# Oxidative Rearrangement of Indoles Enabled by Promiscuous Cryptic Halogenation with Vanadium-Dependent Haloperoxidases

## TL;DR

This paper introduces a new biocatalytic method for making 2-oxindoles using vanadium-dependent enzymes, avoiding harmful chemicals and expanding substrate scope.

## Contribution

A general biocatalytic platform using vanadium-dependent haloperoxidases for oxidative indole rearrangement is developed.

## Key findings

- The enzymatic system effectively converts indoles into 2-oxindoles and 2-spirooxindoles.
- The method is applied in multienzymatic and chemoenzymatic syntheses and late-stage molecule functionalization.
- Gram-scale syntheses of coerulescine and horsfiline were achieved using the developed protocol.

## Abstract

The 2-oxindole class of heterocycles are privileged structural
components in natural products and biologically active compounds.
One of the most attractive methods for accessing 2-oxindoles is through
direct oxidation of indoles, but current methods rely on the use of
chemical oxidizing agents that lead to the generation of harmful waste
products or biocatalytic methods using enzymes with a limited substrate
scope. Herein, we describe the development and application of a general
biocatalytic platform for the oxidative rearrangement of indoles using
enzymatic halide recycling with vanadium-dependent haloperoxidases
(VHPOs) facilitated by a catalytic quantity of halide salt and hydrogen
peroxide as the terminal oxidant. This catalytic system is effective
for the oxidative rearrangement of indoles into 2-oxindoles and 2-spirooxindoles.
The developed protocol has been applied in multienzymatic and chemoenzymatic
synthesis, late-stage functionalization of biologically active molecules,
tryptophan-selective peptide modification, and gram-scale syntheses
of coerulescine and horsfiline.