Practical syntheses of 13-O-[(2-methoxyethoxy)methyl]-22,23-dihydroavermectin B-1 aglycon [dimedectin isopropanol, MK-324] and 13-epi-O-(methoxymethyl)-22,23-dihydroavermectin B-1 aglycon [L-694,554], flea active ivermectin analogues

Practical high yielding syntheses of 13-O-[(2-methoxyethoxy)methyl]-22,23-dihydroavermectin B-1 aglycon (dimedectin 2-propanol, MK-324, 1) and 13-epi-O-(methoxymethyl)-22,23-dihydroavermectin B-1 aglycon (L-694,554, 2), both potent flea insecticides, from ivermectin are presented. The successful selective manipulation of silyl protecting groups on ivermectin aglycon led to the facile preparation of 5,7-O-bis-silyl-22,23-dihydroavermectin B-1 aglycon 7 as the key intermediate for the large scale syntheses of these compounds. Development of a dual pyridine/tertiary amine system for mesylation of the C-13 alpha hydroxyl group of 7 and subsequent displacement with cesium propionate-propionic acid led to the successful inversion of the 13-hydroxy group.