- Dipolar vinyl sulfur fluorescent dyes. Synthesis and photophysics of sulfide, sulfoxide and sulfone based D-π-A compounds
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New vinyl sulfides and sulfoxides were obtained in good yields using the Horner-Wadsworth-Emmons (HWE) reaction. The vinyl sulfides and sulfoxides presented preferentially the E-stereochemistry. The respective vinyl sulfones were obtained in good yields from the vinyl sulfides by a simple oxidation step using mCPBA, solely as the E isomers. These derivatives presented absorption maxima in the UV-A region with molar absorptivity coefficients and radiative rate constant values ascribed to spin and symmetry-allowed 1π-π* electronic transitions. Experimentally, a small solvatochromic effect indicated an almost absent charge transfer character in the ground-state. A fluorescence emission in the violet-green region with a significative redshift on the maxima with increasing solvent polarity was observed, which could be related to a better electron delocalization in the excited state, as a result of an intramolecular charge transfer state. DFT and TD-DFT calculations were performed at the PBE1PBE and CAM-B3LYP levels of theory. No solvatochromic effect was observed in the ground state, but a bathochromic effect was detected in the emission maxima. Starting from sulfides to sulfones, the addition of oxygen atoms improved the charge separation, enabling an ICT state, mainly in P3 and P5. This charge separation was more efficient in the triphenylamino derivatives than among the pyrene derivatives since the first one has a better electron-donating character.
- Mon?alves, Matias,Zanotto, Gabriel M.,Toldo, Josene M.,Rampon, Daniel S.,Schneider, Paulo H.,Gon?alves, Paulo F. B.,Rodembusch, Fabiano S.,Silveira, Claudio C.
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- Direct and straightforward transfer of C1 functionalized synthons to phosphorous electrophiles for accessinggem-P-containing methanes
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The direct transfer of different α-substituted methyllithium reagents to chlorinated phosphorous electrophiles of diverse oxidation state (phosphates, phosphine oxides and phosphines) is proposed as an effective strategy to synthesize geminal P-containing
- Touqeer, Saad,Ielo, Laura,Miele, Margherita,Urban, Ernst,Holzer, Wolfgang,Pace, Vittorio
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supporting information
p. 2425 - 2429
(2021/04/02)
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- Generation of potent Nrf2 activators via tuning the electrophilicity and steric hindrance of vinyl sulfones for neuroprotection
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Oxidative stress is constantly involved in the etiopathogenesis of an ever-widening range of neurodegenerative diseases. As a consequence, effective repression of cellular oxidative stress to a redox homeostatic condition is a promising and feasible strategy to treat, or at least retard the progression of, such disorders. Nrf2, a primary orchestrator of cellular antioxidant response machine, is responsible for detoxifying and compensating for deleterious oxidative stress via transcriptional activation of a diverse array of antioxidant biomolecules. In the framework of our persistent interest in disclosing small molecules that interfere with cellular redox-regulating machinery, we report herein the synthesis, optimization, and biological assessment of 47 vinyl sulfone scaffold-bearing small molecules, most of which exhibit robust neuroprotective effect against H2O2-mediated lesions to PC12 cells. After initial screening, the most potent neuroprotective compounds 9b and 9c with marginal cytotoxicity were selected for the follow-up studies. Our results demonstrate that their neuroprotective effects are attributed to the up-regulation of a panel of antioxidant genes and corresponding gene products. Further mechanistic studies indicate that Nrf2 is indispensable for the cellular performances of 9b and 9c, arising from the fact that silence of Nrf2 gene drastically nullifies their protective action. Taken together, 9b and 9c discovered in this work merit further development as neuroprotective candidates for the treatment of oxidative stress-mediated pathological conditions.
- Song, Zi-Long,Hou, Yanan,Bai, Feifei,Fang, Jianguo
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- Organic material with high photoelectric property and preparation method thereof
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The invention provides an organic material with high photoelectric property, wherein the organic material is a gem-cyclopentane benzothiophene compound, and can be applied to organic electronic devices. Organic light-emitting material and battery cathode material and the like. The structural general formula is as follows. In-flight C1 An aliphatic five-membered or six-membered ring, a geminally-substituted aliphatic five-membered or six-membered ring, or the like is absent. Ar1 Aryl or absent. Ar2 Aryl or absent. The invention provides a gem-cyclopentane-substituted benzothiophene compound with excellent performance, thereby solving the problem of starvation of organic small molecule photoelectric materials, and providing a simple and effective synthetic method for synthesizing substituted benzothiophene based on the novel material.
