- Total synthesis of three natural phenethyl glycosides
-
Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.
- Dong, Hong-Bo,Meng, Jian,Yao, Zhong-Quan,Luo, Hong-Bing,Zhang, Jing-Xia,Du, Wei-Hong,Tang, Ke-Hui,Cao, Sheng-Hua
-
p. 284 - 293
(2020/03/03)
-
- Biotransformation of pungent constituents from ginger (Zingiber officinale Roscoe) by Colletotrichum gloeosporioides yields oxidative ortho–ortho coupling products
-
This work investigated the biotransformation of ginger constituents (zingerone, [6]-shogaol, [6]-gingerol, and methyl-[6]-gingerol) by the pathogenic fungus Colletotrichum gloeosporioides. Experiments were carried out with and without deuterium-labelled compounds. The product metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and liquid chromatography solid phase extraction-nuclear magnetic resonance. Substrates supplied to the fungus were incorporated into metabolic pathways mostly by oxidation reactions, including aromatic carbon–carbon coupling. Zingerone and [6]-gingerol biotransformation products included biphenol dimers. A biodegradation pathway for biphenol formation was proposed based on the presence of the intermediate 4-(2-hydroxyethyl)-2-methoxyphenol, commonly identified from [6]-gingerol and [6]-shogaol biodegradation. This intermediate likely originates from a Baeyer–Villiger reaction followed by hydrolysis. The C–C coupling of molecules could result in phenolic oxidative ortho–ortho coupling, suggesting that biphenol dimers are products of C. gloeosporioides laccase catalysis.
- de ávila, Roberta Marques Dias,Toffano, Leonardo,Fernandes, Jo?o Batista,da Silva, Maria Fátima das Gra?as Fernandes,de Sousa, Lorena Ramos Freitas,Vieira, Paulo Cezar
-
-
- Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as the RXRα Activator to Inhibit Colon Cancer
-
We reported recently that berberine (Ber), a traditional oriental medicine to treat gastroenteritis, binds and activates retinoid X receptor α (RXRα) for suppressing the growth of colon cancer cells. Here, we extended our studies based on the binding mode of Ber with RXRα by design, synthesis, and biological evaluation of a focused library of 15 novel Ber analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than Ber, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing the Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved Ber's tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of Ber-derived RXRα activators as novel effective antineoplastic agents for colon cancer.
- Xu, Beibei,Jiang, Xunjin,Xiong, Jing,Lan, Jun,Tian, Yuan,Zhong, Linhai,Wang, Xinquan,Xu, Ning,Cao, Hanwei,Zhang, Wenqing,Zhang, Hao,Hong, Xiaoting,Zhan, Yan-Yan,Zhang, Yandong,Hu, Tianhui
-
p. 5841 - 5855
(2020/07/03)
-
- Tetrabenazine intermediate as well as synthesis method and application thereof as, well as intermediate product for synthesis (by machine translation)
-
The invention belongs to, the field of drug synthesis, and particularly relates to a butanaphenazine, intermediate and a synthesis method, thereof, as well as a synthesis: method 3,4 - thereof; and, 6,7 . (by machine translation)
- -
-
Paragraph 0082; 0084; 0088; 0090; 0094; 0096; 0100; 0103
(2020/02/14)
-
- BIOISPIRED PROTEASOME ACTIVATORS WITH ANTIAGEING ACTIVITY
-
The present invention relates to novel bio-inspired hybrid compounds of formula I which act as proteasome activators and exhibit anti-ageing activity, as well as methods for their synthesis. These hybrid compounds combine the structural features of hydroxytyrosol and the natural antioxidant vitamin E or its bioisosteres in one molecular scaffold. The compounds of formula I, which include structural proteasome activators (activation by stereochemical interaction), can be used in the production of anti-ageing products, such as cosmetic preparations. Additionally, they can be used in conditions and diseases where the proteasome is down-regulated, as well as proteasome-activation control compounds.
