7021-09-2Relevant articles and documents
Synthesis and Evaluation of Structurally Diverse C-2-Substituted Thienopyrimidine-Based Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase
Lee, Hiu-Fung,Lacbay, Cyrus M.,Boutin, Rebecca,Matralis, Alexios N.,Park, Jaeok,Waller, Daniel D.,Guan, Tian Lai,Sebag, Michael,Tsantrizos, Youla S.
, p. 2471 - 2496 (2022/02/10)
Novel analogues of C-2-substituted thienopyrimidine-based bisphosphonates (C2-ThP-BPs) are described that are potent inhibitors of the human geranylgeranyl pyrophosphate synthase (hGGPPS). Members of this class of compounds induce target-selective apoptosis of multiple myeloma (MM) cells and exhibit antimyeloma activity in vivo. A key structural element of these inhibitors is a linker moiety that connects their (((2-phenylthieno[2,3-d]pyrimidin-4-yl)amino)methylene)bisphosphonic acid core to various side chains. The structural diversity of this linker moiety, as well as the side chains attached to it, was investigated and found to significantly impact the toxicity of these compounds in MM cells. The most potent inhibitor identified was evaluated in mouse and rat for liver toxicity and systemic exposure, respectively, providing further optimism for the potential value of such compounds as human therapeutics.
The effect of solvents on the thermal degradation products of two Amadori derivatives
Li, Rui,Zhang, Shiyi,Zhang, Yudan,Zhao, Mingqin
, p. 9309 - 9317 (2020/03/23)
To enrich the flavor additives of the Maillard reaction, two Amadori analogs, N-(1-deoxy-d-fructosyl-1-yl)-l-phenylalanine ester (Derivative 1) and di-O-isopropylidene-2,3:4,5-?-d-fructopyranosyl phenylalanine ester (Derivative 2), were chemically synthes
Reactivity of an iron-oxygen oxidant generated upon oxidative decarboxylation of biomimetic iron(II) α-hydroxy acid complexes
Paria, Sayantan,Chatterjee, Sayanti,Paine, Tapan Kanti
supporting information, p. 2810 - 2821 (2014/04/03)
Three biomimetic iron(II) α-hydroxy acid complexes, [(Tp Ph2)FeII(mandelate)(H2O)] (1), [(Tp Ph2)FeII(benzilate)] (2), and [(TpPh2)Fe II(HMP)] (3), together with two iron(II) α-methoxy acid complexes, [(TpPh2)FeII(MPA)] (4) and [(Tp Ph2)FeII(MMP)] (5) (where HMP = 2-hydroxy-2- methylpropanoate, MPA = 2-methoxy-2-phenylacetate, and MMP = 2-methoxy-2-methylpropanoate), of a facial tridentate ligand TpPh2 [where TpPh2 = hydrotris(3,5-diphenylpyrazole-1-yl)borate] were isolated and characterized to study the mechanism of dioxygen activation at the iron(II) centers. Single-crystal X-ray structural analyses of 1, 2, and 5 were performed to assess the binding mode of an α-hydroxy/methoxy acid anion to the iron(II) center. While the iron(II) α-methoxy acid complexes are unreactive toward dioxygen, the iron(II) α-hydroxy acid complexes undergo oxidative decarboxylation, implying the importance of the hydroxyl group in the activation of dioxygen. In the reaction with dioxygen, the iron(II) α-hydroxy acid complexes form iron(III) phenolate complexes of a modified ligand (TpPh2*), where the ortho position of one of the phenyl rings of TpPh2 gets hydroxylated. The iron(II) mandelate complex (1), upon decarboxylation of mandelate, affords a mixture of benzaldehyde (67%), benzoic acid (20%), and benzyl alcohol (10%). On the other hand, complexes 2 and 3 react with dioxygen to form benzophenone and acetone, respectively. The intramolecular ligand hydroxylation gets inhibited in the presence of external intercepting agents. Reactions of 1 and 2 with dioxygen in the presence of an excess amount of alkenes result in the formation of the corresponding cis-diols in good yield. The incorporation of both oxygen atoms of dioxygen into the diol products is confirmed by 18O-labeling studies. On the basis of reactivity and mechanistic studies, the generation of a nucleophilic iron-oxygen intermediate upon decarboxylation of the coordinated α-hydroxy acids is proposed as the active oxidant. The novel iron-oxygen intermediate oxidizes various substrates like sulfide, fluorene, toluene, ethylbenzene, and benzaldehyde. The oxidant oxidizes benzaldehyde to benzoic acid and also participates in the Cannizzaro reaction.
