- Intramolecular epoxide ring opening cyclisation reactions involving guanidines
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The cyclisation of N-allyl- and N-homoallylguanidines using DMDO leading to the formation of novel 5- and 6-membered guanidine heterocycles is reported. Several of the products formed displayed weak inhibition of glycosidase enzymes.
- Al Shuhaib, Zainab,Arndt, Marcel,Dennis, Mark,Evans, Daniel M.,Jones, Iestyn,Leitmann, Vera,Murphy, Patrick J.,Roberts, Dion,Rowles, Richard,Sadaghiani, Yones K.,Thornhill, Andrew J.,Nash, Robert J.,Hollinshead, Jackie,Bartholomew, Barbara,Tizzard, Graham J.,Coles, Simon J.
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- Bioactivation of a toxic metabolite of valproic acid, (E)-2-propyl-2,4- pentadienoic acid, via glucuronidation. LC/MS/MS characterization of the GSH- glucuronide diconjugates
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The hepatotoxicity of the anticonvulsant drug valproic acid may be associated with the formation of potentially reactive metabolites, one of which is (E)-2-propyl-2,4-pentadienoic acid ((E)-2,4-diene VPA). This report describes the characterization of new GSH-related conjugates of this diene. Bile samples collected from male Sprague-Dawley rats dosed ip with (E)-2,4- diene VPA (100 mg/kg) were analyzed by LC/MS/MS. Initial Q1 parent ion scanning indicated that the daughter ions m/z 162 and 123 could be derived from the ions at m/z 624 and 480, respectively. Subsequent collision-induced dissociation (CID) of these parent ions revealed a common neutral loss of 176 Da which is diagnostic for glucuronides. A similar neutral loss of 176 Da was observed in daughter ion spectra of the biliary metabolites arising from [2H7]-4-ene VPA dosed ip to rats, where the ion fragments containing the VPA portion were 7 amu higher than those derived from the unlabeled drug. CID of the ion at m/z 624 also gave fragments characteristic for GSH conjugates such as the loss of glycine and glutamate moieties. Based on the MS data, the metabolites were assigned the diconjugate structures 1-O-(2-propyl-5- (glutathion-S-yl)-3-pentenoyl)-β-D-glucuronide (5-GS-3-ene VPA-glucuronide I, MH+, 624) and the corresponding 5-NAC-3-ene VPA-glucuronide (MH+, 480). Further proof of structural identity was obtained from 1H NMR of HPLC- purified metabolites. The amount of biliary 5-GS-3-ene VPA-glucuronide I was 7-fold greater than the corresponding 5-GS-3-ene VPA, the sum of the two metabolites accounting for 6.6% of the dose. Incubation of 1-O-(2-propyl- 2,4-pentadienoyl)-β-D-glucuronide (2,4-diene VPA-glucuronide) with GSH in the presence or absence of GST enzyme led to the formation of 5-GS-3-ene VPA- glucuronide I which was readily detected by LC/MS/MS, suggesting that in vivo the diconjugate may arise from the reaction of GSH with 2,4-diene VPA- glucuronide. To our knowledge, this is the first recorded instance in which glucuronide formation activates a drug to further conjugate with GSH via a Michael addition reaction.
- Tang,Abbott
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- Studies on the ketone-catalyzed decomposition of caroate in aqueous alkaline medium
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The kinetics of ketone-catalyzed decomposition of caroate (peroxomonosulfate) was studied in aqueous alkaline medium at 25°C. The rate follows simple second-order kinetics, first order in each (Ketone) and [PMS]. The rate constant values are independent of hydroxide ion concentrations over the range from 0.05 M to 0.15 M. The experimental results suggest that the nucleophilic addition of SO5-2 ion at the carbonyl carbon leads to the formation of oxirane intermediate in the rate-determining step. Oxirane reacts rapidly with another SO52- to give the parent ketone, oxygen, and SO42-. The observed substituent effect on the activation energy EA and Arrhenius (A) factor suggests that the electron-donating substituents stabilize the activated state and make the entropy of activation more negative. This can be explained by the fact that the mechanism of oxirane formation shifts from concentric to nonconcentric process as we go from acetone to 3-hexanone.
- Selvararani,Medona,Ramachandran
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- Synthesis, structure, and reactivity of unexpectedly stable spiroepoxy-β-lactones obtained by epoxidation of 4-alkylidene-2-oxetanones
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We describe the first synthesis of spiroepoxy-β-lactones obtained via epoxidation of ketene dimers. These compounds display unexpected stability that may be due to a double anomeric effect garnered from analysis of bond lengths by X-ray crystallography of one spirocycle in comparison to calculated bond lengths of related structures. These new strained intermediates display interesting reactivity leading to a butenolide, an α-hydroxyketone, a triol, an α-chloroketone, and an α-azidoketone. Copyright
- Duffy, Richard J.,Morris, Kay A.,Romo, Daniel
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- Characterization of thiol-conjugated metabolites of 2-propylpent-4-enoic acid (4-ene VPA), a toxic metabolite of valproic acid, by electrospray tandem mass spectrometry.
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The hepatotoxicity of the anticonvulsant drug valproic acid (VPA) is most likely associated with the bioactivation of its metabolite 2-propylpent-4-enoic acid (4-ene VPA), which is known to induce hepatic microvesicular steatosis in rats. This paper presents an on-line liquid chromatographic/tandem mass spectrometric (LC/MS/MS) identification of new glutathione (GSH)-related conjugates of the reactive metabolites of 4-ene VPA. Bile samples collected from male Sprague-Dawley rats dosed intraperitoneally with 4-ene VPA or its [2H7]-analogue (100 mg kg-1) were injected on to an ODS column interfaced to a LC/MS/MS instrument using electrospray ionization. LC was developed such that no overlapping of peaks occurred among those metabolites which may potentially produce common fragment ions of interest. Subsequent comparison of LC retention times and MS/MS full fragment ion spectra generated for putative metabolites with that of authentic reference compounds made available by chemical synthesis confirmed the presence of the GSH, cysteinylglycine, cysteine and N-acetylcysteine (NAC) conjugates of 2-(2'-carboxypentanyl)oxirane (4,5-epoxy VPA) and (E)-2-propylpenta-2,4-dienoic acid ((E)-2,4-diene VPA), respectively. Quantitatively, the biliary thiol conjugates accounted for 5% of the dose. This observation is novel for 4-ene VPA metabolism in terms of the degradation of GSH conjugates to the corresponding mercapturic acids possibly occurring within the liver as opposed to an inter-organ process which involves the kidney. In addition, the GSH- and NAC-glucuronide di-conjugates of (E)-2,4-diene VPA were also identified as the biliary metabolites with the GSH-glucuronide di-conjugate being 10% of the corresponding mono-GSH conjugate. Taken together, these data clearly indicate that reactive metabolites of VPA can react with hepatic GSH via several different metabolic pathways and may subsequently produce depletion of GSH that leads to toxic consequences.
