Palhinosides A–H: Flavone Glucosidic Truxinate Esters with Neuroprotective Activities from Palhinhaea cernua

Abstract

Palhinosides A−H (1−8), new flavone glucosidic truxinate esters, including β-truxinate and μ-truxinate forms, were isolated from Palhinhaea cernua. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. The flavone glucoside cyclodimers possess a unique cyclobutane ring in their carbon scaffolds. Compounds 2−7 represent three pairs of stereoisomers (2/3, 4/5, 6/7). The protective effects of 1−8 against the damage of HT-22 cells induced by L-glutamate were evaluated, and compounds 4 and 5 showed better neuroprotective effects than the positive control, Trolox.F lavone glucosidic truxinate esters are cyclodimeric derivatives containing an unusual cyclobutane ring in their carbon scaffolds. Flavonoid glucoside cyclodimers in truxillate or truxinate forms are unusual in plants, and to date only 13 derivatives have been reported from Monochaetum multiflorum, 1 Stachys aegyptiaca, 2 Itoa orientalis, 3 Paepalanthus geniculatus, 4 Ginkgo biloba, 5 Chamaerhodos altaica, and Potentilla anserine. 6,7 Some of these derivatives possess important pharmacological activities, including antioxidant, 4 antineuroinflammatory, and neuroprotective activities. 5 Palhinhaea cernua (family Lycopodiaceae) is widely distributed in southern and eastern China. 8 The whole plants of P. cernua, called "Pu-Di-Wu-Gong" in Chinese, are traditionally used as an herbal medicine for relaxing tendons, healing contusions, and treating rheumatism. 9,10 Previous phytochemical investigations of P. cernua indicated the presence of flavones, 11 neolignans, 12 lycopodium alkaloids, and serratene-type triterpenoids. 13−20 As part of a search for structurally unique and biologically interesting natural products from plants of the family Lycopodiaceae, 12,21,22 the chemical components in the n-BuOH portion of the extract of P. cernua were investigated. As a result, eight new truxinate derivatives, palhinosides A−H (1−8), together with two known compounds, apigenin-7-O-(6″-O-p-coumaroyl)-β-D-glucopyranoside (9) and methyl 4-hydroxycinnamate (10), have been isolated. Their structures were identified by analysis of 1D/2D NMR and MS data, as well as chemical analyses. These flavone glucoside cyclodimers were isolated from the family Lycopodiaceae for the first time. Herein, the isolation, structure elucidation, and neuroprotective effects of the new compounds are described.

Synthesis of 2‐Substituted Cyclobutanones by a Suzuki Reaction and Dephosphorylation Sequence

“…Among the various substituted cyclobutanones, [7] significant research attention has been paid to the synthesis [8] and functionalization of 2substituted cyclobutanones. [4] The synthetic applications of 2substituted cyclobutanones also cover natural product synthesis. [9] In relation to the above-mentioned applications of 2-substituted cyclobutanones, it has been reported that 2alkylated cyclobutanones exhibit both cyto-and genotoxic properties under in vitro conditions.…”

“…[1] The synthesis and various applications of substituted cyclobutanes have been the subject of several reviews. [2] The tetrasubstituted cyclobutane skeleton represents a key part of both katsumadain C [3] and the palhynosides A-H. [4] Moreover, substituted cyclobutane [5] and the cyclobutene [6] ring have been identified as constituents of the sesquiterpenes. Among the various substituted cyclobutanones, [7] significant research attention has been paid to the synthesis [8] and functionalization of 2substituted cyclobutanones.…”

“…The synthesis and various applications of substituted cyclobutanes have been the subject of several reviews [2] . The tetrasubstituted cyclobutane skeleton represents a key part of both katsumadain C [3] and the palhynosides A‐H [4] . Moreover, substituted cyclobutane [5] and the cyclobutene [6] ring have been identified as constituents of the sesquiterpenes.…”

“…Moreover, substituted cyclobutane [5] and the cyclobutene [6] ring have been identified as constituents of the sesquiterpenes. Among the various substituted cyclobutanones, [7] significant research attention has been paid to the synthesis [8] and functionalization of 2‐substituted cyclobutanones [4] . The synthetic applications of 2‐substituted cyclobutanones also cover natural product synthesis [9] .…”

Template-Directed Photochemical Homodimerization and Heterodimerization Reactions of Cinnamic Acids

“…2 In addition, [2 + 2] cycloadducts of cinnamic acids are attractive synthetic targets because of their diverse and promising biological activity profiles and their presence in various natural products. 3 Irradiation of cinnamic acid derivatives in solution leads predominantly to E/Z photoisomerization, and therefore, efforts to achieve these transformations were focused primarily on solid-state photochemistry. 4 Early studies led to the topochemical reaction principles described by Schmidt for photochemical [2 + 2] cycloadditions in solid state.…”