- Functional reversal of (?)-Stepholidine analogues by replacement of benzazepine substructure using the ring-expansion strategy
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(?)-Stepholidine is an active ingredient of the Chinese herb Stephania and naturally occurring tetrahydroprotoberberine alkaloid with mixed dopamine receptor D1 agonistic and dopamine receptor D2 antagonistic activities. In this work, a series of novel hexahydrobenzo[4,5]azepino [2,1-a]isoquinolines were designed and synthesized as ring-expanded analogues of (?)-Stepholidine. Initial pharmacological assays demonstrated that a benzazepine replacement was associated with significant increase in selectivity and functional reversal at dopamine receptor D1. Compound-(?)-15e (Ki?=?5.32?±?0.01?nm) is more potent than (?)-Stepholidine (Ki?=?13?nm) and was identified as a selective dopamine receptor D1 antagonist (IC50?=?0.14?μm). Moreover, molecular modeling suggested that (?)-15e might exert its dopamine receptor D1 antagonistic activities through interacting with the transmembrane helix 7 of dopamine receptor D1.
- Li, Wei,Zhang, Li,Xu, Lili,Yuan, Congmin,Du, Peng,Chen, Jiaojiao,Zhen, Xuechu,Fu, Wei
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p. 599 - 607
(2016/10/06)
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- Interrupted Pummerer Reaction in Latent-Active Glycosylation: Glycosyl Donors with a Recyclable and Regenerative Leaving Group
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Latent O-glycosides, 2-(2-propylthiol)benzyl (PTB) glycosides, were converted into the corresponding active glycosyl donors, 2-(2-propylsulfinyl)benzyl (PSB) glycosides, by a simple and efficient oxidation. Treatment of the PSB donor and various acceptors with triflic anhydride provided the desired glycosides in good to excellent yields. The leaving group, which was activated by an interrupted Pummerer reaction, can be recycled (PSB-OH) and regenerated as the precursor (PTB-OH). A natural hepatoprotective glycoside, leonoside F, was efficiently synthesized in a convergent [3+1] manner with this newly developed method. The present total synthesis also led to a structural revision of this phenylethanoid glycoside.
- Shu, Penghua,Xiao, Xiong,Zhao, Yueqi,Xu, Yang,Yao, Wang,Tao, Jinyi,Wang, Hao,Yao, Guangmin,Lu, Zimin,Zeng, Jing,Wan, Qian
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p. 14432 - 14436
(2016/01/25)
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- Facile synthesis of 4,5,6a,7-tetrahydrodibenzo[de,g]chromene heterocycles and their transformation to phenanthrene alkaloids
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Oxa-Pictet-Spengler cyclization and microwave-assisted C-H arylation have been implemented as key steps in the synthesis of new isochroman heterocycles containing a 4,5,6a,7-tetrahydrodibenzo[de,g]chromene motif. These isochromans may be easily transformed to phenanthrene alkaloids via acidic cleavage of the isochroman ring and standard synthetic manipulations thereafter. The route described is attractive in that it provides access to two biologically interesting scaffolds in simple and high yielding synthetic steps.
- Kapadia, Nirav,Harding, Wayne
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p. 8914 - 8920
(2013/09/23)
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- Synthesis of salidroside analogues and their ability of DPPH radical scavenging activity
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Salidroside is a phenylpropanoid glycoside isolated from Rhodiolarosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 22 novel glycosides have been synthesized and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenge activity of each glycoside has been evaluated. 2-(3,4,5-Trihydroxyphenyl)ethyl β-D-galactopyranoside and 3-(3,4,5-trihydroxyphenyl)propyl β-D-glucopyranoside exhibit significant activity prior to salidroside and Vitamin C with EC50 values of 35.85 μM and 36.71 μM, respectively. The results indicate that the phenolic hydroxyl group of these compounds is important for radical scavenging activity and phenyl ring substitution by electron-donating substituents lead to increased antioxidant activity.
- Zheng, Cheng,Guo, Yibing,Meng, Ying,Dou, Sufeng,Shao, Jian,Yang, Yumin
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p. 654 - 664
(2013/07/11)
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- Synthesis and biological evaluation of isosteric analogs of mandipropamid for the control of oomycete pathogens
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A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1A longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.
- Su, Na,Wang, Zhen-Jun,Wang, Li-Zhong,Zhang, Xiao,Dong, Wei-Li,Wang, Hong-Xue,Li, Zheng-Ming,Zhao, Wei-Guang
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p. 101 - 111
(2012/06/01)
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- Preparation and antioxidant activity of tyrosyl and homovanillyl ethers
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Preparation of tyrosyl and homovanillyl lipophilic derivatives was carried out as a response to the food industry's increasing demand for new synthetic lipophilic antioxidants. Tyrosyl and homovanillyl ethers were synthesized in high yields by a three-step procedure starting from tyrosol (Ty) and homovanillic alcohol (HMV). The antioxidant activity of these new series of alkyl tyrosyl and homovanillyl ethers was evaluated by the Rancimat test in a lipophilic food matrix and by the FRAP, ABTS and ORAC assays and compared to free Ty and HMV as well as two antioxidants widely used in the food industry, butylhydroxytoluene (BHT) and α-tocopherol. The results pointed out the higher activity of homovanillyl series in comparison with tyrosyl series with all the assayed methods. However, while both synthetic series were less antioxidant than BHT and α-tocopherol in a lipophilic matrix after their Rancimat test evaluation, homovanillyl alkyl ethers showed the best reducing power and radical scavenging activity of all evaluated compounds. This batch of synthetic lipophilic compounds, derived from biologically active compounds such as Ty and HMV, provide interesting and potentially bioactive compounds.
