- Efficient conversion of D-mannitol into 1,2:5,6-diacetonide with Aquivion-H as a recyclable catalyst
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Heterogeneous solid catalysis by the commercially available perfluorosulfonic ionomer Aquivion-H allowed 1,2:5,6-diacetonide of D-mannitol (1), immediate precursor of important unichiral C3-synthons, to be efficiently obtained from D-mannitol and 2,2-dimethoxypropane in DMF at room temperature. The 1,2-monoacetonide, whose intermediate formation is the rate-limiting step, could be almost completely converted into 1 with limited concurrent transformation of 1 into triacetonides. In line with recent literature reports, these results indicate that heterogeneous catalysis by Aquivion-H surpasses the performances of homogeneous acidic catalysis assuring, presumably for its peculiar morphology, a higher product selectivity. Easy recovery at the end of the reaction and recyclability are additional advantages of this solid acid catalyst.
- Bolchi, Cristiano,Appiani, Rebecca,Roda, Gabriella,Bertolini, Valentina,Arnoldi, Sebastiano,Pallavicini, Marco
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- ISOPROPYLIDENATION OF D-MANNITOL UNDER NEUTRAL CONDITIONS
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Isopropylidenation of D-mannitol (2) under neutral conditions, by treatment with 2,2-dimethoxypropane in 1,2-dimethoxyethane, is described. 1,2:5,6-Di-O-isopropylidene-D-mannitol is the main equilibrium product, which does not undergo further substitution under the conditions used. 1,2:3,4:5,6-Tri-O-isopropylidene-D-mannitol, the other major product, was shown to be derived mainly from initial 3,4-substitution of 2.The presence of a difunctional ether, of suitable geometry, is a necessary requirement for the reaction.Some mechanistic aspects of the reaction are discussed.
- Chittenden, Gordon J. F.
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- Synthesis of d-mannitol substituted ether-linked bis-1,2,3-triazoles as models of gemini surfactants
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Readily available and low cost D-mannitol was converted into 1,2,5,6-di-O-isopropylidene-D-mannitol (1) in the presence of acetone and zinc chloride. Williamson etherfication of 1 with propargyl bromide afforded the bisalkyne 2 in a very good yield. 1,3-Dipolar cycloaddition of 2 with four different alkyl azides using click conditions gave four novel bistriazoles 3a-d. Removal of the acetal groups of 3a-d afforded the deprotected bistriazoles 4a-d in excellent yields. Products 3 and 4 represent models of gemini surfactants.
- Mohammed, Adnan Ibrahim,Abboud, Zaid Hassan,Alghanimi, Atheer Hamed Odda
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- Total synthesis of diastereomeric marine butenolides possessing a syn-aldol subunit at C10 and C11 and the related C11-ketone
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Two diastereomeric marine butenolides, (4S,10R,11R)- and (4S,10S,11S)-4,11-dihydroxy-10-methyldodec-2-en-1,4-olide, possessing a syn-aldol subunit at C10 and C11 have been efficiently synthesized by using a three-module coupling strategy. The enantiomeric syn-aldol modules prepared by the syn-selective aldol reaction of the norephedrine-derived chiral propionates were coupled with the chiral C3-C7 module via 1,3-dithiane bisalkylation. The butenolide ring was then installed via a high-yielding ring-closing metathesis (RCM) reaction. Oxidation of the diastereomeric C11-alcohols furnished the corresponding C11-ketones, which are produced by the same marine microorganism.
- Wang, Yan,Dai, Wei-Min
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- Synthesis and properties of bio-based polyurethanes bearing hydroxy groups derived from alditols
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Four kinds of bio-based polyurethanes bearing hydroxy groups in the pendants were synthesized by the polyaddition of D-mannitol- and D,L-erythritol-derived diols (1,2:5,6-di-O-isopropylidene-D-mannitol and 1,2-O-isopropylidene-D,L-erythritol) with hexamethylene diisocyanate and methyl (S)-2,6-diisocyanatohexanoate and the subsequent deprotection of the isopropylidene groups. They were hydrolyzed much more quickly than the corresponding protected polyurethanes at 50 °C and pH 7.0, although their hydrolytic degradation rate was lower than that of polyurethanes with saccharic and glucuronic lactone groups, which had been reported in our previous articles. The introduction of D-mannitol units to the polyether-polyurethanes containing poly(oxytetramethylene) glycol units also enhanced their hydrolyzibility.