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Paragraph 0058; 0066-0068
(2021/09/21)
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- Synthesis of gem-Dimethylcyclopentane-Fused Arenes with Various Topologies via TBD-Mediated Dehydro-Diels-Alder Reaction
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The development of efficient methods for the synthesis of substituted polycyclic arenes with various topologies is in high demand due to their excellent electrical and optical properties. In this work, a series of gem-dimethylcyclopentane-fused arenes with more than ten topologies were synthesized via a 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-mediated dehydro-Diels-Alder reaction with moderate to good yields. The introduction of the near-planar gem-dimethylcyclopentane moiety not only impacts the molecular conjugative system but also regulates the intermolecular π-πinteractions and crystal packing, which are critical for the photoelectric performance of arenes. The photophysical properties, molecular geometry, molecular packing of these compounds, and electrochemical properties were investigated by UV-vis absorption, fluorescence emission spectra, DFT calculations, single-crystal X-ray structure analysis, and cyclic voltammetry study.
- Zhang, Liyan,Jin, Tengda,Guo, Yingjie,Martin,Sun, Keju,Dudley, Gregory B.,Yang, Jingyue
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p. 16716 - 16724
(2021/11/16)
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- Isomerisation of Vinyl Sulfones for the Stereoselective Synthesis of Vinyl Azides
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Reported is the construction, and facile base-mediated conversation of ten differently substituted 3-azido E-vinyl sulfones (γ-azido-α,β-unsaturated sulfones) into their isomeric vinyl azide counterparts. The requisite 3-azido E-vinyl sulfones were prepared from 3-bromo E-vinyl sulfones, which in turn were accessed from allyl sulfones via a bromination-elimination sequence. In relation to this a one-pot azidation-isomerisation sequence was developed which enabled the direct formation of the vinyl azides from the corresponding 3-bromo E-vinyl sulfones. Similarly, a convenient one-pot Horner–Wadsworth–Emmons olefination-isomerisation approach was utilised in order to prepare some of the allylic sulfones used in this study. The vinyl azide forming process typically proceeded with high levels of Z-selectivity, although this was dependent on the vinyl sulfone substitution pattern. Thus, with either no substituent or a methyl group in the γ- or β-position, relative to the sulfone, good, to high levels of Z-selectivity (Z/E = 85:15 to ≥ 95:5) were obtained. However, incorporation of an α-sulfonyl methyl substituent led to an E-selective process (Z/E = 20:80). A non-bonding interaction between the azido group and the α-sulfonyl vinylic proton is proposed, which acts as a conformational control mechanism to help guide the stereochemical outcome.
- Collins, Niall,Connon, Robert,Evans, Paul,Sánchez-Sanz, Goar
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supporting information
p. 6228 - 6235
(2020/10/02)
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- ISOTHIOCYANATE COMPOUND AND APPLICATION THEREOF
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The present invention provides an isothiocyanate compound and its application. The compound is an aryl-substituted isothiocyanate compound that has a structure of the general formula I. The isothiocyanate compound of the present invention has very good solubility in water, far better inhibitory activity for XPO1 protein than other non-aryl substituted congeneric compounds, little side effects, and good biological safety and bioavailability, and is quite suitable for clinical application. Therefore, the isothiocyanate compound would have tremendous potential market space and economic benefits.
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Paragraph 0063; 0064
(2018/02/28)
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- An Efficient Protecting-Group-Free Synthesis of Vinylic Sulfoximines via Horner-Wadsworth-Emmons Reaction
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Herein, we report a convenient synthesis of aryl-substituted (E)-vinylic NH-sulfoximines via the Horner-Wadsworth-Emmons reaction without the use of protection-deprotection group strategies.
- Chinthakindi, Praveen K.,Nandi, Ganesh Chandra,Govender, Thavendran,Kruger, Hendrik G.,Naicker, Tricia,Arvidsson, Per I.
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supporting information
p. 1423 - 1427
(2016/05/24)
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- Wittig–Horner mediated synthesis of 4-vinyl sulfide derivatives of pyrazoles
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The synthesis of a series of 4-vinyl sulfide derivatives of 1,3-diarylpyrazoles, including their corresponding sulfoxides and sulfones, is reported. Access to the target vinyl sulfides was stereoselectively achieved, in moderate to good yields, by the n-BuLi-mediated Wittig–Horner reaction of 4-formylpyrazoles with arylthiophosphonates and α-chloroarylthiophosphonates in dimethoxyethane. Their oxidation with H2O2in AcOH and mCPBA in CH2Cl2afforded satisfactory yields of the expected vinyl sulfoxides and vinyl sulfones, respectively. Enrichment in the more stable isomers during both oxidation processes was detected and a plausible general mechanistic explanation was given to these observations.
