PRACTICAL MULTIGRAM APPROACH TO CONFORMATIONALLY CONSTRAINED PROLINE-BASED BUILDING BLOCKS WITH GAMMA-SPIRO CONJUNCTION

Unusual amino acids have arisen as an indispensable instrument at the disposal of modern medicinal chemistry. While extensively exploited as building blocks in the search for new pharmaceuticals, their application goes far beyond and they are currently involved in the exploration of the structure and conformational mobility of peptides, modification and amplification of peptidomimetics’ activity, and others. Herein, we communicate an effective synthetic approach to non-planar, conformationally restricted, sp3-enriched spirocyclic -prolines. The protocol employs readily available nitrile starting materials and conventional experimental procedures. The synthetic sequence is concise and includes three principal stages (one of them is a 4-step through process). The reactions proceed on a multigram scale affording the target prolines in overall good yields. The building blocks synthesized in the study are expected to have practical uses in the field of medicinal chemistry.