- Hashimoto, Kazuhiko,Hashimoto, Naoya,Kamaya, Takehiko,Yoshioka, Junya,Okawa, Haruki
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- Studies on a catalytic version of the Matteson asymmetric homologation reaction
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Studies of a catalytic asymmetric version of the Matteson reaction between dichloromethylboronates and organolithium reagents have been undertaken. From several different chiral catalytic systems studied, only one based on a mannitol derivative has given substantial asymmetric induction close to that previously achieved with a bis(oxazoline) derivative and ytterbium triflate. More detailed study of the latter reaction revealed that fresh ytterbium triflate actually reduced the level of asymmetric induction, while "aged"ytterbium triflate, or a fresh sample that had been treated with water, brought about improved induction. The implications of these findings are discussed.
- Smith, Keith,Saleh, Basil A.,Alshammari, Mohammed B.,El-Hiti, Gamal A.,Elliott, Mark C.
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supporting information
p. 4279 - 4284
(2021/05/31)
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- Novel cytotoxic amphiphilic nitro-compounds derived from a synthetic route for paraconic acids
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A series of precursors for bioactive paraconic acids (PA) were synthesized and their cytotoxicity assessed on human cells in vitro. Two amphiphilic nitro-containing precursors, Nitro-C15-EED and the butanolide Nitro-C12-GBL, were cytotoxic at the micromolar scale, with higher activity on tumor HeLa cells than on HEK-293T of non-tumor origin. The structure of these molecules is simple but different from reported bioactive nitro compounds. Nitro-C12-GBL was generally more cytotoxic, but after short-term (2 h) exposure both compounds reached maximum cytotoxicity. At 72 h post-treatments of HeLa cells the final dose-response for Nitro-C12-GBL (LC50 = 21.9 μmol L?1) was close to that for Nitro-C15-EED (LC50 = 25.3 μmol L?1), corresponding to LC50s ~ 3–3.6 times lower than those on HEK-293T. Short-term treatments with 50 μmol L?1 of these compounds promoted comparable outcomes, reducing tumor cells viability up to 27–36% of the controls and preserving ~70% of HEK-293T viability at 72 h post-treatments. Reduced cytotoxicity was observed in cultures continuously exposed to the compounds for longer periods (24–72 h), especially on tumor cells, underlining short-term treatments as alternatives to antiproliferative strategies. Due to their amphiphilic nature, these compounds show spontaneous surface activity and adsorption onto Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), especially Nitro-C12-GBL. The effects on DPPC monolayers are indicative of a possible physiological action that depends on the interaction with the cell membranes. Coarse-grained molecular dynamics indicate that individualized molecules of Nitro-C15-EED and the less toxic PA precursors are susceptible to trapping into phospholipid films. In contrast, Nitro-C12-GBL consistently forms large aggregates with outward polar domains, which could favor interaction with phospholipid polar heads of biological membranes.
- Ribeiro, Talita A.,Machado-Ferreira, Erik,Guimar?es, Lohaine F.,Cavaleiro, Jéssica,Britto, Alan Messala A.,Redua, Nátaly,de Souza, Lucas Miguel Pereira,Pimentel, André S.,Picciani, Paulo H.S.,Oliveira, Osvaldo N.,Barreto, Cléber Bonfim,Soares, Carlos Augusto G.
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- Nitrosocarbonyl Carbohydrate Derivatives: Hetero Diels-Alder and Ene Reaction Products for Useful Organic Synthesis
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The generation and trapping of two new nitrosocarbonyl intermediates bearing carbohydrate-based chiral substituents is achieved by the mild oxidation of the corresponding nitrile oxides with tertiary amine N -oxides. Their capture with suitable dienes and alkenes afforded the corresponding hetero Diels-Alder cycloadducts and ene adducts from fair to excellent yields. The entire methodology looks highly promising by the easy conversion of aldoximes into hydroxymoyl halides, widening the access to nitrosocarbonyls, versatile tools in organic synthesis.
