A series of substituted 5benzyl-3-(1 -carboxy-2-phenylethyl) hydantoins was prepared by condensation of aromatic aldehydes with the corresponding 5-unsubstituted hydantoin followed by reduction of the intermediate benzylidene derivative. The compounds were assessed as inhibitors of dihydroorotate dehydrogenase from Clostridium oroticum. It was found that hydrophobic and electron-donating substituents in the phenyl ring of the benzyl group favoured binding and irreversible inhibition. The results for the series were correlated with standard substituent parameters from which a mechanism of inhibition was derived. This involved rapid deprotonation of the hydantoin at C-5 followed by ratedetermining removal of hydride, or its equivalent.Dihydro-orotate dehydrogenase (DHODase) is an enzyme in the biosynthetic pathway to pyrimidines and has been recognised as a potential candidate for inhibition in chemotherapy.* We have shown that dihydro-orotate dehydrogenase from CZostridium oroticum was inhibited by the parent member of the series, 5-benzyl-3-( 1 -carboxy-Zphenyl-ethy1)hydantoin t 5a in a time-dependent and irreversible manner.3 On the basis of the intrinsic chemical properties of the inhibitor and a computer-generated comparison of the structures of substrate and inhibitor, we proposed a mechanism in which the 5-benzyl group was oxidised by the enzyme to a benzylidene group; the product would have structure 4a and this would give rise to an a,a-unsaturated carbonyl compound to which the enzyme might be expected to add. The present work was designed to probe further the mechanism of this unexpected reaction and to obtain additional related compounds with potentially improved biological activity.Synthesis.-The previous synthesis starting from ( S ) -* Figures relate to the binary complex of enzyme plus inhibitor.Data are for the racemate, m.p. 187-188°C. bData are for the racemate, m.p. 196-198 "C.

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In recent years significant developments have been made in passively modelocked solid-state lasers by the application of semiconductor-based saturable absorbers1,2. Such saturable absorbers have been developed for use in broadly tunable lasers such as Ti:sapphire and Cr:LiSAF where attractive features such as improved reliability and self-starting are introduced, although at the expense of wavelength tunability compared to Kerr-Lens-Modelocked lasers.