EFFICIENT MULTIGRAM SYNTHESIS OF 3,3-SPIRO-α-PROLINE CONTAINING CHIMERAS

A series of novel spirocyclic α-proline building blocks for drug discovery with a spiro conjunction in position 3 of pyrrolidine was prepared by means of two convenient and practical synthetic approaches. Both alternative routes utilize simple and easily available starting materials – cyclic ketones and esters – and comprise 6- and 7-steps, respectively. The methodologies feature several advantages, including exploitation of simple organic chemistry transformations and suitability for preparation of multigram amounts of the target prolines. Approach to other valuable chemicals – spirocyclic pyroglutamic acids – is also discussed.