- Tang,Abbott
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- Identification of amino acid and glutathione N-conjugates of Toosendanin: Bioactivation of the furan ring mediated by CYP3A4
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Toosendanin (TSN) is a hepatotoxic triterpenoid extracted from Melia toosendan Sieb et Zucc. Considering that TSN contains the structural alert of the furan ring, it is believed that bioactivation of TSN may be responsible for its toxicity. Herein, the bioactivation potential and metabolism profiles of TSN were investigated. After an oral administration of 10 mg/kg TSN to rats, esterolysis and conjugation with amino acids were identified as the main metabolic pathways. The same types of conjugates were detected in liver microsomes in an NADPH-dependent manner. According to the remaining amount of the parent drug, the reactivity of trapping reagents with TSN reactive metabolites was sorted in a decreasing order of Nα-(tert-butoxycarbonyl)-L-lysine (Boc-Lys) > alanine, lysine, taurine, phenylalanine, serine, glutamic acid, glycine, and glutathione (GSH) > cysteine. No conjugates were observed in NADPH and N-acetyl cysteine (NAC)-supplemented human liver microsomal incubations. Further phenotyping studies and the chemical synthesis of the major conjugated standards proved that TSN was bioactivated by CYP3A4 and yielded a cis-butene-1,4-dial intermediate, which was prone to undergo 1,2-addition with the amino group of amino acids and GSH to form 3-pyrroline-2-one adducts. The sulfydryl group of GSH also attacked the intermediate and yielded S-conjugates by 1,4- or 1,2-addition, which would form pyrrole conjugates by further reacting with the amino group. Compared to the well-recognized Sconjugation of the furan ring, N-conjugation with multiple amino acids and GSH played a more important part in the elimination of reactive metabolites of TSN. The significance of these conjugates requires further investigation. (Chemical Equation Presented).
- Yu, Jinghua,Deng, Pan,Zhong, Dafang,Chen, Xiaoyan
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- Metabolism of diosbulbin B in vitro and in vivo in rats: Formation of reactive metabolites and human enzymes involved
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Diosbulbin B (DB), a major constituent of the furano-norditerpenes in Dioscorea bulbifera Linn, exhibits potential antineoplasmic activity and hepatotoxicity. The metabolism and reactive metabolites of DB in vitro (with human and animal liver microsomes) and in vivo in rats were investigated. The human enzymes involved in DB metabolism were identified. DB was first catalyzed into reactive metabolites of 2-butene-1,4-dial derivatives dependent on NADPH and then trapped by Tris base or oxidized to hemiacetal lactones (M12 and M13) in microsomal incubations. Tris base was used as buffer constituent and as a trapping agent for aldehyde. Methoxylamine and glutathione (GSH) were also used as trapping agents. DB metabolism in vivo in rats after oral administration was consistent with that in vitro. The structures of M12 and M13, as well as mono-GSH conjugates of DB (M31), were confirmed by nuclear magnetic resonance spectroscopy of the chemically synthesized products. The bioactivation enzymes of DB were identified as CYP3A4/5, 2C9, and 2C19. CYP3A4 was found to be the primary enzyme using human recombinant cytochrome P450 enzymes, specific inhibitory studies, and a relative activity factor approach for pooled human liver microsomes. Michaelis-Menten constants Kmand Vmaxwere determined by the formation of M31. The reactive metabolites may be related to the hepatotoxicity of DB. The gender difference in CYP3A expression in mice and rats contributed to the gender-related liver injury and pharmacokinetics in mice and rats, respectively. Copyright
- Yang, Baohua,Liu, Wei,Chen, Kaixian,Wang, Zhengtao,Wang, Changhong
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- In Vitro DNA Adduction Resulting from Metabolic Activation of Diosbulbin B and 8-Epidiosbulbin e Acetate
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Diosbulbin B (DBB) and 8-epidiosbulbin E acetate (EEA), belonging to furan-containing diterpenoid lactones, are the primary components of Dioscorea bulbifera L. (DB), a traditional Chinese medicine herb. Our earlier studies indicated that consumption of DBB or EEA induced acute hepatotoxicities. Both DBB and EEA were bioactivated by P450 3A4 to generate the corresponding cis-enedial reactive metabolites which are associated with the hepatotoxicities. It has been proposed that the electrophilic intermediates attack cellular nucleophiles such as protein or DNA, thought to be a mechanism of triggering toxicities. The purposes of our present study were to define the interaction of the electrophilic reactive metabolites originating from DBB and EEA with 2′-deoxyguanosine (dGuo), 2′-deoxycytidine (dCyd), and 2′-deoxyadenosine (dAdo) and to characterize DNA adducts arising from the reactive metabolites of DBB and EEA. The reactive metabolites of DBB and EEA were found to covalently bind to the exocyclic and endocyclic nitrogens of dCyd, dGuo, and dAdo to generate oxadiazabicyclo[3.3.0]octaimine adducts. The reactive metabolites of DBB and EEA also attacked dGuo, dAdo, and dCyd of calf thymus DNA. The DNA adducts possibly contribute to the toxicologies of DBB and EEA.
- Lin, Dongju,Li, Weiwei,Tian, Xutong,Peng, Ying,Zheng, Jiang
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- Preparation of a new 1,2,3-trithiolane, trans-9,10,11-trithiabicyclo[6.3.0]undecane, and its oxidation reactions
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The reaction of trans-cyclooctene with S8O yielded a novel bicyclic 1,2,3-trithiolane and trans-9,10,11-trithiabicyclo[6.3.0]undecane (7). Oxidation of the trithiolane with dimethyldioxirane yielded three monoxides, which are assigned to two isomeric 9-oxides, rel-(1R,8R,9S)-9-oxide (15) and rel-(1R,8R,9R)-9-oxide (16), and 10-oxide (17). Further oxidation of rel-(1R,8R,9S)-9-oxide (15) provided rel-(1R,8R,9S,11S)-9,11-dioxide (18) and rel-(1R,8R,9R,11S)-9,11-dioxide (19), while that of rel-(1R,8R,9R)-9-oxide (16) gave rel-(1R,8R,9R,11S)-9,11-dioxide (19) and rel-(1R,8R,9R,11R)-9,11-dioxide (20). The structures of 18 and 19 were determined by X-ray crystallography. The structures of other oxides were elucidated by the spectroscopic data and results of further chemical transformations. Two isomers, 15 and 16, isomerized to one another. A 9,11-dioxide 20 isomerized to 19, which is in equilibrium with 18, where 18 is thermodynamically the most stable isomer.
