cas 5447-02-9, 3,4-Dibenzyloxybenzaldehyde

Articles about 5447-02-9Total 93 be found

Article title
Article abstract
Author
Journal number and time
Download

Catalytic δ-hydroxyalkynone rearrangement in the stereoselective total synthesis of centrolobine, engelheptanoxides A and C and analogues
A catalytic stereoselective total synthesis of centrolobine and engelheptanoxides A and C has been completed via a metal-free catalytic δ-hydroxyalkynone rearrangement to 2,3-dihydro-4H-pyran-4-one and diastereoselective hydrogenation to the all syn-2,4,6-trisubstituted pyran strategy. The onliest required chirality was introduced by Jacobsen kinetic resolution, which further directed the diastereoselective hydrogenation. A first stereoselective synthesis of engelheptanoxide A is also accomplished. The analogues and derivatives of centrolobine and engelheptanoxides prepared were evaluated for antitubercular activity against M. tuberculosis H37Rv ATCC 27294.
Ahmad, Mohammad N.,Chopra, Sidharth,Fernandes, Rodney A.,Kumar, Praveen
(2021/08/13)

NOVEL AUTOPHAGY-TARGETING CHIMERA (AUTOTAC) COMPOUND, AND COMPOSITION FOR PREVENTING, ALLEVIATING, OR TREATING DISEASES THROUGH TARGET PROTEIN DEGRADATION COMPRISING SAME
The present invention relates to a novel AUTOTAC chimeric compound in which a new p62 ligand and a target-binding ligand are connected by a linker, a stereoisomer, hydrate, solvate or prodrug thereof, and a pharmaceutical or food composition for the prevention or treatment of diseases by degrading the target protein including the same as an active ingredient. They can target specific proteins to adjust their concentrations, and can also deliver drugs and other small molecule compounds to lysosomes. The AUTOTAC chimeric compound according to the present invention can be usefully used as a pharmaceutical composition for the prevention, amelioration or treatment of various diseases by selectively eliminating specific proteins.
-
Paragraph 0092-0093

(2021/06/03)

Synthesis of catechol derived rosamine dyes and their reactivity toward biogenic amines
Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3-and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n-and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9?aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.
Leite, Andreia,Martins, Rui C.,Monteiro-Silva, Filipe,Queirós, Carla,Rangel, Maria,Rodríguez, María T.,Rojo, María J.,Silva, Ana M. G.,Torroba, Tomás
(2021/08/30)

Synthesis and characterisation of novel tricyclic and tetracyclic furoindoles: Biological evaluation as SAHA enhancer against neuroblastoma and breast cancer cells
The dihydropyranoindole structures were previously identified as promising scaffolds for improving the anti-cancer activity of histone deacetylase inhibitors. This work describes the synthesis of related furoindoles and their ability to synergize with suberoylanilide hydroxamic acid (SAHA) against neuroblastoma and breast cancer cells. The nucleophilic substitution of hydroxyin-dole methyl esters with α-haloketones yielded the corresponding arylether ketones, which were subsequently cyclized to tricyclic and tetracyclic furoindoles. The furoindoles showed promising individual cytotoxic efficiency against breast cancer cells, as well as decent SAHA enhancement against cancer cells in select cases. Interestingly, the best IC50 value was obtained with the non-cyclized intermediate.
Arndt, Greg M.,Bingul, Murat,Black, David Stc.,Cheung, Belamy B.,Kumar, Naresh,Marshall, Glenn M.
(2021/09/28)

Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies
A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity. Quinoline derivatives 3f and 3g were identified as potent hDHODH inhibitors while 3k and 3l demonstrated high cytotoxic activity against MCF-7 and A375 cells and good selectivity. In addition, the logD7.4 values obtained by the experimental method were found to be in the range from ?1.15 to 1.69. The chemical structures of all compounds were confirmed by IR, NMR and elemental analysis. The compounds pharmacology on the molecular level was revealed by means of molecular docking, highlighting the structural differences that distinguish highly active from medium and low active hDHODH inhibitors.
Petrovi?, Milena M.,Roschger, Cornelia,Chaudary, Sidrah,Zierer, Andreas,Mladenovi?, Milan,Jakovljevi?, Katarina,Markovi?, Violeta,Botta, Bruno,Joksovi?, Milan D.
(2020/10/21)

Synthesis and SARs of dopamine derivatives as potential inhibitors of influenza virus PAN endonuclease
Currently, influenza PAN endonuclease has become an attractive target for development of new drugs to treat influenza infections. Herein we report the discovery of new PAN endonuclease inhibitors derived from a chelating agent dopamine moiety. A series of dopamine amide derivatives and their conformationally constrained 1,2,3,4-tetrahydroisoquinoline-6,7-diol-based analogs were elaborated and assayed against influenza virus A/WSN/33 (H1N1). Most compounds exhibited moderate to excellent antiviral activities, generating a preliminary SARs. Among them, compounds 14 and 19 showed stronger anti-IAV activity compared with the reference Peramivir. Moreover, 14 and 19 demonstrated a concentration-dependent inhibition of PAN endonuclease based on both FRET assay and SPR assay. Docking studies were also performed to elucidate the binding mode of 14 and 19 with the PAN protein and to identify amino acids involved in their mechanism of action, which were well consistent with the biological data. This finding was beneficial to laying the foundation for the rational development of more effective PAN endonuclease inhibitors.
Liao, Yixian,Ye, Yilu,Li, Sumei,Zhuang, Yilian,Chen, Liye,Chen, Jianxin,Cui, Zining,Huo, Lijian,Liu, Shuwen,Song, Gaopeng
(2020/01/21)