- Corti, Marco,Leusciatti, Marco,Moiola, Mattia,Mella, Mariella,Quadrelli, Paolo
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p. 574 - 586
(2020/10/06)
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- Design and preparation of a novel prolinamide-based organocatalyst for the solvent-free asymmetric aldol reaction
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The preparation of four novel organocatalysts as highly diastereo and enantioselective catalysts for the solvent-free asymmetric aldol reaction was described. These organocatalysts were synthesized in eight steps applying simple and commercially available starting materials. The best results were obtained for the proline-derived catalyst, providing access to the desired adducts in up to 95% yield, 1:19 syn/anti and 98% e.e. Moreover, even sterically bulky aldehydes and substituted cyclohexanones were well tolerated. DFT calculations and control experiments indicated that several hydrogen bonding interactions between the aldehyde and the enamine intermediate are responsible for the stereoselective chiral induction process and that the trifluoroacetate counter-anion is crucial for the attainment of higher stereoselectivities.
- Martins, Rafaela de S.,Pereira, Mathias P.,de Castro, Pedro P.,Bombonato, Fernanda I.
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- Stereocontrolled Synthesis of Tetrafluoropentanols: Multivicinal Fluorinated Alkane Units for Drug Discovery
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A stereodivergent synthesis of four diastereomeric 2,3,4,5-tetrafluoropentanols is disclosed. X-ray crystallographic analysis reveals conformations that manifest sequential stereoelectronic gauche effects (σC-H/C → σC-F*), thereby generating topological diversity via subtle C(sp3)-H to C(sp3)-F exchange. Two representative tetrafluoro arrays have been incorporated into truncated analogues of Gilenya for the management of relapsing remitting multiple sclerosis. These closely similar multivicinal fluoroalkanes have notably different physicochemical profiles and were found to be stable in the presence of human microsomes.
- Bentler, Patrick,Erdeljac, Nathalie,Bussmann, Kathrin,Ahlqvist, Marie,Knerr, Laurent,Bergander, Klaus,Daniliuc, Constantin G.,Gilmour, Ryan
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supporting information
p. 7741 - 7745
(2019/09/03)
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- Iminosugars: Effects of stereochemistry, ring size, and n-substituents on glucosidase activities
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N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus. Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs. Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides. The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 μM and 138 μM, respectively, using DNJ as reference (IC50 134 μM). On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 μM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 μM). Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 μM) of the corresponding D-gluco-piperidine miglustat drug (40a). Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 μM.
- Zamoner, Luís O. B.,Arag?o-Leoneti, Valquiria,Carvalho, Ivone
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- Synthesis and Structure-Activity Relationship Studies of Anti-Inflammatory Epoxyisoprostane Analogues
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The lactone derivative of the epoxyisoprostane EC is a highly effective inhibitor of the secretion of the proinflammatory cytokine IL-6. Herein, a modular synthesis of analogues is described, allowing flexible variations of the cyclic side chain of the parent lactone. A structure-activity relationship study identified a lactam analogue that retains the high activity. Furthermore, the exocyclic allylic alcohol was shown to be crucial for the observed effect.
- Wolleb, Helene,Ogawa, Seiji,Schneider, Michael,Shemet, Andrej,Muri, Jonathan,Kopf, Manfred,Carreira, Erick M.
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p. 3014 - 3016
(2018/05/28)
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- Diverted total synthesis of melodorinol analogues and evaluation of their cytotoxicity
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A series of melodorinol analogues were synthesized via a diverted total synthesis approach, leading to structural modifications on several regions of the molecule. Their cytotoxicity was evaluated against five human cancer cell lines (KB, HeLa-S3, MCF-7, HT-29 and A549). Structure-activity relationship studies revealed key parameters that affect the cytotoxicity. In particular, the novel 4-bromo-furanone analogues exhibited greater cytotoxicity compared to the corresponding non-brominated analogues. The stereochemistry at C-6 and the nature of acyl substituents on the C-6 and C-7 hydroxyl groups also play an important role. The most potent analogues exhibit approximately 15-fold higher cytotoxicity towards KB and HeLa-S3 than melodorinol and also show exceptionally high potency against MCF-7, HT-29 and A549 cell lines.
