Colton, Frank

In 1952, Frank B. Colton (1923-2003) at Searle synthesised and later patented norethynodrel, an isomer of norethisterone. An improved synthesis emerged, in which both compounds were obtained, while the aromatisation and Birch reduction could be avoided. [41,42] As starting point serves 5-androsten-3/l-ol-17-one acetate, to which hypochlorous acid is added. Notable is the thermal or photochemical functionalisation of C-19 with lead tetraacetate/iodine, [43] under formation of a cyclic ether. Hydrolysis ofthe ester and oxidation with chromium trioxide leads to a A -enedione, while HCI is eliminated. Reductive opening ofthe ether gives the 19-hydroxy-compound, which can be oxidised with chromium trioxide to the lOjS-carboxylic acid and then decarboxylated in... 

---