Development of a second-generation Testosterone synthesis route via Biocatalysis

Testosterone is a male hormone which is being manufactured in pharmaceutical industry for many years. Testosterone is the primary sex hormone and anabolic steroid in males. It is also used as a drug to treat male hypogonadism, gender dysphoria, bone loss, certain types of breast cancer, prostate cancer and hypersexuality [01]. It may also be used to increase athletic ability in the form of doping. Most of the time the current manufacturing routes start from 4 androstene 3,17 dione which is chemically converted to Testosterone by a reduction reaction. In this article we present the development of a second-generation route towards Testosterone via Biocatalysis, using an oxidoreductase enzyme. This results in a more sustainable API Testosterone. The overall PMI decreases from 69 to 44. Consequently, the enzymatic route reduces the environmental impact based on material use by 36%. Via proteomics principles we have been able to develop a generally applicable in-house analysis/method to prove absence of residual enzyme with a detection limit as low as 1 ppm.