1028903-71-0Relevant academic research and scientific papers
Synthesis and α-glucosidase inhibition activity of dihydroxy pyrrolidines
Kasturi, Sivaprasad,Surarapu, Sujatha,Uppalanchi, Srinivas,Anireddy, Jaya Shree,Dwivedi, Shubham,Anantaraju, Hasitha Shilpa,Perumal, Yogeeswari,Sigalapalli, Dilep Kumar,Babu, Bathini Nagendra,Ethiraj, Krishna S.
, p. 2818 - 2823 (2017)
A new series of Deacetylsarmentamide A and B derivatives, amides and sulfonamides of 3,4-dihydroxypyrrolidines as α-glucosidase inhibitors were designed and synthesized. The biological screening test against α-glucosidase showed that some of these compounds have the positive inhibitory activity against α-glucosidase. Saturated aliphatic amides were more potent than the olefinic amides. Among all the compounds, 5o/6o having polar –NH2 group, 10f/11f having polar –OH group on phenyl ring displayed 3–4-fold more potent than the standard drugs. Acarbose, Voglibose and Miglitol were used as standard references. The promising compounds 6i, 5o, 6o, 10a, 11a, 10f and 11f have been identified. Molecular docking simulations were done for compounds to identify important binding modes responsible for inhibition activity of α-glucosidase.
Exocyclic deoxyadenosine adducts of 1,2,3,4-diepoxybutane: Synthesis, structural elucidation, and mechanistic studies
Seneviratne, Uthpala,Antsypovich, Sergey,Goggin, Melissa,Dorr, Danae Quirk,Guza, Rebecca,Moser, Adam,Thompson, Carrie,York, Darrin M.,Tretyakova, Natalia
, p. 118 - 133 (2010)
1,2,3,4-Diepoxybutane (DEB) is considered the ultimate carcinogenic metabolite of 1,3-butadiene, an important industrial chemical and environmental pollutant present in urban air. Although it preferentially modifies guanine within DNA, DEB induces a large number of A → T transversions, suggesting that it forms strongly mispairing lesions at adenine nucleobases. We now report the discovery of three potentially mispairing exocyclic adenine lesions of DEB: N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′- deoxyadenosine (compound 2), 1,N6-(2-hydroxy-3-hydroxymethylpropan-1, 3-diyl) -2′-deoxyadenosine (compound 3), and 1,N6-(1- hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (compound 4). The structures and stereochemistry of the novel DEB-dA adducts were determined by a combination of UV and NMR spectroscopy, tandem mass spectrometry, and independent synthesis. We found that synthetic N6-(2-hydroxy-3,4- epoxybut-1-yl)-2′-deoxyadenosine (compound 1) representing the product of N6-adenine alkylation by DEB spontaneously cyclizes to form 3 under aqueous conditions or 2 under anhydrous conditions in the presence of an organic base. Compound 3 can be interconverted with 4 by a reversible unimolecular pericyclic reaction favoring 4 as a more thermodynamically stable product. Both 3 and 4 are present in double stranded DNA treated with DEB in vitro and in liver DNA of laboratory mice exposed to 1,3-butadiene by inhalation. We propose that in DNA under physiological conditions, DEB alkylates the N-1 position of adenine in DNA to form N1-(2-hydroxy-3,4-epoxybut-1-yl)-adenine adducts, which undergo an SN2-type intramolecular nucleophilic substitution and rearrangement to give 3 (minor) and 4 (major). Formation of exocyclic DEB-adenine lesions following exposure to 1,3-butadiene provides a possible mechanism of mutagenesis at the A:T base pairs.
Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors
Xie, Fangzhou,Yang, Fengzhi,Liang, Yaoyao,Li, Liang,Xia, Yu,Jiang, Faqin,Liu, Wenlu,Qi, Yunyue,Chowdhury, Sharmin Reza,Xie, Dongsheng,Fu, Lei
, p. 408 - 422 (2019)
Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways. In this work, a series of cis- and trans-pyrrolidine bisarylethenesulfonic acid esters were prepared and their PTP1B inhibitory potency, selectivity and membrane permeability were evaluated. These novel stereoisomeric molecules especially trans-isomers exhibited remarkable inhibitory activity, significant selectivity as well as good membrane permeability (e.g. compound 28a, IC50 = 120, 1940 and 2670 nM against PTP1B, TCPTP and SHP2 respectively, and Papp = 1.74 × 10?6 cm/s). Molecular simulations indicated that trans-pyrrolidine bisarylethenesulfonic acid esters yielded the stronger binding affinity than their cis-isomers by constructing more interactions with non-catalytic sites of PTP1B. Further biological activity studies revealed that compound 28a could enhance insulin-stimulated glucose uptake and insulin-mediated insulin receptor β (IRβ) phosphorylation with no significant cytotoxicity.
Practical large-scale synthesis of 3,4-isopropylidenedioxypyrrolidine hydrotosylate: Atom economical self-hydrogenolysis of a crystalline borane-benzylamine adduct
Couturier, Michel,Andresen, Brian M.,Jorgensen, Jeffrey B.,Tucker, John L.,Busch, Frank R.,Brenek, Steven J.,Dube, Pascal,Am Ende, David J.,Negri, Joanna T.