Method for preparing 3, 4-dihydroxyphenylethanol
The invention discloses a method for preparing 3, 4-dihydroxyphenylethanol, which comprises the following steps: (1) preparing benzyloxymethyltriphenylphosphorus chloride, (2) preparing 3.4-dibenzyloxy benzaldehyde, (3) preparing 1, 2-dibenzyloxy-4-(2-benzyloxyvinyl)benzene, and (4) preparing 3, 4-dihydroxyphenylethanol. Compared with the prior art, the method has the advantages that 1, raw materials and reagents used in the method are lower in toxicity, safer, cheaper, easier to obtain and convenient to store, and the raw materials and operation cost are greatly reduced, 2, the method has fewreaction steps, is convenient to operate, and is easier for large-scale production, and 3, the method does not generate high-toxicity three wastes, so that the environmental pollution is reduced, andthe ecological environment is protected. Meanwhile, the yield of the prepared product is high and can reach 90% or above.
-
Paragraph 0058; 0060; 0063; 0065

(2020/06/20)

Synthesis, characterization and biological evaluation of novel dihydropyranoindoles improving the anticancer effects of HDAC inhibitors
The dihydropyranoindole scaffold was identified as a promising target for improving the anti-cancer activity of HDAC inhibitors from the preliminary screening of a library of compounds. A suitable methodology has been developed for the preparation of novel dihydropyranoindoles via the Hemetsberger indole synthesis using azido-phenylacrylates, derived from the reaction of corresponding alkynyl-benzaldehydes with methyl azidoacetate, followed by thermal cyclization in high boiling solvents. Anti-cancer activity of all the newly synthesized compounds was evaluated against the SH-SY5Y and Kelly neuroblastoma cells as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Biological studies showed that the tetracyclic systems had significant cytotoxic activity at higher concentration against the neuroblastoma cancer cells. More importantly, these systems, at the lower concentration, considerably enhanced the SAHA toxicity. In addition to that, the toxicity of designated systems on the healthy human cells was found to be significantly less than the cancer cells.
Arndt, Greg M.,Bingul, Murat,Black, David StC,Cheung, Belamy B.,Kumar, Naresh,Marshall, Glenn M.
(2020/03/26)

Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors
A concise 7-step total synthesis of (±)-fumimycin in 11.6% overall yield is reported. An acid-catalyzed intramolecular aza-Friedel–Crafts cyclization was developed to construct the benzofuranone skeleton of the natural product bearing an α,α-disubstituted amino acid moiety in a single step. Regioselective chlorination followed by a Suzuki–Miyaura cross-coupling rapidly enabled the preparation of a library of analogues which were evaluated against peptide deformylase for antibacterial activity.
Zaghouani, Mehdi,B?geholz, Lena A.K.,Mercier, Evan,Wintermeyer, Wolfgang,Roche, Stéphane P.
p. 3216 - 3230
(2019/04/25)

Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition of tyrosinase enzyme is by far the most established strategy. Cinnamic acid is a safe natural product with an (E)-β-phenyl-α,β-unsaturated carbonyl motif that we have previously shown to play an important role in high tyrosinase inhibition. Since cinnamic acid is relatively hydrophilic, which hinders its absorption on the skin, fifteen less hydrophilic cinnamic amide derivatives (1–15) were designed as safe and more potent tyrosinase inhibitors and were synthesized through a Horner-Wadsworth-Emmons reaction. The use of conc-HCl and acetic acid for debenzylation of the O-benzyl-protected cinnamic amides 40–54 produced the following three results. 1) Cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group, irrespective of the amine type of the amides, produced complex compounds with high polarity. 2) Cinnamic amides 40–42, 44, 50–52, and 54 with a benzylamino, or diethylamino group produced the desired debenzylated cinnamic amides 1–3, 5, 10–13, and 15. 3) Cinnamic amides 45–47, and 49 with an anilino moiety provided 3,4-dihydroquinolinones 16–19 through intramolecular Michael addition of the anilide group. Notably, the use of BBr3 as an alternative debenzylating agent for debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four cinnamic amides 4, 5, 9, and 14 showed 3-fold greater tyrosinase inhibitory activity than kojic acid. The docking simulation using tyrosinase indicated that these four cinnamic amides (?6.2 to ?7.9 kcal/mol) bind to the active site of tyrosinase with stronger binding affinity than kojic acid (?5.7 kcal/mol). All four cinnamic amides inhibited melanogenesis and tyrosinase activity more potently than kojic acid in α-MSH-stimulated B16F10 melanoma cells in a dose-dependent manner without cytotoxicity. The strong correlation between tyrosinase activity and melanin content suggests that the anti-melanogenic effect of cinnamic amides is due to tyrosinase inhibitory activity. Considering that the cinnamic amides 4, 9, and 14, which exhibited strong inhibition on mushroom tyrosinase and potent anti-melanogenic effect in B16F10 cells, commonly have a 2,4-dihydroxyphenyl substituent, the 2,4-dihydroxyphenyl substituent appears to be essential for high anti-melanogenesis. These results support the potential of these four cinnamic amides as novel and potent tyrosinase inhibitors for use as therapeutic agents with safe skin-lightening efficiency.
Ullah, Sultan,Kang, Dongwan,Lee, Sanggwon,Ikram, Muhammad,Park, Chaeun,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
p. 78 - 92
(2018/10/24)

Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues
Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids’ structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 μM compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the β-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 – 79.67% inhibition) at 25 μM than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) cyclohexylamino (19) N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 μM was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.
Ullah, Sultan,Park, Chaeun,Ikram, Muhammad,Kang, Dongwan,Lee, Sanggwon,Yang, Jungho,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
p. 43 - 55
(2019/03/11)

Hybridization of β-Adrenergic Agonists and Antagonists Confers G Protein Bias
Starting from the β-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no β-arrestin-2 recruitment at both β1- and β2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and β-arrestin recruitment of the hybrid (S)-22, the full agonist epinephrine, and the β2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.
Stanek, Markus,Picard, Louis-Philippe,Schmidt, Maximilian F.,Kaindl, Jonas M.,Hübner, Harald,Bouvier, Michel,Weikert, Dorothée,Gmeiner, Peter
p. 5111 - 5131
(2019/05/28)

Metal-Free Br?nsted Acid-Catalyzed Rearrangement of δ-Hydroxyalkynones to 2,3-Dihydro-4 H-pyran-4-ones: Total Synthesis of Obolactone and a Catechol Pyran Isolated from Plectranthus sylvestris
A metal-free, Br?nsted acid, pTsOH-catalyzed intramolecular rearrangement of δ-hydroxyalkynones to substituted 2,3-dihydro-4H-pyran-4-ones was developed. The rearrangement occurs with high regioselectivity under mild and open-air conditions. The scope of work was illustrated by synthesizing an array of aliphatic and aromatic substituted 2,3-dihydro-4H-pyran-4-ones in up to 96% yield, 100% atom economy, and complete regioselectivity. Some of the dihydropyranones are utilized for vinylic halogenations and to complete the total synthesis of bioactive natural products, obolactone and a catechol pyran isolated from Plectranthus sylvestris (Labiatae).
Gholap, Sachin P.,Jangid, Dashrath,Fernandes, Rodney A.
(2019/03/19)

Palladium(II)-catalyzed efficient synthesis of wedelolactone and evaluation as potential tyrosinase inhibitor
Tyrosinase is an enzyme widely distributed in nature, which has multiple functions, especially in the melanin biosynthesis pathway. Despite the few clinically available tyrosinase inhibitors for whitening, a great demand remains for novel compounds with low side effects in terms of potential carcinogenicity and improved clinical efficacy. A natural product, wedelolactone (WEL), with a polyhydroxyl moiety, attracted our attention as a potential tyrosinase inhibitor. Before we studied the biological activity of the natural product, a synthetic methodological research was firstly carried to obtain enough raw material. WEL could be obtained efficiently through palladium-catalyzed boronation/coupling reactions and 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ)-involved oxidative deprotection/annulation reactions. Immediately after, the natural product was proven to be an efficient tyrosinase inhibitor. In conclusion, we developed a mild and efficient approach for the preparation of WEL, and the natural product was disclosed to have anti-tyrosinase activity, which could be widely used in multiple fields.
Huang, Huidan,Chen, Jianqiu,Ren, Jie,Zhang, Chaofeng,Ji, Fei
(2019/11/28)

A pure Radix Salviae Miltiorrhizae usually different propyl ester synthesis method (by machine translation)
The invention relates to a pure Radix Salviae Miltiorrhizae usually different propyl ester synthesis method, the method comprising the protocatechuic aldehyde as a starting raw material, after phenmethyl protection phenol hydroxy, Darzens ring oxidation, and then through the arrowhead class catalyst/hydrogen or Raney nickel/hydrogen catalytic reduction, to obtain pure Radix Salviae Miltiorrhizae usually different propyl ester. The method of the invention the synthetic product purity can be up to 98%, a yield of 55%. And the synthesis method of the invention, and is simple, short route, the productive rate is high, and is suitable for large-scale industrial production. (by machine translation)
-
Paragraph 0031; 0056-0057

(2018/04/02)

