I recount my involvement in the development of biologically active, totally synthetic steroid hormones since 1941. The reasons for my approach to the first total synthesis of a potent androgen are given. I touch on the even more important general synthetic outcomes from ideas generated by the search for useful amounts of a cortically active hormone, such as novel angular methylations, partial hydrogenations of aromatic systems (Birch reductions), and novel usages in synthesis based on the unique structures so generated. The Birch process was critical for synthesis of the first oral contraceptives. A need to explain the structures of Birch reduction products and the experimental requirements resulted in further elucidations of the mechanism of reduction processes, notably for aromatic compounds. The first theoretical and practical distinction between structures of products as determined by a reaction rate or an equilibrium position was first exploited experimentally in the deconjugation of cholest-4-en-3-one in the final step of the first facile total synthesis of cholesterol. A knowledge gained of the biosynthesis of steroids and its specific enzymes helped to initiate my general polyketide theory of biosynthesis and also my idea of outdoing enzyme achievements with organometallic complexes ("inorganic enzyme chemistry"). I assert the high historic importance of steroids in promoting the advance of general organic chemistry within many fields.
PIP: Arthur J. Birch, chemistry professor at Australian National University, reviewed his role in developing the biologically active, totally synthetic steroid hormones beginning in 1941 after graduating from Oxford University in the UK. His supervisor asked him to serve at the Dyson Perrins Laboratory at Oxford, affiliated with ICI which was affiliated with the UK Government, to produce cortically active hormones for RAF pilots, since it was rumored that German Luftwaffe pilots used them. His research and ideas led him to develop new angular methylations, partial hydrogenations of aromatic systems (Birch reductions), and new synthesis practices based on the unique structures so generated. The Birch reductions were a key element to synthesis of the first oral contraceptives. Specifically, Gregory Pincus orally administered the synthetic 19-nor ethinyl derivatives obtained from Birch reduction and found them to be active progestagens, leading to the development of oral contraceptives. His research into revealing the structures of chemicals produced by Birch reductions and the experimental requirements brought about more clarity of the mechanism of reduction processes, especially for aromatic compounds. His first attempt to differentiate between structures of products as determined by a reaction rate or an equilibrium position was deconjugation of cholest-4-en-3-one in the last step of the first elementary total synthesis of cholesterol. The knowledge acquired from biosynthesis of steroids and of specific enzymes contributed to his general polyketide theory of biosynthesis and to his theory of outdoing enzyme achievements with organometallic complexes, which he called inorganic enzyme chemistry. Professor Birch's research has maintained the very historic significance of steroids in furthering the progress of general organic chemistry within many fields.