- Synthesis of six-membered carbocyclic ring α,α-disubstituted amino acids and arginine-rich peptides to investigate the effect of ring size on the properties of the peptide
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Cell-penetrating peptides (CPPs) have been attracting attention as tools for intracellular delivery of membrane-impermeant functional molecules. Among the variety of CPPs that have been developed, many are composed of both natural and unnatural amino acids. We previously synthesized α,α-disubstituted α-amino acids (dAAs) containing a five-membered carbocyclic ring in its side chain and revealed the utility of dAAs for the development of novel CPPs. In the present study, we designed a six-membered carbocyclic ring dAA with an amino group on the ring and introduced it into arginine (Arg)-rich peptides to further investigate the value of dAAs for developing CPPs. We also assessed the effects of the size of the dAA carbocyclic ring on cellular uptake of dAA-containing peptides. The stability of the peptide's secondary structure and its membrane permeability were both greater in dAA-containing peptides than in an Arg nonapeptide. However, the number of carbon atoms in the dAA side chain ring had little effect. Nevertheless, these results show the utility of cyclic dAAs in the design of novel CPPs containing unnatural amino acids.
- Asano, Akiko,Doi, Mitsunobu,Iwanari, Kazuki,Kato, Takuma,Kita, Yuki,Oba, Makoto,Tanaka, Masakazu
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- Efficient synthesis of 1,3,5-oxygenated synthons from dimethyl 3-oxoglutarate: First use of borane-dimethyl sulfide complex as a regioselective reducing agent of 3-oxygenated glutarate derivatives
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The selective reduction of dimethyl 3-oxoglutarate was accomplished in different levels. A high yielding sodium borohydride reduction of the keto group is fully described leading to dimethyl 3-hydroxyglutarate. When borane-dimethyl sulfide (BMS) complex was used, a diol or a triol compound can be obtained by selective or total reduction of 3-hydroxy-or 3-oxoglutarate, respectively, allowing an efficient and practical route to 1,3,5-oxygenated compounds.
- Riatto, Valéria B.,Carneiro, Maria N. M.,Carvalho, Venília B.,Victor, Mauricio M.
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Read Online
- Synthetic Access to Benzimidacarbocyanine Dyes to Tailor Their Aggregation Properties
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Developing structure-aggregation relationships of cyanine dyes is crucial for controlling their optical properties for various uses. This study develops a synthetic route and the structure-dependent self-assembly of a family of benzimidacarbocyanine dyes for J- or H-aggregation properties. It was found that both the presence and placement of halogen atoms play a defining role in the resulting supramolecular interactions of these compounds.
- Heyne, Belinda,Press, David J.,Roth, Sophia M.,Sutherland, Todd C.
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p. 8641 - 8651
(2021/07/19)
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- Method for preparing silicon compounds
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The invention provides a method for preparing silicon compounds, and belongs to the field of chemical synthesis. The method for preparing the silicon compounds comprises the following processes that citric acid is used as a raw material for performing oxidative decarboxylation to obtain a compound 1,3-acetone dicarboxylic acid; esterification reaction is carried out to obtain a compound 1,3-acetone dicarboxylic acid dimethyl ester; catalytic hydrogenation reduction is carried out to obtain a compound 3-hydroxyglutaric acid dimethyl ester; etherification reaction is carried out to obtain a compound3-tertiary butyl dimethyl siloxy dimethyl glutarate; saponification, dehydration and purification are carried out to obtain 3-tert-butyl-dimethylsiloxyglutaric anhydride; and a catalyst for catalytic hydrogenation is Cu/ZnO/Al2O3 prepared by a precipitation reduction method. According to the method for preparing the silicon compounds, the catalyst for catalytic hydrogenation is optimized, so that in the hydrogenation reduction reaction, the hydrogenation activity of a Cu catalyst is significantly improved, the selectivity is increased, and the generation of by-products is reduced; and theproduct yield and purity are significantly improved by recrystallization with a mixed solvent.
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- Intramolecular functional group differentiation as a strategy for the synthesis of bridged bicyclic β-amino acids
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Differentiation of identical electrophilic functional groups (carboxylates) by a strategically placed internal nucleophile (an amino group) in cyclic precursors was used as a key general approach to functionalized azabicyclic scaffolds. The utility of the method was demonstrated by the synthesis of three bicyclic β-amino acids (analogues of nipecotic acid), which were prepared in good yields and on a relatively large scale.