Synthesis of a Photo-Caged DOPA Derivative by Selective Alkylation of 3,4-Dihydroxybenzaldehyde
Natural and synthetic polymers containing the catechol moiety of noncoded amino acid 3,4-dihydroxyphenylalanine (DOPA) are capable of metal-coordination and adhesion under wet conditions. Masking the catechol subunit with a photo-cleavable group would provide an opportunity to design tunable adhesion properties that are especially important for biomaterial and biomedicine applications. Herein, we report the regioselective synthesis of a photo-caged DOPA bearing an ortho-nitrobenzyl (oNB) group that is capable of undergoing cleavage upon irradiation with UV light. We developed a selective synthetic route towards a 3-O-oNB alkylated DOPA regioisomer that can be readily incorporated into proteins by using a previously developed bio-expression platform. The synthesis is based on a regioselectivity switch in 3,4-dihydrozybenzaldehyde alkylation upon application of different equivalents of deprotonating base. The enantiomerically pure 3-O-oNB-DOPA was prepared on a gram scale and proved to be generally compatible with the solid-phase peptide synthesis conditions. We also demonstrate the general applicability of the developed synthetic strategy by providing the synthesis of 3-O-methyl-DOPA.
Schneider, Tobias,Kubyshkin, Vladimir,Budisa, Nediljko
p. 2053 - 2063
(2018/05/31)

Electrochemical Dimerization of Phenylpropenoids and the Surprising Antioxidant Activity of the Resultant Quinone Methide Dimers
A simple method for the dimerization of phenylpropenoid derivatives is reported. It leverages electrochemical oxidation of p-unsaturated phenols to access the dimeric materials in a biomimetic fashion. The mild nature of the transformation provides excellent functional group tolerance, resulting in a unified approach for the synthesis of a range of natural products and related analogues with excellent regiocontrol. The operational simplicity of the method allows for greater efficiency in the synthesis of complex natural products. Interestingly, the quinone methide dimer intermediates are potent radical-trapping antioxidants; more so than the phenols from which they are derived—or transformed to—despite the fact that they do not possess a labile H-atom for transfer to the peroxyl radicals that propagate autoxidation.
Romero, Kevin J.,Galliher, Matthew S.,Raycroft, Mark A. R.,Chauvin, Jean-Philippe R.,Bosque, Irene,Pratt, Derek A.,Stephenson, Corey R. J.
p. 17125 - 17129
(2018/12/04)

Design, synthesis and anti-melanogenic effect of cinnamamide derivatives
Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-β-phenyl-α,β-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25 μM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-β-phenyl-α,β-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents.
Ullah, Sultan,Park, Yujin,Ikram, Muhammad,Lee, Sanggwon,Park, Chaeun,Kang, Dongwan,Yang, Jungho,Akter, Jinia,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
p. 5672 - 5681
(2018/10/24)

Efficient synthesis and physicochemical characterization of natural danshensu, its S isomer and intermediates thereof
The synthesis and molecular structure details of R- 3,4-dihydroxyphenyl lactic acid (danshensu) and related compounds, i.e. S isomer and the key intermediates have been described. Danshensu is an important water soluble phenolic acid of Salvia miltiorrhiza herb (danshen or red sag) with numerous applications in traditional Chinese medicine (TCM). Our synthetic approach was based on the Knoevenagel condensation of the protected 3,4-dihydroxybenzaldehyd and Meldrum acid derivative, followed by asymmetric Sharples dihydroxylation, reductive mono dehydroxylation and final deprotection. All compounds were characterized by various spectroscopic techniques: 1H-, 13C- magnetic resonance (NMR); Fourier-transformed infrared (FTIR); Raman, HR mass spectroscopy. For the determination of compound optical purities original HPLC methods were developed which allowed for the efficient resolution of danshensu R and S enantiomers as well as its intermediate enantiomers, using commercially available chiral stationary phases. Furthermore, in order to better understand danshensu specificity as a potential API in drug formulation, the physicochemical properties of the compounds were studied by thermal analysis, including differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
Sidoryk, Katarzyna,Filip, Katarzyna,Cmoch, Piotr,?aszcz, Marta,Cybulski, Marcin
p. 135 - 148
(2017/10/13)

Preparation method of droxidopa
The invention provides a preparation method of droxidopa. The preparation method comprises the following steps: taking 3,4-dihydroxy benzaldehyde as a raw material, performing hydroxyl protection through benzyl chloride to obtain 3,4-dibenzyloxybenzaldehyde, enabling 3,4-dibenzyloxybenzaldehyde and glycine to generate asymmetric condensation reaction under the catalysis of L-threonine aldolase/pyridoxal phosphate, obtaining an L-threo and erythro-3-(3,4-dibenzyloxyphenyl) serine acetate intermediate state through acetic acid salt formation, obtaining intermediate L-threo-3-(3,4-dibenzyloxyphenyl) serine after the intermediate state is heated with water and backflows, and finally removing protected benzyl through Pd/C to prepare the droxidopa. The preparation method provided by the invention has the benefits that the reaction steps are shortened, the process is simplified, meanwhile, the whole total reaction yield is obviously improved, and the raw material cost can be more greatly reduced.
-
Paragraph 0054; 0055

(2017/08/29)

