Shikimic acid 2.3 -sigmatropic rearrangement

The utilization of evolutionary strategies in the laboratory can be illustrated with proteins that catalyze simple metabolic reactions. One of the simplest such reactions is the conversion of chorismate to prephenate (Fig. 3.3), a [3,3]-sigmatropic rearrangement. This transformation is a key step in the shikimate pathway leading to aromatic amino acids in plants and lower organisms [28, 29]. It is accelerated more than a million-fold by enzymes called chorismate mutases [30],... 

Fig. 3.3. Shikimate pathwayforthe biosynthesis of aromatic amino acids in plants and lower organisms. The [3,3]-sigmatropic rearrangement of chorismate into prephenate is shown in the box. PEP, phosphoenolpyruvate.

The reaction in the shikimic acid pathway is, of course, the [3,3]-sigmatropic shift in which chorismic acid rearranges to prephenic acid on the way to aromatic rings (p. 1403). The simpler reaction given here is one of the family of reactions from Chapter 36 (pp. 944-6) using an allylic alcohol and an enol derivative of a carbonyl compound. In this case we have the enol ether of a ketone. We must combine these to make an allyl vinyl ether for rearrangement. 

C,oH oOg, Mu 226.19. P. is unstable in the free form and undergoes decarboxylation with elimination of water to give phenylpyruvic acid. It is an intermediate in the biosynthesis of many aromatic natural products by the shikimate pathway (see chorismic acid, shi-kimic acid). The biosynthesis of P. proceeds from chorismic acid by enzyme-catalyzed [3,3]sigmatropic rearrangement (Claisen rearrangement) under the action of chorismate mutase (EC 5.4.99.5). 

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