Practical Syntheses of 13-O-[(2-Methoxyethoxy)methyl]-22,23-dihydroavermectin B1 Aglycon [Dimedectin Isopropanol, MK-324] and 13-epi-O-(Methoxymethyl)-22,23-dihydroavermectin B1 Aglycon [L-694,554], Flea Active Ivermectin Analogues

Practical high yielding syntheses of 13-O-[(2-methoxyethoxy)methyl]-22,23-dihydroavermectin B1 aglycon (dimedectin 2-propanol, MK-324, 1) and 13-epi-O-(methoxymethyl)-22,23-dihydroavermectin B1 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 B1 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-13α hydroxyl group of 7 and subsequent displacement with cesium propionate−propionic acid led to the successful inversion of the 13-hydroxy group.