- Discovery of novel diphenylbutene derivative ferroptosis inhibitors as neuroprotective agents
-
Ferroptosis is a regulated and iron-dependent cell death. Ferroptosis inhibitors are promising for treating many neurological diseases. Herein, with phenotypic assays, we discovered a new diphenylbutene derivative ferroptosis inhibitor, DPT. Based on this hit, we synthesized fourteen new diphenylbutene derivatives, evaluated their ferroptosis inhibitory activities in HT22 mouse hippocampal neuronal cells, and found that three compounds exhibited improved inhibitory activities compared with DPT. Among these active compounds, compound 3f displayed the most potent anti-ferroptosis activity (EC50 = 1.7 μM). Further studies demonstrated that 3f is a specific ferroptosis inhibitor. And we revealed that different from the classic ferroptosis inhibitors, 3f blocked ferroptosis by increasing FSP1 protein level. Moreover, 3f can penetrate blood-brain barrier (BBB). In a rat model of ischemic stroke, 3f effectively mitigated cerebral ischemic injury. Therefore, we are confirmed that 3f, as a novel ferroptosis inhibitor with a new scaffold, is promising for further development as an agent against neurological diseases.
- Fang, Yuying,Gu, Qiong,Tan, Qingyun,Xu, Jun,Zhou, Huihao
-
-
- In vivo Structure-Activity Relationship of Dihydromethysticin in Reducing Nicotine-Derived Nitrosamine Ketone (NNK)-Induced Lung DNA Damage against Lung Carcinogenesis in A/J Mice
-
Lung cancer is the leading cause of cancer-related deaths and chemoprevention should be developed. We recently identified dihydromethysticin (DHM) as a promising candidate to prevent NNK-induced lung tumorigenesis. To probe its mechanisms and facilitate its future translation, we investigated the structure-activity relationship of DHM on NNK-induced DNA damage in A/J mice. Twenty DHM analogs were designed and synthesized. Their activity in reducing NNK-induced DNA damage in the target lung tissues was evaluated. The unnatural enantiomer of DHM was identified to be more potent than the natural enantiomer. The methylenedioxy functional moiety did not tolerate modifications while the other functional groups (the lactone ring and the ethyl linker) accommodated various modifications. Importantly, analogs of high structural similarity to DHM with distinct efficacy in reducing NNK-induced DNA damage have been identified. They will serve as chemical probes to elucidate the mechanisms of DHM in blocking NNK-induced lung carcinogenesis.
- Hati, Santanu,Hu, Qi,Huo, Zhiguang,Lu, Junxuan,Xing, Chengguo
-
-
- Synthesis and evaluation of antioxidant properties of 2-substituted quinazolin-4(3H)-ones
-
Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3H)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEACCUPRAC, to obtain key information about the structure-antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEACCUPRAC assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3H)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds 25a and 25b), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2, 3-dihydroxyphenyl)quinazolin-4(3H)-one 21e as a potent antioxidant with promising metal-chelating properties.
- Hrast, Martina,Mravljak, Janez,Slavec, Lara,Sova, Matej
-
-
- Method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and diphosphine ligand used in method
-
The invention discloses a method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and a diphosphine ligand used in the method. According to the invention, indole-substituted phosphoramidite diphosphine ligand which is stable in air and insensitive to light is synthesized by utilizing a continuous one-pot method, and the indole-substituted phosphoramidite diphosphine ligand and a rhodium catalyst are used for jointly catalyzing to successfully achieve a hydroformylation reaction of aromatic terminal alkyne and terminal conjugated eneyne under the condition of synthesis gas for the first time, so that an olefine aldehyde structure compound can be rapidly and massively prepared, and particularly, a polyolefine aldehyde structure compound which is more difficult to synthesize in the prior art can be easily prepared and synthesized, and a novel method is provided for synthesis and modification of drug molecules, intermediates and chemical products.