- -
-
Page/Page column 5; 12
(2019/10/01)
-
- Fibrauretine synthetic method (by machine translation)
-
The invention relates to O-vanillin (11) as the starting material, by the acylation reaction generating 2 - acetoxy - 3 - methoxybenzaldehyde (12), by the bromo, hydrolysis reaction to produce the 2 - hydroxy - 6 - bromo - 3 - methoxybenzaldehyde (13), produced by the methylation reaction 6 - bromo - 2, 3 - dimethoxy benzaldehyde (14), produced by the condensation reaction of 2 - (6 - bromo - 2, 3 - dimethoxyphenyl) - 1, 3 - dioxolane (15); and then to 3, 4 - dimethoxy acetic acid (21) as raw materials, generated by the reduction reaction of the 3, 4 - dimethoxy ethanol (22), the acylation reaction generated by 3, 4 - dimethoxy new valeric acid environmentally (23), the acylation reaction is generated by the 2 - ethoxy - 3, 4 - dimethoxy new valeric acid environmentally (24), intermediate (15) and (24) after coupling, cyclized two-step reaction process for preparing the target product fibrauretin. (by machine translation)
- -
-
Paragraph 0050; 0051; 0065
(2018/09/21)
-
- Harnessing open-source technology for low-cost automation in synthesis: Flow chemical deprotection of silyl ethers using a homemade autosampling system
-
An inexpensive homemade 3-axis autosampler was used to facilitate the automation of an acid catalysed flow chemical desilylation reaction. Harnessing open-source software technologies (Python, OpenCV), an automated computer-vision controlled liquid-liquid extraction step was used to provide effective inline purification. A Raspberry Pi single-board computer was employed to interface with the motors used in the autosampler and actuated fluidic valves.
- O'Brien, Matthew,Konings, Lisette,Martin, Matthew,Heap, Jordan
-
supporting information
p. 2409 - 2413
(2017/06/01)
-
- Functional reversal of (?)-Stepholidine analogues by replacement of benzazepine substructure using the ring-expansion strategy
-
(?)-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
-
p. 599 - 607
(2016/10/06)
-
- Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity
-
Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.
- Segaoula, Zacharie,Leclercq, Julien,Verones, Valérie,Flouquet, Nathalie,Lecoeur, Marie,Ach, Lionel,Renault, Nicolas,Barczyk, Amélie,Melnyk, Patricia,Berthelot, Pascal,Thuru, Xavier,Lebegue, Nicolas
-
p. 8422 - 8440
(2016/10/03)
-
- Catalytic Cyclization of o-Alkynyl Phenethylamines via Osmacyclopropene Intermediates: Direct Access to Dopaminergic 3-Benzazepines
-
A novel osmium-catalyzed cyclization of o-alkynyl phenethylamines to give 3-benzazepines is reported. The procedure allows the straightforward preparation of a broad range of dopaminergic 3-benzazepine derivatives. Mechanistic investigations revealed that the process takes place via osmacyclopropene intermediates, which were isolated and characterized by X-ray crystallography.
- álvarez-Pérez, Andrea,González-Rodríguez, Carlos,García-Yebra, Cristina,Varela, Jesús A.,O?ate, Enrique,Esteruelas, Miguel A.,Saá, Carlos
-
supporting information
p. 13357 - 13361
(2015/11/09)
-
- High spatiotemporal control of spontaneous reactions using ultrasound-triggered composite droplets
-
Achieving high spatial and temporal control over a spontaneous reaction is a particularly challenging task with potential breakthroughs in various fields of research including surface patterning and drug delivery. We report here an exceptionally effective method that allows attaining such control. This method relies on a remotely triggered ultrasound-induced release of a reactant encapsulated in a composite microdroplet of liquid perfluorohexane. More specifically, the demonstration was achieved by locally applying a focused 2.25 MHz transducer onto a microfluidic channel in which were injected composite microdroplets containing a solution of an azidocoumarin and an external flow containing a reactive alkyne.
- Bezagu, Marine,Errico, Claudia,Chaulot-Talmon, Victor,Monti, Fabrice,Tanter, Mickael,Tabeling, Patrick,Cossy, Janine,Arseniyadis, Stellios,Couture, Olivier
-
supporting information
p. 7205 - 7208
(2014/06/09)
-
- Short and efficient syntheses of protoberberine alkaloids using palladium-catalyzed enolate arylation
-
A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladiumcatalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50%is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.
- Gatland, Alice E.,Pilgrim, Ben S.,Procopiou, Panayiotis A.,Donohoe, Timothy J.