- Padilha, Gustavo,Kaufman, Teodoro S.,Silveira, Claudio C.
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p. 3349 - 3353
(2016/07/12)
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- Thermal Cycloisomerization of Putative Allenylpyridines for the Synthesis of Isoquinoline Derivatives
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A cascade (cyclo)isomerization/elimination process produces novel isoquinoline derivatives of potential interest for pharmaceutical, biomedical, and energy-related research. Mechanistic experiments support a putative allenylpyridine (reminiscent of the Garratt-Braverman cyclization) as a key intermediate in the cascade process.
- Morrison, Alec E.,Hrudka, Jeremy J.,Dudley, Gregory B.
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supporting information
p. 4104 - 4107
(2016/08/30)
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- Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson's disease therapy
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Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2 signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.
- Woo, Seo Yeon,Kim, Ji Hyun,Moon, Mi Kyeong,Han, Se-Hee,Yeon, Seul Ki,Choi, Ji Won,Jang, Bo Ko,Song, Hyo Jung,Kang, Yong Gu,Kim, Jin Woo,Lee, Jaeick,Kim, Dong Jin,Hwang, Onyou,Park, Ki Duk
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supporting information
p. 1473 - 1487
(2014/03/21)
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- Vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: Design, synthesis, biological and computational evaluation
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A series of vinyl sulfone-containing peptidomimetics were rationally designed, synthesized, and evaluated against Trypanosoma brucei brucei. These electrophilic compounds are likely to exert their antitrypanosomal activity via inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through alkylation of a key cysteine residue within the protease active site. The series was designed to present complementary groups to naturally recognized peptide substrates while probing tolerance to a range of substitutions at the P1, P1′, and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole cell assay), displayed minimal toxicity (>785 times selectivity) when assayed for cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells treated with compound 29, as with K777 (2), exhibited an increase in both the number of multinucleated cells and cells with swollen flagellar pockets. Computational analysis revealed a strong correlation between the hypothetical binding mode in TbCatB/rhodesain and trypanocidal activity in vitro.
- Dunny, Elizabeth,Doherty, William,Evans, Paul,Malthouse, J. Paul G.,Nolan, Derek,Knox, Andrew J.S.
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supporting information
p. 6638 - 6650
(2013/10/01)
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- Chemical introduction of the green fluorescence: Imaging of cysteine cathepsins by an irreversibly locked GFP fluorophore
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An activity-based probe, containing an irreversibly locked GFP-like fluorophore, was synthesized and evaluated as an inhibitor of human cathepsins and, as exemplified with cathepsin K, it proved to be suitable for ex vivo imaging and quantification of cysteine cathepsins by SDS-PAGE.
- Frizler, Maxim,Yampolsky, Ilia V.,Baranov, Mikhail S.,Stirnberg, Marit,Gütschow, Michael
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p. 5913 - 5921
(2013/09/12)
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- Proteomic profiling and potential cellular target identification of K11777, a clinical cysteine protease inhibitor, in Trypanosoma brucei
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We report herein the design, synthesis and application of K11777-derived activity-based probes (ABPs) allowing in situ profiling and identification of potential cellular targets of K11777 in Trypanosoma brucei.
- Yang, Peng-Yu,Wang, Min,He, Cynthia Y.,Yao, Shao Q.
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supporting information; experimental part
p. 835 - 837
(2012/02/05)
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- Organocatalyst-mediated enantioselective intramolecular Michael addition of aldehydes to vinyl sulfones
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Chiral amines with a hydrogen bond donor promote the intramolecular conjugate addition of aldehydes to vinyl sulfones. Chiral cyclic sulfone-aldehydes are obtained in good yields with an ee of up to 82%.
- Bournaud, Chloee,Marchal, Estelle,Quintard, Adrien,Sulzer-Mosse, Sarah,Alexakis, Alexandre
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scheme or table
p. 1666 - 1673
(2010/10/04)
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- An elimination approach to the synthesis of (+)-Scorodonin
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1,2-Elimination of optically-active vinyl sulfoxide-allylic acetates led to corresponding allenynes in excellent yields. When the chirality of the sulfinyl group "matched" that at the allylic position, the chirality at the allylic stereogenic center could be efficiently transferred to the allenic axis.