- Khotavivattana, Tanatorn,Khamkhenshorngphanuch, Thitiphong,Rassamee, Kitiya,Siripong, Pongpun,Vilaivan, Tirayut
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p. 2711 - 2715
(2018/06/12)
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- Assignment of the relative and absolute stereochemistry of two novel epoxides using NMR and DFT-GIAO calculations
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Considering the potential biological application of isobenzofuranones, especially as agrochemical defensives, two novel epoxides, (1aR,2R,2aR,5S,5aS,6S,6aS)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (9), and (1aS,2S,2aR,5S,5aS,6R,6aR)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (10), were synthesized from the readily available D-mannitol in six steps. The multiplicities of the hydrogens located at the bridge of the bicycle are distinct for epoxides 9 and 10 due to W coupling, and this feature was employed to confirm the assignment of these nuclei. Besides analyses of the 2D NMR spectra, the assignments of the nuclei at the epoxide ring were also inferred from information obtained by theoretical calculations. The calculated 1H and 13C NMR chemical shifts for eight candidate structures were compared with the experimental chemical shifts of 9 and 10 by measuring the mean absolute errors (MAE) and by the DP4 statistical analysis. The structures and relative configurations of 9, and 10 were determined via NMR spectroscopy assisted with theoretical calculations. As consequence of the enantioselective syntheses starting from a natural polyol, the absolute configurations of the epoxides 9 and 10 were also defined.
- Moraes,Alvarenga,Demuner,Viana
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p. 109 - 115
(2018/05/03)
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- Preparation method of diacetone-D-mannitol
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The invention relates to a preparation method of diacetone-D-mannitol, belongs to the technical field of medicine synthesizing, and aims at solving the problems of existing byproduct influence and lowyield. The method comprises the following step: reacting D-mannitol and 2, 2-dimethoxy propane in a dioxane solvent in the presence of a pyridinium catalyst, thus obtaining the corresponding productwhich is the diacetone-D-mannitol. According to the method, the synthesizing route has the advantage of being high in selectivity on products; byproducts can be effectively avoided and decreased; theraw material conversion rate can be increased; and the product yield and the purity is high.
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Paragraph 0024-0036; 0037; 0038; 0039
(2018/09/12)
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- 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound and synthesizing method and application thereof
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The invention discloses a 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound. The 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound is shown as a general formula in the specification, wherein R1 refers to hydrogen or ethyl, and R2 refers to a benzene ring, a benzene ring derivative, a heterocyclic ring or fatty hydrocarbon. Biological activity test experiments prove that the 1,3-dimethyl-7-substituted quinazoline-2,4-dione fluorine-containing amide compound shows good inhibiting activity for Monilia albicans, Cryptococcus neoformans and Aspergillus fumigates, is remarkable in chitin synthetase inhibiting activity and good in antibacterial effect and can be used for preparing drugs for resisting pathogenic microorganisms.
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Paragraph 0041; 0042; 0043
(2017/07/31)
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- Geldanamycin-inspired compounds induce direct trans-differentiation of human mesenchymal stem cells to neurons
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Inspired from geldanamycin, the synthesis of a new series of 20-membered macrocyclic compounds is developed. The key features in our design are (i) retention of the fragment having the precise chiral functional groups of geldanamycin at C10, C11, C12 and C14, and (ii) replacement of an olefin moiety with the ester group, and the quinoid sub-structure with the triazole ring. The southern fragment needed for the macrocyclic ring formation was obtained from Evans' syn aldol as the key reaction and with the use of D-mannitol as the cheap source of a chiral starting material. For the synthesis of the northern fragment, we utilized L-ascorbic acid, which provided the desired chiral functional groups at C6 and C7. Further, the chain extension completed the synthesis of the northern fragment. In our approach, the crucial 20 membered macrocyclic ring was formed employing the click chemistry. When tested for their ability to directly trans-differentiate human mesenchymal stem cells to neurons, two novel compounds (20a and 7) from this series were identified and this was further validated by the presence of specific neuronal biomarkers (i.e. nestin, agrin and RTN4).
- Jogula, Srinivas,Soorneedi, Anand Ram,Gaddam, Jagan,Chamakuri, Srinivas,Deora, Girdhar Singh,Indarapu, Ranjith Kumar,Ramgopal, Murali Krishna,Dravida, Subhadra,Arya, Prabhat
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supporting information
p. 110 - 116
(2017/04/26)
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- Preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone
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The invention discloses a preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method comprises the following steps: subjecting a starting raw material D-mannitol to acetone protection and sodium periodate oxidation; then subjecting the treated D-mannitol and a self-made ylide reagent to the Witting reaction; then carrying out selective oxidation by using an aqueous sodium permanganate solution; then successively carrying out sulfonylation, fluorination with potassium fluoride, and ring closing with a concentrated protective group protective group; protecting the hydroxyl group by using benzoyl chloride; and then carrying out purification so as to obtain the final product 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method provided by the invention uses easily available and cheap raw materials, so production cost is greatly reduced; and the operation of the preparation method is coherent and simple, and the quantity of waste gas, waste water and industrial residues is lower than the quantity of waste gas, waste water and industrial residues reported in the prior art.
