Enamine resonance

The higher frequencies of the /3-lactam carbonyl absorption in fused systems has been attributed to increased inhibition of amide resonance as the /3-lactam ring becomes less planar (b-72mI50900 p. 303). For the 3-cephems (61) there is also the possibility of enamine resonance which could further reduce the ability of the /3-lactam nitrogen to contribute to amide resonance. 

The formation of the enamine resonance form is a property of the enamine, and requires no base. 

The presence of the double bond, which differentiates penems from penams, allows enamine resonance which renders the bridgehead nitrogen atom less basic and weakens the C(7)-N(4) bond, and hence facilitates /3-lactam hydrolysis. As a consequence, they are more labile than the penams, and such instability issues narrow the range of chemical reactivity of the penem skeleton. 

When applications of transition state inhibitors to enzymology were introduced by Wolfenden and Lienhard, ° Lienhard suggested two compounds, thiamin thiazolone diphosphate (ThTDP) and thiamin 2-thiothiazolone diphosphate (ThTTDP), as potential transition state analogs. The C2=0 and C2=S bonds, respectively, in place of C2-H in ThDP, resemble the C2=C2a double bond of the enamine resonance structure in Schemes 1 and 2. These compounds have been synthesized and used to good effect on a variety of ThDP enzymes. For reasons not yet clear, they appear to be most inhibitory toward the El components of the... 

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