Synthesis of 1,19-Aza-1,19-desoxy-avermectin B(1a): The First Avermectin Macrolactam.

The first synthesis of 1,19-aza-1,19-desoxy-avermectin B(1a) (2) is described. This new macrolactam, prepared efficiently from avermectin B(1a) (1a) in seven steps, was designed to form an intramolecular hydrogen bond between the amide carbonyl and the adjacent C7 tertiary hydroxyl via a six-center hydrogen bonding network. The presence of this intramolecular hydrogen bond is anticipated to confer additional conformational rigidity to the 16-membered macrocycle.