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Paragraph 0030; 0048
(2017/06/02)
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- Studies towards the synthesis of secoiridoids
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A new approach to secoiridoids, based on the synthesis of the key functionalized intermediates 4 and 5, is presented. These compounds were tested in formal [3+3] cycloadditions. Acyl-chloride 15 was transformed into enol α,β-unsaturated ester 16, which was involved in a N-heterocyclic carbene rearrangement to give an advanced precursor 17 in the total synthesis of secoiridoids.
- Wu, Shaoping,Zhang, Yongmin,Agarwal, Jyoti,Mathieu, Emilie,Thorimbert, Serge,Dechoux, Luc
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p. 7663 - 7669
(2015/09/07)
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- Syntheses of 2-keto-3-deoxy-D-xylonate and 2-keto-3-deoxy-L-arabinonate as stereochemical probes for demonstrating the metabolic promiscuity of sulfolobus solfataricus towards D-xylose and L-arabinose
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Practical syntheses of 2-keto-3-deoxy-D-xylonate (D-KDX) and 2-keto-3-deoxy-L-arabinonate (L-KDA) that rely on reaction of the anion of ethyl 2-[(tert-butyldimethylsilyl)oxy]-2-(dimethoxy phosphoryl) acetate with enantiopure glyceraldehyde acetonide, followed by global deprotection of the resultant O-silyl-enol esters, have been developed. This has enabled us to confirm that a 2-keto-3-deoxy-D-gluconate aldolase from the archaeon Sulfolobus solfataricus demonstrates good activity for catalysis of the retro-aldol cleavage of both these enantiomers to afford pyruvate and glycolaldehyde. The stereochemical promiscuity of this aldolase towards these enantiomeric aldol substrates confirms that this organism employs a metabolically promiscuous pathway to catabolise the C5-sugars D-xylose and L-arabinose.
- Archer, Robert M.,Royer, Sylvain F.,Mahy, William,Winn, Caroline L.,Danson, Michael J.,Bull, Steven D.
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supporting information
p. 2895 - 2902
(2013/03/28)
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- Microwave assisted synthesis of new heterocyclic compounds: 1,2,3-triazoles and tetrazoles and study of their biological activity
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The work includes synthesis of 1,2,3-triazoles via click conditions and using the microwave irradiation starting from two synthesized azides: 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide (5) and perfluorobutylethyl azide (10) and different terminal alkynes. It also includes microwave enhanced synthesis of tetrazoles via the reaction of two synthesized azides i.e., perfluorobutylethyl azide (10) and 1,5-diazidopentane (13) with benzoyl cyanide. Most of the prepared compounds have been characterized by: TLC, FT-IR, 1H NMR, 13C NMR, LC-MS and microelemental analysis.
- Mohammed, Adnan I.,Dawood, Ashour H.,Ali, Khalid F.,Al-Mosawi, Mohsen
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p. 5592 - 5596,5
(2020/09/15)
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- Synthesis of modified peptidoglycan precursor analogues for the inhibition of glycosyltransferase
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The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis. The more active was C16-phosphoglycerate-MurNAc-(l-Ala-d-Glu)-GlcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.
