SYNTHESES OF 4''-EPI-AMINO-4''-DEOXYAVERMECTINS B-1

A practical synthesis of 4''-epi-aminoavermectins is described. High-y ielding imine formation from 4''-oxo-5-O-(allyloxycarbonyl)avermectin B-1 (5a) was effectively accomplished using hexa- or heptamethyldisila zane/zinc chloride. Subsequent reduction with sodium borohydride provi ded the 4''-epi-amines 10a,b and 12, respectively, in 85-90% yields fr om ketone. Synthesis of ketone 5a was accomplished by highly selective and high-yielding monoprotection of avermectin B-1 (3) to afford the C-5-allylcarbonate 4 followed by oxidation of the C-4''-hydroxyl (phen yl dichloro phosphate, DMSO, and TEA). Reductive amination was followe d by removal of the allyl carbonate protecting group with (Ph(3)P)(4)P d(O)-NaBH4. Acidic methanol removal of the C-7-OH trimethylsilyl group s, followed by crystallization as the benzoic acid salts, gave the des ired 4''-epi-(methylamino)-4''-deoxyavermectin B-1 benzoate (1c, MK-24 4, emamectin benzoate) or 4''-epi-amino-4''-deoxyavermectin B-1 benzoa te (14b), respectively, in 60% overall yields.