4-ketoproline derivatives as chiral templates in synthesis.
(2S)-trans-4-Hydroxyproline has been studied as a chiral template for the
preparation of kainoids. Conversion to protected 4-ketoproline derivatives has allowed
functionalisation at C-3 to be investigated. Although the tendency to epimerisation has
caused problems, we have successfully introduced a variety of alkyl side chains with cis
stereochemistry at this position.
Functionalisation of the 3-alkyl-4-ketoprolines at C-4 has been investigated and a
method has been found to prepare compounds which are functionalised stereospecifically
at both C-3 and C-4. These have potential for study as kainate analogues.
During our studies on the synthesis of kainoids, an unusually stereospecific
deuteriation has been discovered. We have exploited this in a synthesis of (2S,3S)-[3-
2Ht]-proline, (2S,3R)-[3-2Ht]-proline and (2S)-[3,3-2H21-proline.