-
supporting information
p. 14555 - 14558
(2015/02/19)
-
- CuI-catalyzed coupling of gem-dibromovinylanilides and sulfonamides: An efficient method for the synthesis of 2-amidoindoles and indolo[1,2-a] quinazolines
-
A Cu(I)-catalyzed, intermolecular protocol for the synthesis of 2-amidoindoles and tetrahydroindolo[1,2-a]quinazolines in shorter time and high yields is reported. The key highlight of this disclosure is the formation of 2-amidoindole and tetrahydroindolo[1,2-a]quinazoline moieties directly from gem-dibromovinylanilides and sulfonamides in a one-pot fashion through the in situ formation of ynamides followed by a base-promoted intramolecular hydroamidation.
- Kiruthika, Selvarangam E.,Perumal, Paramasivan Thirumalai
-
supporting information
p. 484 - 487
(2014/04/03)
-
- Facile synthesis of 4,5,6a,7-tetrahydrodibenzo[de,g]chromene heterocycles and their transformation to phenanthrene alkaloids
-
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
-
p. 8914 - 8920
(2013/09/23)
-
- PROCESS FOR PRODUCTION OF HYDROXYTYROSOL USING ORGANOMETALLIC COMPOUNDS
-
Disclosed is a process for the production of a 4-(2-hydroxyalkyl)-1,2-benzenediol, comprising the steps of (a) providing protected 1,2-benzenediol having the 1,2-hydroxyl groups protected, (b) halogenating the protected 1,2-benzenediol to obtain a protected 4-halo-1,2-benzenediol having the 1,2-hydroxyl groups protected, (c) reacting, in the presence of a metal or organometallic compound, the protected 4-halo-1,2-benzenediol to protected 4-(2-hydroxyalkyl)-1,2-benzenediol having the 1,2-hydroxyl groups protected, and (d) deprotecting the protected 4-(2-hydroxyalkyl)-1,2-benzenediol to obtain the 4-(2-hydroxyalkyl)-1,2-benzenediol. Also disclosed is the use of 1,2-benzenediol for the production of hydroxytyrosol.
- -
-
Page/Page column 12
(2012/02/02)
-
- Copper-catalyzed enantioselective additions to oxocarbenium ions: Alkynylation of isochroman acetals
-
We have developed an enantioselective, copper(I)-catalyzed addition of terminal alkynes to racemic isochroman acetals. This method is one of the first transition-metal-catalyzed approaches to enantioselective additions to prochiral oxocarbenium ions. In this reaction, TMSOTf is used to form the oxocarbenium ion in situ under conditions compatible with simultaneous formation of the chiral copper acetylide. By using a bis(oxazoline) ligand, good yields and enantioselectivities are observed for a variety of enantioenriched 1-alkynyl isochromans.
- Maity, Prantik,Srinivas, Harathi D.,Watson, Mary P.
-
supporting information; experimental part
p. 17142 - 17145
(2011/12/13)
-
- Microwave-assisted synthesis of 5-substituted 2-aminothiophenes starting from arylacetaldehydes
-
An easy three-step pathway for the synthesis of arylacet-aldehydes from the corresponding carboxylic acids in very high yields is described. Their use as precursors of 5-substituted-2-aminothiophenes is illustrated via a microwave-assisted Gewald reaction. This method allows obtaining the expected compounds in a shorter time and with better yields and purities than the classical procedures. Georg Thieme Verlag Stuttgart - New York.
- Revelant, Germain,Dunand, Sandrine,Hesse, Stephanie,Kirsch, Gilbert
-
p. 2935 - 2940
(2011/11/01)
-
- Synthesis and biological evaluation of isosteric analogs of mandipropamid for the control of oomycete pathogens
-
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
-
p. 101 - 111
(2012/06/01)
-
- One-pot synthesis of aminoenone via direct reaction of the chloroalkyl enone with NaN3: Rapid access to polycyclic alkaloids
-
(Figure presented) A new one-pot procedure for the preparation of aminoenone from chloroalkyl enone and sodium azide was demonstrated. The structure of the presumed triazoline intermediate in this process was confirmed by X-ray analysis for the first time. As the application of this methodology, the synthesis of polycyclic alkaloid hexahydroapoerysopine (1a) was achieved through an efficient synthetic route.
