The global market of steroidal drugs and intermediates is estimated to be over a billion dollars. Novel strategies and improved protocols for the synthesis and production of steroids are therefore highly desired to meet modern synthesis criteria as sustainability, safety, and cost. A major breakthrough in the field may come from the adoption of enabling chemical technologies as flow chemistry. In this regard, while many syntheses have already benefited from flow systems, steroid synthesis and manipulation remain largely unexplored so far. In this communication, we describe the development of a continuous processing method for the synthesis of 16-dehydropregnenolone acetate, a key intermediate for the production of several natural steroids, sex hormones, and drugs. The synthesis starts from diosgenin, a cheap and readily available plant-derived sapogenin, and it is based on a revised Marker’s degradation. As a result, besides the known benefits of flow chemistry over batch protocols, our approach supersedes the bottlenecks of previous methods, exhibits a good productivity, can be easily monitored by in-line analysis and assisted by automation software, and proves robustness and amenability for future process intensification efforts and kilo-scale preparations.
Development of a Continuous Flow Synthesis of 16-Dehydropregnenolone Acetate: A Powered Entry into Steroids from Plants
Mancino V;Cerra B;Gioiello A
2018
Abstract
The global market of steroidal drugs and intermediates is estimated to be over a billion dollars. Novel strategies and improved protocols for the synthesis and production of steroids are therefore highly desired to meet modern synthesis criteria as sustainability, safety, and cost. A major breakthrough in the field may come from the adoption of enabling chemical technologies as flow chemistry. In this regard, while many syntheses have already benefited from flow systems, steroid synthesis and manipulation remain largely unexplored so far. In this communication, we describe the development of a continuous processing method for the synthesis of 16-dehydropregnenolone acetate, a key intermediate for the production of several natural steroids, sex hormones, and drugs. The synthesis starts from diosgenin, a cheap and readily available plant-derived sapogenin, and it is based on a revised Marker’s degradation. As a result, besides the known benefits of flow chemistry over batch protocols, our approach supersedes the bottlenecks of previous methods, exhibits a good productivity, can be easily monitored by in-line analysis and assisted by automation software, and proves robustness and amenability for future process intensification efforts and kilo-scale preparations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
