21086-33-9Relevant articles and documents
Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives
Pereira, Glaécia A. N.,Souza, Gisele C.,Santos, Lourivaldo S.,Barata, Lauro E. S.,Meneses, Carla C. F.,Krettli, Antoniana U.,Daniel-Ribeiro, Cláudio Tadeu,Alves, Cláudio Nahum
, p. 464 - 472 (2017)
The absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventional antimalarial drugs result in a worrisome scenario making the search for new drugs a priority. In the present study, the activities of nine neolignan derivatives were evaluated as follows: (i) against blood forms of chloroquine-resistant Plasmodium falciparum (clone W2), using the tritiated hypoxanthine incorporation and anti-HRPII assays; (ii) for cytotoxic activity against cultured human hepatoma cells (HepG2); and (iii) for intermolecular interaction with the P. falciparum cysteine protease of falcipain-2 (F2) by molecular docking. The neolignan derivatives 9 and 10 showed activity against the blood form of the chloroquine-resistant P. falciparum clone W2 and were not cytotoxic against cultured human hepatoma cells. A molecular docking study of these two neolignans with FP2 revealed several intermolecular interactions that should guide the design of future analogs.
Chemical diversification of essential oils, evaluation of complex mixtures and identification of a xanthine oxidase inhibitor
García,Ramallo,Salazar,Furlan
, p. 57245 - 57252 (2016)
A set of chemically engineered essential oils has been generated through chemical diversification by reaction with bromine. The impact of the reaction over the chemical composition of the mixtures was qualitatively demonstrated through GC-MS and utilizing multivariate analysis of 1H NMR and GC-MS. Most of the components of the essential oils are transformed by the reaction expanding the chemical diversity of the mixtures. Biological changes between essential oils and brominated essential oils were demonstrated through image analysis of xanthine oxidase autography profiles. The highest biological activity increase was obtained for the Foeniculum vulgare Mill essential oil. Coupling of xanthine oxidase autography with the BIOMSID strategy allowed the identification of the molecular formula of the active compound. Bioguided fractionation of the mixture led to the isolation of (RS)-2-bromo-1-(4-methoxyphenyl) propan-1-one for being responsible for the observed bioactivity. This xanthine oxidase inhibitor could have been formed from the inactive natural component anethole. The inhibitory potency of this semisynthetic compound was in the same order of magnitude as allopurinol, the most used inhibitor.
Aldol-Tishchenko Reaction of α-Oxy Ketones: Diastereoselective Synthesis of 1,2,3-Triol Derivatives
Sedano, Carlos,Virumbrales, Cintia,Suárez-Pantiga, Samuel,Sanz, Roberto
supporting information, p. 3725 - 3734 (2021/07/02)
α-Oxy ketones, easily accessible by conventional routes, can be selectively deprotonated generating an enolate intermediate, which upon treatment with paraformaldehyde undergoes an aldol-Tishchenko reaction, leading to relevant 1,2,3-triol fragments in a totally diastereoselective manner. The excellent stereocontrol in the generation of a quaternary stereocenter is attributed to stereoelectronic effects in the Evans intermediate. This methodology allows overcoming some limitations of our previously reported strategy, based on the reaction of α-lithiobenzyl ethers with esters and paraformaldehyde, broadening the scope of the obtained polyols. Synthetic applications of this process include the preparation of a new dilignol model and some functionalized oxetanes.
Reactivity of substrates with multiple competitive reactive sites toward NBS under neat reaction conditions promoted by visible light
Grjol, Bla?,Jereb, Marjan
, p. 5235 - 5248 (2021/06/07)
Regioselectivity of visible-light-induced transformations of a range of (hetero)aryl alkyl-substituted ketones bearing several competitive reactive sites (α-carbonyl, benzyl and aromatic ring) with N-bromosuccinimide (NBS) was studied under solvent-free reaction conditions (SFRC) and in the absence of inert-gas atmosphere, radical initiators and catalysts. An 8-W energy-saving household lamp was used for irradiation. Heterogeneous reaction conditions were dealt with throughout the study. All substrates were mono- or dibrominated at the α-carbonyl position, and additionally, some benzylic or aromatic bromination was observed in substrates with benzylic carbon atoms or electron-donating methoxy groups, respectively. Surprisingly, ipso-substitution of the acyl group with a bromine atom took place with (4-methoxynaphthyl) alkyl ketones. While the addition of the radical scavenger TEMPO (2,2,6,6-tetramethylpiperidin-1-yloxy) decreased the extent of α- and ring bromination, it completely suppressed the benzylic bromination and α,α-dibromination with NBS under SFRC.
