A series of 1-acylamino boronic acids (IA-VA), analogues of the amino acids phenylalanine, phenylglycine, alanine, valine, and isoleucine, were prepared as potential transition-state inhibitors of the serine proteases alpha-chymotrypsin and elastase, by a boronate homologation reaction. The corresponding difluoroboranes (IB-VB), produced from the boronic acids by treatment with HF, were more easily purified than the boronic acids. Since the difluoroboranes readily hydrolyze in water, they proved to be convenient precursors for the boronic acids. The phenylalanine and phenylglycine analogues I and II were good competitive inhibitors of alpha-chymotrypsin (Ki = 0.3-8 microM), and the alanine, valine, and isoleucine analogues (III-IV) proved to be good inhibitors of elastase (Ki = 0.1-35 microM). On the basis of their high affinity and the tendency of boronic acids to form borate complexes, these acylamino boronic acids may be behaving as transition-state inhibitors.