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Cover Feature: Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug Discovery (Chem. Eur. J. 21/2018)
Author(s) -
Kirichok Alexander A.,
Shton Irina O.,
Pishel Irina M.,
Zozulya Sergey A.,
Borysko Petro O.,
Kubyshkin Vladimir,
Zaporozhets Olha A.,
Tolmachev Andrei A.,
Mykhailiuk Pavel K.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800624
Subject(s) - drug discovery , pipecolic acid , chemistry , proline , combinatorial chemistry , stereochemistry , cyclopentane , drug , amino acid , biology , biochemistry , pharmacology
A new spirocyclic amino acid for drug discovery , a surrogate for l ‐proline/pipecolic acids, is described. The synthesis of multifunctional spirocycles starts from the commonly available cyclic carboxylic acids, for example, cyclobutane carboxylate, cyclopentane carboxylate, and l ‐proline. The whole sequence includes only two chemical steps: synthesis of azetidinones and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to the wide use of spirocyclic building blocks in drug discovery in the nearest future. More information can be found in the Communication by P. K. Mykhailiuk et al. on page 5444.