Abstract:
A new synthetic pathway to analogues of the aglucones of naturally occurring
cyclic hydroxamic acids (2,4-dihydroxy-l,4-benzoxazin-3-ones) has been developed.
The new pathway involves the coupling of substituted nitrophenols wdth /-propyl-abromo-
O-methoxymethylglycolate. These materials were reductively cyclised to
reveal the hydroxamic acid functionality. Removal of the C-2 0-methoxymethyl
protecting group was achieved chemoselectively using boron trichloride. The
analogue 7-methoxy-2,4-dihydroxy-l,4-benzoxazin-3-one (DIMBOA) was assayed
with papain and a semilog plot of activity of papain in the presence of excess
DIMBOA was found to be linear. A single exponential equation was suggested as the
model for kinetic analysis. '^ Nuclear magnetic resonance (NMR) spectra of a
couple of hydroxamates were acquired as reference standards for future mechanistic
studies of these compounds as thiol protease inhibitors. A 10% '^-labeled sample
ofDIMBOA was also prepared for future mechanistic studies using NMR techniques.
