Synthesis and Structure-Chirality Relationship Analysis of Steroidal Quinoxalines to Design and Develop New Chiral Drugs

Rashid Mehmood,Charles Christopher Sorrell,Naghmana Rashid,Shakir Ullah,Maria John Newton Amaldoss

doi:10.3390/chemistry3010030

Rashid Mehmood, Charles Christopher Sorrell + Show 3 more

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https://doi.org/10.3390/chemistry3010030

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Abstract

Of the utmost importance of chirality in organic compounds and drugs, the present work reports structure-chirality relationship of three steroidal quinoxalines, which were synthesised by condensing diaminobenzenes with cholestenone. All the compounds were purified and characterised by varying analytical tools prior to their chiroptical analysis by circular dichroism (CD) technique. The substituent groups on quinoxalines contributed to determining the chiroptical properties of the compounds. The positive Cotton effects have been observed in the CD spectra of unsubstituted and methyl-substituted quinoxalines, which indicated their P helicity. Importantly, chloro-substituent on quinoxalines produced different CD behaviour, which can be attributed to the presence of three lone pairs of electrons on Cl atom. The present work provides guidelines for determining the chiral properties of steroidal quinoxalines, which can be useful to design and develop potential molecules of biological importance.

Highlights

The 2016 Nobel Prize in Chemistry, awarded to Prof
Characterisation of the synthesised compound was done by using varying analytical instruments including melting point apparatus (MP; Gallenkamp, Sanyo MPD350, West Midlands, UK), nuclear magnetic resonance spectrometer (NMR; Bruker Avance 300–400 MHz, Billerica, MA, USA), Fourier transform infra-red spectrophotometer (FTIR; Perkin-Elmer, Waltham, MA, USA), mass spectrometer (MS; Varian MAT 312, Palo Alto, CA, USA and Bruker micrOTOF-QTM, Billerica, MA, USA), and circular dichroism spectropolarimeter (CD; JASCO J-810, Tokyo, Japan)
5α-cholest-3-eno-[3,4-b]-7’(8 )-methylquinoxaline (III): Anhydrous toluene (50 mL) was introduced in 250 mL double-neck round bottomed flask, which was sealed with reflux assembly setup under inert atmosphere

Summary

Introduction

The 2016 Nobel Prize in Chemistry, awarded to Prof. Bernard L. Molecular geometry, is an intrinsic property of molecules and ions which determines their effectiveness and specificity [2,3]. The extreme case of this was observed in 1957, when a racemic mixture of thalidomide, morning sickness alleviator, reportedly affected thousands of newborn babies worldwide. It was prescribed for pregnant women during the first trimester, but it prevented the growth and nourishment of the fetus, resulting in severe birth defects [4]. Since human physiological systems are selective in interacting with racemic drug, each enantiomer of the racemate metabolises via distinct mechanism to induce different biological effects. One enantiomer of a racemic mixture may initiate beneficial actions, while the other may be harmful for the body [6]

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Conclusion