- Ishii, Akihiko,Suzuki, Manami,Yamashita, Remi
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- The Smelling Principle of Vetiver Oil, Unveiled by Chemical Synthesis
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Vetiver oil, produced on a multiton-scale from the roots of vetiver grass, is one of the finest and most popular perfumery materials, appearing in over a third of all fragrances. It is a complex mixture of hundreds of molecules and the specific odorant, responsible for its characteristic suave and sweet transparent, woody-ambery smell, has remained a mystery until today. Herein, we prove by an eleven-step chemical synthesis, employing a novel asymmetric organocatalytic Mukaiyama–Michael addition, that (+)-2-epi-ziza-6(13)en-3-one is the active smelling principle of vetiver oil. Its olfactory evaluation reveals a remarkable odor threshold of 29 picograms per liter air, responsible for the special sensuous aura it lends to perfumes and the quasi-pheromone-like effect it has on perfumers and consumers alike.
- Ouyang, Jie,Bae, Hanyong,Jordi, Samuel,Dao, Quang Minh,Dossenbach, Sandro,Dehn, Stefanie,Lingnau, Julia B.,Kanta De, Chandra,Kraft, Philip,List, Benjamin
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- Kinetics and mechanism of the highly efficient generation of singlet oxygen in dimethyldioxirane decomposition induced by the chloride ion
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The decomposition of dimethyldioxirane induced by the chloride anion has been investigated by methods of infrared chemiluminescence and quantum chemistry. The reaction leads to efficient generation of singlet excited molecular oxygen 1O2 (the excitation yield in acetone is 61%). A mechanism of peroxide decomposition is proposed in which the key reactions are the addition of the chloride ion to an oxygen atom of dioxirane, resulting in dioxirane ring opening and the formation of the 2-chlorooxy-2-hydroxy propane alcoholate (k1), and the interaction of the latter with another dimethyldioxirane molecule. This interaction results either in the formation of an adduct, which further decomposes to evolve 1O2, and catalyst regeneration (k2) or in the formation of the 2-chloroxyisopropyl radical, which leads to the irreversible consumption of the chloride ion catalyst (k3). The decay kinetics of the infrared chemiluminescence of 1O2 has been studied in a wide range of reactant concentrations. The temperature dependence of the rate constant of the reaction of dimethyldioxirane with the chloride ion has been determined by a kinetic analysis of the mechanism proposed: log(2k1) = (11.1 ± 0.7) - (46 ± 4)/Θ, where Θ = 2.3RT kJ/mol. Estimation of the ratio of the rates of the reaction of the 2-chlorooxy-2- hydroxy propane alcoholate with dimethyldioxirane via two pathways (k 3/k2) has demonstrated that the fraction of the process involving electron transfer does not exceed 1.5% under the experimental conditions examined. Nevertheless, the latter reaction, which withdraws the chloride ion from the catalytic cycle of dimethyldioxirane decomposition yielding singlet oxygen, has a marked effect on the overall kinetics of the process. Pleiades Publishing, Ltd., 2012.
- Ovchinnikov,Kazakov,Khursan
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- Kraft pulp bleaching using dimethyldioxirane: Stability of the oxidants
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Dimethyldioxirane (DMD) is a cyclic peroxide made by oxidizing acetone with peroxymonosulfate (PMS) in water buffered at pH 7.5 using sodium bicarbonate. It has been shown that DMD generation can be achieved in situ within a pulp suspension allowing very selective TCF bleaching of kraft pulp. This process involves simultaneous generation of DMD, reaction of PMS and DMD with residual lignin, and spontaneous decomposition of both oxidants. The first part of this work is a kinetics study of the decomposition of PMS and DMD as a function of pH under conditions similar to those for in situ bleaching. The effect of chelation as well as the effect of transition metal ions on decomposition rate was also investigated. DMD is very sensitive to pH and its half-life is very short under alkaline conditions. The presence of any transition metal ion that can be involved in a one-electron transfer is detrimental to DMD stability. However, fast reaction of DMD with pulp almost counteracts the effect of metal ions.
- Bouchard
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- Chemiluminescence during decomposition of dimethyldioxirane
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Chemiluminescence in the visible spectral region during decomposition of dimethyldioxirane in a cumene-acetone mixture at 22-52 deg C has been detected.Arrhenius parameters of this process have been obtained. - Keywords: organic proxides; dimethyldioxirane; chemiluminescence; reaction mechanism.
- Kazakov, D. V.,Kabal'nova, N. N.,Voloshin, A. I.,Shereshovets, V. V.,Kazakov, V. P.
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- Regioselectivities of (4 + 3) cycloadditions between furans and oxazolidinone-substituted oxyallyls
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The (4 + 3) cycloadditions of oxazolidinone-substituted oxyallyls and unsymmetrically substituted furans lead to syn regioselectivity when the furan has a 2-Me or 2-COOR substituent, while anti regioselectivity is obtained with a 3-Me or 3-COOR group. DFT calculations are performed to explain the selectivities. The reactivities and regioselectivities are consistent with the ambiphilic reactivity of amino-oxyallyls with furans.
- Lohse, Andrew G.,Krenske, Elizabeth H.,Antoline, Jennifer E.,Houk,Hsung, Richard P.
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- Total Synthesis of Ritterazine B
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The first total synthesis of the cytotoxic alkaloid ritterazine B is reported. The synthesis features a unified approach to both steroid subunits, employing a titanium-mediated propargylation reaction to achieve divergence from a common precursor. Other key steps include gold-catalyzed cycloisomerizations that install both spiroketals and late stage C-H oxidation to incorporate the C7′ alcohol.
- Nakayama, Yasuaki,Maser, Michael R.,Okita, Tatsuya,Dubrovskiy, Anton V.,Campbell, Taryn L.,Reisman, Sarah E.
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supporting information
p. 4187 - 4192
(2021/04/06)
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- Congo red and nigrosine dye degradation using dimethyl dioxirane as an oxidising agent
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The advanced oxidation of Congo red (CR) and Nigrosine (NI) using the combined action of dimethyl dioxirane as an oxidising agent is described in this study. The effects of several parameters, such as the concentration of the oxidising agent, the initial dye concentration, and the pH, have been investigated. At room temperature, the oxidising agent dimethyl dioxirane was employed to test the degradation of CR and NI dyes. On the degradation efficiency of CR and NI, pH’s effects, oxidising agent, and initial dye concentration were examined. The absorbance of CR and NI dyes before and after degradation was measured using UV-Visible spectroscopy. The functional group existing in the dyes before and after degradation was determined using FT-IR spectroscopy.
- Rose, A. Leema,Vinotha, S.
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p. 1221 - 1228
(2021/11/17)
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- Total Synthesis of Talatisamine
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Talatisamine (1) is a member of the C19-diterpenoid alkaloid family, and exhibits K+ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5-membered-ring structure (ABCDEF-ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6-membered AE-ring 7 and aromatic 6-membered D-ring 6. AE-ring 7 was constructed from 2-cyclohexenone (8) through fusing an N-ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7, an oxidative dearomatization/Diels–Alder reaction sequence generated fused pentacycle 4 b. The newly formed 6/6-membered ring system was then stereospecifically reorganized into the 7/5-membered BC-ring of 3 via a Wagner–Meerwein rearrangement. Finally, Hg(OAc)2 induced an oxidative aza-Prins cyclization of 2, thereby forging the remaining 5-membered F-ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8.
