Towards Fuligopyrone B: Explorative Work and Route Scouting

Abstract

In 2023, fuligopyrone B was extracted and isolated from Fuligo septica. No remarkable biological activity was observed. It did, however, have a noteworthy UV-absorption at 325 nm. This indicated a potential function as sun protection for the yellow fruiting body of Fuligo septica. The primary objective of this study was to develop a synthesis route for fuligopyrone B and establish an effective procedure for the regioselective chlorination of the 4-hydroxy-2-pyrone ring system. The planned convergent synthesis of fuligopyrone B is based on two commercially available starting materials: pyridinium sulfonate salt and 3-butyn-1-ol.

The pyridinium sulfonate salt was successfully converted into methyl (2E,4E)-5-(4-((tert-butyldimethylsilyl)oxy)phenyl)penta-2,4-dienoate in a 4-step synthesis. The 2,4-dienoate was then ready to be coupled with 6-(2-aminoethyl)-3-chloro-2-oxo-2H-pyran-4-yl acetate in an amide formation to later form fuligopyrone B. The synthesis of the acetate proved to be more challenging. During this project 3-butyn-1-ol was converted to 6-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-chloro-2-oxo-2H-pyran-4-yl acetate in a 6-step synthesis. One of the future tasks for this project will therefore be to convert the silyl ether into an amine to form the desired acetate, and then couple it with the 2,4-dieonate to later form fuligopyrone B.

During the project a new regioselective chlorination of 4-hydroxy-2-pyrone ring system was developed in our laboratory. The procedure involved NCS and TEB in an electrophilic aromatic substitution, where TEB is used in catalytic amounts. It was tested on several 4-hydroxy-2-pyrone ring systems with successful outcomes. However, the yield seemed to vary depending on the scale and the different 4-hydroxy-pyrone ring systems. Further research is therefore required to improve the new regioselective chlorination.