Formose reaction

The formose reaction, discovered by Aleksandr Butlerov in 1861 [Butlerov, A. C. R. Acad. Sci. 1861, 53, 145-147] ["Self-organizing biochemical cycles " PNAS | November 7, 2000 | vol. 97 | no. 23 | 12503-1250 DOI|10.1073/pnas.220406697] , involves the formation of sugars from formaldehyde. Formose is a contraction of formaldehyde and aldose.

Reaction and mechanism

The reaction is catalyzed by a base and a divalent metal such as calcium hydroxide. The intermediary steps taking place are aldol reactions, reverse Aldol reactions, and aldose-ketose isomerizations. Intermediates are glycolaldehyde, glyceraldehyde, dihydroxyacetone, and tetrose sugars. In 1959, Breslow proposed a mechanism for the reaction, consisting of the following steps: [Breslow, R. Tetrahedron Lett. 1959, 1, 21, 22-26.]

The reaction begins with two formaldehyde molecules condensing to make glycolaldehyde 1 which further reacts in an aldol reaction with another equivalent of formaldehyde to make glyceraldehyde 2. An aldose-ketose isomerization of 2 forms dihydroxyketone 3 which can react with 2 to form ribulose 4, and through another isomerization ribose 5. Molecule 3 also can react with formaldehyde to produce tetrulose 6 and then aldoltetrose 7. Intermediate 7 can split into 2 in a retro-aldol reaction.

Significance

The formose reaction is of importance to the question of the origin of life as it is a path from simple formaldehyde to complex sugars like ribose and from there to RNA. In one experiment simulating early Earth conditions, pentoses formed from mixtures of formaldehyde, glyceraldehyde, and borate minerals such as colemanite Ca₂B₆O₁₁5H₂O or kernite Na₂B₄O₇. ["Borate Minerals Stabilize Ribose" A. Ricardo, "et al." Science 303, 196 (2004); DOI|10.1126/science.1092464] Adding to the interest in the formose reaction is the fact that both formaldehyde and glycolaldehyde have been observed spectroscopically in outer space.

References