- -
-
Paragraph 0163; 0164
(2021/05/29)
-
- Consolidated production of coniferol and other high-value aromatic alcohols directly from lignocellulosic biomass
-
Sustainable production of fine chemicals and biofuels from renewable biomass offers a potential alternative to the continued use of finite geological oil reserves. However, in order to compete with current petrochemical refinery processes, alternative biorefinery processes must overcome significant costs and productivity barriers. Herein, we demonstrate the biocatalytic production of the versatile chemical building block, coniferol, for the first time, directly from lignocellulosic biomass. Following the biocatalytic treatment of lignocellulose to release and convert ferulic acid with feruloyl esterase (XynZ), carboxylic acid reductase (CAR) and aldo-keto reductase (AKR), this whole cell catalytic cascade not only achieved equivalent release of ferulic acid from lignocellulose compared to alkaline hydrolysis, but also displayed efficient conversion of ferulic acid to coniferol. This system represents a consolidated biodegradation-biotransformation strategy for the production of high value fine chemicals from waste plant biomass, offering the potential to minimize environmental waste and add value to agro-industrial residues.
- Tramontina, Robson,Galman, James L.,Parmeggiani, Fabio,Derrington, Sasha R.,Bugg, Timothy D. H.,Turner, Nicholas J.,Squina, Fabio M.,Dixon, Neil
-
supporting information
p. 144 - 152
(2020/01/13)
-
- Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
-
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
- Aleku, Godwin A.,Leys, David,Roberts, George W.
-
p. 3927 - 3939
(2020/07/09)
-
- METHOD OF SELECTIVELY OXIDIZING LIGNIN
-
A method of selectively reacting lignin or a lignin-derived reactant to yield an aromatic product. The method includes the step of reacting lignin or a lignin-derived reactant with a molybdenum-containing catalyst, in a solvent, and optionally in the presence of an oxidant, for a time and a temperature wherein at least a portion of the lignin or lignin-derived reactant is selectively converted into an aromatic product, preferably coniferaldehyde and/or sinapaldehyde.
- -
-
Paragraph 0022
(2019/06/20)
-
- Biotransformation of eugenol to vanillin by a novel strain Bacillus safensis SMS1003
-
Due to the extensive applications of vanillin as flavored compound and increasing consumers concern for its natural and environment friendly mode of production, present work was focused on the selection of bacterial isolate capable of producing vanillin using eugenol biotransformation. Bacterial strain SMS1003 is evidenced as the potential strain for vanillin production and identified as Bacillus safensis (GeneBank accession no. MG561863) using biochemical tests and molecular phylogenic analysis of its 16S rDNA gene sequence. Molar yield of vanillin reached up to 10.7% (0.055 g/L) at 96 h of biotransformation using growing culture of B. safensis SMS1003 in following culture conditions: eugenol concentration 500 mg/L; temperature 37 °C; initial pH 7.0; inoculum volume 4%; volume of culture media 10%; and shaking speed 180 rpm. Vanillin was detected as the single metabolite with a molar yield of 26% (0.12 g/L) at 96 h using resting cells of B. safensis SMS1003. Product confirmation was based on spectral scan using photodiode array detector, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and mass spectroscopy.
- Singh, Archana,Mukhopadhyay, Kunal,Ghosh Sachan, Shashwati
-
p. 291 - 303
(2019/01/04)
-
- DDQ-mediated oxidation of allylarenes: Expedient access to cinnamaldehyde-containing phenylpropanoids
-
Phenylpropanoid natural products containing a cinnamaldehyde motif were easily synthesized from allylarenes mediated by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation. Representative examples described herein are five types of 4-hydroxycinnamaldehyde derivatives from monolignols biosynthesis, Boropinal C, and 7-methoxywutaifuranal from plant extracts. Especially, simple synthesis of 7-methoxywutaifuranal was exploited through selective mono-oxidation and subsequent isomerization-ring-closing-metathesis strategy.
- Jiang, Tao-Shan,Zhang, Qingqing,Li, Guohui,Cheng, Xi,Cai, Yongping
-
p. 4611 - 4616
(2019/02/01)
-
- Selective oxidation of lignin model compounds
-
Lignin, the planet’s most abundant renewable source of aromatic compounds, is difficult to degrade efficiently to well-defined aromatics. We developed a microwave-assisted catalytic Swern oxidation system using an easily prepared catalyst, MoO2Cl2(DMSO)2, and DMSO as the solvent and oxidant. It demonstrated high efficiency in transforming lignin model compounds containing the units and functional groups found in native lignins. The aromatic ring substituents strongly influenced the selectivity of β-ether phenolic dimer cleavage to generate sinapaldehyde and coniferaldehyde, monomers not usually produced by oxidative methods. Time-course studies on two key intermediates provided insight into the reaction pathway. Owing to the broad scope of this oxidation system and the insight gleaned with regard to its mechanism, this strategy could be adapted and applied in a general sense to the production of useful aromatic chemicals from phenolics and lignin.
