Stereoselective introduction of tetracyclines hydroxyl group at 12(a) position in synthesis of tetracyclines

In the process for the stereospecific 12a hydroxylation of a 12a deoxytetracycline precursor wherein said precursor is contacted with molecular oxygen, said precursor being selected from the group consisting of ##SPC21##

• tautomeric forms thereof, and mono- or polysubstituted derivatives thereof having substituents selected from the group consisting of bromo, iodo, chloro, fluoro, trifluoromethyl, nitro, cyano, amino, cyanoto, thiocyanato, azido, lower alkyl amino, hydroxy, alkanoyl amino, lower alkyl, and lower mono-substituted alkyl having fluoro, lower alkyl mercapto, lower alkoxy, lower alkyl amino, alkanoyl oxy, and alkanoyl amino groups;
• the improvement comprising carrying out said 12(a) hydroxylation in the presence of a strong base selected from the group consisting of alkali metal amides, alkali metal butoxides, alkali metal alkyls of 1 to 6 carbon atoms, alkali metal hydrides and magnesium alkoxides;
• said reaction being carried out in the presence of a non-protic solvent which is inert with respect to the tetracycline structure in the presence of said strong base, and which does not release protons in the presence of said strong base.