SYNTHESIS OF 1,19-AZA-1,19-DEOXY-AVERMECTIN B-1A - THE FIRST AVERMECTIN MACROLACTAM

The first synthesis of 1,19-aza-1,19-desoxy-avermectin B-1a (2) is des cribed. This new macrolactam, prepared efficiently from avermectin B-1 a (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 intra molecular hydrogen bond is anticipated to confer additional conformati onal rigidity to the 16-membered macrocycle.