- Gao, Ruili,Li, Yanding,Kim, Hoon,Mobley, Justin K.,Ralph, John
-
-
- Transition-metal-free conversion of lignin model compounds to high-value aromatics: Scope and chemoselectivity
-
An efficient and straightforward reaction protocol for the conversion of lignin model compounds was developed based on a simple system consisting of a base, oxygen, and a green solvent under mild conditions in the absence of metals. This protocol was successfully applied to the cleavage of both 'β-O-4' dimeric and trimeric compounds, and a controlled selective degradation was achieved depending on the bond type. The feasibility of this method to provide aromatic compounds in high yields from lignin by a sequential oxidative dehomologation reaction was clearly demonstrated.
- Lee, Tae Woo,Yang, Jung Woon
-
p. 3761 - 3771
(2018/08/21)
-
- Synthesis method of 4-hydroxycinnamaldehyde compound
-
The invention relates to the field of organic synthesis and agricultural chemistry, and particularly discloses a synthesis method of a 4-hydroxycinnamaldehyde compound shown as a formula II. The synthesis method comprises the following steps: with 4-hydroxy-allylbenzene as a raw material, firstly performing hydroxyl protection, then with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an oxidant and water (H2O) as a nucleophile, oxidizing an allyl group into alpha, beta-unsaturated aldehyde (namely, a cinnamaldehyde structure) under a relatively mild condition, and finally performing deprotection to obtain a target product. The invention elaborates a novel synthesis method of the 4-hydroxycinnamaldehyde compound. The novel synthesis method has the characteristics of no transition metalparticipation, a simple and mild reaction condition, high product yield and the like, and has a wide application prospect in the field of the agricultural chemistry, especially in plant science and bioenergy conversion.
- -
-
Paragraph 0037; 0038; 0039
(2018/03/26)
-
- Modular synthesis of (E)-cinnamaldehydes directly from allylarenes via a metal-free DDQ-mediated oxidative process
-
An efficient synthesis of (E)-cinnamaldehydes by a metal-free DDQ-mediated oxidative transformation of allylarenes was developed. The protocol provides a practical method to prepare diverse (E)-cinnamaldehydes with broad functional group tolerance in good to excellent yields, including easy access to natural products randainal and geranyloxy sinapyl aldehyde from plant extracts. Finally, the mechanism of a single-electron transfer process was proposed.
- Xu, Ting-Ting,Jiang, Tao-Shan,Han, Xiao-Lan,Xu, Yuan-Hong,Qiao, Jin-Ping
-
p. 5350 - 5358
(2018/08/03)
-
- Microwave-Assisted Synthesis of Phenylpropanoids and Coumarins: Total Synthesis of Osthol
-
Herein we describe a one-pot microwave-assisted method for the synthesis of cinnamic acid and coumarin derivatives. The synthesis begins with an aldehyde synthon, and the chosen reaction conditions determine whether a cinnamic acid or coumarin derivative is formed. A regioselective Claisen rearrangement was also efficiently incorporated into the synthetic sequence to further increase the complexity of the product. Notably, this approach provides high product yields and selectivities without the need of a phenol protecting group.
- Konrádová, Daniela,Kozubíková, Hana,Dole?al, Karel,Pospí?il, Ji?í
-
p. 5204 - 5213
(2017/09/29)
-
- Selective Oxidation of Activated Alcohols by Supported Gold Nanoparticles under an Atmospheric Pressure of O2: Batch and Continuous-Flow Studies
-
In the hunt for a simple, mild, and scalable protocol for gold nanoparticle-catalyzed oxidation of benzylic and allylic alcohols under O2, we have used commercially available gold nanoparticles supported on alumina to selectively oxidize a large range of activated alcohols to the corresponding carbonyl compounds in good yields (68–99 %) and with excellent selectivity (ca. 100 %). The true heterogeneous nature of the catalysis by gold was demonstrated, allowing us to further adapt this protocol to continuous-flow reactors by using the tube-in-tube technology, in which higher yields were obtained thanks to an improved oxygenation of the reaction medium.