Catalytic Lewis and Br?nsted acid syn-diastereoselective benzylic substitutions of α-hydroxy-β-nitro- and α-hydroxy-β-azido-alkyl arenes
Chénard, étienne,Cusson, Jean-Philippe,Hanessian, Stephen,Hensienne, Rapha?l
, p. 292 - 306 (2020/06/17)
A series of alkyl and alkenyl p-methoxy arenes containing α,β-disubstituted diamino and amino alcohol groups were synthesized from β-nitro and β-azido benzylic alcohols in the presence of AuCl3 as catalyst. The formation of predominantly syn-disubstituted products were rationalized on the basis of mechanistic considerations and transition state models relying on A1,3-allylic strain. The products could have utility in the design of medicinally relevant compounds and as chiral ligands for asymmetric catalysis. A new synthesis of (+)-sertraline (Zoloft) was achieved.
Novel benzene-based carbamates for ache/bche inhibition: Synthesis and ligand/structure-oriented sar study
Bak, Andrzej,Kozik, Violetta,Kozakiewicz, Dariusz,Gajcy, Kamila,Strub, Daniel Jan,Swietlicka, Aleksandra,Stepankova, Sarka,Imramovsky, Ales,Polanski, Jaroslaw,Smolinski, Adam,Jampilek, Josef
, (2019/05/10)
A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl-and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl-compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure–activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host–target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.
ESTROGEN RECEPTOR-MODULATING COMPOUNDS
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Paragraph 000242; 000268, (2019/08/08)
Described herein are compounds that are estrogen receptor modulators of formula I' Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
Synthesis of α,β-dibromo ketones by photolysis of α-bromo ketones with N-bromosuccinimide: Photoinduced β-bromination of α-bromo ketones
Moon, Da Yoon,An, Sejin,Park, Bong Ser
, (2019/10/28)
Irradiation of α-bromopropiophenones in the presence of NBS results in the formation of α,β-dibromopropiophenones, which can be viewed as β-bromination of α-bromopropiophenones. The reaction is believed to go through a series of reactions; photoinduced C–Br bond cleavage, elimination of HBr to give α,β-unsaturated ketone intermediates, and addition of Br2, which are formed by the reaction between HBr and NBS. From mechanistic studies of the reaction, we have also found a very convenient method for α-debromination of the α,β-dibromopropiophenones which is by simple irradiation of the dibromo ketones in acetone or 2-propanol without the use of any additives. Our results demonstrate that bromine can be added into or eliminated from the alpha, beta, or both positions to the carbonyl group by photochemical methods, which make synthetic options of bromine containing carbonyl compounds versatile.
Formal Total Synthesis of Hybocarpone Enabled by Visible-Light-Promoted Benzannulation
Chen, Wei,Guo, Renyu,Yang, Zhen,Gong, Jianxian
, p. 15524 - 15532 (2019/01/03)
The formal total synthesis of hybocarpone was achieved in eight steps from commercially available 1,2,4-trimethoxybenzene. Key transformations include a visible-light-promoted benzannulation to construct the key α-naphthol intermediate and a modified CAN-mediated dimerization/hydration cascade sequence to generate the vicinal all-carbon quaternary centers in a stereocontrolled manner. The total synthesis of boryquinone was also achieved in seven steps.
Structure-activity relationships of talaumidin derivatives: Their neurite-outgrowth promotion in vitro and optic nerve regeneration in vivo
Harada, Kenichi,Zaha, Katsuyoshi,Bando, Rina,Irimaziri, Ryo,Kubo, Miwa,Koriyama, Yoshiki,Fukuyama, Yoshiyasu
, p. 86 - 94 (2018/02/19)
(–)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan, shows potent neurotrophic activities such as neurite-outgrowth promotion and neuroprotection. Previously, we found that (–)-(1S,2R,3S,4R)-stereoisomer 2 exhibited more significant activity than did the natural product talaumidin (1). However, the preparation of optically active (–)-2 requires a complicated synthetic route. To explore new neurotrophic compounds that can be obtained on a large scale, we established a short step synthetic route for talaumidin derivatives and synthesized fourteen analogues based on the structure of (–)-2. First, we synthesized a racemic compound of (–)-2 (2a) and assessed its neurotrophic activity. We found that the neurotrophic property of racemic 2a is similar in activity to that of (–)-2. Using the same synthetic methodology, several talaumidin derivatives were synthesized to optimize the oxy-functionality on aromatic rings. As a result, bis(methylenedioxybenzene) derivative 2b possessed the highest neurotrophic activity. Furthermore, examination of the structure-activity relationships of 2b revealed that the 2,5-diphenyl-tetrahydrofuran structure was an essential structure and that two methyl groups on THF ring could enhance neurotrophic activity. In addition, compounds 2a and 2b were found to induce mouse optic nerve regeneration in vivo.
