Penicillamine stereochemistry

No structure determinations on simple bis(thiolato)gold(I) complexes have yet been reported, but they are assumed to have linear stereochemistry as in [Au(S203)2]3 and in the complex D-penicillamine derivative Na[Au2Ni2(pen)4], of structure (21)., 269 270... 

This synthesis requires the separation of the diastereoisomers of 92 (obtained from D-penicillamine). An attempt to control the stereochemistry was developed by the Merck group in 1974, in a total synthesis based on the [2+2] cycloaddition of the ketene derived from azidoacetyl chloride and the chiral thiazoline 94. The reaction only gives the /ra .r-pcnam derivative 95, which could be epimerized via the Schiff base 96 (cisltrans ratio = 2 1) (Scheme 51). The separated tyr-isomcr has been transformed into synthetic penicillin G <1974JOC437>. 

The biological and pharmacological activity of chiral compounds depends upon their stereochemistry [75] with many showing enantioselective differences in their pharmacokinetics and pharmacodynamics, e.g. the D-isomer of penicillamine has useful therapeutic properties while the L-isomer is toxic. This growing awareness of the relationship between chirality and activity provided the impetus to develop chromatographic techniques for both the analytical and preparative scale separations of racemates. 

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