- Giorgi, Pascal D.,Elizarov, Nelli,Antoniotti, Sylvain
-
p. 1830 - 1836
(2017/05/29)
-
- Novel multifunctional dopamine D2/D3receptors agonists with potential neuroprotection and anti-alpha synuclein protein aggregation properties
-
Our ongoing drug development endeavor to design compounds for symptomatic and neuroprotective treatment of Parkinson's disease (PD) led us to carry out a structure activity relationship study based on dopamine agonists pramipexole and 5-OHDPAT. Our goal was to incorporate structural elements in these agonists in a way to preserve their agonist activity while producing inhibitory activity against aggregation of α-synuclein protein. In our design we appended various catechol and related phenol derivatives to the parent agonists via different linker lengths. Structural optimization led to development of several potent agonists among which (?)-8a, (?)-14 and (?)-20 exhibited potent neuroprotective properties in a cellular PD model involving neurotoxin 6-OHDA. The lead compounds (?)-8a and (?)-14 were able to modulate aggregation of α-synuclein protein efficiently. Finally, in an in vivo PD animal model, compound (?)-8a exhibited efficacious anti-parkinsonian effect.
- Luo, Dan,Sharma, Horrick,Yedlapudi, Deepthi,Antonio, Tamara,Reith, Maarten E.A.,Dutta, Aloke K.
-
p. 5088 - 5102
(2016/10/22)
-
- Cobalt-catalyzed Aerobic Oxidation of Eugenol to Vanillin and Vanillic Acid
-
A novel, simple, one-step method of synthesizing vanillin and vanillic acid from eugenol has been developed. The method uses ligand- and additive-free Co(OAc)2·4H2O as catalyst and molecular oxygen as oxidant to achieve catalytic process without isomerizing eugenol. Extensive screening efforts were used to optimize eugenol to obtain vanillin and vanillic acid. Under optimal conditions, the reaction provided vanillin and vanillic acid with 68.5% and 15.2% yields, respectively. Apart from the desired products, coniferyl alcohol 9-methyl ether and 4-hydroxy-3-methoxycinnamaldehyde as two intermediates were also detected in the reaction process. Level changes of all compounds over time were presented in the reaction. The reaction pathway from eugenol to vanillic acid was validated by conducting several control experiments. Furthermore, a possible reaction mechanism dominated by a circular redox reaction from Co(III) and Co(II) species was proposed. This method offers a potentially practical alternative for manufacturing vanillin and vanillic acid efficiently.
- Mao, Haifang,Wang, Lizhi,Zhao, Feifei,Wu, Jianxin,Huo, Haohua,Yu, Jun
-
p. 261 - 266
(2016/04/19)
-
- Characterization of the monolignol oxidoreductase AtBBE-like protein 15 L182V for biocatalytic applications
-
Monolignol oxidoreductases from the berberine bridge enzyme-like (BBE-like) protein family (pfam 08031) catalyze the oxidation of monolignols to the corresponding aldehydes. In this report, we explore the potential of a monolignol oxidoreductase from Arabidopsis thaliana (AtBBE-like protein 15) as biocatalyst for oxidative reactions. For this study we employed a variant with enhanced reactivity towards oxygen, which was obtained by a single amino acid exchange (L182V). The pH and temperature optima of the purified AtBBE-like protein 15 L182V were determined as well as the tolerance toward organic co-solvents; furthermore the substrate scope was characterized. The enzyme has a temperature optimum of 50 °C and retains more than 50% activity between pH 5 and pH 10 within 5 min. The enzyme shows increased activity in the presence of various co-solvents (10–50% v/v), including acetonitrile, 2-propanol, 1,4-dioxane, and dimethyl sulfoxide. Primary benzylic and primary or secondary allylic alcohols were accepted as substrates. The enantioselectivity E in the oxidation of secondary alcohols was good to excellent (E>34 to?>200).
