 different sugars have been separated from one reaction mixture. Ribose occurs in this mixture, but is not particularly abundant. It is difficult to envision how the relative yield of ribose, needed for formation of RNA, could be greatly increased in this reaction, or how any prebiotic reaction producing sugars could give mostly ribose.
The second problem with ribose is its instability. Its half-life for decomposition is 73 minutes at 100 ˚C pH7 and 44 years at 0 ˚C pH7 Therefore, ribose cannot be considered a prebiotic reagent unless it is used immediately after its prebiotic synthesis. The three other pentoses and eight hexoses are similarly unstable. It therefore has become apparent that ribonucleotides could not have been the first components of prebiotic nucleic acids.