Synthesis and Structural Analysis of Angular Monoprotected Diamines Based on Spiro[3.3]heptane Scaffold

The synthesis of all stereoisomers of spiro[3.3]­heptane-1,6-diamines suitably protected for use as building blocks in drug discovery is reported. Structural analysis revealed the similarity between the spiro[3.3]­heptane and cyclohexane scaffolds. Comparison of the distance between functional groups and their spatial orientation proved that (1S,4r,6R)- and (1R,4r,6S)-1,6-disubstituted spiro­[3.3]­heptanes can be considered as restricted surrogates of cis-1,4-disubstituted cyclohexane derivatives. Similarly, (1S,4s,6R)- and (1R,4s,6S)-1,6-disubstituted spiro[3.3]­heptanes are the restricted surrogates of trans-1,3-disubstituted cyclohexanes. Such replacement can be recommended for use in optimization of ADME parameters of lead compounds in drug discovery.