Radical reactions aldosterone

Among the numerous applications of this reaction reported over four decades, some typical examples of the functionalization are outlined in Schemes 3 to 10. Thus, Scheme 3 outlines the well-known Barton transformation of corticosterone acetate nitrite into aldosterone acetate oxime which, with nitrous acid, gives aldosterone 12-acetate [4]. The yield of 18-oxime is, however, rather low (21 %), since attack by the 11/3-alkoxyl radical on C-19 competes with the desired attack on C-18. Incorporation of the 1,2-double bond into the nitrite prevented undesired C-19 attack by the radical and a far better yield (47 %) of 18-oxime was achieved [5] (Scheme 4). This example may indicate that the Barton reaction is sensitive to... 

The book explores the invention of new chemical reactions for use in the synthesis of biologically and economically important compounds. It begins with a mechanistic study of the industrial importance of the pyrolysis of chlorinated alkanes. It continues with a theory on the biosynthesis of phenolate derived alkaloids involving phenolate radical coupling. Included in the book is a description of the work on nitrite photolysis (the Barton Reaction) which involved the invention of new radical chemistry leading to a simple synthesis of the hormone, aldosterone. In two final chapters Dr Shyamal Parekh views Professor Barton s pioneering work from the modern perspective, with a review of recent applications in industry and research. 

These examples are the most weU-known applications of the reaction found by Barton as well as by his colleagues. The irradiation of corticosterone acetate nitrite affords aldosterone acetate oxime, which with nitrous acid gives aldosterone 12-acetate (Scheme 13). The overall yield, however, is rather low (15%) because an attack by the lip-alkoxyl radical on C19 competes with the desired attack on CIS. The incorporation of the 1,2-double bond into the nitrite could avoid an undesired C19 attack by the radical a far better yield (47%) of 19-oxime was achieved, as shown in Scheme 14. These examples of the functionalization may indicate that the Barton reaction is sensitive to structural changes and that the distance and conformation requirements between the alkoxyl radical and the methyl group, which are in a 1,3-diaxial relationship, is rather strict (Scheme 14). 

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