- Zhao, Yu-Ming,Gu, Peiming,Tu, Yong-Qiang,Zhang, Hai-Jun,Zhang, Qing-Wei,Fan, Chun-An
-
supporting information; experimental part
p. 5289 - 5295
(2010/10/19)
-
- Osmium-catalyzed 7-endo heterocyclization of aromatic alkynols into benzoxepines
-
[Figure Presented] The wizard of Os: Regioselective osmiumcatalyzed 7-endo heterocyclization of aromatic alkynols affords benzoxepines in good yields. The proposed catalytic cycle involves the key formation of osmiumvinylidene complexes via an alkynyl-hydride-osmium(IV) complex from the starting alkynol.
- Varela-Fernandez, Alejandro,Garcia-Yebra, Cristina,Varela, Jesus A.,Esteruelas, Miguel A.,Saa, Carlos
-
supporting information; experimental part
p. 4278 - 4281
(2010/08/07)
-
- Synthetic pseudopterosin analogues: A novel class of antiinflammatory drug candidates
-
The synthesis and in vivo anti-inflammatory activity of a series of pseudopterosin analogues are presented. Synthetic tricyclic catechol aglycons with different substitution patterns were monofucosylated or -xylosylated. Anti-inflammatory activity was conserved over a wide range of structural modifications. The most active synthetic compound 33 reduced phorbol myristate acetate (PMA)-induced inflammation in the mouse ear by 72% at 50 μg/ear. This corresponds to 80% of the activity of natural pseudopterosin A.
- Flachsmann, Felix,Schellhaas, Kurt,Moya, Claudia E.,Jacobs, Robert S.,Fenical, William
-
scheme or table
p. 8324 - 8333
(2011/02/22)
-
- Highly efficient formal synthesis of cephalotaxine, using the stevens rearrangement-acid lactonization sequence as a key transformation
-
Cephalotaxine (1), the major alkaloid isolated from Cephalotaxus species, has attracted considerable attention due to the promising antitumor activity of several of its derivatives and its unique structural features. Herein we describe a highly efficient formal synthesis of 1 employing the [2,3]-Stevens rearrangement-acid lactonization sequence as a key transformation from readily available (3,4-dimethoxyphenyl)acetic acid, methyl prolinate, and allyl bromide.
- Sun, Mo-Ran,Lu, Hong-Tao,Wang, Yan-Zhi,Yang, Hua,Liu, Hong-Min
-
experimental part
p. 2213 - 2216
(2009/08/07)
-
- Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase
-
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate pathway found in most bacteria is a validated anti-infective drug target. Fosmidomycin, a potent DXR inhibitor, is active against Gram-negative bacteria. A coordination chemistry and structure based approach was used to discover a novel, lipophilic DXR inhibitor with an IC50 of 1.4 μM. It exhibited a broad spectrum of activity against Gram-negative and -positive bacteria with minimal inhibition concentrations of 20-100 μM (or 3.7-19 μg/mL).
- Deng, Lisheng,Sundriyal, Sandeep,Rubio, Valentina,Shi, Zheng-Zheng,Song, Yongcheng
-
supporting information; experimental part
p. 6539 - 6542
(2010/04/04)
-
- Synthesis of alkaloids of Galipea officinalis by alkylation of an α-amino nitrile
-
A new synthetic approach directed towards the synthesis of naturally occurring 2-alkyl-tetrahydroquinolines is described. The C-C bonds in the α position relative to the nitrogen atom were formed by the reversal of the polarity of the C=N bond of α-amino nitrile 6, which was prepared electrochemically from 1-(phenylethyl)-tetrahydroquinoline. A NaBH 4-mediated reductive decyanation process furnished benzylic amines 16a-d as mixtures of diastereomers (50-60% de). The catalytic hydrogenolysis of these amines was performed in the presence of Pearlman's catalyst to give the tetrahydroquinolines 17a-d in yields ranging from 70% to 95%. Methylation of the free nitrogen atom afforded the title compounds 1-4 in 70-90% yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Shahane, Saurabh,Louafi, Fadila,Moreau, Julie,Hurvois, Jean-Pierre,Renaud, Jean-Luc,Van De Weghe, Pierre,Roisnel, Thierry
-
experimental part
p. 4622 - 4631
(2009/05/07)
-
- A Modular Synthesis of the Lamellarins: Total Synthesis of Lamellarin G Trimethyl Ether
-
A modular synthesis of the lamellarin family of natural products has been developed that is based on the application of three iterative halogenation/cross-coupling reaction sequences. The ability to halogenate the pyrrole core in a regioselective fashion, even in the presence of highly electron-rich aryl substituents, has been established. The compatibility of Suzuki coupling conditions with free alcohols and phenols in the boronic acids has been employed to reduce the number of protection/deprotection steps. Indeed, the presence of a free phenol on boronic acid 3 has been determined to be critical for the successful final coupling in route to lamellarin G trimethyl ether, since protected versions fail to undergo coupling.