- Tymtsunik, Andriy V.,Kokhan, Serhii O.,Ivon, Yevhen M.,Komarov, Igor V.,Grygorenko, Oleksandr O.
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p. 22737 - 22748
(2016/03/26)
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- Synthesis and anti-tubercular activity of 2-nitroimidazooxazines with modification at the C-7 position as PA-824 analogs
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Tuberculosis (TB) is a major global health problem, and new drug targets and scaffolds need to be identified to combat the emergence of drug resistant TB. The nitroimidazooxazine PA-824 represents a new class of bio-reductive drug to treat TB. In this study we report a 2-nitroimidazooxazine derivative with modification at the C-7 position that exhibited better activity than PA-824 against Mycobacterium tuberculosis (Mtb) H37Rv strain in vitro. From 7a as a key intermediate, we functionalized with benzyl ether (8), phenyl ether (9), benzyl carbonate (10) and benzyl carbamate (11). Among the 23 compounds produced, 8a-R (MIC = 0.078 μM) with trifluoromethoxy benzyl group was 5-fold more potent than PA-824 (MIC = 0.390 μM) in the in vitro assays against the wild-type Mtb, and the phenyl ether compound 9g-R (MIC = 0.050 μM) exhibited the most potent antimycobacterial activity.
- Kang, Young-Goo,Park, Chan-Yong,Shin, Hongsuk,Singh, Ramandeep,Arora, Garima,Yu, Chan-Mo,Lee, Ill Young
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supporting information
p. 3650 - 3653
(2015/08/06)
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- Amidine dications as superelectrophiles
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2-Dimethylalkylammonium pyridinium and 2-dimethylalkylammonium pyrimidinium ditriflate salts are very powerful methylating agents toward phosphorus (triphenylphosphine) and nitrogen (triethylamine) nucleophiles. In competition experiments with triethylamine as nucleophile, these N-methyl disalts are more reactive methylating agents than dimethyl sulfate. Reaction of the pyridinium dications with water as an oxygen nucleophile leads to attack at the 2-position of the heteroaromatic ring and displacement of an ammonium group; 2-hydroxypyridinium compounds are formed in the first instance, which are easily converted to 2-pyridones. Extending the scope of the reactions, a tricationic 2,6-bis(dimethylalkylammonium) pyridinium salt has also been prepared and characterized and its reactivity as a methylating agent assessed in comparison with that of the dications.
- Corr, Michael J.,Roydhouse, Mark D.,Gibson, Kirsty F.,Zhou, Sheng-Ze,Kennedy, Alan R.,Murphy, John A.
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supporting information; experimental part
p. 17980 - 17985
(2010/04/01)
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- Dual macrolactonization/pyran-hemiketal formation via acylketenes: Applications to the synthesis of (-)-callipeltoside A and a lyngbyaloside B model system
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Two for one: Thermal generation of acylketenes in diol-containing substrates results in the title transformation. This transformation expands the scope of acylketene macrolactonizations and their application to the synthesis of complex macrolides. Triol and tetraol substrates have also been cyclized in highly regioselective fashion. Additionally, the challenging macrolactonization of a tertiary alcohol was achieved. (Chemical Equation Presented).
- Hoye, Thomas R.,Danielson, Michael E.,May, Aaron E.,Zhao, Hongyu
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supporting information; experimental part
p. 9743 - 9746
(2009/05/30)
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- Scandium triflate catalyzed transesterification of carboxylic esters
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The direct transesterification of carboxylic esters is efficiently catalyzed with Sc(OTf)3 (10 mol%) in boiling alcoholic solvent. Methyl, ethyl, isopropyl, and allyl esters were prepared from a broad range of different substrates in high yields. The application of microwave irradiation led to significantly reduced reaction times. Georg Thieme Verlag Stuttgart.
- Remme, Nicole,Koschek, Katharina,Schneider, Christoph
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p. 491 - 493
(2007/12/27)
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- Optical resolution of 3-(silyloxy)glutaric acid half esters and their utilization for enantioconvergent synthesis of a HMG-CoA reductase inhibitor
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Useful chiral synthons, (3R)- and (3S)-[(tert- butyldimethylsilyl)oxy]pentanedioic acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from (S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and (S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.