- Kamakura, Daiki,Todoroki, Hidenori,Urabe, Daisuke,Hagiwara, Koichi,Inoue, Masayuki
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supporting information
p. 479 - 486
(2019/11/25)
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- Derivatization reaction of triacetylpyranosyldihydropyrrole and application of derivative products
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The invention discloses a derivatization reaction of triacetylpyranosyldihydropyrrole and application of derivative products. A compound 1, namely triacetylpyranosyldihydropyrrole, is used as a reaction substrate. The reaction substrate is subjected to an addition reaction of a pyrrole ring double bond to obtain a compound 2; the reaction substrate is subjected to an epoxidation reaction of a pyrrole ring double bond to obtain a compound 3; the reaction substrate is subjected to a ring-opening reaction of a pyranose ring to obtain a compound 4; and the reaction substrate is subjected to a protective reaction to obtain a compound 5. The invention also discloses application of derivative products, the compounds 2-5, in the preparation of drugs for inhibiting proliferation of human breast cancer cells MCF-7 and application in the preparation of drugs for inhibiting activity of acetylcholinesterase and butyrylcholinesterase. According to the invention, a variety of derivatization reactionscan be performed to prepare the drug compounds with effects of tumor resistance and cholinesterase activity inhibition, and the derivatization reaction process has characteristics of mild reaction conditions, simple operation and high reaction yield.
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Paragraph 0018-0026
(2020/05/01)
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- Two-Phase Synthesis of Taxol
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Taxol (a brand name for paclitaxel) is widely regarded as among the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural (plant material) or biosynthetically derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol.
- Kanda, Yuzuru,Nakamura, Hugh,Umemiya, Shigenobu,Puthukanoori, Ravi Kumar,Murthy Appala, Venkata Ramana,Gaddamanugu, Gopi Krishna,Paraselli, Bheema Rao,Baran, Phil S.
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supporting information
p. 10526 - 10533
(2020/07/27)
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- Stereoselective Protection-Free Modification of 3-Keto-saccharides
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Unprotected 3-keto-saccharides have become readily accessible via site-selective oxidation, but their protection-free functionalization is relatively unexplored. Here we show that protecting groups are obsolete in a variety of stereoselective modifications of our model substrate methyl α-glucopyranoside. This allows the preparation of rare sugars and the installation of click handles and reactive groups. To showcase the applicability of the methodology, maltoheptaose has been converted into a chemical probe, and the rare sugar evalose has been synthesized.
- Bianca, Simona,Duca, Margherita,Marinus, Nittert,Minnaard, Adriaan J.,Mouthaan, L. M. C. Marc,Poolman, Bert,Tahiri, Nabil,Van Den Noort, Marco,Witte, Martin D.
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supporting information
(2020/07/24)
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- Method for preparing ketone peroxide by ferrite compound as catalyst
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The invention discloses a method for preparing ketone peroxide by a ferrite compound as a catalyst. The method comprises that ketone and hydrogen peroxide undergo a reaction in the presence of a ferric oxide as a catalyst and the hydrogen peroxide is finally added when the temperature is raised to the reaction temperature. The ferric oxide replaces a titanium-silicon molecular sieve catalyst so that the cost of the catalyst is significantly reduced and the catalyst is easy to recover. The reaction conditions are low, the reaction conversion rate and selectivity are high under mild reaction conditions, the application range is wide, and the method can be used for production of a variety of ketones and its ketone peroxides and has very good application prospects.
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Paragraph 0030
(2019/01/21)
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- Site-selective Oxidative Dearomatization of Phenols and Naphthols into ortho-Quinols or Epoxy ortho-Quinols using Oxone as the Source of Dimethyldioxirane
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A novel reactivity of dimethyldioxirane, generated in situ from Oxone and acetone, with substituted phenols and naphthols is reported. This methodology allowed the synthesis of ortho-quinols or epoxy ortho-quinols from a site-selective oxidative dearomatization process, with good yields under very mild conditions. A short total synthesis of natural product lacinilene C methyl ether is also described using this process as the key step. (Figure presented.).
- Cabrera-Afonso, María J.,Carre?o, M. Carmen,Urbano, Antonio
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supporting information
(2019/08/21)
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- Catalytically Enantioselective Synthesis of Acyclic α-Tertiary Amines through Desymmetrization of 2-Substituted 2-Nitro-1,3-diols
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Highly enantioselective synthesis of acyclic α-tertiary amines through asymmetric desymmetrization is reported. This approach is based on chiral phosphoric acid mediated, enantioselective, oxidative desymmetrization of 2-substituted 2-nitro-1,3-diolbenzylidine acetals in the presence of DMDO as an oxidant. The method allows for the formation of a wide variety of chiral 2-nitro-1,3-diols in high enantioselectivity, which could be transformed into optically pure, unnatural α-alkyl series. The synthetic utility of this method has been further demonstrated by the expedient construction of the core structure of natural products manzacidins enantioselectively.
- Meng, Shan-Shui,Tang, Wu-Bang,Zheng, Wen-Hua
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supporting information
p. 518 - 521
(2018/02/10)
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- Unexpected regioselectivity observed in the bromination and epoxidation reactions of p-benzoquinone-fused norbornadiene: An experimental and computational study
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The bromination reaction of p-benzoquinone-fused norbornadiene was studied at various temperatures (?78,??50, 0, 25, and 77?°C). At room temperature, the double bonds of the p-benzoquinone units were mainly brominated. The double bond of the norbornene unit also underwent a bromination reaction in a yield of only 2%. However, the reaction at??78?°C resulted in the formation of products derived from the attack of bromine on the norbornene double bond with higher charge density. In contrast to the bromination reaction, the epoxidation reaction of the same compound with m-chloroperbenzoic acid and dimethyldioxirane exclusively resulted in the formation of products derived from the addition to the double bond of norbornadiene. The regioselectivity observed was investigated and the results were supported by theoretical calculations.
- Essiz, Selcuk,Dalkilic, Erdin,Sari, Ozlem,Dastan, Arif,Balci, Metin
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p. 1640 - 1649
(2017/03/08)
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- Synthesis and Neurotrophic Activity Studies of Illicium Sesquiterpene Natural Product Analogues
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Neurotrophic natural products hold potential as privileged structures for the development of therapeutic agents against neurodegeneration. However, only a few studies have been conducted to investigate a common pharmacophoric motif and structure–activity relationships (SARs). Here, an investigation of structurally more simple analogues of neurotrophic sesquiterpenes of the illicium family is presented. A concise synthetic route enables preparation of the carbon framework of (±)-Merrilactone A and (±)-Anislactone A/B on a gram scale. This has allowed access to a series of structural analogues by modification of the core structure, including variation of oxidation levels and alteration of functional groups. In total, 15 derivatives of the natural products have been synthesized and tested for their neurite outgrowth activities. Our studies indicate that the promising biological activity can be retained by structurally simpler natural product analogues, which are accessible by a straightforward synthetic route.
