Highly efficient synthesis of 2(S)-3(R,S)-2-amino-4,4-difluoro-1,6-diphenyl-3-hydroxyhexane - the key intermediate for a series of potent HIV proteinase inhibitors

Article abstract of DOI:10.1016/0022-1139(94)03223-M

Many α,α-difluoroketones such as 2S-(N-benzyloxycarbonyl-valinyl)amino-3-oxo-4,4-difluoro-1,6-diphenyl-hexane (1), with the strongly electronegative fluorines next to the carbonyl group, are usually fully hydrated.As a result of 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 bromodifluoromethylphenylacetylene provided the key intermediate for the synthesis of a series of potent HIV proteinase inhibitors exemplified by 1. - Keywords: Synthesis; Aminodifluorodiphenylhydroxyhexane; HIV proteinase inhibitors; NMR spectroscopy; Mass spectrometry