Monoprotected Diamines Derived from 1,5‐Disubstituted (Aza)spiro[2.3]hexane Scaffolds

• Published in: European journal of organic chemistry 2021-12, Vol.2021 (47), p.6570-6579
• Main Authors: Malashchuk, Andrii, Chernykh, Anton V., Perebyinis, Mariana Y., Komarov, Igor V., Grygorenko, Oleksandr O.
• Format: Article
• Language: English
• Subjects: Diamines; Exit vector plots; Molecular rigidity; Peptidomimetics; Spirocyclic compounds
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202001614

Synthesis of monoprotected diamines derived from 1,5‐disubstituted spiro[2.3]hexane and 5‐azaspiro[2.3]hexane scaffolds is described. In both cases, the method relied on the cyclopropanation of the corresponding cyclobutane or azetidine derivatives. In the case of monoprotected 1,5‐diaminospiro[2.3]hexanes, the title products were obtained as single diastereomers. X‐Ray diffraction studies supported by exit vector plot (EVP) analysis showed that the obtained building blocks are promising piperidine/cycloalkane isosteres with potential utility to drug discovery. Also, conformations observed in the crystalline state for the two different diastereomers of 1,5‐diaminospiro[2.3]hexane derivatives prompt their application in design of β‐turn and sheet‐like peptidomimetics, respectively. Synthesis of monoprotected diamines derived from 1,5‐disubstituted (aza)spiro[2.3]hexane scaffolds is described. Structural characterization of the obtained spirocyclic compounds provided a rationale for their applications in design of saturated ring isosteres and peptidomimetics.