PRACTICAL SYNTHESES OF -[(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 ANALOGS

Practical high yielding syntheses of -[(2-methoxyethoxy)methyl]-22,23- dihydroavermectin B-1 aglycon (dimedectin 2-propanol, MK-324, 1) and 1 3-epi-O-(methoxymethyl)-22,23-dihydroavermectin B-1 aglycon (L-694,554 , 2), both potent flea insecticides, from ivermectin are presented. Th e successful selective manipulation of silyl protecting groups on iver mectin 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/ter tiary amine system for mesylation of the C-13 alpha hydroxyl group of 7 and subsequent displacement with cesium propionate-propionic acid le d to the successful inversion of the 13-hydroxy group.