- Dumbre, Shrinivas,Derouaux, Adeline,Lescrinier, Eveline,Piette, Andre,Joris, Bernard,Terrak, Mohammed,Herdewijn, Piet
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supporting information; experimental part
p. 9343 - 9351
(2012/07/14)
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- Total synthesis of (-)-cleistenolide
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An efficient and short total synthesis of (-)-cleistenolide (1) from D-mannitol with an overall yield of 23.6% is described. The chiron approach for the synthesis of (-)-cleistenolide involves a one-C-atom Wittig olefination, a selective allylic triethylsilyl protection, and a Grubbs-catalyzed ring-closure-metathesis (RCM) reaction as the key steps. Copyright
- Chanti Babu, Dokuburra,Ashalatha, Kankati,Rao, Chitturi Bhujanga,Jondoss, Jon Paul Selvam,Venkateswarlu, Yenamandra
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scheme or table
p. 2215 - 2220
(2012/01/31)
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- Synthesis and bioluminescence-inducing properties of autoinducer (S)-4,5-dihydroxypentane-2,3-dione and its enantiomer
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The autoinducer (4S)-4,5-dihydroxypentane-2,3-dione ((S)-DPD, AI-2) facilitates chemical communication, termed 'quorum sensing', amongst a wide range of bacteria, The synthesis of (S)-DPD is challenging in part due to its instability. Herein we report a novel synthesis of (S)-DPD via (2S)-2,3-O-isopropylidene glyceraldehyde, through Wittig, dihydroxylation and oxidation reactions, with a complimentary asymmetric synthesis to a key precursor. Its enantiomer (R)-DPD, was prepared from d-mannitol via (2R)-2,3-O-isopropylideneglyceraldehyde. The synthesized enantiomers of DPD have AI-2 bioluminescence-inducing properties in the Vibrio harveyi BB170 strain.
- Kadirvel, Manikandan,Stimpson, William T.,Moumene-Afifi, Souad,Arsic, Biljana,Glynn, Nicola,Halliday, Nigel,Williams, Paul,Gilbert, Peter,McBain, Andrew J.,Freeman, Sally,Gardiner, John M.
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supporting information; experimental part
p. 2625 - 2628
(2010/07/13)
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- An efficient and enantioselective total synthesis of naturally occurring L-783277
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Naturally occurring L-783277 which belongs to 14-membered resorcylic acid lactones (RALs) turned out to be a potent kinase inhibitor against MEK (MAP kinase kinase). We successfully accomplished efficient and enantioselective total synthesis of L-783277 based on convergent assembly of one aromatic unit and two chiral building blocks with efficient orthogonal protection-deprotection strategy. Three key steps composed of olefin cross metathesis, addition of acetylene derivative to aldehyde, and Yamaguchi macrolactonization were subsequently employed to construct the framework of L-783277. The optical rotation value of L-783277 is for the first time presented in this Letter.
- Choi, Hwan Geun,Son, Jung Beom,Park, Dong-Sik,Ham, Young Jin,Hah, Jung-Mi,Sim, Taebo
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scheme or table
p. 4942 - 4946
(2011/01/04)
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- Enantioselective total synthesis of (-)-Clavosolide A and B
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Enantioselective total synthesis of (-)-clavosolide A and B was reported in full including the synthesis of proposed structure of (-)-clavosoldie A (1), revised structure of (-)-clavosoldie A (5), and revised structure of (-)-clavosoldie B (6). The relative and absolute stereochemistries of the natural products were confirmed unambiguously by comparing the optical rotation values and 1H and 13C NMR spectra of them.
- Son, Jung Beom,Kim, Si Nae,Kim, Na Yeong,Hwang, Min-Ho,Lee, Wonsun,Lee, Duck Hyung
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scheme or table
p. 653 - 663
(2010/08/19)
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- Inhibition of Escherichia coli glycosyltransferase MurG and Mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimics
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Glycosyltransferase MurG catalyses the transfer of N-acetyl-d-glucosamine to lipid intermediate I on the bacterial peptidoglycan biosynthesis pathway, and is a target for development of new antibacterial agents. A transition state mimic was designed for MurG, containing a functionalised proline, linked through the α-carboxylic acid, via a spacer, to a uridine nucleoside. A set of 15 functionalised prolines were synthesised, using a convergent dipolar cycloaddition reaction, which were coupled via either a glycine, proline, sarcosine, or diester linkage to the 5′-position of uridine. The library of 18 final compounds were tested as inhibitors of Escherichia coli glycosyltransferase MurG. Ten compounds showed inhibition of MurG at 1 mM concentration, the most active with IC50 400 μM. The library was also tested against Mycobacterium tuberculosis galactosyltransferase GlfT2, and one compound showed effective inhibition at 1 mM concentration.
- Trunkfield, Amy E.,Gurcha, Sudagar S.,Besra, Gurdyal S.,Bugg, Timothy D.H.
