Discovery of Neuritogenic <i>Securinega</i> Alkaloids from <i>Flueggea suffruticosa</i> by a Building Blocks‐Based Molecular Network Strategy

He, Qi‐Fang; Wu, Zhen‐Long; Li, Liuren; Sun, Wanyang; Wang, Guiyang; Jiang, Ren‐Wang; Hu, Lijun; Shi, Lei; He, Rong‐Rong; Wang, Ying; Ye, Wen‐Cai

doi:10.1002/anie.202103878

Cited by 61 publications

(38 citation statements)

References 35 publications

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“…These findings have built the foundation to access all known C4-oxygenated securinine-type alkaloids. Furthermore, our discoveries en route to monomeric high-oxidation state securinine-type alkaloids synthesis would serve as the basis for the exploration of even more complex high-order and high-oxidation state securinine-type alkaloids 6 , 8 , 11 . Those will be the subject of our forthcoming reports.…”

Section: Discussionmentioning

confidence: 99%

“…In that regard, recent isolation campaigns from Securinega suffruticosa resulted in an outburst of discoveries of novel C4-oxygenated securinine-type alkaloids that show oxidative and (or) stereochemical variations around the piperidine ring A (Fig. 1 ) 6 – 11 . With respect to the structure determination of natural products, the continued development of computational chemistry has enabled the estimation of spectroscopic data of complex molecules 12 .…”

Section: Introductionmentioning

confidence: 99%

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Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

et al. 2022

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Securinega alkaloids have fascinated the synthetic chemical community for over six decades. Historically, major research foci in securinega alkaloid synthesis have been on the efficient construction of the fused tetracyclic framework that bears a butenolide moiety and tertiary amine-based heterocycles. These “basic” securinega alkaloids have evolved to undergo biosynthetic oxidative diversifications, especially on the piperidine core. However, a general synthetic solution to access these high-oxidation state securinega alkaloids is lacking. In this study, we have completed the total synthesis of various C4-oxygenated securinine-type alkaloids including securingines A, C, D, securitinine, secu’amamine D, phyllanthine, and 4-epi-phyllanthine. Our synthetic strategy features stereocontrolled oxidation, rearrangement, and epimerization at N1 and C2–C4 positions of the piperidine core within (neo)securinane scaffolds. Our discoveries provide a fundamental synthetic solution to all known securinine-type natural products with various oxidative and stereochemical variations around the central piperidine ring.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

et al. 2022

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“…The targeted isolation of the seed analogues could be realized by searching the location of the “seed” ( Klitgaard et al, 2015 ; Allard et al, 2016 ; Trautman and Crawford, 2016 ; Naman et al, 2017 ; Olivon et al, 2017a , b ; Nothias et al, 2018 ). When a molecular network is combined with fragmentation patterns, the range of metabolites would be narrowed, and the precision of targeted-isolation-compounds would be improved ( He et al, 2021 ). Thus, molecular networking based on the (U)HPLC-MS/MS technique would provide a more convenient approach for dereplication and targeting-isolation of new seco -sativene sesquiterpenoids in the future.…”

Section: Discussionmentioning

confidence: 99%

UPLC-Q-TOF-MS/MS Analysis of Seco-Sativene Sesquiterpenoids to Detect New and Bioactive Analogues From Plant Pathogen Bipolaris sorokiniana

Wang

Yang

et al. 2022

Front. Microbiol.

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Seco-sativene sesquiterpenoids are an important member of phytotoxins and plant growth regulators isolated from a narrow spectrum of fungi. In this report, eight seco-sativene sesquiterpenoids (1–8) were first analyzed using the UPLC-Q-TOF-MS/MS technique in positive mode, from which their mass fragmentation pathways were suggested. McLafferty rearrangement, 1,3-rearrangement, and neutral losses were considered to be the main fragmentation patterns for the [M+1]+ ions of 1–8. According to the structural features (of different substitutes at C-1, C-2, and C-13) in compounds 1–8, five subtypes (A–E) of seco-sativene were suggested, from which subtypes A, B/D, and E possessed the diagnostic daughter ions at m/z 175, 189, and 203, respectively, whereas subtype C had the characteristic daughter ion at m/z 187 in the UPLC-Q-TOF-MS/MS profiles. Based on the fragmentation patterns of 1–8, several known compounds (1–8) and two new analogues (9 and 10) were detected in the extract of plant pathogen fungus Bipolaris sorokiniana based on UPLC-Q-TOF-MS/MS analysis, of which 1, 2, 9, and 10 were then isolated and elucidated by NMR spectra. The UPLC-Q-TOF-MS/MS spectra of these two new compounds (9 and 10) were consistent with the fragmentation mechanisms of 1–8. Compound 1 displayed moderate antioxidant activities with IC50 of 0.90 and 1.97 mM for DPPH and ABTS+ scavenging capacity, respectively. The results demonstrated that seco-sativene sesquiterpenoids with the same subtypes possessed the same diagnostic daughter ions in the UPLC-Q-TOF-MS/MS profiles, which could contribute to structural characterization of seco-sativene sesquiterpenoids. Our results also further supported that UPLC-Q-TOF-MS/MS is a powerful and sensitive tool for dereplication and detection of new analogues from crude extracts of different biological origins.

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“…Monoterpenoid indole alkaloids (MIAs) are important secondary metabolites widely distributed in the members of plant families Apocynaceae, Loganiaceae, and Rubiaceae [ 1 ]. These compounds have attracted considerable interest in drug research for their complex structures and diverse biological activities, such as ganglion blocking [ 2 ], anticancer [ 3 , 4 , 5 ], anti-inflammatory [ 6 ], antibacterial [ 7 ], vasorelaxant [ 8 ], and neuroprotective activities [ 9 ]. The plant Gardneria multiflora (Loganiaceae family) is widely distributed in the south of the Qinling Mountains-Huaihe River Line and north of the Nanling Mountains in China [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Three New Monoterpenoid Indole Alkaloids from the Leaves of Gardneria multiflora and Their Vasorelaxant and AChE Inhibitory Activities

Zhang

Chen

et al. 2021

Molecules

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Three novel monoterpenoid indole alkaloids gardflorine A (1), gardflorine B (2), and gardflorine C (3) were isolated from the leaves of Gardneria multiflora. Their structures, including absolute configurations, were established on the basis of spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and circular dichroism experiments. All the compounds were evaluated for their vasorelaxant and acetylcholinesterase (AChE) inhibitory activities. Compound 1 exhibited potent vasorelaxant activity, with an EC50 value of 8.7 μM, and compounds 2 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities, with IC50 values of 26.8 and 29.2 μM, respectively.

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Discovery of Neuritogenic Securinega Alkaloids from Flueggea suffruticosa by a Building Blocks‐Based Molecular Network Strategy

Cited by 61 publications

References 35 publications

Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core

UPLC-Q-TOF-MS/MS Analysis of Seco-Sativene Sesquiterpenoids to Detect New and Bioactive Analogues From Plant Pathogen Bipolaris sorokiniana

Discovery of Three New Monoterpenoid Indole Alkaloids from the Leaves of Gardneria multiflora and Their Vasorelaxant and AChE Inhibitory Activities

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