# Borylation via iridium catalysed C–H activation: a new concise route to duocarmycin derivatives

## TL;DR

A new efficient method for making a powerful anti-cancer compound called duocarmycin SA using a chemical process called C–H activation.

## Contribution

A concise and efficient synthetic route to duocarmycin derivatives using iridium-catalyzed C–H activation and borylation.

## Key findings

- The ethyl ester analogue of duocarmycin SA was synthesized in 11 linear steps from commercial materials.
- A borylated intermediate was formed via C–H activation and used for peptide coupling reactions.
- The method allows for easy conversion to the free hydroxyl analogue of the compound.

## Abstract

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C–H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.

A concise synthesis of an alkylation subunit of the duocarmycins is achieved via a C–H-activation approach. The ethyl ester analogue of duocarmycin SA can be made in eleven linear steps from a commercially available precursor.