- Madrona,Pereira-Caro,Bravo,Mateos,Espartero
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scheme or table
p. 1169 - 1178
(2012/05/05)
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- Total synthesis and biological evaluation of viscolin, a 1,3-diphenylpropane as a novel potent anti-inflammatory agent
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Total synthesis of viscolin, an anti-inflammatory 1,3-diphenylpropane isolated from Viscum coloratum, employing the Wittig reaction is reported. Key steps in the synthesis of viscolin depend on the selection of protecting groups to maintain the para hydroxyl group that is the most critical chemical structure influencing the biological activity of viscolin and the utilization of microwave-assisted Wittig olefination reaction. Anti-inflammatory potency of the synthetic viscolin, its precursor product 16, and its analogue 17, through their effects on reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokine production in leukocytes and microglial cells were evaluated. Excellent inhibition of ROS and NO production in inflammatory cells could confer the synthetic viscolin to be a potent anti-inflammatory agent for the treatment of oxidative stress-induced diseases.
- Su, Chung-Ren,Shen, Yuh-Chiang,Kuo, Ping-Chung,Leu, Yann-Lii,Damu, Amooru G.,Wang, Yea-Hwey,Wu, Tian-Shung
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p. 6155 - 6160
(2007/10/03)
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- MERGED ION CHANNEL MODULATING COMPOUNDS AND USES THEREOF
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Merged compounds of ion channel modulating compounds, including, for example, merged compounds of the ion channel modulating compound of the following formula: (I) are described herein, as well as methods of making and using such merged compounds and pharmaceutical compositions containing such merged compounds.
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Page/Page column 68
(2008/06/13)
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- Simple Synthesis of the Enantiomeric (E)-9-Hydroxy-2-decenoic Acids
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The enantiomeric (E)-9-Hydroxy-2-decenoic acids (1), components of the swarm settling pheromone in Apis mellifica L. (honey bee) have been synthesized.The lithium derivative of 1-hexyne was treated with (R)-(+)-methyloxirane (2), (S)-(-)-2 or (+/-)-2 to give the alkynols (R)-(-)-3, (S)-(+)-3 or (+/-)-3, which could be isomerized with the sodium salt of 1,3-propanediamine to give (R)-(-)-8-nonyn-2-ol (4) and (+/-)-4.These were methoxycarbonylated to produce the esters (R)-(-)-5, (S)-(+)-5 or (+/-)-5.Selective hydrogenation in pyridine with Pd/BaSO4 as catalyst gave the (Z)-esters (R)-(-)-6, (S)-(+)-6 or (+/-)-6 which could be isomerized with photochemically generated phenylthio radicals to produce the (E)-esters (R)-(-)-7, (S)-(+)-7- or (+/-)-7.The acids present in the pheromone (R)-(-)-1, (S)-(+)-1 and (+/-)-1 could be obtained by basic hydrolysis of the esters.The minor but important component 8 of the swarm settling pheromone has been synthesized by treating the Grignard reagent obtained from 5-bromo-guaiacol benzyl ether with ethylene oxide to give 9 in high yield.Hydrogenolytic removal of the benzyl group in 9 produced 8 directly. - Key Words: Apis mellifica L. / Pheromones / Alkynols / 2-Decenoic acid, (E)-9-hydroxy
- Schweitzer, Stefan,Voss, Gundula,Gerlach, Hans
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p. 189 - 192
(2007/10/02)
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- Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 2. The amide bond 'B-region'
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A series of compounds incorporating replacements for the amide bond 'B- region' moiety of capsaicin have been synthesized, including vanillylamides and esters, homovanillic acid amides and esters, ureas, and thioureas. These have been tested in an in vitr
- Walpole,Wrigglesworth,Bevan,Campbell,Dray,James,Masdin,Perkins,Winter
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p. 2373 - 2380
(2007/10/02)
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- Quinolizidines. XXII. An Extension of the "3-Acetylpyridine Route" to the Syntheses of 9-Hydroxy-10-methoxy- and 10-Hydroxy-9-methoxybenzoquinolizidine-Type Alangium Alkaloids
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Alternative syntheses of the Alangium alkaloids bearing the 9-hydroxy-10-methoxy- and 10-hydroxy-9-methoxybenzoquinolizidine skeletons (types 3 and 4) have now become feasible through generally applicable routes starting from 3-acetylpyridine.The route
- Fujii, Tozo,Ohba, Masashi,Sakaguchi, Jun
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p. 3628 - 3640
(2007/10/02)
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