6282-42-4Relevant academic research and scientific papers
Subsupercritical Water Generated by Inductive Heating Inside Flow Reactors Facilitates the Claisen Rearrangement
Oltmanns, Mona,Kirschning, Andreas
supporting information, p. 1942 - 1946 (2020/11/13)
Claisen rearrangement of electron-deficient O-allylated phenols, including fluorine-modified phenols, is facilitated in aqueous media at high temperatures and pressures under flow conditions, as opposed to organic solvents. The O-allylation of phenols can be coupled with the Claisen rearrangement in an integrated flow system.
A Structure-Reactivity Relationship of the Tandem Asymmetric Dihydroxylation on a Biologically Relevant Diene: Influence of Remote Stereocenters on Diastereofacial Selectivity
Gill, Daniel M.,Male, Louise,Jones, Alan M.
supporting information, p. 7568 - 7577 (2019/12/11)
The Sharpless asymmetric dihydroxylation (AD) finds widespread use in natural product and drug molecule syntheses, in part, due to its efficiency and predictability. However, the tandem AD of dienes is much less studied, but important in complex molecular synthesis. Herein, a biologically relevant tandem AD is reported, and several anomalies are discovered with the accepted model. These include the formation of unpredicted diastereoisomers, with matched and mismatched stereocenters contradicting the Sharpless mnemonic device. From a structural analysis of the tandem AD, we present a strategy to improve asymmetric induction in sterically hindered alkenes using double diastereodifferentiation from a 9-bond distant stereocenter. A theoretical justification for the unpredicted stereoselectivity, accounting for the influence of steric hindrance and pre-installed chirality, is proposed.
Small-molecules that covalently react with a human prolyl hydroxylase-towards activity modulation and substrate capture
Bush, Jacob T.,Le?niak, Robert K.,Yeh, Tzu-Lan,Belle, Roman,Kramer, Holger,Tumber, Anthony,Chowdhury, Rasheduzzaman,Flashman, Emily,Mecinovi?, Jasmin,Schofield, Christopher J.
supporting information, p. 1020 - 1023 (2019/01/28)
We describe covalently binding modulators of the activity of human prolyl hydroxylase domain 2 (PHD2) and studies towards a strategy for photocapture of PHD2 substrates. Reversible active site binding of electrophile bearing compounds enables susbsequent covalent reaction with a lysine residue (K408) in the flexible C-terminal region of PHD2 to give a modified protein that retains catalytic activity.
Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors
Li, Daqiang,Zhang, Xiaotuan,Ma, Xiaodong,Xu, Lei,Yu, Jianjun,Gao, Lixin,Hu, Xiaobei,Zhang, Jiankang,Dong, Xiaowu,Li, Jia,Liu, Tao,Zhou, Yubo,Hu, Yongzhou
, p. 9177 - 9204 (2018/10/24)
Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure-activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, β5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.
Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry
Blincoe, William D.,Rodriguez-Granillo, Agustina,Saurí, Josep,Pierson, Nicholas A.,Joyce, Leo A.,Mangion, Ian,Sheng, Huaming
, p. 694 - 703 (2018/04/14)
Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighbor
Fluorescence sensing of dichlorvos pesticide by the luminescent Tb(III)-3-ally-salicylohydrazide probe
Ibrahim, Ibrahim Ahmed,Abbas, Abbas Mamdoh,Darwish, Hatem Medhat
, p. 1541 - 1546 (2017/12/08)
A fluorescent probe was developed and characterized, it consisted of terbium(III) with 3-ally-salicylohydrazide in ethanol, in which the 1:2 [Tb3+:S1] molar ratio was the best stoichiometric ratio for the probe. The ligand 3-ally-sal
Oxidative cyclization of alkenoic acids promoted by AgOAc
Carrillo-Arcos, Ulises A.,Rojas-Ocampo, Jonathan,Porcel, Susana
supporting information, p. 479 - 483 (2016/01/09)
Alkenoic acids derived from salicylic acid and analogues undergo an unexpected oxidative cyclization process triggered by AgOAc leading to 4H-benzo[d][1,3]dioxin-4-ones. The process is affected by the substitution on the aryl and the allyl units.
Ring-closing metathesis reaction-based synthesis of new classes of polyether macrocyclic systems
Naveen,Babu, Srinivasarao Arulananda
, p. 7758 - 7781 (2015/09/08)
Ring closing metathesis (RCM) reactions of suitable substrates having terminal olefins, which are assembled from various linkers and hydroxy benzaldehydes and syntheses of a wide range of 16-30 membered, new crown ether-type polyether, aza-polyether, bis aza-polyether macrocycles and dilactone moiety embedded polyether macrocycles (macrolides) are reported. After the ring-closure reaction, installation of different functional groups and functional group modification on the periphery of the synthesized polyether/crown ether macrocycles obtained in the RCM reactions are accomplished using the epoxidation, oxidation and catalytic hydrogenation-based synthetic transformations. Along this line, the syntheses of a variety of polyether macrocycles possessing epoxide or α-hydroxy ketone or 1,2-diol functionalities at the periphery have been shown. Furthermore, the synthesized α-hydroxy ketone functionality installed polyether macrocycles were subjected to the allylation and Reformatsky type reactions to obtain homoallyl alcohol moiety-based and lactone ring-appended polyether macrocycles.
Recyclable CuO nanoparticles-catalyzed synthesis of novel-2,5-disubstituted 1,3,4-oxadiazoles as antiproliferative, antibacterial, and antifungal agents
Murty,Penthala, Raju,Buddana, Sudheer Kumar,Prakasham,Das, Pompi,Polepalli, Sowjanya,Jain,Bojja, Sreedhar
, p. 4579 - 4594 (2016/02/20)
A series of new 2,5-disubstituted 1,3,4-oxadiazoles have been conveniently synthesized through an oxidative C-O coupling by direct C-H bond activation of N-aroyl-N-arylidinehydrazines using a catalytic quantity of CuO nanoparticles. Twenty compounds have been synthesized in good to excellent yields (75-90 %). All the synthesized compounds were evaluated for their in vitro antiproliferative, antibacterial, and antifungal activity. Compounds 8d and 10d are more promising antiproliferative agents with IC50 value of 3.66 and 3.89 μM in MCF-7 cell line, and compounds 8a and 10a were showed more potent antifungal activity than standard drug.
Discovery and structure-activity relationship of novel 2,3- dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2 h)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 Inhibitors
Patel, Maulik R.,Bhatt, Aaditya,Steffen, Jamin D.,Chergui, Adel,Murai, Junko,Pommier, Yves,Pascal, John M.,Trombetta, Louis D.,Fronczek, Frank R.,Talele, Tanaji T.
, p. 5579 - 5601 (2014/08/05)
Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3′,4′-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4′-hydroxyl/4′-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.
