Holotrichones A and B, potent anti-leukemic lindenane-type sesquiterpene trimers with unprecedented complex carbon skeletons from a rare Chloranthus species

• Published in: Chinese chemical letters Vol. 35; no. 12; pp. 109682 - 474
• Main Authors: Wang, Xue-Jiao, Xin, Jun-Li, Xiang, Hong, Zhao, Ze-Yu, He, Yu-Hang, Wang, Haibo, Mei, Guangyao, Mao, Yi-Cheng, Xiong, Juan, Hu, Jin-Feng
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2024; School of Pharmacy,Fudan University,Shanghai 201203,China%School of Pharmacy,Fudan University,Shanghai 201203,China%Zhejiang Hongyuan Pharmaceutical Co.,Ltd.,Linhai 317016,China; Institute of Natural Medicine and Health Products,School of Pharmaceutical Sciences,Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation,Taizhou University,Taizhou 318000,China
• Subjects: Acute myeloid leukemia; Cell apoptosis; Chloranthus holostegius var. trichoneurus; Holotrichones; Lindenane-type sesquiterpene trimers; Chloranthus holostegius var. trichoneurus; Holotrichones; Lindenane-type sesquiterpene trimers; Acute myeloid leukemia; Cell apoptosis
• ISSN: 1001-8417
• DOI: 10.1016/j.cclet.2024.109682

Two lindenane-type sesquiterpene (LDS) trimers with unprecedented carbon skeletons, holotrichones A (1) and B (2), were obtained from the whole plant of Chloranthus holostegius var. trichoneurus by a ultra performance liquid chromatography-photodiode array detector-mass spectrometry (UPLC-PDA-MS)-guided isolation strategy. Compound 1 represents the first LDS trimer incorporating a unique 3/5/6/6-fused framework, in which a lindenane-type monomer and the 2-methylbutyryl substituent of an LDS dimer is bridged by a six-membered ring system. Compound 2 is the first hetero-trimer fused by an LDS dimer with a p-benzoquinone-meroterpenoid, featuring an unusual 3/5/6/6/3/5/6/6/6 nonacyclic system fused by the sesquiterpenoid unit and a 2-geranyl-6-methyl-2,5-cyclohexadien-1,4-dione moiety. In compound 2, the dimeric LDS moiety is equipped with a rare oxaspiro[4.5]decane system. Their structures, including absolute configurations, were established by spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. The plausible biogenetic pathway speculation indicated that hetero- and homo-Diels-Alder additions may dominate the formation of these highly fused polycyclic frameworks. Both compounds 1 and 2 induced the human acute myeloid leukemia MV-4–11 cell death via apoptosis induction, which deserves further investigation on this new chemical class of LDS oligomers for their anti-leukemic potential. Two lindenane-type sesquiterpene (LDS) trimers (1, 2) with unprecedented carbon skeletons were isolated and characterized from a rare Chloranthus species. Compound 1 is an LDS trimer incorporating a unique 3/5/6/6-fused framework, while 2 features a novel hybrid skeleton of an LDS dimer with an oxaspiro[4.5]decane core and a benzoquinone-meroterpenoid. They exhibited cytotoxicities against MV-4–11 AML cells via inducing apoptosis. [Display omitted]