P62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis
Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome. Upon binding to its ligand, p62 acts as a modulator of macroautophagy, inducing autophagosome biogenesis. Through these dual functions, cells can activate p62 and induce selective autophagy upon the accumulation of autophagic cargoes. We also propose that p62 mediates the crosstalk between the ubiquitin-proteasome system and autophagy through its binding Nt-Arg and other N-degrons.
Cha-Molstad, Hyunjoo,Yu, Ji Eun,Feng, Zhiwei,Lee, Su Hyun,Kim, Jung Gi,Yang, Peng,Han, Bitnara,Sung, Ki Woon,Yoo, Young Dong,Hwang, Joonsung,McGuire, Terry,Shim, Sang Mi,Song, Hyun Dong,Ganipisetti, Srinivasrao,Wang, Nuozhou,Jang, Jun Min,Lee, Min Jae,Kim, Seung Jun,Lee, Kyung Ho,Hong, Jin Tae,Ciechanover, Aaron,Mook-Jung, Inhee,Kim, Kwang Pyo,Xie, Xiang-Qun,Kwon, Yong Tae,Kim, Bo Yeon
(2017/08/01)

N-(ALKANOYL)-7-OXO-6-SULFOOXY-1,6-DIAZABICYCLO[3.2.1]OCTANE-2-CARBONYLHYDRAZIDE DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS
Compounds of Formula (I), or a stereoisomer or a pharmaceutically acceptable salt thereof, their preparation, pharmaceutical compositions comprising such compounds and their use in treating and/or preventing bacterial infections are disclosed.
-
Page/Page column 16

(2018/01/20)

Synthetic method for piceatannol derivatives and pharmaceutical compounds containing the piceatannol derivatives
The piceatannol derivatives were easily synthesized using a Wittig-Horner reaction, a Colvin rearrangement and a Sonogashira reaction. According to the result of investigating the anti-inflammatory activity of compounds synthesized in RAW264.7 macrophages induced by LPS, compounds 6 to 8 showed remarkable activity at the concentration of 10 andmu;M, and a compound 7 (90.1%), a compound 8 (60.8%) and a compound 6 (55.2%) showed no cytotoxicity. The present invention aims to provide a method for efficiently synthesizing the piceatannol derivatives and to confirm the biological activity of synthesized piceatannol derivatives.COPYRIGHT KIPO 2017
-
Paragraph 0023; 0028; 0029

(2017/10/31)

Design, synthesis, and evaluation of A-ring-modified lamellarin N analogues as noncovalent inhibitors of the EGFR T790M/L858R mutant
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC50 (WT) = 31.8 nM; IC50 (T790M/L858R) = 8.9 nM]. The effects of A-ring-substituents on activity were rationalized by docking studies.
Fukuda, Tsutomu,Umeki, Teppei,Tokushima, Keiji,Xiang, Gao,Yoshida, Yuki,Ishibashi, Fumito,Oku, Yusuke,Nishiya, Naoyuki,Uehara, Yoshimasa,Iwao, Masatomo
supporting information
p. 6563 - 6580
(2017/11/17)

Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis
Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried out a high throughput screening and identified compound 4 as a moderate DRAK2 inhibitor with an IC50value of 3.15?μM. Subsequent SAR studies of hit compound 4 led to the development of novel benzofuran-3(2H)-one series of DRAK2 inhibitors with improved potency and favorable selectivity profiles against 26 selected kinases. Importantly, most potent compounds 40 (IC50?=?0.33?μM) and 41 (IC50?=?0.25?μM) were found to protect islet β-cells from apoptosis in dose-dependent manners. These data support the notion that small molecule inhibitors of DRAK2 represents a promising strategy for the treatment of diabetes.
Wang, Sheng,Xu, Lei,Lu, Yu-Ting,Liu, Yu-Fei,Han, Bing,Liu, Ting,Tang, Jie,Li, Jia,Wu, Jiangping,Li, Jing-Ya,Yu, Li-Fang,Yang, Fan
p. 195 - 208
(2017/03/02)

Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90
In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.
Jiang, Long,Yin, Ruijuan,Wang, Xueting,Dai, Jiajia,Li, Jing,Jiang, Tao,Yu, Rilei
supporting information
p. 24 - 33
(2017/04/21)

Danshensu mixes turns on lathe to a method for the synthesis of
The invention relates to a synthesis method of racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate. The method comprises the following steps: carrying out Darzens epoxidation on an initial raw material benzyl protected protocatechualdehyde, and carrying out palladium catalyst/hydrogen or Raney nickel/hydrogen catalytic reduction to obtain racemic bornyl beta-(3,4-dihydroxyphenyl)-alpha-hydroxypropionate. The purity and the yield of a product synthesized by adopting the method reach 98% and 48.6% respectively. The synthesis method has the advantages of simple and easily available raw material, short route, high yield, and suitableness for large scale industrialized production.
-
Paragraph 0030; 0058; 0059; 0060

(2017/01/02)

Total Synthesis of the Antiviral Natural Product Houttuynoid B
The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker-Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5-endo-dig cyclization and converted into a stable 1-hydroxybenzotriazole-derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.
Kerl, Thomas,Berger, Florian,Schmalz, Hans-Günther
supporting information
p. 2935 - 2938
(2016/03/25)

