Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemo-enzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.

Automated summary

A method for late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties to alter their biological properties was studied. Two hydroxy-bearing allyl pyrophosphates were synthesized. A chemo-enzymatic approach using a promiscuous indole prenyltransferase enzyme was demonstrated, introducing a dual reactive hydroxy-bearing allyl moiety directly onto the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.