An Efficient and Environmentally Benign Chemical Synthesis of Testolactone

Testolactone was obtained commercially by microbial transformation of either testosterone or progesterone and also synthetically, albeit in low yield. The only chemical synthesis of 1 so far described in the literature starting from dehydroepiandrosterone (2) is shown in Scheme 1. The strategy followed in this synthetic approach consisted in the initial formation of the lactone ring by a BaeyerVilliger oxidation with peracetic acid of ring D of the protected derivative 3, followed by the introduction of the additional double bond in the ring A of intermediate 5 by selenium dioxide oxidation. Our first approach was a rather direct and classical one, our main concern was to achieve a more efficient synthetic route. However, we then began to consider the idea of replacing hazardous chemicals by more benign alternatives hoping to maintain the same degree of efficiency.