- Pils, Sabine,Schnabl, Kordula,Wallner, Silvia,Daniel, Bastian,Macheroux, Peter,Kljajic, Marko,Kupresanin, Nina,Breinbauer, Rolf,Fuchs, Michael,Rocha, Raquel,Schrittwieser, Joerg H.,Kroutil, Wolfgang
-
-
- Mechanistic investigation of the Zn/Pd/C catalyzed cleavage and hydrodeoxygenation of lignin
-
While current biorefinery processes use lignin only for its heat value, the conversion of lignin to high value chemicals is an area of increasing interest. Herein we present a detailed mechanistic study of the hydrodeoxygenation (HDO) of lignin by using a synergistic Pd/C and ZnII catalyst through use of both lignin model compounds and lignocellulosic biomass. Spectroscopic data coupled with the study of lignin model compounds suggest that ZnII activates and facilitates removal of the hydroxyl group at the Cγ position of the β-O-4 ether linkage. Activation is proposed to occur through formation of a six-membered ring complex of ZnII coordinated to the oxygen atoms at Cα and Cγ of the lignin model compound guaiacylglycerol-β-guaiacyl.
- Klein, Ian,Marcum, Christopher,Kentt?maa, Hilkka,Abu-Omar, Mahdi M.
-
supporting information
p. 2399 - 2405
(2016/05/19)
-
- Synthesis and assessment of the antioxidant and antitumor properties of asymmetric curcumin analogues
-
In this study, 12 asymmetric curcumin (CUR) analogues and 5 symmetric curcumin derivatives were synthesized, the antioxidant activity of these derivatives were evaluated by radicals 1,1-diphenyl-2- picryl-hydrazyl (DPPH) assay, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay, ROO. (TRAP) assay and O2-. (NET) assay and anti-proliferative activities of these analogues were assessed against the human hepatoma cell line (SMMC-7721), the human breast cancer cell line (MCF-7) and the human prostate cancer cell lines (PC-3). Most of the asymmetric compounds showed stronger antioxidant activities than Vitamin C (Vc). Curcumin analogues reducing free radicals contain two reaction mechanisms: H-atom and electron transfer mechanisms. Compound 14 showed the most significant antioxidant activity compared with curcumin and other derivatives. Shorted the carbon chain of 14 can reduce the OeH bond dissociation enthalpy (BED) to improve the antioxidant activity. The antioxidant activity of 25 was similar to curcumin. All of the compounds performed better in an anti-proliferate assay than curcumin, especially compound 25, which exhibited the preferential cytotoxic activity against MCF- 7 cells(25, IC50 = 9.11 μM, curcumin, IC50 = 70.2 μM). Considering these data, future studies should be performed to assess the therapeutic values of these asymmetric curcumin analogues.
- Li, Qingyong,Chen, Jian,Luo, Shuyue,Xu, Jialin,Huang, Qiaoxian,Liu, Tianyu
-
p. 461 - 469
(2015/03/04)
-
- Exploring the synthetic applicability of a new carboxylic acid reductase from Segniliparus rotundus DSM 44985
-
A new carboxylic acid reductase (CAR) gene from Segniliparus rotundus DSM 44985 was overexpressed in Escherichia coli. The recombinant enzyme exhibited high activity toward a variety of aromatic and aliphatic carboxylic acids. Especially, it effectively reduced 4-hydroxybenzoic acid (8a) and 4-nitrobenzoic acid (19a), toward which the known Nocardia CAR exhibited no or little activity. The recombinant E. coli cells co-expressing the Segniliparus CAR and Nocardia PPTase genes catalyzed the reductions of vanillic acid (20a) and 3,4-dihydroxyphenylacetic acid (25a) to give vanillyl alcohol (20c) and 3-hydroxytyrosol (25c) with high yield, respectively. The endogenous aldehyde reductases of E. coli should be responsible for the further reduction of the produced aldehydes. These results demonstrated that Segniliparus CAR was a useful addition to the biocatalyst tool-box for the reduction of carboxylic acids and might find applications in the synthesis of valuable bio-based chemicals from renewable resources.
