title: Synthesis and structural analysis of angular monoprotected diamines based on spiro[3.3]heptane scaffold.
abstract: 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.
authors.affiliation: †Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv 02660, Ukraine.|‡Enamine Ltd., Alexandra Matrosova Street 23, Kyiv 01103, Ukraine.
authors.forename: Anton V
authors.initials: AV
authors.lastname: Chernykh
authors.affiliation: ‡Enamine Ltd., Alexandra Matrosova Street 23, Kyiv 01103, Ukraine.|§Institute of High Technologies, Taras Shevchenko National University of Kyiv, Volodymyrska 60, Kyiv 01601, Ukraine.
authors.forename: Dmytro S
authors.initials: DS
authors.lastname: Radchenko
authors.affiliation: ∥Department of Chemistry, Taras Shevchenko National University of Kyiv, Volodymyrska 64, Kyiv 01601, Ukraine.
authors.forename: Oleksandr O
authors.initials: OO
authors.lastname: Grygorenko
authors.affiliation: ⊥Westfalische Wilhelms-Universitat Munster, Institute of Organic Chemistry, Corrensstrasse 40, Munster 48149, Germany.
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Daniliuc
authors.affiliation: †Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv 02660, Ukraine.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Volochnyuk
authors.affiliation: ‡Enamine Ltd., Alexandra Matrosova Street 23, Kyiv 01103, Ukraine.|§Institute of High Technologies, Taras Shevchenko National University of Kyiv, Volodymyrska 60, Kyiv 01601, Ukraine.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Komarov
mesh_terms: D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000737:chemistry*; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013141:Spiro Compounds / Q000737:chemistry*
chemical_list: D003510:Cyclohexanes; D003959:Diamines; D013141:Spiro Compounds