Transformation of josamycin in alkaline solution—intramolecular SN2 substitution or E1cB elimination and intramolecular Michael addition?

The conversion of josamycin (1) into its α,β-unsaturated derivative 2 was optimized to avoid formation of undesired josamycin bicyclic derivatives of type 3 under alkali treatment. The influence of various 1:base stoichiometry, temperature and reaction time on the conversion was monitored by 1H NMR spectroscopy. Spectroscopic studies indicated clearly that the transformation of 1 in alkaline solution involves as the first step, the formation of α,β-unsaturated derivative 2 via an E1cB stereoselective elimination and as the second step, the intramolecular Michael addition leading to the formation of two diastereomeric bicyclic derivatives 3a and 3b.