- Richers, Johannes,P?thig, Alexander,Herdtweck, Eberhardt,Sippel, Claudia,Hausch, Felix,Tiefenbacher, Konrad
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supporting information
p. 3178 - 3183
(2017/03/13)
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- A catalytic enantioselective approach to tetrol bearing vicinal all-carbon quaternary stereogenic centers
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The first highly enantioselective catalytic protocol for selective manipulation of tetrol benzylidene acetals through chiral phosphoric acid mediated oxidative desymmetrization is reported. This efficient approach provides a general access to vicinal all-carbon quaternary stereogenic center structural motifs, as well as structures containing vicinal tertiary and quaternary stereocenters enantioselectively. The synthetic utility has been furthermore demonstrated by transformations and gram-scale processes.
- Yang, Hui,Cao, Kou-Sen,Zheng, Wen-Hua
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supporting information
p. 3737 - 3740
(2017/04/03)
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- DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE
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Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
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Page/Page column 136
(2017/04/11)
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- Macrocycles All Aflutter: Substitution at an Allylic Center Reveals the Conformational Dynamics of [13]-Macrodilactones
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The shapes adopted by large-ring macrocyclic compounds play a role in their reactivity and their ability to be bound by biomolecules. We investigated the synthesis, conformational analysis, and properties of a specific family of [13]-macrodilactones as models of natural-product macrocycles. The features of our macrodilactones enabled us to study the relationship between stereogenic centers and planar chirality through the modular synthesis of new members of this family of macrocycles. Here we report on insights gained from a new [13]-macrodilactone that is substituted at a position adjacent to the alkene in the molecule. Analysis of the compound, in comparison to an α-substituted regioisomer, by using X-ray crystallography, NMR coupling constants, and reaction-product characterization in concert with computational chemistry, revealed that the alkene unit is dynamic. That is, the data support a model in which the alkene in our [13]-macrodilactones oscillates between two conformations. A difference in reactivity of one conformation compared to the other leads to manifestation of this dynamic behavior. The results underscore the local conformational dynamics observed in some natural-product macrocycles, which could have implications for biomolecule binding.
- Rutledge, Kelli M.,Hamlin, Trevor A.,Baldisseri, Donna M.,Bickelhaupt, F. Matthias,Peczuh, Mark W.
-
supporting information
p. 2623 - 2633
(2017/10/07)
-
- Synthesis, Optical Properties, and Electronic Structures of Tetrakis(pentafluorophenyl)tetrathiaisophlorin Dioxide
-
The synthesis, structure, optical and redox properties, and electronic structure of tetrakis(pentafluorophenyl)tetrathiaisophlorin dioxide (12) are reported. Oxidation of tetrakis(pentafluorophenyl)tetrathiaisophlorin (11) with dimethyldioxirane afforded the oxidized product, which was the tetrathiaisophlorin with two thiophene 1-oxide moieties (12). More significant nonplanarity and greater bond length alternation in 12 than those of 11 were observed by X-ray structural analysis. The absorption spectrum of 12 contains two bands at λ=348 and 276 nm, with a weak tail that extends to λ≈650 nm. Analysis of the magnetic circular dichroism spectrum of 12, based on Michl's 4N-perimeter model and molecular orbital calculations, indicate that the broad band at λ=348 nm appears to contain N2and P2bands, and 12 is classified as a 4nπ system, similar to 11. The nuclear-independent chemical shift values and1H NMR spectroscopy data indicate that 12 has more antiaromatic character than 11.
- Mishra, Vijay Lakshmi,Furuyama, Taniyuki,Kobayashi, Nagao,Goto, Kenta,Miyazaki, Takaaki,Yang, Jye-Shane,Shinmyozu, Teruo
-
p. 9190 - 9197
(2016/07/14)
-
- Asymmetric epoxidation of chromenes mediated by iminium salts: Synthesis of mollugin and (3S,4R)-trans-3,4-dihydroxy-3,4-dihydromollugin
-
Organocatalytic asymmetric epoxidation of chromenes mediated by iminium salt catalysts under non-aqueous conditions provided ees as high as 99%. Contrastingly, reaction under aqueous conditions can form the corresponding diol products with ees as high as 71%. The process has been used for the synthesis of the East African medicinal plant metabolite (3S,4R)-trans-3,4-dihydroxy-3,4-dihydromollugin.
- Bulman Page, Philip C.,Chan, Yohan,Noor Armylisas, Abu Hassan,Alahmdi, Mohammed
-
p. 8406 - 8416
(2016/12/06)
-
- Isocyanate-free route to poly(carbohydrate-urethane) thermosets and 100% bio-based coatings derived from glycerol feedstock
-
Glycerol serves as the exclusive bio feedstock for the preparation of high purity sorbitol tricarbonate (STC) as new intermediate for poly(carbohydrate-urethane) thermosets and 100% bio-based non-isocyanate polyhydroxyurethane (NIPU) coatings. In this process, glycerol-based acrolein is dimerized, carbonated, and oxidized, thus producing the highly reactive diepoxy functional ethylene carbonate (DOC), which by facile chemical CO2 fixation yields high purity STC. Opposite to most state-of-the-art multifunctional five-membered cyclic carbonates and regardless of the feedstock used for its manufacture, STC enables amine curing at ambient temperature even in the absence of catalysts. According to FT-IR and NMR spectroscopic analyses of the amine/carbonate reaction kinetics, the internal cyclic carbonate group is 3 times more reactive with respect to the two terminal carbonate groups. This is attributed to the electron-withdrawing effect of terminal cyclic carbonates. Curing STC with a blend of bio-based flexible and rigid diamines such as dimer fatty acid-based diamine (Priamine 1074) and isophorone diamine affords poly(carbohydrate-urethane) thermosets and NIPU coatings exhibiting substantially improved thermal and mechanical properties.
- Schmidt, Stanislaus,Ritter, Benjamin S.,Kratzert,Bruchmann, Bernd,Mülhaupt, Rolf
-
p. 7268 - 7276
(2016/10/22)
-
- Asymmetric hydroxylative phenol dearomatization promoted by chiral binaphthylic and biphenylic iodanes
-
The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues. Although remarkable progress has recently been made in organoiodine-catalyzed reactions using a terminal oxidant in stoichiometric amounts, there is still a significant need for "flaskable" chiral iodane reagents. Herein, we describe the synthesis of new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO-mediated oxidation into either λ3- or λ5-iodanes, and the evaluation of their capacity to promote asymmetric hydroxylative phenol dearomatization (HPD) reactions. Most notably, a C2-symmetrical biphenylic λ5-iodane promoted the HPD-induced conversion of the monoterpene thymol into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol)) with enantiomeric excesses of up to 94 %.