- Duan, Yitao,Yao, Peiyuan,Chen, Xi,Liu, Xiangtao,Zhang, Rui,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
-
-
- NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
-
A compound having formula I is useful for treating a neurodegenerative disease: I, R1 is an C1-12 organyl group; is a C1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R2 are C1-12 organyl groups; R7, R8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C1-8 alkyl, C1-8 alkoxyl, C2-8 alkenyl, C2-10 alkynyl, C5-7 cycloalkyl, C5-7 cycloalkenyl, halo, C1-4 aldehyde, or -NR4q where R4 is H, C1-8 alkyl, C2-8 alkenyl, C4-8 cycloalkyl, C4-8 cycloalkenyl, or C6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C6-12 aryl group, C5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin- 4(1H)-one; p is an integer from 1 to 6; and Zm is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.
- -
-
-
- Synthesis, cytotoxicity against human oral cancer KB cells and structure-activity relationship studies of trienone analogues of curcuminoids
-
A general method for the synthesis of substituted (1E,4E,6E)-1,7- diphenylhepta-1,4,6-trien-3-ones, based on the aldol condensations of substituted 4-phenylbut-3-en-2-ones and substituted 3-phenylacrylaldehydes, was achieved. The natural trienones 4 and 5 have been synthesized by this method, together with the trienone analogues 9-20. These analogues were evaluated for their cytotoxic activity against human oral cancer KB cell line. The structure-activity relationship study has indicated that the analogues with the 1,4,6-trien-3-one function are more potent than the curcuminoid-type function. Analogues with meta-oxygen function on the aromatic rings are more potent than those in the ortho- and para-positions. Free phenolic hydroxy group is more potent than the corresponding methyl ether analogues. Among the potent trienones, compounds 11, 18 and 20 were more active than the anticancer drug ellipticine. All compounds were also evaluated against the non-cancerous Vero cells and it was found that compounds 11, 12 and 17 were much less toxic than curcumin (1); they showed high selectivity indices of 35.46, 33.46 and 31.68, respectively. These analogues are regarded as the potent trienones for anti-oral cancer study.
- Chuprajob, Thipphawan,Changtam, Chatchawan,Chokchaisiri, Ratchanaporn,Chunglok, Warangkana,Sornkaew, Nilubon,Suksamrarn, Apichart
-
supporting information
p. 2839 - 2844
(2014/06/10)
-
- Mechanistic study of the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle
-
The mechanism for the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle is proposed to proceed by single-electron oxidation of coniferyl alcohol, subsequent reaction with one of the oxygen atoms of taxifolin's catechol moiety, and finally, further oxidation to form four of the major components of silymarin: silybin A, silybin B, isosilybin A, and isosilybin B. This mechanism is significantly different from a previously proposed process that involves the coupling of two independently formed radicals.
- Althagafy, Hanan S.,Meza-Avina, Maria Elena,Oberlies, Nicholas H.,Croatt, Mitchell P.
-
p. 7594 - 7600
(2013/09/02)
-
- DEPOLYMERIZATION OF LIGNIN USING SOLID ACID CATALYSTS
-
The invention provides for a process for the depolymerization of lignin in an inert atmosphere to result in substituted phenolic monomer compounds. The process is catalysed by heterogeneous solid acid catalysts and is carried out in batch or continuous mode.
- -
-
Page/Page column 6; 7
(2012/12/13)
-
- Characterization of two isozymes of coniferyl alcohol dehydrogenase from Streptomyces sp. NL15-2K
-
We purified two isozymes of coniferyl alcohol dehydrogenase (CADH I and II) to homogeneity from cellfree extracts of Streptomyces sp. NL15-2K. The apparent molecular masses of CADH I and II were determined to be 143 kDa and 151 kDa respectively by gel filtration, whereas their subunit molecular masses were determined to be 35,782.2 Da and 37,597.7 Da respectively by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Thus, it is probable that both isozymes are tetramers. The optimum pH and temperature for coniferyl alcohol dehydrogenase activity were pH 9.5 and 45 °C for CADH I and pH 8.5 and 40 °C for CADH II. CADH I oxidized various aromatic alcohols and allyl alcohol, and was most efficient on cinnamyl alcohol, whereas CADH II exhibited high substrate specificity for coniferyl alcohol, and showed no activity as to the other alcohols, except for cinnamyl alcohol and 3-(4-hydroxy-3-methoxyphenyl)- 1-propanol. In the presence of NADH, CADH I and II reduced cinnamaldehyde and coniferyl aldehyde respectively to the corresponding alcohols.
