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Updated: Apr 4, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
A General Method for Synthesis of Unclosed Cryptands via H-Bond Templated Macrocyclization and Subsequent Mild
Kajetan Dabrowa1, Patryk Niedbala1, Maciej Majdecki2
1Institute of Organic Chemistry, Polish Academy of Sciences , Kasprzaka 44/52, 01-224 Warsaw, Poland.
Abstract:
A practical four-step synthesis of a model 26-membered N-Boc-protected macrocycle, starting from commercially available and inexpensive materials, is reported. The crucial macrocyclization step does not require high-dilution conditions and is completed in a short time (8 h). The high yield of macrocyclization (61%) is achieved owing to templation by intramolecular H-bonds and a chloride anion, which both help to adopt a favorable folded conformation of the open-chain intermediate. Finally, mild, selective, and efficient incorporation of intraannular amide function leading to five diversely functionalized unclosed cryptands (UCs) is described.
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