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.