Glyceraldehyde induction period

Butlerov found out that in alkaline medium (calcium hydroxide), formaldehyde HCHO polymerizes to form about 20 different sugars as racemic mixtures, Butlerov 1861. The reaction requires a divalent metal ion. Breslow found a detailed mechanism of reaction that explains the reaction products, (Breslow 1959). He found that glycol-aldehyde is the first product that is subsequently converted into glyceral-dehyde (a triose), di-hydroxy-acetone, and then into various other sugars, tetrose, pentose, and hexose. The formose reaction advances in an autocatalytic way in which the reaction product is itself the catalyst for that reaction with a long induction period. The intermediary steps proceed via aldol and retro-aldol condensations and, in addition, keto-enol tautomerizations. It remains unexplained how the phosphorylation of 3-glyceraldehyde leads to glycral-3-phosphate (Fig. 3.6). Future work should study whether or not ribozymes exist that can carry out this reaction in a stereo-specific way. 

As indicated in the Introduction, the condensation of formaldehyde into monosaccharides by basic catalysis has been known since the last century. The synthesis starts with the formation of glycolaldehyde which is a slow reaction and is responsible for the induction period observed in the condensation of formaldehyde to sugars. Once sufficient amounts of glycolaldehyde have been formed, an autocatalytic process ensues which transforms glycolaldehyde into glyceraldehyde and dihydroxyacetone, and then into all the possible tetroses, pentoses and hexoses. The principal mechanism is a base catalyzed aldol condensation, somewhat similar to the enzyme catalyzed biochemical transformations of sugars. A common mineral, kaolinite, has been found to be an efficient catalyst for this reaction. Ribose is indeed one of the important monosaccharides formed in this reaction. 

In a continuation of his studies on asymmetric P-lactam synthesis, Evans [42] utilized a,P-epoxyaldehydes 49a and 49b, prepared in two steps from achiral allylic alcohols via Sharpless asymmetric epoxidation and Swern oxidation, as chiral glyoxal synthons for the ketene-imine cycloaddition. Diastereosel-ection was excellent, ranging from 90 10 to 97 3 with overall yield of 50 up to 84% (for Schiff base formation and cycloaddition) after recrystallization or chromatographic purification of the major diastereomer. The sense of asymmetric induction correlated with that obtained in the analogous glyceraldehyde reaction, as established by periodic acid cleavage to aldehydes 51. 

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