- Zhang, Yan,Wu, Yikang
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p. 1635 - 1639
(2011/07/30)
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- Stereocontrolled synthesis of trans-cyclopropyl sulfones from terminal epoxides
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(Figure presented) Treatment of a range of (enantiopure) epoxides with the sodium salt of diethyl (phenylsulfonyl)methylphosphonate in DME at 140 °C for 4 h gives a variety of (enantiopure) trans-cyclopropyl sulfones with high diastereoselectivity.
- Bray, Christopher D.,De Faveri, Giorgio
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supporting information; experimental part
p. 4652 - 4655
(2010/09/14)
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- Peptidyl allyl sulfones
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The present disclosure provides compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the disclosure include peptidyl allyl sulfone compositions that inhibit proteases, for example cysteine proteases, either in vivo or in vitro.
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Page/Page column 7; 9; 13
(2008/06/13)
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- Electrochemical partial fluorination of organic compounds. 80. Synthesis of cyclic α-arylthio-α-monofluorophosphonate esters
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Seven-membered cyclic α-monofluorophosphonate esters such as 2-allyloxy-3-fluoro-3-phenylthio-4,7-dihydro-[1, 2]-oxaphosphinine-2-oxide were successfully synthesized in moderate total yield as 41% from open-chain allyl phosphonates having an α-arylthio group as an electroauxiliary using an alternative sequence of anodic fluorination and ring-closing olefin metathesis (RCM). On the other hand, in an attempt to synthesize an eight-membered analogue, a different type of seven-membered fluorinated cyclic product was formed predominantly by the RCM reaction between the allyloxy groups.
- Cao, Yi,Hidaka, Asami,Tajima, Toshiki,Fuchigami, Toshio
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p. 9614 - 9617
(2007/10/03)
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- Peptidyl allyl sulfones: A new class of inhibitors for clan CA cysteine proteases
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A new series of peptidyl allyl sulfone inhibitors was discovered while trying to synthesize epoxy sulfone inhibitors from vinyl sulfones using basic oxidizing conditions. The various dipeptidyl allyl sulfones were evaluated with calpain I, papain, cathepsins B and L, cruzain and rhodesain and found to be potent inhibitors. In comparison to the previously developed class of vinyl sulfone inhibitors, the novel dipeptidyl allyl sulfones were more potent inhibitors than the corresponding dipeptidyl vinyl sulfones. It was observed that the stereochemistry of the vinyl sulfone precursor played a role in the potency of the dipeptidyl allyl sulfone inhibitor.
- G?tz, Marion G.,Caffrey, Conor R.,Hansell, Elizabeth,McKerrow, James H.,Powers, James C.
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p. 5203 - 5211
(2007/10/03)
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- A nonhydrolyzable analogue of phosphotyrosine, and related aryloxymethano- and aryloxyethano-phosphonic acids as motifs for inhibition of phosphatases
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Nonhydrolyzable analogues of both stereoisomers of phosphotyrosine, and a series of related aryloxy (or thio) methyl and aryloxy (or thio) ethyl phosphonic acids of the general formula RX-(CH2)n-PO 3H2 (where X = O or S and n = 1 or 2), have been tested as nonhydrolyzable mimetics of phosphatase substrates. These compounds were tested against a panel of phosphatases (two alkaline phosphatases, a protein-tyrosine phosphatase, and two serine/threonine phosphatases) with different active site motifs. The compounds exhibit competitive inhibition toward all enzymes tested, with the best inhibition expressed toward the Ser/Thr phosphatases. The stereoisomers of the phosphotyrosine analogues exhibited an unexpected difference in their inhibitory properties toward the protein-tyrosine phosphatase from Yersinia. The Ki for the d isomer is 33-fold lower than that of the l isomer, and is more than an order of magnitude lower than the reported Km of the substrate l-phosphotyrosine.
- Iyer, Subashree,Younker, Jarod M.,Czyryca, Przemyslaw G.,Hengge, Alvan C.
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p. 5931 - 5935
(2007/10/03)
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- Free radical desulfenylation and deselenylation of α-sulfur and α-seleno substituted phosphonates with the n-Bu3SnH/AIBN reagents system.