- Bosset, Cyril,Coffinier, Romain,Peixoto, Philippe A.,El Assal, Mourad,Pouysegu, Laurent,Quideau, Stephane,Miqueu, Karinne,Sotiropoulos, Jean-Marc
-
supporting information
p. 9860 - 9864,5
(2014/10/15)
-
- PROCESS FOR IXABEPILONE, AND INTERMEDIATES THEREOF
-
The present invention relates to a novel process of making ixabepilone, ixabepilone derivatives and analogues, and intermediates thereof.
- -
-
Paragraph 0288-0289; sheet 20
(2014/09/29)
-
- Chiral phosphoric acid catalyzed highly enantioselective desymmetrization of 2-substituted and 2,2-disubstituted 1,3-diols via oxidative cleavage of benzylidene acetals
-
A highly enantioselective catalytic protocol for the desymmetrization of a wide variety of 2-substituted and 2,2-disubstituted 1,3-diols is reported. This reaction proceeds through the formation of an "ortho ester" intermediate via oxidation of 1,3-diol benzylidene acetal by dimethyldioxirane (DMDO) and the subsequent proton transfer catalyzed by chiral phosphoric acid (CPA). The mechanism and origins of enantioselectivity of this reaction are identified using DFT calculations. The oxidation by DMDO is rate-determining, and the phosphoric acid significantly accelerates the proton transfer; the attractive interactions between the benzylidene part of the substrate and the 2,4,6-triisopropyl group of CPA are the key to high enantioselectivity.
- Meng, Shan-Shui,Liang, Yong,Cao, Kou-Sen,Zou, Lufeng,Lin, Xing-Bang,Yang, Hui,Houk,Zheng, Wen-Hua
-
supporting information
p. 12249 - 12252
(2014/10/16)
-
- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
-
Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.
- -
-
Paragraph 0272
(2015/01/16)
-
- Practical and efficient large-scale preparation of dimethyldioxirane
-
An improved procedure for large-scale and also commercially viable preparation of dimethyldioxirane (DMDO), a common and widely used oxidation agent in organic synthesis, was developed using a conventional laboratory plant. All reaction parameters were optimized, and the stability of a freshly prepared solution of DMDO in acetone was monitored over an extended period of time to ensure long-term use after preparation, transport, and storage. This discontinuous approach, suitable for batch processing, is of interest basically to research laboratories but also to suppliers in the research and fine chemicals market.
- Mikula, Hannes,Svatunek, Dennis,Lumpi, Daniel,Gloecklhofer, Florian,Hametner, Christian,Froehlich, Johannes
-
p. 313 - 316
(2013/04/24)
-
- APP SPECIFIC BACE INHIBITORS (ASBIs) AND USES THEREOF
-
In certain embodiments APP-specific BACE inhibitors (ASBIs) are provided as well as uses thereof. In certain embodiments methods of preventing or delaying the onset of a pre-Alzheimer's condition and/or cognitive dysfunction, and/or ameliorating one or more symptoms of a pre-Alzheimer's condition and/or cognitive dysfunction, or preventing or delaying the progression of a pre-Alzheimer's condition or cognitive dysfunction to Alzheimer's disease are provided where the method involves administering to a subject in need thereof an APP specific BACE inhibitor (ASBI) in an amount sufficient to prevent or delay the onset of a pre-Alzheimer's cognitive dysfunction, and/or to ameliorate one or more symptoms of a pre-Alzheimer's cognitive dysfunction, and/or to prevent or delay the progression of a pre-Alzheimer's cognitive dysfunction to Alzheimer's disease. In certain embodiments the ASBI is a flavonoid (e.g. galangin) or flavonoid progrug (e.g., galangin prodrug).
- -
-
Paragraph 0294
(2013/10/08)
-
- Synthesis, characterization, and metabolism studies of fluspidine enantiomers
-
The enantiomers of the potent σ1 ligand fluspidine (1) were prepared by using chiral preparative HPLC. Synthesis of racemic tosylate 2 and subsequent separation of enantiomers yielded (R)-2 and (S)-2 in excellent enantiomeric purities. The fluspidine enantiomers (R)-1 and (S)-1 were synthesized from (R)-2 and (S)-2 by nucleophilic substitution with tetra-n-butylammonium fluoride, affording (R)-1 with 99.6 % ee and (S)-1 with 96.4 % ee. Tosylates (R)-2 and (S)-2 can also serve as precursors for the radiosynthesis of enantiomerically pure radiotracers [18F](R)-1 and [18F](S)-1. The absolute configuration of the pure enantiomers was elucidated by comparison of their CD spectra with a calculated CD spectrum of a simplified model compound. In receptor binding studies, both enantiomers displayed very high σ1 receptor affinity and selectivity against the σ2 receptor. (R)-Fluspidine ((R)-1) is the eutomer, with a Ki value of 0.57 nM and a eudysmic ratio of 4. Incubation of (R)-1 and (S)-1 with rat liver microsomes led to the identification of seven and eight metabolites, respectively. Although the S-configured enantiomer formed additional metabolite (S)-1-3, it is metabolically more stable than (R)-1. Enantiomeric excitement! To develop a PET tracer for human studies, enantiomers of the potent σ1 ligand fluspidine were prepared and biologically evaluated. (R)-Fluspidine is the eutomer, with a σ1 affinity of 0.57 nM. During incubation with rat liver microsomes, (S)-fluspidine is metabolically more stable than its R-configured enantiomer. Eight metabolites of (S)-fluspidine and seven metabolites of (R)-fluspidine were identified. Copyright
- Holl, Katharina,Falck, Evamaria,Koehler, Jens,Schepmann, Dirk,Humpf, Hans-Ulrich,Brust, Peter,Wuensch, Bernhard
-
p. 2047 - 2056
(2014/01/06)
-
- EPOXIDE BASED LINKERS
-
The present invention provides new compositions and methods for the preparation and use of multifunctional epoxide based linkers. These reagents read-to-use and water-soluble linker, and are equipped with a highly reactive functional group. They can be used in a variety of applications, including linking materials to nanoparticles and nanotubes, as well as in the attachment of imaging and therapeutic agents to molecules for biomedical indications.