- Nishimura, Motohiro,Kohno, Kunie,Nishimura, Yoshio,Inagaki, Masanori,Davies, Julian
-
experimental part
p. 1770 - 1777
(2012/02/02)
-
- Insights into lignin primary structure and deconstruction from Arabidopsis thaliana COMT (caffeic acid O-methyl transferase) mutant Atomt1
-
The Arabidopsis mutant Atomt1 lignin differs from native lignin in wild type plants, in terms of sinapyl (S) alcohol-derived substructures in fiber cell walls being substituted by 5-hydroxyconiferyl alcohol (5OHG)-derived moieties. During programmed lignin assembly, these engender formation of benzodioxane substructures due to intramolecular cyclization of their quinone methides that are transiently formed following 8-O-4′ radical-radical coupling. Thioacidolytic cleavage of the 8-O-4′ inter-unit linkages in the Atomt1 mutant, relative to the wild type, indicated that cleavable sinapyl (S) and coniferyl (G) alcohol-derived monomeric moieties were stoichiometrically reduced by a circa 2:1 ratio. Additionally, lignin degradative analysis resulted in release of a 5OHG-5OHG-G trimer from the Atomt1 mutant, which then underwent further cleavage. Significantly, the trimeric moiety released provides new insight into lignin primary structure: during polymer assembly, the first 5OHG moiety is linked via a C8-O-X inter-unit linkage, whereas subsequent addition of monomers apparently involves sequential addition of 5OHG and G moieties to the growing chain in a 2:1 overall stoichiometry. This quantification data thus provides further insight into how inter-unit linkage frequencies in native lignins are apparently conserved (or near conserved) during assembly in both instances, as well as providing additional impetus to resolve how the overall question of lignin macromolecular assembly is controlled in terms of both type of monomer addition and primary sequence.
- Moinuddin, Syed G. A.,Jourdes, Michael,Laskar, Dhrubojyoti D.,Ki, Chanyoung,Cardenas, Claudia L.,Kim, Kye-Won,Zhang, Dianzhong,Davin, Laurence B.,Lewis, Norman G.
-
experimental part
p. 3928 - 3946
(2010/09/17)
-
- GC/MS-positive ion chemical ionization and MS/MS study of volatile benzene compounds in five different woods used in barrel making
-
Extracts from acacia, chestnut, cherry, mulberry, and oak wood, used in making barrels for aging wine and spirits were studied by GC/MS positive ion chemical ionization (PICI). Wood chips were extracted by a 50% water/ethanol solution and a tartrate buffer pH 3.2-12% ethanol (model wine) solution. The principal compounds identified in extracts were guaiacol-containing aldehydes and alcohols, such as benzaldehyde and derivatives, vanillin and syringaldehyde, cinnamaldehyde and coniferaldehyde, eugenol and methoxyeugenol, guaiacol and methoxyguaiacol derivatives. PICI using methane as reagent gas produced a high yield of the protonated molecular ion of volatile phenols, compound identification was confirmed by collision-induced-dissociation (CID) experiments on [M + H]+ species. MS/MS fragmentation patterns were studied with standard compounds: guaiacol-containing molecules were characterized by neutral methyl and methanol losses, benzaldehyde derivatives by CO loss. Acacia wood extracts contained significant syringaldehyde and anisaldehyde, but no eugenol and methoxyeugenol. Significant syringaldehyde, eugenol and methoxyeugenol, and high vanillin were found in chestnut and oak wood extracts; low presence of volatile benzene compounds was found in mulberry wood extracts. Cherry wood extracts were characterized by the presence of several benzaldehyde derivatives and high trimethoxyphenol. Copyright
- Flamini, Riccardo,Dalla Vedova, Antonio,Cancian, Davide,Panighel, Annarita,De Rosso, Mirko
-
p. 641 - 646
(2008/02/05)
-
- Efficient one-pot, two-step synthesis of (E)-cinnmaldehydes by dehydrogenation-oxidation of arylpropanes using DDQ under ultrasonic irradiation
-
A general, efficient and new approach to the synthesis of cinnamaldehydes with trans-selectivity has been accomplished starting from arylpropanes. One-pot, two-step dehydrogenation and oxidation of arylpropanes with excess DDQ in dioxane containing a few drops of acetic acid gave (E)-cinnmaldehydes under ultrasound irradiation.
