retro-aldol reaction
Summary
The retro-aldol reaction is the reverse of aldol addition: a β-hydroxy aldehyde or ketone splits at the bond between its α and β carbons into two carbonyl compounds, with an enolate as the departing group. Glycolysis uses it when aldolase cleaves fructose 1,6-bisphosphate.
Detail
Meaning: Aldol addition joins two carbonyl compounds into a β-hydroxy aldehyde or ketone, and the step is reversible. In the retro-aldol reaction, base removes the OH proton, the alkoxide reforms a C=O, and the bond between the carbinol carbon (Cβ) and the α carbon breaks. The electrons leave as a resonance-stabilized enolate, which is protonated to give the second carbonyl compound. Acid can do the same through an enol.
On the MCAT: The usual setting is glycolysis. Aldolase cleaves fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. The step is uphill under standard conditions and proceeds because the next reaction removes glyceraldehyde 3-phosphate (Le Châtelier's principle). Aldolase (class I) forms a Schiff base with an active-site lysine. Organic questions may ask you to draw the two fragments from a β-hydroxy carbonyl or predict that removing a product favors cleavage. Heating an aldol normally gives dehydration to the enone instead.
Common confusion: Retro-aldol is not dehydration. Losing water from an aldol product breaks the C–O bond and gives a conjugated enone. Retro-aldol breaks the C–C bond and loses no water, so the two products together contain all the atoms of the reactant. It needs the hydroxyl on the β carbon.
Sources
- Organic Chemistry (Klein)
- Organic Chemistry (Wade)
- Lehninger Principles of Biochemistry
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.