- -
-
Page/Page column 26
(2012/05/20)
-
- FUSED PENTACYCLIC ANTI - PROLIFERATION COMPOUNDS
-
The present invention relates to novel compounds of formula (I) wherein X, Q, R1, R2, R3, R4, R5, R6, R7, R8, R21, R22 and R23 are as defined herein. The compounds of formula (I) are inhibitors of telomerase enzyme function and are accordingly useful for the treatment cellular proliferation disorders, such as cancer
- -
-
Page/Page column 51-52
(2013/02/28)
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- Stereoselective synthesis of deoxycarbaheptopyranose derivatives: 5a-carba-6-deoxy-α-dl-galacto-heptopyranose and 5a-carba-6-deoxy-α- dl-gulo-heptopyranose
-
Two new deoxycarbaheptopyranoses, 5a-carba-6-deoxy-α-dl-galacto- heptopyranose and 5a-carba-6-deoxy-α-dl-gulo-heptopyranose were prepared starting from cyclohexa-1,4-diene. The addition of dichloroketene to cyclohexa-1,4-diene followed by the subsequent reductive elimination and Baeyer-Villiger oxidation in turn led to the formation of a bicyclic lactone. Reduction of the lactone moiety followed by acetylation gave a diacetate with cis-configuration. The introduction of additional acetate functionality into the molecule was achieved by singlet oxygen ene-reaction. The formed hydroperoxide was reduced and then acetylated. The triacetate was further functionalized either by direct cis-hydroxylation using OsO4 or by epoxidation followed by a ring-opening reaction to give the title heptopyranose derivatives. One of the synthesized molecules, galacto-heptopyranose exhibited enzyme specific inhibition against α-glycosidase. On the other hand, they did not show any inhibition for α-amylase. However, both compounds, gulo-heptopyranose and galacto-heptopyranose increased the activity of α-amylase.
- Horasan Kishali, Nurhan,Doan, Dilem,?ahin, Ertan,Gunel, Aslihan,Kara, Yunus,Balci, Metin
-
experimental part
p. 1193 - 1200
(2011/03/22)
-
- Stereoelectronic factors in the stereoselective epoxidation of glycals and 4-deoxypentenosides
-
Glycals and 4-deoxypentenosides (4-DPs), unsaturated pyranosides with similar structures and reactivity profiles, can exhibit a high degree of stereoselectivity upon epoxidation with dimethyldioxirane (DMDO). In most cases, the glycals and their corresponding 4-DP isosteres share the same facioselectivity, implying that the pyran substituents are largely responsible for the stereodirecting effect. Fully substituted dihydropyrans are subject to a "majority rule", in which the epoxidation is directed toward the face opposite to two of the three groups. Removing one of the substituents has a variable effect on the epoxidation outcome, depending on its position and also on the relative stereochemistry of the remaining two groups. Overall, we observe that the greatest loss in facioselectivity for glycals and 4-DPs is caused by removal of the C3 oxygen, followed by the C5/anomeric substituent, and least of all by the C4/C2 oxygen. DFT calculations based on polarized-π frontier molecular orbital (PPFMO) theory support a stereoelectronic role for the oxygen substituents in 4-DP facioselectivity, but less clearly so in the case of glycals. We conclude that the anomeric oxygen in 4-DPs contributes toward a stereoelectronic bias in facioselectivity whereas the C5 alkoxymethyl in glycals imparts a steric bias, which at times can compete with the stereodirecting effects from the other oxygen substituents.
- Alberch, Laura,Cheng, Gang,Seo, Seung-Kee,Li, Xuehua,Boulineau, Fabien P.,Wei, Alexander
-
experimental part
p. 2532 - 2547
(2011/06/19)
-
- Investigation of the thermal and photochemical reactions of ozone with 2,3-dimethyl-2-butene
-
The matrix isolation technique, combined with infrared spectroscopy and twin jet codeposition, has been used to characterize intermediates formed during the ozonolysis of 2,3-dimethyl-2-butene (DMB). Absorptions of early intermediates in the twin jet experiments grew up to 200% upon annealing to 35 K. A number of these absorptions have been assigned to the elusive Criegee intermediate (CI) and secondary ozonide (SOZ) of DMB, transient species not previously observed for this system. Also observed was the primary ozonide (POZ), in agreement with earlier studies. The wavelength dependence of the photodestruction of these product bands was explored with irradiation from λ ≥ 220 to ≥580 nm. Merged jet (flow reactor) experiments generated "late" stable oxidation products of DMB. A recently developed concentric jet method was also utilized to increase yields and monitor the concentration of intermediates and products formed at different times by varying the length of mixing distance (d = 0 to -11 cm) before reaching the cold cell for spectroscopic detection. Identification of intermediates formed during the ozonolysis of DMB was further supported by 18O and scrambled 16,18O isotopic labeling experiments as well as theoretical density functional calculations at the B3LYP/6-311++G(d,2p) level.
- Coleman, Bridgett E.,Ault, Bruce S.
-
experimental part
p. 12667 - 12674
(2011/02/27)
-
- NUCLEOPHILIC FLUORINATION OF AROMATIC COMPOUNDS
-
Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18] fluoride ion derived from anhydrous [F- 18]KF/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me4NF, Et4NF, n-Bu4NF, (PhCH2)4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F- 18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.
- -
-
Page/Page column 7-8
(2010/04/03)
-
- Concerning the nucleophilic displacement of a methylsulfanyl group on substituted pyrimidinones
-
The nucleophilic displacement of a methylsulfanyl group (SMe) at the C2-position on a pyrimidin-4-one scaffold was achieved after oxidation into a methylsulfonyl group (SO2Me) using dimethyldioxirane (DMDO), a powerful electrophilic oxygen atom transfer agent. The introduction of amino groups as well as formation of carbon-carbon bonds was thus demonstrated. Georg Thieme Verlag Stuttgart.
- Kikelj, Vincent,Grosjean, Sylvain,Meslin, Jean-Claude,Julienne, Karine,Deniaud, David
-
experimental part
p. 2811 - 2815
(2010/10/19)
-
- NO-CARRIER-ADDED NUCLEOPHILIC [F-18] FLUORINATION OF AROMATIC COMPOUNDS
-
Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No- carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F- 18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F- 18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F- 18]fluoro-L-dopa.
- -
-
Page/Page column 20-21
(2010/11/03)
-
- Functionalization of iron oxide nanoparticles with a versatile epoxy amine linker
-
A synthetically diverse linker molecule consisting of both a terminal epoxide and a terminal amine has been synthesized and shown to have the desired reactivity. Proof of principle experimentation showed that the prepared linker molecule possessed the ability to be reactive towards dextran coated iron nanoparticles, essentially converting the surface alcohols to amines with an efficiency on average of 50 linkers per nanoparticle. Once the surface of the nanoparticles had been functionalized, the iron nanoparticles were subsequently functionalized with both folic acid and fluorescein isothiocyanate, with an average efficiency of 20 and 3 molecules per nanoparticle, respectively. The labeled nanoparticles were then incubated with both folate receptor positive and negative cell lines, which showed a preferential accumulation of the particles in the receptor positive cell line. In addition to the fluorescence based assays, accumulation of the nanoparticles was demonstrated using T2-weighted MRI imaging, which showed that the iron core of the nanoparticle was present within the desired cell line. Overall, this linker has shown the ability to functionalize the surface of nanoparticles and can theoretically be used to label a wide variety of other targeting agents or imaging agents for in vivo therapies or diagnostics. The Royal Society of Chemistry 2010.
