Green synthesis of enantiopure quinoxaline alcohols using Daucus carota

• Published in: Chirality (New York, N.Y.) N.Y.), 2019-04, Vol.31 (4), p.312-320
• Main Authors: Meshram, Sneha H., Ramesh, Tungana, Nanubolu, Jagadeesh Babu, Srivastava, Ajay Kumar, Adari, Bhaskar Rao, Sahu, Nivedita
• Format: Article
• Language: English
• Subjects: Absolute configuration; Alcohol; Alcohols; asymmetric reduction; Bioactive compounds; Bioavailability; biocatalyst; Biocatalysts; Biological activity; Chemical industry; Chemical synthesis; Configurations; Crystallography; Daucus carota; Enantiomers; Environmental health; Ethanol; Green chemistry; Health hazards; Ketones; Molecular properties; Organic chemistry; Pharmacology; Pharmacophores; Physicochemical properties; Public health; Quinoxaline; Quinoxalines; sustainable bioreduction; Swiss ADME analysis
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23057

Green chemistry comprises a new approach in the synthesis of biologically active compounds using biocatalysts, thus diminishing the hazards for human health and environmental pollution. Asymmetric bioreduction is one of the most widely employed strategies in chemoenzymatic synthesis to produce enantiomerically pure chiral alcohols. The present study highlights the use biocatalyst Daucus carota for selective bioreduction of quinoxaline ketones 1a‐6a to their corresponding optically pure alcohols 1b‐6b in high yields (up to 84%) and good enantioselectivity (up to 98%). The absolute configuration of the chiral product (R)‐1‐(3‐methyl 7‐nitroquinoxalin‐2‐yl) ethan‐1‐ol 2b was confirmed by X‐ray crystallography studies. The chiral R‐configuration of the products obtained was confirmed by absolute configuration studies and was assigned following anti‐Prelogs rule. Quinoxaline pharmacophores form a part of well‐known potent drug molecules; hence, the chiral products were studied for determination of their molecular properties using SwissADME property analyser. All the chiral products show no Lipinski rule violations and are expected to have good oral bioavailability. As per the molecular properties prediction studies, the compound 6b (R)‐1‐(6,7‐dichloro‐3‐ methylquinoxalin‐2‐yl) ethanol is observed to show the best physicochemical properties to be a good lead molecule. Thus, the sustainable methodology was developed, and it confirms the synthesis of novel quinoxaline chiral alcohols in a simple, inexpensive, and eco‐friendly condition using D carota.