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experimental part
p. 2651 - 2663
(2010/06/16)
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- Total synthesis of (+)-aspicilin from D-mannitol
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The total synthesis of the 18-membered lichen macrolide, (+)-aspicilin, has been accomplished utilizing the Swern oxidation, Masamune-Roush olefination, and ring-closing metathesis of a trienic ester as key steps. d-Mannitol has been utilized as the chiral pool material for the construction of the olefinic aldehyde and the Jacobsen hydrolytic kinetic resolution has been employed for the construction of the olefinic phosphonate ester.
- Yadav,Rao, T. Srinivasa,Ravindar,Reddy, B. V. Subba
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scheme or table
p. 2828 - 2830
(2010/03/03)
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- Synthesis and anti-HIV activity of conformationally restricted bicyclic hexahydroisobenzofuran nucleoside analogs
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A chiral synthesis of a series of hexahydroisobenzofuran (HIBF) nucleosides has been accomplished via glycosylation of a stereo-defined (syn-isomer) sugar motif 16 with the appropriate silylated bases. All nucleoside analogs were obtained in 52-71% yield as a mixture of α- and β-anomeric products increasing the breadth of the novel nucleosides available for screening. The structure of the novel bicyclic HIBF nucleosides was established by a single crystal X-ray structure of the β-HIBF thymine analog 22b. Furthermore, the sugar conformation for these nucleosides was established as N-type. Among the novel HIBF nucleosides synthesized, twenty-five compounds were tested as inhibitor of HIV-1 in human peripheral blood mononuclear (PBM) cells and seven were found to be active (EC50 = 12.3-36.2 μM). Six of these compounds were purine analogs with β-HIBF inosine analog 22o being the most potent (EC50 = 12.3 μM) among all compounds tested. The striking resemblance between didanosine (ddI) and 22o may explain the potent anti-HIV activity.
- Diaz-Rodriguez, Alba,Sanghvi, Yogesh S.,Fernandez, Susana,Schinazi, Raymond F.,Theodorakis, Emmanuel A.,Ferrero, Miguel,Gotor, Vicente
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scheme or table
p. 1415 - 1423
(2009/10/24)
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- PROCESS AND INTERMEDIATES OF 2,2' DIFLUORONUCLEOSIDES
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The present invention provides novel 1-trihaloacetimido-2-deoxy-2,2'-difluoro-3,5-di-O-protected ribose intermediates. The compounds are useful in the preparation of 2'-deoxy-2,2'-difluoro-beta nucleosides and more particularly 2'-deoxy-2,2'-difluoro-beta cytidine and other beta anomer nucleosides and its salts having antiviral and anticancer activity
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Page/Page column 7
(2008/06/13)
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- Palladium(II)-catalyzed cyclization of urethanes and its application to a total synthesis of 1-deoxynojirimycin
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We have employed a palladium(II)-catalyzed cyclization of allylic alcohol as a key reaction to achieve a total synthesis of the azasugar 1-deoxynojirimycin from o-mannitol. This reaction should be useful for the stereoselective construction of natural poly-substituted piperidine derivatives.
- Yokoyama, Hajime,Kobayashi, Hisatake,Miyazawa, Masahiro,Yamaguchi, Seiji,Hirai, Yoshiro
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p. 283 - 292
(2008/09/17)
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- GLYCO-PHOSPHORYLATED BIOLOGICALLY ACTIVE AGENTS
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Abstract The present invention relates to a compound of formula I: (I) wherein DX is a radical of a biologically active agent comprising atom X; X is selected from O and N; and A is a radical of a saccharide, or an acid, salt, or ester thereof. Further, the invention relates to a pharmaceutical composition comprising compound of formula I, a process of preparing the same and method of management of tumor, inflammation, infection and promoting passage across blood-brain barrier.
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Page/Page column 20
(2008/06/13)
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- COMPOSITIONS FOR INCREASING BIOAVAILABILITY OF PEPTIDES OR PROTEINS AND METHOD THEREOF
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The present invention relates to a compound of formula I: (A)-(L)-(B) I wherein (B) is a hydrophobic moiety; (L) is a linker which which covalently links saccharide (A) and hydrophobic moiety (B); and (A) is a saccharide which is unsubstituted at the hydroxyl group of the anomeric position.