- Nickels, Michael,Xie, Jingping,Cobb, Jared,Gore, John C.,Pham, Wellington
-
experimental part
p. 4776 - 4780
(2011/08/05)
-
- Iminohydantoin lesion induced in DNA by peracids and other epoxidizing oxidants
-
The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-lh) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-chloroperbenzoic acid (m-CPBA) and dimethyldioxirane (DMDO) as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT)(AACAA)] with DMDO. 2-lh has notbeen reported as an oxidative lesion at the level of single/double-stra nded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification, suggesting that 2-lh maybe a stable biomarker in vivo. The oxidation products have been structu rally characterized and the reaction mechanism has been probed by oxidation of the monomeric species dGuo, dGMP, and dGTP. DMDO selectively oxidizes the guanine moiety of dGuo, dGMP, and dGTP to 2-lh, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer throughrotation about the formamido C-N bond. Labeling studies with [ 18O 2 ]-m-CPBA and H 2 18 O to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring-opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-lh base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker.
- Ye, Wenjie,Sangaiah, R.,Degen, Diana E.,Gold, Avram,Jayaraj, K.,et al.
-
experimental part
p. 6114 - 6123
(2009/09/26)
-
- Preparation, X-ray structure, and oxidative reactivity of N-(2-iodylphenyl)tosylamides and 2-iodylphenyl tosylate: Iodylarenes stabilized by ortho-substitution with a sulfonyl group
-
(Chemical Equation Presented) New tosyl derivatives of 2-iodylaniline and 2-iodylphenol were prepared by the dimethyldioxirane oxidation of the corresponding 2-iodophenyltosylamides or 2-iodophenyl tosylate and isolated as stable, microcrystalline products. Single-crystal X-ray diffraction analysis of N-(2-iodylphenyl)-N,4-dimethylbenzenesulfonamide revealed pseudocyclic structure formed by intramolecular I...O interactions between the hypervalent iodine center and the sulfonyl oxygens in the tosyl group. This tosylamide has an excellent solubility in organic solvents and is a potentially useful hypervalent iodine oxidant.
- Mailyan, Artur K.,Geraskin, Ivan M.,Nemykin, Victor N.,Zhdankin, Viktor V.
-
supporting information; experimental part
p. 8444 - 8447
(2010/01/16)
-
- Palladium-catalysed enantioselective α-hydroxylation of β-ketoesters
-
Highly enantioselective α-hydroxylation of cyclic and acyclic 1,3-ketoesters can be achieved with up to 98% ee using a dicationic palladium(ii) catalyst and dimethyldioxirane as oxidant.
- Smith, Alexander M.R.,Billen, Denis,Hii, King Kuok
-
supporting information; experimental part
p. 3925 - 3927
(2010/01/06)
-
- Identification of a chromone-based retinoid containing a polyolefinic side chain via facile synthetic routes
-
Attempts to prepare substituted chromones as novel retinoids revealed that some chromones were unstable under Wadsworth-Horner-Emmons reaction conditions. Hence, Wittig reactions were used to prepare chromone-based compounds as potential retinoids. Firstly, Wittig reagents prepared from 3-bromomethyl-chromen-4-one were reacted with olefinic-aldehydes to provide the target compounds with all-trans side chains in good yield. The approach supplies a useful general route to structurally diverse chromone-based compounds possessing a variety of side chains. Sequential Wittig reactions were used also to prepare a chromone-based retinoid. These novel compounds were evaluated in binding assays and a high affinity RAR ligand was identified. Crystal structures obtained for two key precursors aided the interpretation of binding data.
- Sun, Weilin,Carroll, Patrick J.,Soprano, Dianne R.,Canney, Daniel J.
-
body text
p. 4339 - 4342
(2010/04/24)
-
- Syntheses of bipyridine-N-oxides and bipyridine-N,N'-dioxides
-
Dimethyldioxirane (DMD) was used to synthesize heterocyclic aromatic N-oxides enabling the product isolation and reaction solutions to be free of potentially dangerous peroxide intermediates. Additionally, this work combines important crystallographic, spectroscopic, and melting point data to shed light on inconsistent literature previously reported for the identity of 2,4'-bipyridine-N'-oxide.
- McKay,Lashlee III,Maina,Wheeler,Brown
-
experimental part
p. 181 - 188
(2010/07/05)
-
- Continuous Method For The Production Of A Dioxirane
-
Continuous processes comprising: oxidizing a ketone with a solution comprising active oxygen in a reactor in the presence of a buffer substance and a stripping gas to form a gas stream comprising a dioxirane and a liquid stream; and continuously drawing the gas stream comprising the dioxirane and the liquid stream from the reactor; wherein a liquid phase residence time of 1 minute to 4 hours and a normalized condensate mass flow rate of at least 500 g/mol of active oxygen are maintained.
- -
-
Page/Page column 4-5
(2008/12/07)
-
- An investigation by means of correlation analysis into the mechanisms of oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane in various solvents
-
Relative rate constants have been measured for the oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane in acetone, in mixtures of acetone with aprotic co-solvents of both higher and lower relative permittivity, and in aqueous acetone mixtures. Correlation analyses of the effects of substituents in the different solvents show that, with one exception, reactions take place via a single step mechanism in which the formation of the new SO bond and the elimination of acetone occur concertedly. The exception was oxidation of the sulfides in aqueous acetone containing the highest proportion of water of those studied (20% v/v). Here, the behaviour of the reaction is consistent with a two-step mechanism in which the oxidant reversibly attacks the sulfide to form an open-chain sulfonium betaine that subsequently fragments to sulfoxide and acetone. There is no evidence for the participation of an intermediate dioxathietane as has been found in the case of sulfide oxidations by (trifluoromethyl)methyldioxirane in CH2Cl2 and similar aprotic solvents. It is not justified to generalise a mechanism involving a betaine, with or without a derived dioxathietane, to the reactions of dimethyldioxirane in acetone. This journal is The Royal Society of Chemistry.
- Hanson, Peter,Hendrickx, Ramon A.A.J.,Smith, John R. Lindsay
-
p. XX745-761
(2008/09/17)
-
- Synthesis of epi-oxetin via a serine-derived 2-methyleneoxetane
-
(Chemical Equation Presented) The unique reactivity of 2-methyleneoxetanes and 1,5-dioxaspiro[3.2]hexanes has been exploited for the synthesis of epi-oxetin (26), an oxetane-containing β-amino acid. While the preparation of the natural product oxetin (1) was the original goal, the unexpected diastereoselectivity of an precedented reduction provided the epi-oxetin framework. The methodology described herein should be amenable for the preparation of oxetin with a change in nitrogen protection.
- Blauvelt, Marisa L.,Howell, Amy R.
-
p. 517 - 521
(2008/09/17)
-