EFFICIENT MULTIGRAM SYNTHESIS OF 3,3-Spiro-Α-Proline CONTAINING CHIMERAS

Abstract

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.

Practical Multigram Approach to Conformationally Constrained Proline-Based Building Blocks With Gamma-Spiro Conjunction

“…As part of our ongoing efforts on the design and synthesis of advanced building blocks for medicinal chemistry, quite recently we have reported two practical multigram protocols to reach spirocyclic proline topology with a spiro portion in position 3 of the pyrrolidine ring. 15 This work was motivated by several reasons. First, natural products serve as privileged templates in the discovery of modern drugs, thus giving inspiration for many researchers.…”