Hemi-Synthesis of Chiral Imine, Benzimidazole and Benzodiazepines from Essential Oil of Ammodaucus leucotrichus subsp. leucotrichus.

Farid Chebrouk,Leila Boukenna,Filipe Paz,Ricardo Mendes,Oualid Talhi,Mónica Válega,Khodir Madani,Khaldoun Bachari,Artur Silva,Brahim Cherfaoui

doi:10.3390/molecules24050975

Abstract

The hemi-synthesis of chiral imine, benzimidazole and benzodiazepine structures is reported by the condensation of (S)-(−)-perillaldehyde, the major phytochemical of Ammodaucus leucotrichus subsp. leucotrichus essential oil, with different amine derivatives of 2,3-diaminomaleonitrile, o-phenylenediamine and 3-[(2-aminoaryl)amino]dimedone. The reaction proceeds in situ at ambient temperature without prior isolation of the natural (S)-(−)-perillaldehyde. Final products precipitate in the ethanolic reaction medium. 2D NMR and single-crystal X-ray diffraction studies were used to unequivocally characterize the structures in solution and in the solid state, respectively. Chiral HPLC analysis confirms the formation of unique enantiomers and diastereomeric mixtures.

Highlights

Over the past decades, there has been a growing transition in drugs from natural materials, natural products, or their simple derivatives to more potent natural-mimicking synthetic prototypes [1].Essential oils’ components still play a major role in this combinatorial chemistry and are considered promising sources of stereospecific structures
We propose the hemi-synthesis of novel chiral imine, benzimidazole and benzodiazepine structures from the essential oil of A. leucotrichus by condensation of its major constituent (S)-(−)-perillaldehyde (81.0%) with different amine substrates, such as
The final products 1–4 are chiral because the condensation reactions are carried out over the aldehyde group, maintaining the configuration of the asymmetric centre of (S)-perillaldehyde

Summary

Introduction

There has been a growing transition in drugs from natural materials, natural products, or their simple derivatives to more potent natural-mimicking synthetic prototypes [1]. Essential oils’ components still play a major role in this combinatorial chemistry and are considered promising sources of stereospecific structures. They can serve as substrates in hemi-synthesis, leading to new active molecules. (+)-carotol, the major constituent of carrot seed essential oil, was used as a starting material in the hemi-synthesis of ten cytotoxic hydroindene-derived chiral synthons [2]. A novel series of essential oils oriented chiral esters with high insecticidal activity have been synthesized based on the scaffold of the natural pyrethrin [3]. Cymbopogon schoenanthus essential oil is mainly composed of piperitone (68.2%), which was used for in situ preparation of three anti-parasitic carbasones [4]

Methods

Results

Conclusion