- Konoike, Toshiro,Okada, Tetsuo,Araki, Yoshitaka
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p. 3037 - 3040
(2007/10/03)
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- Nonionic superbase-catalyzed silylation of alcohols
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Herein we report a very effective and mild procedure for the silyl protection of a wide variety of substrate alcohols, including primary, secondary, allylic, propargylic, benzylic, hindered secondary, tertiary, acid-sensitive, and base-sensitive alcohols and also hindered phenols. The silylation reagent used is tert-butyldimethylsilyl chloride (TBDMSCl) and the catalyst is P(MeNCH2CH2)3N, 1b, both of which are commercially available. The reactions are carried out in acetonitrile from 24 to 40 °C and on rare occasions in DMF from 24 to 80 °C. The effect of solvent, catalyst concentration, and temperature and reaction time on the silylation of alcohols and the excellent compatibility of our method with a variety of functional groups is discussed. An efficient method for recycling the catalyst is also presented. Although representative primary alcohols, secondary alcohols, and phenols were silylated using the more sterically hindered reagent tert-butyldiphenylsilyl chloride (TBDPSCl) in the presence of lb as a catalyst, tertiary alcohols were recovered unchanged.
- D'Sa, Bosco A.,McLeod, Dale,Verkade, John G.
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p. 5057 - 5061
(2007/10/03)
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- Synthesis of macrocyclic polyhydroxy tetralactams derived from L-tartaric acid and β-hydroxyglutaric acid
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The synthesis of new 16-, 18-, 19- or 20-membered secondary tetralactams with L-tartaric acid or β-hydroxyglutaric acid moieties is investigated. The stepwise synthesis with an intermediate diamide diamine provides overall good yields (30-55%) compared with other processes using an intermediate diamide diacid or direct macrocyclization. This synthetic pathway leads to symmetrical or unsymmetrical polyhydroxytetralactams with variable hydroxyl group number. Use of mild acylating agents in this approach allows to avoid the protection-deprotection steps of hydroxyl groups.
- Arnaud, Nathalie,Picard, Claude,Cazaux, Louis,Tisnes, Pierre
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p. 13757 - 13768
(2007/10/03)
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- Reduction of 2-Substituted 3-Oxoglutarates Mediated by Baker's Yeast. Variation in Enantioselectivity without Corresponding Variation in Diastereoselectivity
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The reduction of 2-substituted 3-oxoglutarates by yeast yields a new class of chiral building blocks, 2-allyl- and 2-propargyl-3-hydroxyglutarates.These are useful as starting points for the synthesis of, inter alia, branched chain analogs of sugars and nucleosides.When allyl is the side chain, the principal product has the absolute configuration (2S,3S), proven by correlation with a compound whose absolute configuration was established by crystallography.Several features of this yeast-mediated reduction are noteworthy.First, its diastereoselectivity is higher than its enantioselectivity, especially with the propargyl side chain.Further, with all substrates, variation in enantioselectivity is not manifested by a variation in diastereoselectivity.This example therefore serves as a warning for those using yeast-mediated reactions that diastereoselectivity cannot be accepted as a substitute for direct measurements of enantioselectivity, even with analogous substrates and similar reaction conditions.Finally, an unexpected metabolism of impurities in the starting material by the yeast made the overall transformation preparatively useful.
- Arslan, Tuncer,Benner, Steven A.
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p. 2260 - 2264
(2007/10/02)
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- SYNTHESIS OF (-)-TALAROMYCINS A AND B
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Highly enantiomerically pure (-)-talaromycins A and B undecane> were synthesized starting from chiral building blocks of microbial origin.
- Mori, Kenji,Ikunaka, Masaya
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- Azotized emetine analogues: synthesis and evaluation of the anti-amebic and anti-tumoral action of aza-3 emetine and attempted synthesis of aza-2 emetine
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The synthesis of the N,N-bis-(acetylhomoveratrylamido)-1-hydroxymethyl and 1-carboxypropylamines (III a) and (III b) is described. Until now, these molecules could not been cyclized to the corresponding isoquinoline compounds. An attempted synthesis of 3-azaemetine by condensing homoveratrylamine with acetonedicarboxylic acid or its esters did not yield the expected diamide (XIV). However, by subjecting 1,3-bis-(1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)acetone (XV) to a reducing aminoalkylation, one obtained the corresponding ethylamino derivative (XVI) which could be cyclized through Mannich reaction to give 3-azaemetine. The pharmacological screening showed 3-azaemetine to be less toxic than emetine in the mouse and without antiamebic and antitumor activity against P 388 Leukaemia in the mouse (25).
- Gilbert,Gansser,Viel,Cavier,Chenu,Hayat
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p. 237 - 252
(2007/10/05)
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