Intramolecular Diels-Alder Cycloaddition: 7-Isocyanoamphilecta- 11(20),15-diene (Miyaoka), (–)-Scabronine G (Kanoh), Basiliolide B (Stoltz), Hirsutellone B (Uchiro), Echinopine A (Chen)

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Neurotrophic Factors ◽  
Claisen Rearrangement ◽  
Diels Alder ◽  
Relative Configuration ◽  
Intramolecular Cycloaddition ◽  
Quaternary Centers ◽  
Astrocytoma Cells ◽  
National University ◽  
Seoul National University ◽  
1321N1 Astrocytoma

The amphilectane diterpenes, exemplified by 7-isocyanoamphilecta-11(20),15-diene 3, have been little investigated. In the course of a synthesis of 3, Hiroaki Miyaoka of the Tokyo University of Pharmacy and Life Sciences took advantage (Synlett 2011, 547) of the kinetic enolization and silylation of 1 to convert it into a trienone that spontaneously cyclized to 2. Scabronine G 6, isolated from the mushroom Sarcodon scabrosus, was found to enhance the secretion of neurotrophic factors from 1321N1 astrocytoma cells. To set the absolute configuration of the two quaternary centers that are 1, 4 on the cyclohexane ring of 6, Naoki Kanoh and Yoshiharu Iwabuchi of Tohoku University cyclized (Org. Lett. 2011, 13, 2864) 4 to 5. Although described by the authors as a double Michael addition, this transformation has the same connectivity as an intramolecular Diels-Alder cycloaddition. The diterpenes isolated from the genus Thapsia, represented by basiliolide B 9, induce rapid mobilization of intracellular Ca2+ stores. Brian M. Stoltz of Caltech effected (Angew. Chem. Int. Ed. 2011, 50, 3688) Claisen rearrangement of 7 to give an intermediate that cyclized to 8 as a mixture of diastereomers. A significant challenge in the synthesis was the assembly of the delicate enol ether/lactone of 9. Hirsutellone B 12, isolated from Hirsutella nivea, shows significant antituberculosis activity. Hiromi Uchiro of the Tokyo University of Science found it useful (Org. Lett. 2011, 13, 6268) to protect the intermediate unsaturated keto ester by intermolecular cycloaddition with pentamethylcyclopentadiene before constructing the triene of 10. Simple thermolysis reversed the intermolecular addition, opening the way to intramolecular cycloaddition to give 11. The tetracyclic ring system of the diterpene echinopine A 15 represents a substantial synthetic challenge. David Y.-K. Chen of Seoul National University approached this problem (Org. Lett. 2011, 13, 5724) by Pd-mediated cyclization of 13 to the diene, which then underwent intramolecular Diels-Alder cycloaddition to give 14, with control of the relative configuration of two of the three ternary centers of 15. Double bond migration followed by oxidative cleavage of the resulting cyclohexenone then set the stage for the intramolecular cyclopropanation that completed the synthesis of 15.

scholarly journals Predictors of cervical myelopathy and hydrocephalus in young children with achondroplasia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Youngbo Shim ◽  
Jung Min Ko ◽  
Tae-Joon Cho ◽  
Seung‐Ki Kim ◽  
Ji Hoon Phi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Young Children ◽  
Cervical Myelopathy ◽  
Treatment Method ◽  
Foramen Magnum ◽  
Resonance Imaging ◽  
Timely Manner ◽  
Frontal Horn ◽  
National University ◽  
Seoul National University

Abstract Background Cervical myelopathy and hydrocephalus occasionally occur in young children with achondroplasia. However, these conditions are not evaluated in a timely manner in many cases. The current study presents significant predictors for cervical myelopathy and hydrocephalus in young children with achondroplasia. Methods A retrospective analysis of 65 patients with achondroplasia who visited Seoul National University Children’s Hospital since 2012 was performed. The patients were divided into groups according to the presence of cervical myelopathy and hydrocephalus, and differences in foramen magnum parameters and ventricular parameters by magnetic resonance imaging between groups were analyzed. Predictors for cervical myelopathy and hydrocephalus were analyzed, and the cut-off points for significant ones were calculated. Results The group with cervical myelopathy showed foramen magnum parameters that indicated significantly lower cord thickness than in the group without cervical myelopathy, and the group with hydrocephalus showed significantly higher ventricular parameters and ‘Posterior indentation’ grade than the group without hydrocephalus. ‘Cord constriction ratio’ (OR 5199.90, p = 0.001) for cervical myelopathy and ‘Frontal horn width’ (OR 1.14, p = 0.001) and ‘Posterior indentation’ grade (grade 1: OR 9.25, p = 0.06; grade 2: OR 18.50, p = 0.01) for hydrocephalus were significant predictors. The cut-off points for cervical myelopathy were ‘Cord constriction ratio’ of 0.25 and ‘FM AP’ of 8 mm (AUC 0.821 and 0.862, respectively) and ‘Frontal horn width’ of 50 mm and ‘Posterior indentation’ grade of 0 (AUC 0.788 and 0.758, respectively) for hydrocephalus. Conclusion ‘Cord constriction ratio’ for cervical myelopathy and ‘Frontal horn width’ and ‘Posterior indentation’ grade for hydrocephalus were significant predictors and may be used as useful parameters for management. ‘Posterior indentation’ grade may also be used to determine the treatment method for hydrocephalus.

scholarly journals Caveolin-1 Regulates P2Y2 Receptor Signaling during Mechanical Injury in Human 1321N1 Astrocytoma

