Prephenic acid theory

An alternative to the aromatic amino acids hypothesis is one which invokes their proximate precursor, viz. a hydrated prephenic acid in which the potential ring E of yohimbine is already in a reduced state and has in addition the carboxyl. An important conclusion arising out of this theory was the prediction of a uniform stereochemistry in indole alkaloids of Type I at the carbon equivalent C-15 of yohimbine. This hypothetical biogenesis—the prephenic acid theory is Ulustrated in Chart 2.3. 

Prephenic acid theory of indole alkaloid biosynthesis... 

Some of the most interesting applications of organic structural theory to the elucidation of biosynthetic pathways were stimulated by efforts to formulate mechanisms for the biosynthesis of alkaloids. Conversely, consideration of implied biogenetic relations have occasionally helped structural determination. An important aspect of theories concerning alkaloid biosynthesis has been the assumed role of the aromatic amino acids in their formation. Only limited experimental evidence is available in this area. The incorporation of tyrosine- 8-C into morphine has been shown to be in accordance with a theory for its formation from 3,4-dihydroxyphenyl-alanine plus 3,4-dihydroxyphenylacetaldehyde. A stimulating theory of the biosynthesis of indole alkaloids, based on a condensation between trypt-amine and a rearrangement product of prephenic acid, has recently been published. The unique stereochemistry of C15 of these alkaloids had an important part in the formulation of the theory. Experimental proof of this theory would be valuable for several areas of alkaloid chemistry and biosynthesis. 

QM-MM simulations were used to generate trajectories for the steered molecular dynamics calculation of the free energy profile for the conversion of two molecules (chorismate to prephenate) involved in the biosynthesis of amino acids. The results showed good agreement with those obtained from umbrella sampling. Only fair agreement with experiment was attributed to the accuracy of the density function theory calculations. 

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