Cyathane diterpenes from Chinese mushroom Sarcodon scabrosus and their neurite outgrowth-promoting activity
>Two novel cyathane diterpenoids, designated scabronines K (1) and L (2), were isolated from the fruiting bodies of the basidiomycete Sarcodon scabrosus together with four known analogues, sarcodonins G (3), A (5), M (6), and scabronine H (4). Their structures were elucidated on the basis of extensive spectroscopic analysis including 2D-NMR (HMBC, HSQC, ROESY, (1)H,(1)H-COSY) and MS experiments. The isolated compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Among these compounds, only sarcodonins G and A (3 and 5) at 25 μM showed significant neurite outgrowth (neuritegenesis)-promoting activity in the presence of 20 ng/mL NGF after 24h treatment. Their structure-neurite inducing activity relationship was also discussed.
https://pubmed.ncbi.nlm.nih.gov/21530015/
Scabronine G Methyl Ester Improves Memory-Related Behavior and Enhances Hippocampal Cell Proliferation and Long-Term Potentiation via the BDNF-CREB Pathway in Olfactory Bulbectomized Mice
>A previous study reported that scabronine G methyl ester (SG-ME) potentially enhances the in vitro secretion of neurotrophic factors such as nerve growth factor via the protein kinase C (PKC)-ζ pathway. However, it remains unknown whether SG-ME can improve cognitive dysfunctions in olfactory bulbectomized (OBX) mice. To address this question, we evaluated SG-ME-treated and untreated OBX mice in a passive avoidance test. We also investigated potential effects of SG-ME on several parameters: cell proliferation and cAMP response element-binding protein (CREB) phosphorylation in the hippocampal dentate gyrus by immunohistochemistry, brain-derived neurotrophic factor (BDNF) levels in the hippocampus by Western blotting, p-CREB levels in the hippocampus by MapAnalyzer, and long-term potentiation (LTP) by electrophysiology. On the 14th day after surgery OBX mice showed altered passive avoidance and decreases in both cell proliferation and long-term potentiation in the hippocampus, while these changes were reversed by SG-ME (20 μg/mouse) 24 h after the treatment. The improvement in memory deficits was prevented when SG-ME was co-administeredwith either zeta inhibitory peptide (PKC-ζ inhibitor), anti-BDNF antibody, ANA-12 (TrkB antagonist)
... keep reading on reddit ➡A cornucopia: Sessile soft corals as well as certain higher plants produce a multitude of casbane diterpenes with different oxygenation patterns. A new synthetic approach to this family of natural products (see structural framework) was designed that allows a large subset to be encompassed, yet is short, efficient, and selective. Key to success was a combination of catalytic cyclopropanation, alkyne metathesis, and trans‐hydrometalation chemistry.
Abstract
Of the more than 100 casbane diterpenes known to date, only the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not a single but a variety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family. The key design elements are a catalyst‐controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross‐coupling, and the efficient closure of the strained macrobicyclic framework by ring‐closing alkyne metathesis. A hydroxy‐directed catalytic trans‐hydrostannation allows for late‐stage diversity. These virtues are manifested in the concise total syntheses of depressin, yuexiandajisu A, and ent‐pekinenin C. The last compound turned out to be identical to euphorhylonal A, the structure of which had clearly been misassigned.
https://ift.tt/3gpyAQS
A new diterpene synthase (CaCS) from Catenulispora acidiphila and its products were identified. The enzyme mechanism was studied by isotopic labelling experiments and usage of substrate analogues with blocked reactivity, resulting in a series of derailment products. Their chemistry was studied, leading to the biomimetic synthesis of a diterpenoid analogue of a brominated sesquiterpene known from the red seaweed Laurencia microcaldia.
Abstract
A new diterpene synthase from the actinomycete Catenulispora acidiphila was identified and the structures of its products were elucidated, including the absolute configurations by an enantioselective deuteration approach. The mechanism of the cationic terpene cyclisation cascade was deeply studied through the use of isotopically labelled substrates and of substrate analogues with partially blocked reactivity, resulting in derailment products that gave further insights into the intermediates along the cascade. Their chemistry was studied, leading to the biomimetic synthesis of a diterpenoid analogue of a brominated sesquiterpene known from the red seaweed Laurencia microcladia.
https://ift.tt/2UbdgEm
Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c00557
Chengsen Cui, Brendan G. Dwyer, Chang Liu, Daniel Abegg, Zhong-Jian Cai, Dominic G. Hoch, Xianglin Yin, Nan Qiu, Jie-Qing Liu, Alexander Adibekian, and Mingji Dai
https://ift.tt/38s4hX9
The spongian trio : The first total syntheses of three unusual norrisolide‐type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late‐stage ring‐scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans ‐hydrindane system, and a crucial retro Diels–Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3‐b]furan system.
