Total Synthesis and Biological Evaluation of Sericetin for Protection against Cisplatin-Induced Acute Kidney Injury

Abstract

A concise synthesis of sericetin (1) was performed in four steps from readily available 3-Obenzylgalangin (4), featuring electrocyclization to produce the tricyclic core and a sequential aromatic Claisen/Cope rearrangement to incorporate the 8-prenyl group of 1. In addition, the therapeutic potential of sericetin (1), isosericetin (2), and three prenylated tetracyclic synthetic intermediates (11, 12, and 14) against cisplatin-induced nephrotoxicity using renal tubular cells were evaluated. Compound 14 showed therapeutic potential against cisplatin-induced kidney damage.P renylated flavonoids are a subclass of flavonoids that possess a wide range of biological properties, such as antioxidant, anticancer, antifungal, and estrogenic activities. 1 The addition of a lipophilic prenyl group to these flavonoids could increase their lipophilicity, thereby increasing their permeabilities and bioavailabilities in vivo. 2 Sericetin (1), a prenylated flavonoid, was first isolated from the root-bark of Mundulea sericea in 1960 (Figure 1). This

Perplexing Polyphenolics: The Isolations, Syntheses, Reappraisals, and Bioactivities of Flavonoids, Isoflavonoids, and Neoflavonoids from 2016 to 2022

“…Subsequently, it was prenylated to 357 , which was treated with diethylaniline in a Claisen rearrangement to give compound 360 via the two intermediate isomers, 358 and 359 . Compound 360 was deprotected to yield the final product, sericetin ( 361 ) [ 92 ].…”

“…Compound 361 decreased cell viability, while compound 360 only showed a marginal increase. Compound 357 significantly increased cell viability, inhibiting ROS generation and reducing cleaved caspase-3 levels [ 92 ].…”

Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues

“…Then the −MOM protecting groups at C-4 and C-6 of 9a were removed by treatment with a diluted HCl solution to generate 10a (88%) . Compound 10a was subsequently treated with 3-methyl-2-butenal ( 11 ) in the presence of Ca­(OH) 2 to obtain 6,7-pyran adduct 12a (45%). − It is worth mentioning that only the 6,7-pyran product was obtained, while the corresponding 7,8-cyclized product was not detected despite the apparent similarity of the two positions. Compound 12a was coupled with 3-methylbut-2-en-1-ol ( 13 ) under the classical Mitsunobu conditions (diethyl azodicarboxylate (DEAD), triphenylphosphine [P­(Ph) 3 ] in dry tetrahydrofuran (THF)) to give 5-prenyl ether 14 .…”