62640-67-9Relevant academic research and scientific papers
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
Novel composite phosphonium salt as well as preparation method and antibacterial application thereof
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Paragraph 0021-0022, (2017/01/26)
The invention belongs to the technical field of fine chemical synthesis and particularly relates to a novel composite phosphonium salt as well as a preparation method and an antibacterial application thereof. The novel composite phosphonium salt adopts a
Synthesis of 2-phenylnaphthalenes from styryl-2-methoxybenzenes
Mudududdla, Ramesh,Sharma, Rohit,Abbat, Sheenu,Bharatam, Prasad V.,Vishwakarma, Ram A.,Bharate, Sandip B.
supporting information, p. 12076 - 12079 (2015/02/19)
A new simple and efficient method for the synthesis of 2-phenylnaphthalenes from electron-rich 1-styryl-2-methoxybenzenes has been described. The reaction proceeds via TFA catalyzed C-C bond cleavage followed by intermolecular [4+2]-Diels-Alder cycloaddition of an in situ formed styrenyl trifluoroacetate intermediate. The quantum chemical calculations identified the transition state for the cycloaddition reaction and helped in tracing the reaction mechanism. The method has been efficiently utilized for synthesis of the phenanthrene skeleton and a naphthalene-based potent and selective ER-β agonist. This journal is
Transition-metal-free method for the synthesis of benzo[b]thiophenes from o -halovinylbenzenes and K2S via direct SNAr-type reaction, cyclization, and dehydrogenation process
Zhang, Xiaoyun,Zeng, Weilan,Yang, Yuan,Huang, Hui,Liang, Yun
supporting information, p. 1687 - 1692 (2013/09/02)
A new, highly efficient procedure for the synthesis of benzothiophenes from easily available o-halovinylbenzenes and potassium sulfide has been developed. The reaction tolerated a wide range of functionalities, and various 2-substituted benzo[b]thiophenes
Unequivocal experimental evidence for a unified lithium salt-free wittig reaction mechanism for all phosphonium ylide types: Reactions with β-heteroatom-substituted aldehydes are consistently selective for cis-oxaphosphetane-derived products
Byrne, Peter A.,Gilheany, Declan G.
supporting information; experimental part, p. 9225 - 9239 (2012/07/14)
The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism. Notably, a cooperative effect of ortho-substituents in the case of semi-stabilized ylides is confirmed and is accommodated by the cycloaddition mechanism. The effect is also shown to operate in reactions of triphenylphosphine-derived ylides and has previously been observed for reactions under aqueous conditions, thus for the first time providing evidence that kinetic control is in operation in both of these cases.
Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL
Bruncko, Milan,Oost, Thorsten K.,Belli, Barbara A.,Ding, Hong,Joseph, Mary K.,Kunzer, Aaron,Martineau, Darlene,McClellan, William J.,Mitten, Michael,Ng, Shi-Chung,Nimmer, Paul M.,Oltersdorf, Tilman,Park, Cheol-Min,Petros, Andrew M.,Shoemaker, Alexander R.,Song, Xiaohong,Wang, Xilu,Wendt, Michael D.,Zhang, Haichao,Fesik, Stephen W.,Rosenberg, Saul H.,Elmore, Steven W.
, p. 641 - 662 (2007/10/03)
Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
Facile SN2′ coupling reactions of Wittig reagents with dimethyl bromomethylfumarate: Synthesis of enes, dienes, and related natural products
Patel, Ramesh M.,Argade, Narshinha P.
, p. 4900 - 4904 (2008/02/07)
(Chemical Equation Presented) A new simple and efficient synthetic protocol with an ample scope has been demonstrated, by employing SN2′ coupling reactions of a variety of Wittig reagents with dimethyl bromomethylfumarate to obtain the corresponding enes, dienes, and related natural and unnatural products.
Insecticidal substituted-2,4-diamino-5,6,7,8-tetrahydroquinazolines
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, (2008/06/13)
There is provided an insecticidal composition comprising, in admixture with an agriculturally acceptable carrier, an insecticidally effective amount of a tetrahydroquinazoline compound of the formula STR1 wherein R, R1, R2, R3, R5, R6, R7, R8, and R9 are as defined herein, and methods of using the same. Certain novel substituted-phenyl tetrahydroquinazoline compounds per se are also identified.
Relative Reactivity and Stereoselectivity in the Wittig Reactions of Substituted Benzaldehydes with Benzylidenetriphenylphosphorane
Yamataka, Hiroshi,Nagareda, Katsushi,Ando, Katsuhiro,Hanafusa, Terukiyo
, p. 2865 - 2869 (2007/10/02)
Carbonyl carbon-14 kinetic isotope effects and substituent effects on the relative reactivity and on the cis-trans product ratio were determined in the Wittig reaction of XC6H4CHO with Ph3P=CHC6H4Y in THF at 0 deg C.The isotope effect and the Hammett ρ value were positive under both Li salt-free (12k/14k = 1.060 +/- 0.003 and ρx = 2.77 +/- 0.15) and Li salt-present (12k/14k = 1.015 +/- 0.004 and ρx = 1.38 +/- 0.12) conditions, although they were much larger in the former case.These, together with the absence of enone isomerization for the benzylidene ylide reported previously, suggested that the reactions proceed via a polar cycloaddition transition state of considerable nucleophilic character.The cis-trans ratio of the product stilbene was essentially unchanged (40:60 in the salt-free and 60:40 in the Li salt-present reaction) by the change in concentration, the mode of addition, and the molar ratio of aldehyde and ylide, and it was varied only slightly for most substituents X and Y.However, the ratio was significantly varied when o-MeO or o-Cl was introduced as X.The results could be rationalized by assuming a chelating interaction between the lone pair of the ortho substituents and the phosphorous of the ylide.
