Anti-inflammatory Dimeric 2-(2-Phenylethyl)chromones from the Resinous Wood of Aquilaria sinensis

Abstract

Sixteen new 2-(2-phenylethyl)chromone dimers, including four pairs of enantiomers (1a/1b, 3a/3b, 6a/6b, and 8a/8b), along with eight optically pure analogues (2, 4, 5, 7, and 9-12) were isolated from the resinous wood of Aquilaria sinensis. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1-10 feature an unusual 3,4-dihydro-2 H-pyran ring linkage connecting two 2-(2-phenylethyl)chromone monomeric units, while compounds 11 and 12 possess an unprecedented 6,7-dihydro-5 H-1,4-dioxepine moiety in their structures. A putative biosynthetic pathway of the representative structures via a diepoxy derivative of a chromone with a nonoxygenated A-ring is also proposed. Compounds 1a/1b, 2, 3a/3b, 5, 7, 8a/8b, and 10-12 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC values in the range 7.0-12.0 μM.

Overview of sesquiterpenes and chromones of agarwood originating from four main species of the genus Aquilaria

“…Yang et al obtained 1-6 from an EtOH extract of A. sinensis, which belong to the group of 2-(2-phenylethyl)chromones; 65 they later extracted 7-9 from an EtOAc-EtOH extract. 66 In addition, 10-12 were isolated by Liu et al 85 Wang et al 51 isolated compounds 54-57, which belong to the group of 2-(2-phenylethyl)chromone derivatives, from resinous wood, together with ve known compounds, 1, 6, 9, 29, and 58, from a MeOH extract.…”

UPLC-MS-guided isolation of single ether linkage dimeric 2-(2-phenylethyl)chromones from Aquilaria sinensis

“…5,6 Interestingly, 2-(2-phenylethyl) chromone dimers and trimers have been derived from agarwood recently; even though the rst batch from Kalimantan agarwood was reported by Siu Kiyosawa's group, [7][8][9][10][11] the process could not be traced until the analogues were rediscovered again in 2017. [12][13][14][15][16] These distinctive structures originating from agarwood showed diverse linkages between the subunits via carboncarbon bonds and/or ether bonds. However, not more than twenty structures featuring a single ether linkage between the 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and 2-(2-phenylethyl)chromone units have been reported since the rst one was found, 3,16 and they exhibited various biological activities including acetylcholinesterase (AChE) inhibition, antineuroin-ammatory action, and cytotoxicity in pharmacological researches.…”

“…However, not more than twenty structures featuring a single ether linkage between the 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and 2-(2-phenylethyl)chromone units have been reported since the rst one was found, 3,16 and they exhibited various biological activities including acetylcholinesterase (AChE) inhibition, antineuroin-ammatory action, and cytotoxicity in pharmacological researches. [7][8][9][10][11][12][13][14][15][16] Previous phytochemical studies on the chemical constituents of articial hole-induced agarwood originating from A. sinensis contributed to the identication of a series of sesquiterpenes 17 and 2-(2-phenylethyl)chromone derivatives, [18][19][20] including four 2-(2-phenylethyl)chromone dimers. 13 Herein, the ongoing studies targeted the distinct characterization of the 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and 2-(2-phenylethyl)chromone dimer derivatives guided by UPLC-MS, which led to the isolation and elucidation of eleven 2-(2-phenylethyl) chromone dimers with an ether linkage, as well as the identi-cation of their absolute congurations.…”

The antioxidation and antiproliferation activity of flavonoids from Aquilaria agallocha and Aquilaria sinensis

“…Agarwood is a well-known as incense in the oriental region such as in Taiwan, Thailand and China used as a sedative, analgesic, and digestive agent in traditional medicine. Flavonoid glycoside, volatile oil, benzenoid, sesquiterpenes and chromone derivatives were isolated and identified from the seed, leaves or stem of these plants [2][3][4][5][6][7][8][9][10]. Phytochemical constituents obtained from the agarwood including apigenin-7, 4'-dimethylether, genkwanin, quercetin, kaemperfol and 5, 6, 7, 8-tetrahydro-2-(2-phenylethtl) chromes with different pharmacological activities [8,11,12].…”

“…Phytochemical constituents obtained from the agarwood including apigenin-7, 4'-dimethylether, genkwanin, quercetin, kaemperfol and 5, 6, 7, 8-tetrahydro-2-(2-phenylethtl) chromes with different pharmacological activities [8,11,12]. The plant Aquilaria sinensis and Aquilaria agallocha have several pharmacological activities and shows antioxidant, anti-diabetic, antiinflammatory, and antibacterial activities [2][3][4][5][6][11][12][13][14].…”