Chiral N-heterocyclic carbene ligands for asymmetric catalytic oxindole synthesis
Jia, Yi-Xia,Hillgren, J. Mikael,Watson, Emma L.,Marsden, Stephen P.,Kuendig, E. Peter
supporting information; scheme or table, p. 4040 - 4042 (2009/03/11)
The Pd-catalysed asymmetric intramolecular α-arylation of amide enolates containing heteroatom substituents gives chiral 3-alkoxy or 3-aminooxindoles in high yield and with enantioselectivities up to 97% ee when a new chiral N-heterocyclic carbene ligand is used. The Royal Society of Chemistry.
Enantiomerically pure α-methoxyaryl acetaldehydes as versatile precursors: a facile chemo-enzymatic methodology for their preparation
Singh, Buddh,Gupta, Pankaj,Chaubey, Asha,Parshad, Rajinder,Sharma, Shiromani,Taneja, Subhash C.
experimental part, p. 2579 - 2588 (2009/04/05)
A facile and efficient synthesis of optically active α-methoxyaryl acetic acids (up to 95% ee), α-methoxyaryl ethanols (up to 93% ee) and α-methoxyaryl acetonitriles (up to 93% ee) was achieved via Arthrobacter sp. lipase-catalyzed kinetic resolution of masked aldehydes as the key synthons, that is, α-hydroxyaryl acetaldehyde acetals.
New oxidative transformations of alkenes and alkynes under the action of diacetoxyiodobenzene
Yusubov,Zholobova,Filimonova,Chi, Ki-Whan
, p. 1735 - 1742 (2007/10/03)
Treatment of alkenes and alkynes with diacetoxyiodobenzene activated by mineral and organic acids predominantly results in oxidative rearrangement. 1,4-Diphenylbutadiene in MeOH gives 3,4-dimethoxy-1,4-diphenylbut-1-ene.
Resolution of (±)-mandelic- and (±)-2-(chiorophenoxy)propionic-acid derivatives by crystallization of their diastereomeric amides with (R)- or (S)-α-arylethylamines
Jourdain, Franck,Hirokawa, Takahiko,Kogane, Tamizo
, p. 2509 - 2512 (2007/10/03)
An alternative and cost effective route for the resolution in high ees (95-99%) of (±)-mandelic-and (±)-2-(chlorophenoxy)propionic- acid derivatives is reported. The key step involves the covalent derivatization and separation of their diastereomeric amides with (R)- or (S)-α- arylethylamines.
Spectroscopy and photochemistry of phenylacetic acid esters and related substrates. The stereoelectronic dependence of the aryl/carboxyl bichromophore interaction
Kasper,Nash,Morrison
, p. 2792 - 2798 (2007/10/02)
The 254-nm-initiated Norrish Type II photofragmentation of the ethoxyethyl esters of a series of phenylacetic acids (1b-4b) has been studied in order to further elaborate the aryl/ester interaction that is photochemically and photophysically evident in these systems. The ethoxyethyl ester of benzonorbornene-1-carboxylic acid (5) has also been prepared and studied, as has a rigid tricyclic lactone (6) which places the chromophores in an optimal stereoelectronic relationship for interaction. The experimental work is accompanied by Hartree-Fock (HF), Natural Bond Orbital (NBO), and Configuration Interaction with Single Excitations (CIS) calculations on the methyl esters of phenylacetic acid (1a) and α-methoxyphenylacetic acid (4a). The calculations confirm extensive through-space (TS) and through-bond (TB) interactions between the aryl and ester π* orbitals but fail to provide conformational or electronic arguments to explain the unusually high reactivity of the α-methoxy series.
The enantioselective influence on the hydrolysis of nitroarylesters of 2-methoxy-2-phenylacetic acids by cyclodextrins
Beyrich,Friedrich,Schreck
, p. 34 - 38 (2007/10/02)
2-Nitrophenyl-, 4-nitrophenyl- and 2,4-dinitrophenylesters of the (P)-,(S)- and (R/S)-2-methoxy-2-phenylacetic acid (MPE) are produced to study the catalytic influence of cyclodextrins (CD) on the hydrolysis of chiral esters. γ-CD demonstrates a higher effect than α-CD, which does not decrease by increasing the pH value. The stability constants of the complexes are not very different. The cleavage of the (S)-enantiomers by α-, hydroxypropyl (HP)-β- and γ-CD is lower than that of the (R)-enantiomers whereby the extent of difference depends on the kind of the substrate. Most distinctly one can recognize the reaction of MPE-4-nitrophenylester to HP-β-CD. Obviously the interaction of the D-glucose unit of the CD with the (S)-substrate leads to a diastereomer which is energetically discriminated against the (R)-substrate resulting in an inhibition of hydrolysis. Because the same especially appears with HP-β-CD it is demonstrated that the enantioselectivity of CD demands an optimum of adaptability of the substrate existing in small limits only.