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 622
Author(s):  
Magdiel Martínez ◽  
Namyr A. Martínez ◽  
Jorge D. Miranda ◽  
Héctor M. Maldonado ◽  
Walter I. Silva Ortiz
Keyword(s):  
Cell Viability ◽  
Mechanical Injury ◽  
P2y2 Receptor ◽  
Caspase 9 ◽  
Post Injury ◽  
Caveolin 1 ◽  
Receptor Coupling ◽  
Downstream Signaling ◽  
Astrocytoma Cells ◽  
1321N1 Astrocytoma

Caveolae-associated protein caveolin-1 (Cav-1) plays key roles in cellular processes such as mechanosensing, receptor coupling to signaling pathways, cell growth, apoptosis, and cancer. In 1321N1 astrocytoma cells Cav-1 interacts with the P2Y2 receptor (P2Y2R) to modulate its downstream signaling. P2Y2R and its signaling machinery also mediate pro-survival actions after mechanical injury. This study determines if Cav-1 knockdown (KD) affects P2Y2R signaling and its pro-survival actions in the 1321N1 astrocytoma cells mechanical injury model system. KD of Cav-1 decreased its expression in 1321N1 cells devoid of or expressing hHAP2Y2R by ~88% and ~85%, respectively. Cav-1 KD had no significant impact on P2Y2R expression. Post-injury densitometric analysis of pERK1/2 and Akt activities in Cav-1-positive 1321N1 cells (devoid of or expressing a hHAP2Y2R) revealed a P2Y2R-dependent temporal increase in both kinases. These temporal increases in pERK1/2 and pAkt were significantly decreased in Cav-1 KD 1321N1 (devoid of or expressing a hHAP2Y2R). Cav-1 KD led to an ~2.0-fold and ~2.4-fold decrease in the magnitude of the hHAP2Y2R-mediated pERK1/2 and pAkt kinases’ activity, respectively. These early-onset hHAP2Y2R-mediated signaling responses in Cav-1-expressing and Cav-1 KD 1321N1 correlated with changes in cell viability (via a resazurin-based method) and apoptosis (via caspase-9 expression). In Cav-1-positive 1321N1 cells, expression of hHAP2Y2R led to a significant increase in cell viability and decreased apoptotic (caspase-9) activity after mechanical injury. In contrast, hHAP2Y2R-elicited changes in viability and apoptotic (caspase-9) activity were decreased after mechanical injury in Cav-1 KD 1321N1 cells expressing hHAP2Y2R. These findings support the importance of Cav-1 in modulating P2Y2R signaling during mechanical injury and its protective actions in a human astrocytoma cell line, whilst shedding light on potential new venues for brain injury or trauma interventions.

scholarly journals Components of Metabolic Syndrome in Korean Adults: A Hospital-Based Cohort at Seoul National University Bundang Hospital

2019 ◽  
Vol 28 (2) ◽  
pp. 118-128 ◽  
Author(s):  
Soo Lim ◽  
Se Hee Min ◽  
Ji Hyun Lee ◽  
Lee Kyung Kim ◽  
Dong-Hwa Lee ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Korean Adults ◽  
National University ◽  
Seoul National University

Climate related variations in atmospheric nitrous oxide concentration during the Mid- to Late Holocene

2021 ◽  
Author(s):  
Syed Azharuddin ◽  
Jinho Ahn ◽  
Yeongjun Ryu ◽  
Ed Brook
Keyword(s):  
Nitrous Oxide ◽  
Late Holocene ◽  
Ice Core ◽  
Progressive Increase ◽  
La Niña ◽  
La Nina ◽  
National University ◽  
Seoul National University ◽  
Sudden Decrease ◽  
Nitrous Oxide Concentration

<p>Nitrous oxide (N<sub>2</sub>O) is an important greenhouse gas with sources that respond to the biogeochemical processes on land and ocean. The major sources of atmospheric N<sub>2</sub>O are nitrification and denitrification occurring in terrestrial soils and the ocean. Here we present a new high-resolution atmospheric N<sub>2</sub>O record obtained from South Pole Ice (SPICE) core site covering the Mid- to Late Holocene (since ~5.5 ka). The N<sub>2</sub>O analysis was performed in a specialised wet extraction facility installed at Seoul National University that used small ice samples (<20 g) to yield a high precision (average standard deviation of ~1ppb) record. The new N<sub>2</sub>O data agree well with existing records on the millennial scale and reveal new details on the multi-centennial scale. Our results show a progressive increase in atmospheric N<sub>2</sub>O during 5.5 to 3.2 ka which correlates well with the increase of marine denitrification around the Arabian Sea (AS) and Peru-Chile Margin (PCM) as well as Indian monsoon precipitation around the same period. A local minimum in N<sub>2</sub>O is observed around 2.8 ka, possibly related to a sudden decrease in Western Tropical South (WTS) Pacific sea surface temperature and increased La-Nina like conditions which may have supressed denitrification along PCM. These conditions may have further influenced the monsoons and reduced denitrification in land soils. Our record also shows a local N<sub>2</sub>O maximum around 2.2 ka which may correspond to relaxed La-Nina like conditions around WTS Pacific. Subsequently, the N<sub>2</sub>O further dropped to attain a pronounced minimum around 1.4 ka. Similar N<sub>2</sub>O minima are also observed in Styx (Antarctica) and  NEEM (Greenland) ice core records, demonstrating the robustness of the signals.</p>

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