- Handy, Scott T.,Zhang, Yanan,Bregman, Howard
-
p. 2362 - 2366
(2007/10/03)
-
- Medicinal uses of phenylaikanols and derivatives
-
A compound of formula (I), a pharmaceutically acceptable derivative thereof, wherein Ph is a phenyl radical R1is H, OH, OC1-4alkyl, NO2; R2is OH, OC1-4alkyl, OC═OC1-4alkyl or OC═OPh where the Ph can be optionally substituted by halogen, C1-3alkyl or NO2; R1and R2along with the two carbon atoms of the phenyl ring to which they are attached can combine to form a 5 or 6 membered heterocyclic ring comprising 1 or 2 heteroatoms selected from O, S or N; R3is an optionally substituted hydroycarby radical; R4is H, CH3, OH or ═O; when R4is ═O, then the carbon to which R4is attached is not bonded to H; W is C(═O)—CH2, CH═CH—, CH2CO, CH(OH)—CH2, C(CH3)(OH)CH2, CH2CH(OH), CH2C(CH3)OH, CO, CHOH, C(CH3)(OH), CH2, CH2CH2; X is —CH—OH, C(CH3)OH, CH2, CH(CH3) or —C═O; Y is —CH—OH, C(CH3)OH, CH2, CH(CH3) or —C═O; provided that one of W, X or Y has an OH group.
- -
-
-
- Development of novel reactions using hypervalent iodine(III) reagents: Total synthesis of sulfur-containing pyrroloiminoquinone marine product, (±)-makaluvamine F
-
Novel and efficient intramolecular nucleophilic substitution reactions of phenol ethers using activated hypervalent iodine species have been developed and their application to the total synthesis of strongly cytotoxic makaluvamine F (1), a member of sulfur-containing pyrroloiminoquinone marine products, is described.
- Kita, Yasuyuki,Egi, Masahiro,Takada, Takeshi,Tohma, Hirofumi
-
p. 885 - 897
(2007/10/03)
-
- 2-substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1- yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioavailability
-
In this paper we describe the synthesis of a series of α-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxycyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into an antagonist. All of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. On the basis of the improvement in affinity realized for the α-phenylethyl analogue 3, in this paper we explored the effects of substitution on the aromatic ring as a strategy to increase the affinity of these compounds for group II mGluRs. Affinity for group II mGluRs was measured using [3H]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1- aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. Meta substitution on the aromatic ring of 3 with a variety of substituents, both electron donating (e.g., methyl, hydroxy, amino, methoxy, phenyl, phenoxy) and electron withdrawing (e.g., fluorine, chlorine, bromine, carboxy, trifluoromethyl) gave from 1.5- to 4.5-fold increases in affinity. Substitution with p-fluorine, as in 97 (IC50 = 0.022 ± 0.002), was the exception. Here, a greater increase in affinity was realized than for either the ortho- or meta-substituted analogues; 97 was the most potent compound resulting from monosubstitution of the aromatic. At best, only modest increases in affinity were realized for certain compounds bearing either two chlorines or two fluorines, and two methoxy groups gave no improvement in affinity (all examined in a variety of substitution patterns). Three amino acids, 4, 5, and 104, were resolved into their four constituent isomers, and affinity and functional activity for group II mGluRs was found to reside solely in the S,S,S-isomers of each, consistent with 1. With an IC50 = 2.9 ± 0.6 nM, the resolved xanthylmethyl compound 168 was the most potent compound from this SAR. Amino acid 168 demonstrated high plasma levels following intraperitoneal (ip) administration and readily penetrated into the brain. This compound, however, had only limited (~5%) oral bioavailability. Systemic administration of 168 protected mice from limbic seizures produced by the mGluR agonist 3,5-dihydroxyphenylglycine, with an ED50 = 31 mg/kg (ip, 60 min preinjection). Thus, 168 represents a valuable tool to study the role of group II mGluRs in disease.
