The study of coumarin dates back to 1820 when coumarin was first extracted from tonka bean by Vogel. Compounds containing coumarin backbone are a very important group of compounds due to their usage in pharmacy and medicine. Properties and biological activities of coumarin derivatives have a significant role in the development of new drugs. Therefore, many different methods and techniques are developed in order to synthesize coumarin derivatives. Coumarin derivatives could be obtained from different starting materials with various methods but with big differences in yield. This review summarized various methods, techniques and reaction conditions for synthesis of coumarins from different compounds such as aldehydes, phenols, ketones and carboxylic acids.

Recent Advances in the Synthesis of Coumarin Derivatives from Different Starting Materials.

Rational approaches, design strategies, structure activity relationship and mechanistic insights for therapeutic coumarin hybrids.

Keeping in view various pharmacological attributes of indole and coumarin derivatives, a new series of indolindione–coumarin molecular hybrids was rationally designed and synthesized. All synthesiz...

Design, Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of Novel Indolinedione-Coumarin Molecular Hybrids.

Coumarin is a natural product with aromatic and fragrant characteristics, widespread in the entire plant kingdom. It is found in different plant sources such as vegetables, spices, fruits, and medicinal plants including all parts of the plants-fruits, roots, stems and leaves. Coumarin is found in high concentrations in certain types of cinnamon, which is one of the most frequent sources for human exposure to this substance. However, human exposure to coumarin has not been strictly determined, since there are no systematic measurements of consumption of cinnamon-containing foods. The addition of pure coumarin to foods is not allowed, since large amounts of coumarin can be hepatotoxic. However, according to the new European aroma law, coumarin may be present in foods only naturally or as a flavoring obtained from natural raw materials (as is the case with cinnamon). In this paper, the overview of the current European regulations on coumarin levels in food is presented, along with the most common coumarin food sources, with a special emphasis on cinnamon-containing food. Human exposure to coumarins in food is also reviewed, as well as the methods for determination and separation of coumarin and its derivatives in food.

https://www.mdpi.com/2304-8158/9/5/645/pdf

Coumarins in Food and Methods of Their Determination.

Keeping in view various pharmacological attributes of curcumin, coumarin, and isatin derivatives, triazole-tethered monocarbonyl curcumin-coumarin and curcumin-isatin molecular hybrids have been synthesized and evaluated for their antibacterial potential against Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) human pathogenic bacterial strains. Among all hybrid molecules, A-4 and B-38 showed the most potent antibacterial activity with inhibition zones of 29 and 31 mm along with MIC values of 12.50 and 6.25 μg/mL, respectively. Structure-activity relationship that emerged from biological data revealed that the two-carbon alkyl chain between triazole and coumarin/isatin moiety is well tolerable for the activity. Bromo substitution at the fifth position of isatin, para-cholo substitution in the case of curcumin-isatin, and para-methoxy in the case of curcumin-coumarin hybrids on ring A of curcumin are most suitable groups for the antibacterial activity. Various types of binding interactions of A-4 and B-38 within the active site of dihydrofolate reductase (DHFR) of S. aureus are also streamlined by molecular modeling studies, suggesting their capability in completely blocking DHFR.

Karina Pérez-Cruz

Papers

Synthesis and antioxidant study of new polyphenolic hybrid-coumarins