# Enantioselective Total Synthesis of Daedaleanol B from (+)-Sclareolide

## TL;DR

Scientists synthesized a natural compound called daedaleanol B from a readily available starting material and confirmed its structure and cancer-fighting potential.

## Contribution

The first enantioselective total synthesis of daedaleanol B from (+)-sclareolide is reported, with confirmation of its absolute configuration.

## Key findings

- The synthesis produced daedaleanol B with NMR data matching the natural product.
- Both hydroxy-daedaleanol and daedaleanol B showed antiproliferative effects in colorectal cancer cells.
- Daedaleanol B exhibited higher antiproliferative activity compared to hydroxy-daedaleanol.

## Abstract

Daedaleanol B is a drimane-derived merosesquiterpenoid isolated from the brown-rot fungus Daedalea incana. Herein, we report its first enantioselective total synthesis from commercially available (+)-sclareolide. A one-pot transformation afforded 11-acetoxy drimane-8α-ol, which was saponificated and selectively esterified with enantiopure L-pyroglutamic acid to give crystalline hydroxy-daedaleanol. Single-crystal X-ray diffraction of this intermediate, together with the known configuration of the chiral starting materials, enabled assignment of the absolute configuration of the daedaleanol B framework. Final elimination provided daedaleanol B, whose NMR data matched those reported for the natural product. Both hydroxy-daedaleanol and daedaleanol B exhibited time- and concentration-dependent antiproliferative effects in HT-29 colorectal cancer cells, with higher activity observed for daedaleanol B.