Efficient synthesis of natural products with a 3,6-disubstituted 4-hydroxy-2H-pyran-2-one framework

Publication Type

Contribution to conference

Authors

Schmidt, D.; Conrad, J.; Mika, S.; Klaiber, I.; Beifuss, U.

Year of publication

2007

Published in

Planta Medica

Pubisher

Georg Thieme Verlag , Stuttgart

Band/Volume

73/

Page (from - to)

872

Conference name

55th Annual Congress of the Society for Medicinal Plant Research

Conference location

Graz

Conference date

02.09.2007

3,6-disubstituted 4-hydroxy-2H-pyran-2-ones have generated a lot of interest in medicinal chemistry since this structural scaffold is found in many biologically active natural products. Sch-419560 has recently been isolated from the fermentation culture of Pseudomonas fluorescens and exhibited remarkable antibiotic properties.
3,3-Dimethylallylconrauanalactone was isolated from the bark of Garcinia conrauana Engl. (Guttiferae), Aurantiacone from the leaf resin of Diplacus aurantiacus.
Here we report on the total synthesis of these natural products: The 2-alkylated 5-hydroxy-3-oxopent-4-enoic acid esters were prepared according to Lygo's method by reacting the dianions of 2-alkylated ethyl acetoacetates under selective γ-acylation with N-acyl-2-methyl-aziridines.
The 5-hydroxy-3-oxopent-4-enoic acid ethyl esters were transformed to produce the bispotassium salts. The free 5-hydroxy-3-oxopent-4-enoic acids were released with aqueous tartaric acid solution and lactonized under mild conditions with TFAA or Ac₂O-pyridine.
The primarily formed O-acetyl derivatives were finally hydrolyzed with potassium carbonate to give the 4-hydroxy-2H-pyran-2-ones.