Warfarin tautomers

Figure 6.2 Three largely different warfarin tautomers out of aght [32], as discussed above.

Warfarin is an interesting compound in that, in addition to ionising, it exhibits keto-enol tautomerism. This means that warfarin exists in two constitutional isomeric forms (tautomers) that are in equilibrium with each other, although one of the forms is usually present to a much higher degree than the other. See Figure 3.8. 

The 1,5-dicarbonyl disconnection (a), seen more clearly on the keto tautomer (73) of Warfarin, is strategically excellent as it separates two branch points and gives simple starting materials, coumarin (74) and the enone (75) (Chapter 20). 

Identify warfarin as an a, /3, y, etc., lactone. Identify each part of warfarin that can undergo keto-enol tau-tomerization and show the tautomer at that position. 

An apparently trivial but important point to be considered is the generation of structures. Although for simple systems all the possible tautomeric forms can be easily drawn, in other cases the situation is less clear for example, 15 sttuctures for xanthine were provided to the participants in the SAMPL2 challenge as many as 40 sttuctures (tautomers and conformers) have been considered for warfarin [8]. Several tools exist to handle the tautomer enumeration problem [9], but these rely on experimental data and/or empirical rules (mosdy pJC values) and hence not all types of tautomerism might be described correctly. 

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