Access to the cis-Fused Stereoisomers of Proline Analogues Containing an Octahydroindole Core

An overview of the synthetic methods developed to build all the cis-fused stereoisomers of octahydroindole-2-carboxylic acid and its alpha-methylated derivative in enantiomerically pure form is presented. Both asymmetric synthetic strategies (auxiliary-or substrate-controlled processes) and procedures based on the resolution of racemic compounds (chemical, enzymatic, and chromatographic processes) are summarized. Special emphasis has been placed on those strategies able to provide multigram quantities of enantiopure compounds, a prerequisite to make downstream biological applications feasible.