- Joshi, Bhupendra P.,Sharma, Anuj,Sinha, Arun K.
-
p. 2590 - 2593
(2007/10/03)
-
- A stabilized formulation of IBX (SIBX) for safe oxidation reactions including a new oxidative demethylation of phenolic methyl aryl ethers
-
(Matrix presented) SIBX is a nonexplosive formulation of IBX that can be used as a suspension in a variety of standard organic solvents such as refluxing EtOAc and THF to oxidize safely alcohols into aldehydes and ketones. The use of hot THF is limited to the oxidation of allylic and benzylic alcohols. Most yields are comparable to those obtained with IBX or DMP. SIBX can also be used to perform oxygenative demethylation of 2-methoxyarenols into orthoquinones and catechols.
- Ozanne, Aurelie,Pouysegu, Laurent,Depernet, Dominique,Francois, Bruno,Quideau, Stephane
-
p. 2903 - 2906
(2007/10/03)
-
- Methoxyphenols from burning of Scandinavian forest plant materials
-
Semivolatile compounds in smoke from gram-scale incomplete burning of plant materials were assessed by gas chromatography and mass spectrometry. Gas syringe sampling was shown to be adequate by comparison with adsorbent sampling. Methoxyphenols as well as 1,6-anhydroglucose were released in amounts as large as 10 mg kg-1 of dry biomass at 90% combustion efficiency. Wood, twigs, bark and needles from the conifers Norway spruce and Scots pine emitted 12 reported 2-methoxyphenols in similar proportions. Grass, heather and birchwood released the same 2-methoxyphenols but also the corresponding 2,6-dimethoxyphenols which are characteristic of angiosperms. The methoxyphenols are formed from lignin and differ in structure by the group in para position relative to the phenolic OH group. Prominent phenols were those with trans-l-propenyl and ethenyl groups in that position. Vanillin, 4- hydroxy-3-methoxybenzaldehyde, was a prominent carbonyl compound from the conifer materials. (C) 2000 Elsevier Science Ltd.
- Kjaellstrand, Jennica,Ramnaes, Olle,Petersson, Goeran
-
p. 735 - 741
(2007/10/03)
-
- Microbial synthesis of coniferyl alcohol by the fungus Byssochlamys fulva V107
-
Coniferyl alcohol (123 mM=21.9 g/1) was synthesized from eugenol with a yield of 94.6% in a 36 h fed-batch bioconversion using resting cells of the fungus Byssochlamys fulva V107.
- Furukawa, Hirotaka,Wieser, Marco,Morita, Hiroshi,Nagasawa, Toru
-
p. 1141 - 1142
(2007/10/03)
-
- A mild synthesis of coumaryl, coniferyl, sinapyl aldehydes and alcohols
-
Acetylconiferyl aldehyde is obtained from acetylvanillin by a Wittig reaction under phase-transfer conditions; basic hydrolysis gives coniferyl aldehyde, or after reduction with sodium borohydride affords coniferyl alcohol. This method is extended to the sinapyl and coumaryl series.
- Daubresse,Francesch,Mhamdi,Rolando
-
p. 369 - 371
(2007/10/02)
-
- NOUVELLE SYNTHESE DE PRECURSEURS PHENOLIQUES DES LIGNINES UTILISANT LES SELS D'IMINIUM DES ACIDES p-HYDROXY CINNAMIQUES
-
4-Hydroxy cinnamic esters, thiolesters, aldehydes and alcohols, or related compounds, implied in the biosynthesis of lignins are easily synthesized in good yields from iminium salts of coumaric 1a, ferulic 1b and sinapic 1c acids.No prior protection of the phenol group is needed in this method.
- Duran, E.,Gorrichon, L.,Cazaux, L.,Tisnes, P.
-
p. 2755 - 2758
(2007/10/02)
-