Method for synthesizing kukoamine A and analogue thereof
The invention relates to the technical field of medicines, and relates to a method for synthesizing a natural product kukoamine A and analogue thereof. The method comprises the following steps: (1) performing a nucleophilic reaction on hydroxyl, halogen or C1-C10 alkoxy or C1-C10 alkyl substituted or unsubstituted benzaldehyde and malonic acid to obtain a compound 1; (2) reacting the compound 1 in the step (1) with N-hydroxy succinimide to obtain a compound 2; (3) reacting the compound 2 with spermine to obtain a compound 3; and (4) reacting the compound 3 with hydrogen to reduce carbon-carbon double bond, and purifying. The preparation method is simple, and provides a compound base to pharmacological activity research of compounds with similar structures.
-
Paragraph 0037; 0038

(2017/01/02)

Synthesis of 3-arylisocoumarins by using acyl anion chemistry and synthesis of thunberginol A and cajanolactone A
A new strategy for the synthesis of 3-arylisocoumarins and 8-hydroxy-3-arylisocoumarins was investigated by using acyl anion chemistry for the initial C-C bond formation. The obtained keto esters and keto lactones as intermediates underwent based-promoted intramolecular cyclization to afford 3-arylisocoumarins in good yields. The developed methodology was applied for the synthesis of the important natural products thunberginol A and cajanolactone A.
Sudarshan, Kasireddy,Manna, Manash Kumar,Aidhen, Indrapal Singh
p. 1797 - 1803
(2015/05/27)

Ring substitution influences oxidative cyclisation and reactive metabolite formation of nordihydroguaiaretic acid analogues
Nordihydroguaiaretic acid (NDGA) is a natural polyphenol with a broad spectrum of pharmacological properties. However, its usefulness is hindered by the lack of understanding of its pharmacological and toxicological pathways. Previously we showed that oxidative cyclisation of NDGA at physiological pH forms a dibenzocyclooctadiene that may have therapeutic benefits whilst oxidation to an ortho-quinone likely mediates toxicological properties. NDGA analogues with higher propensity to cyclise under physiologically relevant conditions might have pharmacological implications, which motivated this study. We synthesized a series of NDGA analogues which were designed to investigate the structural features which influence the intramolecular cyclisation process and help to understand the mechanism of NDGA's autoxidative conversion to a dibenzocyclooctadiene lignan. We determined the ability of the NDGA analogues investigated to form dibenzocyclooctadienes and evaluated the oxidative stability at pH 7.4 of the analogues and the stability of any dibenzocyclooctadienes formed from the NDGA analogues. We found among our group of analogues the catechols were less stable than phenols, a single catechol-substituted ring is insufficient to form a dibenzocyclooctadiene lignan, and only compounds possessing a di-catechol could form dibenzocyclooctadienes. This suggests that quinone formation may not be necessary for cyclisation to occur and the intramolecular cyclisation likely involves a radical-mediated rather than an electrophilic substitution process. We also determined that the catechol dibenzocyclooctadienes autoxidised at comparable rates to the parent catechol. This suggests that assigning in vitro biological activity to the NDGA dibenzocyclooctadiene is premature and requires additional study.
Asiamah, Isaac,Hodgson, Heather L.,Maloney, Katherine,Allen, Kevin J.H.,Krol, Ed S.
supporting information
p. 7007 - 7014
(2015/11/11)

Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
p. 925 - 937
(2015/03/31)

Coumarin moiety can enhance abilities of chalcones to inhibit DNA oxidation and to scavenge radicals
Coumarin and chalcone are naturally occurring compounds, and coumarin as a functional group was combined with chalcone in this work, aiming to test the inhibitory effects of coumarin-substituted chalcones on the oxidation of DNA and on scavenging radicals. It was found that the antioxidant activity of hydroxyl group attaching to coumarin can be increased by hydroxyl groups attaching to chalcone. The double hydroxyl groups at adjacent position exhibited high abilities to inhibit Cu2+/glutathione-induced oxidation of DNA and to trap 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+) as well as 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). Especially, the double hydroxyl groups in chalcone were able to protect DNA against 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-induced oxidation significantly. On the other hand, the hydroxyl group attaching to coumarin exhibited high ability to inhibit OH-induced oxidation of DNA. Therefore, coumarin-appended chalcones exhibited higher antioxidant effectiveness with only single or double phenolic hydroxyl groups contained.
Xi, Gao-Lei,Liu, Zai-Qun
p. 8397 - 8404
(2015/03/04)

2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands
Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D1 and D2 DR and establish the structure-activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D1 and D2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D1 DR but dramatically reduced the selectivity for D2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation.
Párraga, Javier,Cabedo, Nuria,Andujar, Sebastián,Piqueras, Laura,Moreno, Laura,Galán, Abraham,Angelina, Emilio,Enriz, Ricardo D.,Ivorra, María Dolores,Sanz, María Jesús,Cortes, Diego
p. 150 - 166
(2013/10/01)