Abstract
The first total syntheses of three unusual norrisolide‐type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late‐stage ring‐scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans‐hydrindane system, and a crucial retro Diels–Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3‐b]furan system, which is commonly seen in rearranged spongian diterpenes.
https://ift.tt/35EMAAO
The features of two iconic chemical classes are united in the structure of the highly complex diterpene canataxpropellane and set a daunting challenge that has been met by the Gaich group. Their daring strategy and its benefit to the field of terpene chemistry is presented and discussed in this Highlight.
https://ift.tt/2VFb2xq
Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that prenyltransferase LtmE and cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we reconstitute the biosynthetic pathway for lolitrems employing a recently established genome‐editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical‐induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analog.
https://ift.tt/2CG22Cs
https://www.ncbi.nlm.nih.gov/pubmed/31306736
Fürstenau CR1, de Souza ICC2, de Oliveira MR3.
Abstract
The oxidative phosphorylation (OXPHOS) system located in the mitochondria is the main source of adenosine triphosphate (ATP) in mammals. The mitochondria are also the main site of reactive oxygen species (ROS) production in those cells. Disruption of the mitochondrial redox biology has been seen in the onset and progression of neurodegenerative diseases. In this regard, we have tested here whether kahweol (KW; C20H26O3), a diterpene present in coffee, would be able to promote mitochondrial protection in the human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2). A pretreatment (for 12 h) with KW (at 10 μM) decreased the impact of H2O2 (at 300 μM) on the levels of oxidative stress markers in the mitochondrial membranes, as well as reduced the production of ROS by the organelles. KW pretreatment also suppressed the effects of H2O2 on the activity of components of the OXPHOS. The KW-induced mitochondria-related effects were blocked by inhibition of the phosphoinositide 3-kinase/Akt (PI3K/Akt) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of the heme oxygenase-1 (HO-1) enzyme abrogated the KW-induced protective effects on the mitochondria. Therefore, KW promoted mitochondrial protection by the PI3K/Akt and p38 MAPK/Nrf2/HO-1 axis in H2O2-challenged SH-SY5Y cells.
I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.
Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.
Do your worst!
A cornucopia: Sessile soft corals as well as certain higher plants produce a multitude of casbane diterpenes with different oxygenation patterns. A new synthetic approach to this family of natural products (see structural framework) was designed that allows a large subset to be encompassed, yet is short, efficient, and selective. Key to success was a combination of catalytic cyclopropanation, alkyne metathesis, and trans‐hydrometalation chemistry.
Abstract
Of the more than 100 casbane diterpenes known to date, only the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not a single but a variety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family. The key design elements are a catalyst‐controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross‐coupling, and the efficient closure of the strained macrobicyclic framework by ring‐closing alkyne metathesis. A hydroxy‐directed catalytic trans‐hydrostannation allows for late‐stage diversity. These virtues are manifested in the concise total syntheses of depressin, yuexiandajisu A, and ent‐pekinenin C. The last compound turned out to be identical to euphorhylonal A, the structure of which had clearly been misassigned.
https://ift.tt/3gpyAQS
Of the more than 100 casbane diterpenes known to date, only the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not a single but a variety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family. The key design elements are a catalyst controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks via chemoselective hydroboration/cross coupling, and the efficient closure of the strained macrobicyclic framework by ring closing alkyne metathesis. Of arguably highest relevance is the fact that a hydroxy‐directed catalytic trans ‐hydrostannation allows for late‐stage diversity. These virtues are manifested in concise total syntheses of depressin, yuexiandajisu A, and ent ‐pekinenin C; the latter turned out to be identical with euphorhylonal A, which had obviously been misassigned in the literature.
https://ift.tt/3gpyAQS
A new diterpene synthase from the actinomycete Catenulispora acidiphila was identified and the structures of its products were elucidated, including the absolute configurations by an enantioselective deuteration approach. The mechanism of the cationic terpene cyclisation cascade was deeply studied through the use of isotopically labelled substrates and of substrate analogs with partially blocked reactivity, resulting in derailment products that gave further insights into the intermediates along the cascade. Their chemistry was studied, leading to the biomimetic synthesis of a diterpenoid analog of a brominated sesquiterpene known from the red seaweed Laurencia microcladia.
https://ift.tt/2UbdgEm
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b11838
https://ift.tt/3aaUqDl
