Structural Determination of Two Isomers of Betamethasone by NMR Spectroscopy

Two isomers of betamethasone 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methylpregna-1,4-diene-3,20-dione (1), were isolated from the mother liquor of a manufacturing process and were characterized by NMR spectroscopy, They were identified as 8 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-9 beta-pregna-1,4-diene-3,20-dione (2) and 14 beta-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-8 alpha,9 beta-pregna-1,4-diene-3,20-dione (3). The stereochemistries of 2 and 3 were assigned on the basis of proton-proton and proton-fluorine NOE experiments, The structure of the former was confirmed by x-ray crystallographic analysis.