HIGHLY EFFICIENT SYNTHESIS OF -2-AMINO-4,4-DIFLUORO-1,6-DIPHENYL-3-HYDROXYHEXANE - THE KEY INTERMEDIATE FOR A SERIES OF POTENT HIV PROTEINASE-INHIBITORS

Many alpha,alpha-difluoroketones such as linyl)amino-3-oxo-4,4-difluor o-1,6-diphenyl-hexane (1), with the strongly electronegative fluorines next to the carbonyl group, are usually fully hydrated. As a result o f the hydration of the carbonyl group, the difluoroketones can act as transition-state analog inhibitors of certain proteinases. Reformatsky reaction of aldehyde N-t-butyloxycarbonyl L-phenylalaninal (3), with bromodifluoromethylphenyl acetylene provided the key intermediate for the synthesis of a series of potent HIV proteinase inhibitors exemplif ied by 1.