- Ornstein, Paul L.,Bleisch, Thomas J.,Arnold, M. Brian,Kennedy, Joseph H.,Wright, Rebecca A.,Johnson, Bryan G.,Tizzano, Joseph P.,Helton, David R.,Kallman, Mary Jeanne,Schoepp, Darryle D.,Hérin, Marc
-
p. 358 - 378
(2007/10/03)
-
- SECOIRIDOID GLYCOSIDES FROM JASMINUM MULTIFLORUM
-
In addition to 10-hydroxyoleuropein and 10-hydroxyligustroside, three new secoiridoid glycosides, multifloroside, multiroside, and 10-hydroxyoleoside-11-methyl ester have been isolated from the water soluble fraction of Jasminum multiflorum.Their structures were established by spectroscopic analyses and chemical correlations. 10-Hydroxyoleuropein and multifloroside were found to possess coronary dilating and cardiotropic activities.
- Shen, Ya-Ching,Lin, Chia-Yin,Chen, Chung-Hsiung
-
p. 2905 - 2912
(2007/10/02)
-
- IRIDOID AND PHENOLIC GLYCOSIDES FROM HARPAGOPHYTUM PROCUMBENS
-
Key Word Index - Harpagophytum procumbens; Pedaliaceae; iridoid and phenolic glycosides; synthesis.A novel bioside, β-(3',4'-dihydroxyphenyl)ethyl-O-α-L-rhamnopyranosyl(1 -> 3)-β-D-glucopyranoside, was obtained from the secondary roots of Harpagophytum procumbens.It is accompained by the known iridoid glucosides harpagoside, procumbide, and its 6'-O-p-coumaroyl ester, and phenolic glycosides, acteoside and isoacteoside, the latter pair being obtained from H. procumbens for the first time.The structures of these metabolites were differentiated by high resolution NMR studies, while that of the bioside is additionally supported by synthesis.
- Burger, Johann F. W.,Brandt, E. Vincent,Ferreira, Daneel
-
p. 1453 - 1458
(2007/10/02)
-
- Comparative Studies on the Constituents of a Parasitic Plant and Its Host. III. On the Constituents of Boschniakia rossica FEDTSCH, et FLEROV. (2)
-
Two iridoid glucosides, namely boschnaloside (2), (+)-pinoresinol-β-D-glucopyranoside (3), a new oligosaccharide (=β-D-glucopyranosyl(1->4)-α-L-rhamnopyranosyl-(1->3)-D-(4-O-caffeoyl)-glucopyranose) (4), and a new phenylpropanoid glycoside named rossicaside A (5) have been isolated from Boschniakia rossica FEDTSCH, et FLEROV (Orobanchaceae) and their structures have been determined.Keywords--Boschniakia rossica; Orobanchaceae; boschnaloside; boschnaside; (+)-pinoresinol-β-D-glucoside; acetylated oligosaccharide; rossicaside A; phenylpropanoid glycoside
- Konishi, Tenji,Narumi, Yoko,Watanabe, Kazuaki,Kiyosawa, Shiu,Shoji, Junzo
-
p. 4155 - 4161
(2007/10/02)
-
- PRODUCTION OF HYDROXYPHENYLETHANOL GLYCOSIDES IN SUSPENSION CULTURES OF SYRINGA VULGARIS
-
Cell suspension cultures of Syringa vulgaris accumulate up to 16 percent of their dry wt as a mixture of hydroxyphenylethanol glycosides.The main component is the caffeoyl ester, verbascoside (acteoside).Tyrosine and tyramine are efficient biosynthetic precursors of the 4-hydroxy- and 3,4-dihydroxyphenylethanol moieties of these glycosides.Key Word Index- Syringa vulgaris; Oleaceae; lilac; cell cultures; biosynthesis; hydroxyphenylethanol glycosides; salidroside; verbascoside; caffeic acid.
- Ellis, B. E.
-
p. 1941 - 1944
(2007/10/02)
-