Antioxidant effectiveness generated by one or two phenolic hydroxyl groups in coumarin-substituted dihydropyrazoles
A cascade operation was designed to synthesize nine coumarin-substituted dihydropyrazoles with only one or two phenolic hydroxyl groups contained. Antioxidant abilities of the obtained compounds were evaluated by inhibiting 2,2′-azobis(2-amidinopropanehydrochloride) (AAPH)-, Cu2+/ glutathione (GSH)-, and .OH-induced oxidation of DNA. It was found that less phenolic hydroxyl groups can enhance the abilities of coumarin-substituted dihydropyrazoles to protect DNA against the oxidation. Moreover, these coumarin-substituted dihydropyrazoles were employed to scavenge 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. It was found that double phenolic hydroxyl groups were more beneficial for enhancing the abilities of coumarin-substituted dihydropyrazoles to quench the aforementioned radicals. Therefore, dihydropyrazole linked with coumarin exhibited powerful antioxidant effectiveness even in the case of less phenolic hydroxyl groups involved.
Xi, Gao-Lei,Liu, Zai-Qun
p. 385 - 393
(2013/10/01)

Revision of the structure and total synthesis of altenuisol
A total synthesis of the reported structure of altenuisol is described. Comparison of the 1H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds - a structure originally proposed as the structure of altertenuol - matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23% yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided. Total synthesis of altenuisol, a minor toxin in ubiquitous Alternaria spp. revealed that the originally proposed structure was not correct. Altenuisol was proved to have an isomeric structure by total synthesis. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nemecek, Gregor,Cudaj, Judith,Podlech, Joachim
scheme or table
p. 3863 - 3870
(2012/09/25)

Identification, synthesis, and biological evaluation of metabolites of the experimental cancer treatment drugs indotecan (LMP400) and indimitecan (LMP776) and investigation of isomerically hydroxylated indenoisoquinoline analogues as topoisomerase i poisons
Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.
Cinelli, Maris A.,Reddy, P. V. Narasimha,Lv, Peng-Cheng,Liang, Jian-Hua,Chen, Lian,Agama, Keli,Pommier, Yves,Van Breemen, Richard B.,Cushman, Mark
p. 10844 - 10862
(2013/02/25)

Efficient synthesis of hydroxytyrosol from 3,4-dihydroxybenzaldehyde
Hydroxytyrosol is a naturally occurred orthodiphenolic component of olive oil. A variety of biological functions for this molecule have been reported. We report herein an efficient and practical method for the chemical synthesis of hydroxytyrosol from 2,3-dihydroxybenzaldehyde. Taylor & Francis Group, LLC.
Zhang, Zhao-Li,Chen, Jinglei,Xu, Qiongming,Rao, Cui,Qiao, Chunhua
experimental part
p. 794 - 798
(2012/01/17)

Inhibition of Acyl-CoA: Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules
A major effort in Alzheimers disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo.
Pokhrel, Laxman,Maezawa, Izumi,Nguyen, Thi D. T.,Chang, Kyeong-Ok,Jin, Lee-Way,Hua, Duy H.
p. 8969 - 8973
(2013/01/15)

Efficient and practical asymmetric synthesis of isopropyl (R)-3-(3′,4′-dihydroxyphenyl)-2-hydroxypropanoate and its enantiomer
The highly enantioselective synthesis of (R)-isopropyl 3-(3′, 4′-dihydroxyphenyl)-2-hydroxypropanoate and its enantiomer has been achieved starting from 3,4-dihydroxybenzaldehyde. The stereogenic centers were established through asymmetric dihydroxylation of (E)-isopropyl 3,4-bis(benzyloxy) cinnamate. A convenient manipulation in selective catalytic hydrogenation and deprotection was also accomplished in HCl-iPrOH employing 10% Pd/C catalyst.
Chen, Ming,Chen, Hui,Wang, Yuzhen,Wang, Haibo,Nan, Yefei,Zheng, Xiaohui,Jiang, Ru
experimental part
p. 4 - 7
(2011/04/17)

Dimerization of piceatannol by Momordica charantia peroxidase and α-glucosidase inhibitory activity of the biotransformation products
Stilbenes, especially those oligomers, have great potential to be antihyperglycemic agents. In this study, eight stilbene dimers, including five new ones, were obtained by biotransformation of piceatannol using Momordica charantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic evidences. These piceatannol dimers displayed potential α-glucosidase inhibitory activities, and trans double bond, tetrahydrofuran ring, and free adjacent phenolic dihydroxyls were found to be important for their activities. Enzymatic biotransformation of stilbenes by M. charantia peroxidase (MCP) was showed to be a prominent way to produce oligomeric stilbenes for antihyperglycemic development.
Wan, Xiang,Wang, Xiao-Bing,Yang, Ming-Hua,Wang, Jun-Song,Kong, Ling-Yi
experimental part
p. 5085 - 5092
(2011/10/08)

Biological evaluation of KRIBB3 analogs as a microtubule polymerization inhibitor
A series of KRIBB3 analogs were synthesized by modifying substituents at aryl moieties of KRIBB3 for examining structure-activity relationships, and their inhibitory activities on microtubule polymerization were evaluated. The presence of free phenolic hydrogens in aryl moieties of KRIBB3 analogs plays an important role in inhibition of microtubule polymerization.
Lee, Sangku,Kim, Jae Nyoung,Lee, Hyeong Kyu,Yoon, Kab Seog,Shin, Ki Deok,Kwon, Byoung-Mog,Han, Dong Cho
experimental part
p. 977 - 979
(2011/03/21)

Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)
According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A-and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC50=0.27 μM).
Ma, Lei,Yang, Zhengyi,Li, Chenjing,Zhu, Zhiyuan,Shen, Xu,Hu, Lihong
experimental part
p. 643 - 648
(2012/04/10)

Synthesis and evaluation of C-ring aromatized analogues of phenanthridone alkaloids
Phenanthridone alkaloids are envisaged as an attractive lead for the development of anticancer agents. We have prepared a series of aromatized analogues on the basis of the structure of this class of alkaloids with the hope of finding the simplified compounds with comparable activities. The obtained analogues were evaluated for their cytotoxic effect against several cancer cell lines and found to be virtually inactive. These observations together with molecular modeling studies strongly suggest that the stereochemistries of hydroxyl groups in C-ring of phenanthridone alkaloids are crucial to biological effects.
Lee, Seokwoo,Hwang, Soonho,Yu, Shuai,Jang, Wonyoung,Lee, Yun Mi,Kim, Sanghee
scheme or table
p. 1065 - 1070
(2012/07/14)

H2O2/phosphonium ionic liquid: An efficient and simple approach for benzyl halides oxidation
An efficient oxidation of benzyl halide has been done using aqueous hydrogen peroxide (30%) in trihexyl(tetradecyl)phosphonium-tetrafluroborate ionic liquid the protocol is simple mild offering excellent yield of product.
Dake, Satish A.,Kulkarni, Ravibhushan S.,Rode, Ambadas B.,Shinde, Pravin S.,Ghumbre, Sushil K.,Magar, Rupali L.,Pawar, Rajendra P.
experimental part
p. 491 - 494
(2011/09/14)

Total synthesis of 14C-labeled procyanidin B2
During the last decades, many in vitro and in vivo studies have shown the beneficial effects on health of procyanidins. However, their absorption and metabolism is still not fully understood and some aspects are still controversial. In order to have a clearer picture of the metabolism of procyanidins, the use of labelled compounds is essential. In this context, the enantioselective synthesis of 14C-radiolabelled procyanidin B2 was developed in our laboratories. It was achieved in fourteen 'hot' steps, involving as key steps the Sharpless dihydroxylation of an elaborated alkene, a stereoselective intramolecular cyclization to benzylated (+)-catechin and the condensation of two (-)-epicatechin units. 11 mCi of protected procyanidin B2 were obtained from 524 mCi of potassium [14C]cyanide. Copyright
Viton, Florian,Landreau, Cyrille,Rustidge, David,Little, Gill,Robert, Fabien,Williamson, Gary,Barron, Denis
p. 371 - 374
(2011/05/05)

General synthesis of epi-series catechins and their 3-gallates: Reverse polarity strategy
A general synthetic route to the epi-series catechins was developed based on the reverse polarity strategy. Aromatic nucleophilic substitution reaction followed by the sulfinyl-metal exchange and cyclization enabled stereo-controlled access to various members of epi-series catechins and their 3-gallates.
Ohmori, Ken,Yano, Takahisa,Suzuki, Keisuke
supporting information; experimental part
p. 2693 - 2696
(2010/08/21)

Concise total syntheses of aspalathin and nothofagin
Chemical Fig. Reprentation Syntheses of the C-glycosyl flavone natural products aspalathin and nothofagin have been accomplished in eight steps from tribenzyl glucal, tribenzylphloroglucinol, and either 4-(benzyloxy) phenylacetylene or 3,4-bis(benzyloxy)phenylacetylene. The key step of the syntheses involves a highly stereoselective Lewis acid promoted coupling of 1,2-di-o-acyl-3,4,6-tribenzylglucose with tribenzylphloroglucinol, which gives rise to the corresponding β-C-aryl glycoside in 30-65% yields.
Yepremyan, Akop,Salehani, Baback,Minehan, Thomas G.
scheme or table
p. 1580 - 1583
(2010/06/17)

Structure and formation of the fluorescent compound of lignum nephriticum
The intense blue fluorescence of the infusion of Lignum nephriticum (Eysenhardtia polystachya), first observed in the sixteenth century, is due to a novel four-ring tetrahydromethanobenzofuro[2,3-c/]oxacine which is not present in the plant but is the end product of an unusual, very efficient iterative spontaneous oxidation of at least one of the tree's flavonoids.
Acuna, A. Ulises,Amat-Guerri, Francisco,Morcillo, Purificacion,Liras, Marta,Rodriguez, Benjamin
supporting information; experimental part
p. 3020 - 3023
(2009/12/05)

First total synthesis of14C-labeled procyanidin B2 - A milestone toward understanding cocoa polyphenol metabolism
The idea that foods consumed for pure pleasure could provide health benefits received much recognition in the recent years. Among these foods, cocoa and dark chocolate are particularly rich in procyanidins, one of the major dietary families of polyphenols. We developed the first asymmetric total synthesis of procyanidin B2 and applied it to the preparation of a regioselectively radiolabeled 14C-analogue, which will be used to strengthen our knowledge on the metabolism of procyanidins. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
Viton, Florian,Landreau, Cyrille,Rustidge, David,Robert, Fabien,Williamson, Gary,Barron, Denis
supporting information; experimental part
p. 6069 - 6078
(2009/05/27)