Synthesizing a natural product

Abstract

Seqens’s facility in Villeneuve-la-Garenne, France, was established almost 130 years ago to extract the malaria treatment quinine from the bark of the cinchona tree. It is considered one of the oldest pharmaceutical chemical sites in the world. Today, Villeneuve is making the main ingredient in one of the world’s newest drugs: Mithra Pharmaceuticals’ oral contraceptive, Estelle, approved by the US Food and Drug Administration on April 15 and now marketed by Mayne Pharma. The ingredient is estetrol, a natural estrogen touted as having a better side-effect profile than the estrogen in most contraceptives. Synthesizing it for use in a drug, though, is no easy task. Like the site where estetrol is being made, the story behind the new drug is many years old. Estetrol was first identified in 1965 by Egon Diczfalusy, a reproductive endocrinologist at the Karolinska Institute. But Diczfalusy didn’t pursue its potential as a contraceptive, says Jean-Manuel