Chiral Vicinal Diamines Derived from Mefloquine

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Jul 27

PMID 34314190

Citations 2

Authors

Dawid J Kucharski

Rafal Kowalczyk

Przemyslaw J Boratynski

Affiliations

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Abstract

Novel 1,2-diamines based on the mefloquine scaffold prepared in enantiomerically pure forms resemble 9-amino- alkaloids. Most effectively, 11-aminomefloquine with an configuration was obtained by conversion of 11-alcohol into azide and hydrogenation. Alkylation of a secondary amine unit was needed to arrive at diastereomeric -11-aminomefloquine and to introduce diversity. Most of the substitution reactions of the hydroxyl group to azido group proceeded with net retention of the configuration and involved actual aziridine or plausible aziridinium ion intermediates. Enantiomerically pure products were obtained by the resolution of either the initial mefloquine or one of the final products. The evaluation of the efficacy of the obtained vicinal diamines in enantioselective transformations proved that -11-aminomefloquine is an effective catalyst in the asymmetric Michael addition of nitromethane to cyclohexanone (up to 96.5:3.5 er) surpassing -aminoquinine in terms of selectivity.

Citing Articles

Enantioselective 1,3-Dipolar Cycloaddition Using ()-α-Amidonitroalkenes as a Key Step to the Access to Chiral -3,4-Diaminopyrrolidines.

Garcia-Minguens E, Ferrandiz-Saperas M, de Gracia Retamosa M, Najera C, Yus M, Sansano J Molecules. 2022; 27(14).

PMID: 35889453 PMC: 9316397. DOI: 10.3390/molecules27144579.

A Review of Modifications of Quinoline Antimalarials: Mefloquine and (hydroxy)Chloroquine.

Kucharski D, Jaszczak M, Boratynski P Molecules. 2022; 27(3).

PMID: 35164267 PMC: 8838516. DOI: 10.3390/molecules27031003.

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