Recent approaches to chiral 1,4-dihydropyridines and their fused analogues

Martins Rucins, Aiva Plotniece, Eiva Bernotiene, Wei Bor Tsai, Arkadij Sobolev

Research output: Contribution to journalReview articlepeer-review

Abstract

The purpose of this review is to highlight recent developments in the synthesis of chiral 1,4-dihydropyridines and their fused analogues. 1,4-Dihydropyridines are among the most active calcium antagonists that are used for the treatment of hypertension. Enantiomers of unsymmetrical 1,4-dihydropyridines often show different biological activities and may have even an opposite action profile. Hantzsch synthesis usually produces racemic mixtures of unsymmetrical 1,4-dihydropyridines. Therefore, the development of stereoselective synthesis of 1,4-dihydropyridines is one of the priorities of medicinal chemistry. Over the years, numerous methodologies have been developed for the production of enantiopure 1,4-dihydropyridines, such as stereoselective synthesis using chiral auxiliaries and chiral cyclocondensation partners, chromatographical methods, resolution of diastereomeric 1,4-dihydropyridine salts, enzyme catalysed kinetic resolution, or asymmetrisation of ester groups of 1,4-dihydropyridines. These approaches have been studied in detail and are relatively well established. The catalytic asymmetric approach holds the greatest promise in delivering the most practical and widely applicable methods. Substantial progress has been made toward the development of enantioselective organocatalytic methods for the construction of the chiral dihydropyridines. However, most of them do not provide a convenient way to pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates. Organocatalytic enantioselective desymmetrisation of prochiral 1,4-dihydropyridine-3,5-dicarbaldehydes also has great promise in the synthesis of pharmacologically important 1,4-dihydropyridine-3,5-dicarboxylates.

Original languageEnglish
Article number1019
Pages (from-to)1-21
Number of pages21
JournalCatalysts
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 2020
Externally publishedYes

Keywords

  • 1,4-dihydropyridines
  • Asymmetric synthesis
  • Calcium channel antagonists
  • Chirality
  • Enzyme-catalysed hydrolysis
  • Multicomponent reactions
  • Organocatalysis
  • Resolution of diastereomeric salts
  • Separation
  • Six-membered N-heterocycles

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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