523-59-1Relevant academic research and scientific papers
Therapeutic evaluation of synthetic peucedanocoumarin III in an animal model of Parkinson’s disease
Ham, Sangwoo,Kim, Heejeong,Yoon, Jin-Ha,Kim, Hyojung,Song, Bo Reum,Choi, Jeong-Yun,Lee, Yun-Song,Paek, Seung-Mann,Maeng, Han-Joo,Lee, Yunjong
, (2019/11/13)
The motor and nonmotor symptoms of Parkinson’s disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate β sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated β sheet aggregate (β23), and prevented β23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII’s neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.
ISOSAMIDIN ANALOG AND SAMIDIN ANALOG PRODUCTION METHOD
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Paragraph 0077, (2018/10/19)
PROBLEM TO BE SOLVED: To provide a simple method of industrial-scale production of an isosamidin analog or samidin analog. SOLUTION: In the production method, a compound represented by the formula (1) in the figure is 1) senecioylated and 2) acetylated. [X is O or the like; R1 are each independently a C1-3 alkyl group or the like; R2 is H or the like; R3 are each a C1-3 alkyl group; m is an integer from 0 to 2; n is 1 or 2; and the symbol * represents an asymmetric center.] SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
A One-Pot Synthesis of Pyranocoumarins Through Microwave-Promoted Propargyl Claisen Rearrangement/Wittig Olefination
Schmidt, Bernd,Schultze, Christiane
, p. 223 - 227 (2018/01/26)
The reaction between propargyl ethers of hydroxybenzaldehydes and the ylide ethyl (triphenylphosphoranylidene)acetate was carried out under microwave irradiation to regioselectively afford angular pyranocoumarins. The chromene and coumarin heterocyclic scaffolds were simultaneously formed in the same synthetic step without changing the reaction conditions. The natural products seselin, braylin, and dipetalolactone were among the products synthesized by this method.
Antidiabetic effect, antioxidant activity, and toxicity of 3′,4′-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats
Domínguez-Mendoza, Elix Alberto,Cornejo-Garrido, Jorge,Burgue?o-Tapia, Eleuterio,Ordaz-Pichardo, Cynthia
supporting information, p. 4086 - 4091 (2016/08/01)
Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3′,4′-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15?mg/kg (p?50) >2000?mg/kg and, at this dose, no signs of toxicity or death were reported after 14?days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested.
Cp?Co(III)-Catalyzed Annulations of 2-Alkenylphenols with CO: Mild Access to Coumarin Derivatives
Liu, Xu-Ge,Zhang, Shang-Shi,Jiang, Chun-Yong,Wu, Jia-Qiang,Li, Qingjiang,Wang, Honggen
supporting information, p. 5404 - 5407 (2015/11/18)
Cp?Co(III)-catalyzed annulations of 2-alkenylphenols with CO for the synthesis of coumarin derivatives have been developed. The reaction features mild reaction conditions, broad substrate scope, and good functional group tolerance. Preliminary mechanistic studies were conducted, suggesting that C-H activation is the turnover limiting step. Furthermore, the efficiency of this reaction was demonstrated by the rapid total synthesis of three natural products herniarin, xanthyletin, and seselin.
Towards heterogeneous organocatalysis: Chiral iminium cations supported on porous materials for enantioselective alkene epoxidation
Bulman Page, Philip C.,Mace, Andrew,Arquier, Damien,Bethell, Donald,Buckley, Benjamin R.,Willock, David J.,Hutchings, Graham J.
, p. 2330 - 2339 (2013/09/02)
Enantiomerically pure iminium cations have been supported on a microporous support (zeolite Y) and on a mesoporous support (Al-MCM-41). These materials are effective asymmetric catalysts for the epoxidation of a range of aryl alkenes, giving high conversions quickly and with enantioselectivities similar to or in some cases even higher than are achievable using the corresponding iminium tetraphenylborates under homogeneous conditions. The catalysts can be simply recycled by filtration and washing. The methodology is illustrated in the synthesis of two natural products, (-)-(3′S)-lomatin and (+)-(3′S,4′R)-trans-khellactone, showing the general efficacy of our approach. The Royal Society of Chemistry 2013.
Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor
Marumoto, Shinsuke,Miyazawa, Mitsuo
supporting information; experimental part, p. 784 - 788 (2012/03/22)
The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC50 value of 9.9 μM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5- methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC50 values 25.0 μM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors.
Gold nanoparticles supported on TiO2 catalyse the cycloisomerisation/oxidative dimerisation of aryl propargyl ethers
Efe, Christina,Lykakis, Ioannis N.,Stratakis, Manolis
supporting information; body text, p. 803 - 805 (2011/04/12)
Gold nanoparticles supported on TiO2 (～1%) catalyse in high yields the selective cycloisomerisation of aryl propargyl ethers into the corresponding 2H-chromenes, under heterogeneous conditions. 2H,2′H-3, 3′-Bichromenes resulting from a catalytic oxidative dimerization pathway are also formed as by-products. The Royal Society of Chemistry 2011.
Anti-AIDS agents 83. Efficient microwave-assisted one-pot preparation of angular 2,2-dimethyl-2H-chromone containing compounds
Zhou, Ting,Shi, Qian,Lee, Kuo Hsing
experimental part, p. 4382 - 4386 (2010/09/12)
A novel and efficient microwave-assisted one-pot reaction was developed to synthesize angular 2,2-dimethyl-2H-chromone-containing compounds, which is the first and key step in the synthesis of potent DCK and DCP anti-HIV agents. The newly developed microwave synthesis conditions dramatically shortened the reaction time from 2 days to 4 h with improved yields.
Highly enantioselective total synthesis of (-)-(3'S)-lomatin and (+)-(3'S,4'/?)-frans-khellactone
Page, Philip C. Bulman,Appleby, Louise F.,Day, David,Chan, Yohan,Buckley, Benjamin R.,Allin, Steven M.,McKenzie, Michael J.
supporting information; experimental part, p. 1991 - 1993 (2009/09/08)
Concise highly enantioselective three-step syntheses are described for (-)-(3'S)-lomatin and (+)-(3'S,4'fl)-frans-khellactone from 7-hydroxy- coumarin in 97% ee and in 57% and 58% overall yields, respectively, using nonaqueous enantioselective epoxidation
