Asymmetric organocatalyzed synthesis of coumarin derivatives

Abstract

Coumarin derivatives are essential scaffolds in medicinal and synthetic chemistry. Compounds of this class have shown important activities, such as anticancer and antiparasitic, besides the commercially available drugs. These properties led to the development of efficient and greener synthetic methods to achieve the 2H-chromen-2-one core. In this context, the advances in asymmetric organocatalyzed synthesis of coumarin derivatives are discussed in this review, according to the mode of activation of the catalyst.

Synthesis of warfarin analogs: conjugate addition reactions of alkenyl-substituted N-heterocycles with 4-hydroxycoumarin and related substrates

“… 3 Enantioselective addition reactions have also been developed. 4 Our group recently described the Michael addition reactions of 1,3-dicarbonyl compounds with vinyl-substituted N-heterocycles ( eqn (2) ). 5 Based on this chemistry, we hypothesized that 4-hydroxycoumarins would exhibit similar nucleophilic reactivity with vinyl-substituted N-heterocycles.…”

Advances on Greener Asymmetric Synthesis of Antiviral Drugs via Organocatalysis

“…In this respect, a recent trend in the chemical science and pharmaceutical industry is the dismissal of catalytic metal complexes and their replacement with organocatalysts. The efficacy and synthetic versatility of asymmetric organocatalysis [15,16] and the use of a plethora of highly effective small-molecule organocatalysts have enriched the field of organic synthesis, including chiral proline derivatives, N-heterocyclic carbenes, chiral thioureas, and Brønsted acids as well as phase-transfer catalysts (PTC), such as the quaternary ammonium salts derived from cinchona alkaloids [17].…”

“…In Table 1, we present selected chiral antiviral drugs, the anti-HIV agents being the major examples [23], highlighting the asymmetric strategy employed as a crucial step to achieve their total synthesis. It is worth noting that most of the synthetic routes use chiral pools, including amino acids, as starting materials (entries 3,4,6,12,13,[15][16][17]. Chiral resolution using either enzymes or metal catalysts has also been successfully employed (entries 1, 2, 8, 9, 14) and only in a few cases have enantioselective organocatalyzed methods been employed (entries 10 and 11).…”

l-Proline-Catalyzed Three-Component Reaction of 4-Chloro-3-formylcoumarin, Sodium Sulfide, and α-Halo Ketones: A Direct Approach to Thieno[3,2-c]coumarins

“…[1][2][3][4] The wide range of versatile applications of coumarins underpin ongoing efforts in the construction of new coumarin compounds and the screening for their potential applications. [4][5][6][7][8][9][10] Coumarin cores are found in many marketed pharmaceuticals 11,12 and molecules that exhibit interesting biological activities, such as antiviral, 13 anticancer, 14 antibacterial, 15 antidiabetic, 16 antifungal, 17 or antihypertensive activities 18 among many others. 6 Furthermore, coumarin-based compounds are also employed as fluorescent sensors and dyes, 19,20 as food additives, 21 and in the cosmetic industry.…”