Tryptophan aromatic nuclei

NH group deactivates both the ethylenic bond and the aromatic nucleus. As the reactivity of tryptophane (8) in alkaline solution (k = 1-8 x 108 M-1 sec-1) (Braams, 1966) is significantly lower than that reported for... 

Electrophilic substitution of aromatic nuclei in tyrosine and tryptophan side chains has frequently been reported in connection with acidolytic removal of blocking groups. C-Benzylation and tert.butylation of the tyrosine side chain and N-alkylation of the indole nucleus in tryptophan are often attributed to the alkyl cations generated in the reaction. This common side reaction is caused, however, mainly by the alkylating agents formed in the process, such as benzyl bromide or tert.butyl trifluoroacetate. The same is true for the S-alkylation of the methionine side chain. Conversion of the thioether to a sulfonium salt can... 

To rationalize these data, Floss et al. proposed the mechanism shown in Scheme 55 wherein a direct electrophilic aromatic substitution reaction from an enzyme-bound DMAPP ion pair species alkylates C-4 of the tryptophan nucleus [82]. The minor product, where partial loss of stereochemical integrity is sacrificed, was envisioned to occur via rotation around the C-l/C-2 bond of the allylic carbocation species as shown in Scheme 55. Poulter et al. subsequently published a mechanistic study on DMAT synthase that is fully consistent with this interpretation [84]. 

Of the three aromatic amino acids phenylalanine, tyrosine and tryptophan, phenylalanine has been classified with the hydrophobic amino acids which have a non-polar side chain and tyrosine with those containing a hydroxyl group. This leaves tryptophan, the largest and rarest of the amino acids which contains the heterocyclic indole nucleus as its bulky R group. Trytophan is the parent compound for the neurotransmitter serotonin which is 5-hydroxytryptamine. 

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