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Selestive desulfenylation and deselenylation of α-sulfur- and α-seleno-substituted phosphonates under free radical condition are described.Chemoselectivity and scope of title reaction were studied using phosphonates additionaly functionalized in the α-position alkyl, phenyl,ethoxy,chloro,carbonyl and sulfenyl groups.It was found the reduction of a halogen tolerates the presence of the sulfenyl group and the latter could be reduced in the presence of the sulfinyl and sulfonyl moieties.Moreover,one sulfenyl group was selectively removed from α-phosphoryl dithioacetals and the phenylsulphenyl group was reduced preferentially in the presence of the methylsulfenyl one. Key words:Desulfenylation,deselenylation,α-phosphoryl sulfides,α-phosphoryl selenides, tri-n-butyltinhydride,α,α-azaisobutyronitrile.
- Balczewski,Piotr
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p. 113 - 122
(2007/10/03)
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- Approaches to the Synthesis of Retronecine from Some Pyrrolidine Precursors
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Procedures are described for the attempted conversion of the pyrrolidine (2) into a bicyclic system that would ultimately lead to retronecine (3). The only molecule to be isolated from these attempts was the epimeric ketone (6), and AM1 and MM2 calculations were used to probe this apparently favoured isomerization. Alternative procedures were then investigated that sought to convert the pyrrolidine (1) into precursors to retronecine, and notable successes were obtained with the addition of the amine (21) to both nitroethene and ethyl 2-diethylphosphonoacrylate. However, not only were these precursors resistant to further transformations into retronecine, but also the problem of epimerization again arose. Consequently, AM1 calculations were again employed, and an X-ray structure determination of ethyl (7R,8R)-7-benzyloxy-1-benzyloxymethyl-5,6,7,8-tetrahydro-3H-pyrrolizine-2-carboxylate (39) is reported. Attempts to convert (39) into a diastereoisomer of retronecine were unsuccessful.
- Clare, Brian W.,Ferro, Vito,Skelton, Brian W.,Stick, Robert V.,White, Allan H.
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p. 805 - 824
(2007/10/02)
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- Stereospecific Reductive Desulfurization of Vinyl Sulfoxides with tert-Butyllithium and an Internal Proton Source
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Trienyl and allenyl phenyl sulfoxides can be reduced stereospecifically with retention of configuration in good yields using tert-butyllithium with methanol (MeOH) as an internal (in situ) proton source.The method can be easily modified to give stereospecifically deuterium-labeled compounds.While simple monoene sulfoxides afford attenuated yields of reduced olefin, the method is useful for the reduction of more sensitive and complex polyene sulfoxides as exemplified by the reduction of trienyl sulfoxides 2b, 3b, 9 and allenyl sulfoxide 10 and by a brief review of additional examples which have emerged from this laboratory.That the reduction proceeds through the direct protonation of sulfurane intermediates such as 35 or 35' is an attractive mechanistic hypothesis, but several other possibilities exist.A pathway involving a vinyllithium as a reactive intermediate is considered to be less likely.
- Theobald, Paula G.,Okamura, William H.
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p. 741 - 750
(2007/10/02)
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- A Facile Synthesis of Diethyl 1-(Phenylthio)alkylphosphonates
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The title compounds have been obtained in moderate yields by the reaction of diethyl 1-hydroxyalkylphosphonates with thiophenol in the presence of the triphenylphosphine/diethyl azodicarboxylate system.
- Gajda, Tadeusz
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p. 327 - 328
(2007/10/02)
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- AN EFFICIENT PREPARATION OF DIETHYL PHENYLSULFONYLMETHYLPHOSPHONATE
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A simple, efficient, and inexpensive method for the preparation of diethyl phenylsulfonylmethylphosphonate (4a), and derivatives thereof, is described.
- Blumenkopf, Todd A.
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p. 139 - 148
(2007/10/02)
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- NEW SYNTHETIC METHOD OF O,S-THIOACETALS OF FORMYLPHOSPHONATES
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The reaction of diethyl phosphonate with N-chlorosuccinimide (NCS) affords α-chloromethanephosphonate(5), which can be converted into a variety of O,S-thioacetals of formylphosphonates(2) by reaction with alcohols.
- Kim, Taek Hyeon,Oh, Dong Young
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p. 3479 - 3482
(2007/10/02)
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- Arylthiovinylcyclopropanecarboxylate insecticides
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Arylthiovinylcyclopropanecarboxylates having the general formula STR1 are disclosed. The insecticidal efficacy and preparation of the compounds and novel intermediates therefor are also described and exemplified.
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