Semisynthetic macrolide antibacterials derived from tylosin. Synthesis of 23-O-demycinosyltylosin and related compounds

The synthesis of a versatile intermediate 4‴-O-(dimethyl-t-butylsilyl)tylosin, directly from tylosin, is described. Its utility in the synthesis of selected acyl derivatives of tylosin, as well as in the synthesis of 23-O-demycinosyltylosin, is discussed. Limitations to its use where 3-O-acyl groups are present in the macrolide were evident. A number of acyl derivatives and 23-substituted derivatives of 23-O-demycinosyltylosin, as well as their hydrazones, have been prepared using the above methodology.