Neoflavones. 2. Methods for Synthesizing and Modifying 4-Arylcoumarins

Abstract

Literature data up to 2003 were presented and information on methods for preparing and modifying natural 4-arylcoumarins and their synthetic analogs were systematized.The first part of this review [1] presented data on the physicochemical and pharmacological properties of natural 4-arylcoumarins. Natural neoflavones and their synthetic analogs can be used as medical preparations because of their wide spectrum of biological activity and low toxicity. However, this necessitates the development of preparative synthetic methods. Therefore, the second part reviews completely all presently known synthetic approaches to the construction and modification of neoflavones.

SLC26A3 inhibitor identified in small molecule screen blocks colonic fluid absorption and reduces constipation

“…Supplemental Tables 1 and 2 (supplemental material available For further studies, DRA inh -A250 was resynthesized ( Figure 3C) by Pechmann condensation of 2-methylresorcinol with dimethyl acetylsuccinate to yield 7-hydroxycoumarin (intermediate 1), which was further alkylated with 3-bromobenzyl bromide to give coumarin ester (intermediate 2) (23,24). Hydrolysis of the coumarin ester gave the corresponding 3-acetic acid-coumarin DRA inh -A250 in good yield ( Figure 3C).…”

Structural Modifications at the C-4 Position Strongly Affect the Glucuronidation of 6,7-Dihydroxycoumarins

“…The direct modification of the catechol group would potentially diminish their bioactivity, and structural changes on the nonpharmacophore groups are more reasonable strategies for the structural modification of 6,7-DHCs. During the past half century, many coumarin derivatives, including many C-4 derivatives, were synthesized and reported because these derivatives can be readily synthesized and various substituents can be easily introduced to the C-4 position by total synthesis or semisynthesis (Garazd et al, 2005). Several previous studies also found that C-4 hydrophilic modification does not affect the antioxidant and the anticancer activities of 6,7-DHCs (Kostova, 2005;Lin et al, 2008).…”

“…4-ME has exhibited enhanced intestinal anti-inflammatory activity in rat colitis (Witaicenis et al, 2010), and 4-PE is a potent rat lens aldose reductase 2 inhibitor (Kato et al, 2010). Recently, owing to the easy accessibility of the structural modification in this position (Garazd et al, 2005), various substitution groups such as aryl groups and heterocyclic rings have been introduced to C-4 position to obtain products with potentially enhanced or new activities (Mashelka and Audi, 2006;Kini et al, 2012;Sokmen et al, 2013).…”

Synthesis and biological evaluation of novel neoflavonoid derivatives as potential antidiabetic agents

“…The structure of the most effective compound ( Owing to the potential biological activity and structural diversity of neoavonoid, they have attracted an appreciable amount of attention in the synthetic community in recent decades. 19 There are numerous reports of their synthesis in literature, but most of them have some disadvantages such as using expensive raw materials, delivering low regioselectivities and not economical or environmental friendly. 20 Consequently, researchers are still looking for more environmental benign and economical synthetic processes.…”