Structurally Diverse Sesquiterpenoids from Chloranthus henryi var. hupehensis and Their Anti‐inflammatory Activities

Abstract

Comprehensive SummaryIn this study, 27 new sesquiterpenoids: twenty monomers and seven dimers, with diverse structures, along with one known chlorajaponilide F (25) were isolated from the aerial parts of Chloranthus henryi var. hupehensis. Structurally, chlorahupetolides A (1) and B (2), two eudesmane‐type merosesquiterpenoids with an undescribed C18 carbon framework, and chlorahupetene E (18) are the first example of dimers comprising two eudesmane sesquiterpenoids bridged by a four‐membered ring in the Chloranthus. Their structures were characterized by nuclear magnetic resonance (NMR), electronic circular dichroism (ECD), and X‐ray diffraction analysis. In the RAW264.7 macrophages model of inflammation induced by LPS, compounds 12, 18, and 25 significantly reduced NO production in a dose dependent manner and without cytotoxicity. The mRNA expression of COX‐2 was considerably inhibited by treatments with compounds 12, 18, and 25.

Chemistry and bioactivity of lindenane sesquiterpenoids and their oligomers

“…78 The keto–enol tautomers of 282 and 283 (2 : 5) were determined based on the protonated molecule and NMR. 78 Similar to that of 248–251 , 69,144,165 the eudesmane unit of C-8/C-8′-linked linderanoids D ( 284 ) and E ( 285 ) may originate from lindenane by opening of the C1–C3 bond. 78 …”

“…The active Δ 15′(4′) and allyl Me-13 undergo oxidation, esterification and rearrangement to form diverse homo-[4 + 2] dimers, including shizukaol N ( 119 ), 138 shizukaol M ( 120 ), 138 shizukaol I ( 121 ), 139 chlorahololide D ( 122 ), 140 shizukaol K ( 123 ), 138 multistalide B ( 124 ), 141 sarcandrolide A ( 125 ), 107 shizukaol C ( 126 ), 142 shizukaol L ( 127 ), 138 sarcandrolide B ( 128 ), 61 13′- O -methyl succinylshizukaol C ( 129 ), 50 chololactones E–F ( 130–131 ), 75 sarglabolides H–K ( 132–135 ), 143 fortunilide M ( 136 ), 90 chlojapolide A ( 137 ), 137 fortunilides A–C ( 138–140 ), 65 chlorahupetol F ( 141 ), 144 shizukaol O ( 142 ), 138 sarcandrolide J ( 143 ), 116 chlomultiol A ( 144 ), 145 sarcanolide E ( 145 ), 146 and shizukaols D–E ( 146–147 ). 139,142 Chlorahololide D ( 122 ) was also reported by Luo's group as henriol D in the same year.…”

“…Sarglabolide A ( 184 ) was found to be the first case in which a 17-membered macrocyclic ester ring was constructed. 143 Sarglafuran A ( 185 ) 150 and chlorahupetols C ( 186 ) and D ( 187 ) 144 possess the [4 + 2]-type LS dimer scaffold with a unique furan ring moiety.…”

“…Chlorahololide E ( 214 ), 140 spicachlorantins H ( 215 ), 152 I ( 216 ) 152 and chlojapolide G ( 217 ) 137 possess a Δ 15′(4′) double bond. Chloramultilide D ( 218 ), 160 chloramultiol D ( 219 ), 149 chloramultiol B ( 220 ), 149 chloramultiol C ( 221 ), 149 chlorahololide F ( 222 ), 140 chloramultiol E ( 223 ), 149 sarcandrolide D ( 224 ), 107 chlorasessilifol B ( 225 ), 155 fortunilide I ( 226 ) 49 and chlorahupetol F ( 228 ) 144 were obtained via various oxidation and derivatization reactions involving the Δ 15′(4′) double bond and the methyl group at C-13′.…”

“…164 Fortunoid A ( 247 ) was a rearranged lindenane dimer with a bicyclo[3.3.1]nonane core in the Northern Hemisphere, 69 which was converted through oxidative cleavage of the Δ 4(5) double bond and subsequent nucleophilic addition (Scheme 2). According to the basic structures, the eudesmane moiety of fortunoid B ( 248 ), 69 chlorahupetols B ( 249 ) 144 and A ( 250 ), 144 and horienoid B ( 251 ) 165 may originate in LSs via opening of the cyclopropane moiety (Scheme 2). Thus, we classify these compounds as homo-dimers, where 248 (ref.…”