, p. 42 - 48 (2002)
An efficient four-step sequence has been developed for the synthesis of 3,4-isopropylidenedioxypyrrolidine hydrotosylate starting from inexpensive N-benzylmaleimide. This approach features a novel N-debenzylation procedure that utilizes the corresponding
A methodology for simultaneous fluorogenic derivatization and boronate affinity enrichment of 3-nitrotyrosine-containing peptides
Dremina, Elena S.,Li, Xiaobao,Galeva, Nadezhda A.,Sharov, Victor S.,Stobaugh, John F.,Schoeneich, Christian
experimental part, p. 184 - 196 (2012/05/19)
We synthesized and characterized a new tagging reagent, (3R,4S)-1-(4-(aminomethyl)phenylsulfonyl)pyrrolidine-3,4-diol (APPD), for the selective fluorogenic derivatization of 3-nitrotyrosine (3-NT) residues in peptides (after reduction to 3-aminotyrosine) and affinity enrichment. The synthetic 3-NT-containing peptide, FSAY(3-NO2)LER, was employed as a model for method validation. Furthermore, this derivatization protocol was successfully tested for analysis of 3-NT-containing proteins exposed to peroxynitrite in the total protein lysate of cultured C2C12 cells. The quantitation of 3-NT content in samples was achieved through either fluorescence spectrometry or boronate affinity chromatography with detection by specific fluorescence (excitation and emission wavelengths of 360 and 510 nm, respectively); the respective limits of detection were 95 and 68 nM (19 and 13 pmol total amount) of 3-NT. Importantly, the derivatized peptides show a strong retention on a synthetic boronate affinity column, containing sulfonamide-phenylboronic acid, under mild chromatographic conditions, affording a route to separate the derivatized peptides from large amounts (milligrams) of nonderivatized peptides and to enrich them for fluorescent detection and mass spectrometry (MS) identification. Tandem MS analysis identified chemical structures of peptide 3-NT fluorescent derivatives and revealed that the fluorescent derivatives undergo efficient backbone fragmentations, permitting sequence-specific identification of protein nitration at low concentrations of 3-NT in complex protein mixtures. Copyright
Synthesis of iminodiacetaldehyde derivatives as building blocks for pharmacologically active agents
Fricke, Yvonne,Kopp, Nicole,Wuensch, Bernhard
experimental part, p. 791 - 796 (2010/09/11)
The preparation of iminodiacetaldehyde derivatives is reported via oxidative cleavage of 3,4-dihydroxypyrrolidines with sodium periodate. High yields of iminodiacetaldehydes are obtained starting from N-acyl-protected pyrrolidines, whereas the basic N-benzyl-protected derivative does not yield the expected dialdehyde. A cis-configured dihydroxypyrrolidine, prepared from 2,5-dihydropyrrole, reacts considerably faster with sodium periodate than the corresponding trans-configured derivatives which are obtained in three steps from (R,R)-tartaric acid. Georg Thieme Verlag Stuttgart.
Manganese catalyzed cis-dihydroxylation of electron deficient alkenes with H2O2
Saisaha, Pattama,Pijper, Dirk,Van Summeren, Ruben P.,Hoen, Rob,Smit, Christian,De Boer, Johannes W.,Hage, Ronald,Alsters, Paul L.,Feringa, Ben L.,Browne, Wesley R.
supporting information; experimental part, p. 4444 - 4450 (2010/11/05)
A practical method for the multigram scale selective cis-dihydroxylation of electron deficient alkenes such as diethyl fumarate and N-alkyl and N-aryl-maleimides using H2O2 is described. High turnovers (>1000) can be achieved with this efficient manganese based catalyst system, prepared in situ from a manganese salt, pyridine-2-carboxylic acid, a ketone and a base, under ambient conditions. Under optimized conditions, for diethyl fumarate at least 1000 turnovers could be achieved with only 1.5 equiv. of H2O2 with d/l-diethyl tartrate (cis-diol product) as the sole product. For electron rich alkenes, such as cis-cyclooctene, this catalyst provides for efficient epoxidation.
Incorporation of biotinylated manganese-salen complexes into streptavidin: New artificial metalloenzymes for enantioselective sulfoxidation
Pordea,Mathis,Ward
experimental part, p. 930 - 936 (2009/05/27)
Incorporation of achiral biotinylated manganese-salen complexes into streptavidin yields artificial metalloenzymes for aqueous sulfoxidation using hydrogen peroxide. Four biotinylated salen ligands were synthesized and their manganese complexes were teste
Enantiomerically pure polyhydroxylated acyliminium ions. Synthesis of the glycosidase inhibitors (-)-swainsonine and (+)-castanospermine
Miller, Scott A.,Chamberlin, A. Richard
, p. 8100 - 8112 (2007/10/02)
Hydroxylactams, which are useful precursors of acyl iminium ions for cationic cyclization, are most often prepared by hydride reduction of imides. This procedure is not directly applicable, however, to the enantioselective preparation of any highly substituted hydroxy lactam that would be derived from a meso imide, since such a reduction with the usual achiral agents must produce a racemic product. Two enantioselective methods of preparing representative examples of this type of substituted hydroxylactam have therefore been explored. Reduction of a meso imide with a number of enantiomerically pure chiral reducing agents has been found to give up to 56% ee of the corresponding hydroxylactam. Much higher levels of enantiomeric purity are readily obtainable by direct synthesis from monosaccharide lactones derived from either ribose or lyxose, affording either enantiomeric series of hydroxy lactams, (+)-9α, 14-16, and (-)-9α, 20-23, respectively. One such hydroxylactam, 23 has been converted into the mannosidase inhibitor (-)-swainsonine via a synthetic route that features a novel multiple reduction of a vinylogous N-acylurethane to establish the correct ring juncture stereochemistry. Extension of the monosaccharide strategy to the enantioselective synthesis of six-membered-ring hydroxylactams also allows a facile preparation of 29, leading to the glucosidase inhibitor (+)-castanospermine and the new indolizidine alkaloid 1,8a-diepicauistanospermine.