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Page/Page column 56
(2008/06/13)
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- Study of the synthesis of poecillanosine
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The synthesis of poecillanosine, a natural N-hydroxy-N-nitroso-alkylamine compound, was studied. Poecillanosine was shown to be unstable under acidic nitrosation conditions. Only degradation compounds of poecillanosine were obtained under such conditions, however, the O-methyl derivative of poecillanosine was synthesised and confirmed.
- Xian, Ming,Shuhler, Brian J.
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p. 1209 - 1212
(2007/10/03)
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- Synthesis of (S,R,R,R)-α,α′-iminobis(methylene)bis(6- fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol)
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The β1-adrenergic antagonist (S,R,R,R)-α, α′-iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2- methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed. Georg Thieme Verlag Stuttgart.
- Wang, Nai-Xing,Yu, An-Guang,Wang, Gui-Xia,Zhang, Xiu-Hui,Li, Qian-Shu,Li, Zhen
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p. 1154 - 1158
(2008/02/02)
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- AN IMPROVED ONE POT PROCESS FOR MAKING KEY INTERMEDIATE FOR GEMCITABINE HCL
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An improved one pot process for preparing 2-deoxy-D-erythro-2,2-difluoro-pentafuranose-1-ulose-3,5-dibenzoate of Formula (I) comprising hydrolysis of (erythro:threo) alkyl-3-dioxalan-4-yl-2,2-difluoro-3-hydroxy propionate of Formula (III) where alkyl group is having C1-C4 number of carbon atoms using a mild acid and selectively isolating 2-deoxy-D-erythro-2,2-difluoro-pentafuranose-1-ulose-3,5-dibenzoate from the mixture of erythro and threo enantiomers using ethyl acetate, ethylene dichloride and diisopropyl ether as solvents with improved yield and purity.
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Page/Page column 11-12; 14
(2010/11/27)
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- METHOD FOR THE PREPARATION OF D-ERYTHRO-2,2-DIFLUORO-2-DEOXY-1-OXORIBOSE DERIVATIVE
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3R-carboxylate enantiomer derivative of formula (III) can be prepared easily and selectively by the method of the present invention, and a highly pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose derivative can be prepared efficiently from the compound of formula (III) as an intermediate.
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Page/Page column 10-11
(2010/02/15)
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- Stereoselective synthesis of (+)-SCH 351448: A unique ligand system for sodium, calcium, and other cations
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(+)-SCH 351448 (Na+ salt A) was synthesized employing ring-closing olefin metathesis reaction of an open diene diester intermediate for construction of the 28-membered macrodiolide structure. The open diene diester was prepared from the monomeric hydroxy carboxylic acid and two different olefin fragments. The monomeric hydroxy acid was synthesized via Julia-Julia coupling reaction of intermediates derived from the same olefinic fragments. Oxane units in these fragments were prepared by radical cyclization reactions of β-alkoxyacrylates. Analogous SCH 351448 salts incorporating other mono- and divalent cations may be prepared. Under acidic conditions, SCH 351448 (Na+ salt A) was the most stable complex, but SCH 351448 (Ca2+ salt) and (Na+ salt B) appear to be physiologically important species.
- Kang, Eun Joo,Cho, Eun Jin,Ji, Mi Kyung,Lee, Young Eun,Shin, Dong Mok,Choi, Soo Young,Chung, Young Keun,Kim, Jong-Seo,Kim, Hie-Joon,Lee, Sueg-Geun,Lah, Myoung Soo,Lee, Eun
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p. 6321 - 6329
(2007/10/03)
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- Total synthesis of (-)-microcarpalide from d-mannitol
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The total synthesis of the actin-targeting metabolite (-)-microcarpalide is described. Ring-closing metathesis of a dienic ester was used as the key step. d-Mannitol was used as the chiral pool material for the construction of the olefinic acid moiety as well as the olefinic alcohol moiety of the molecule.
- Ghosh, Subhash,Rao, R. Vengal,Shashidhar
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p. 5479 - 5481
(2007/10/03)
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- A convenient synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]- (1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3H,4H-dihydro- 2H-2-chromenyl]-(1R)-1, 2-ethanediol
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1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol, important pharmaceutical intermediates, were synthesized from natural chiral pool D-mannitol. Georg Thieme Verlag Stuttgart.
- Yu, An-Guang,Wang, Nai-Xing,Xing, Ya-Lan,Zhang, Jun-Ping,Yang, Yun-Xu,Wang, Wu-Wei,Sheng, Rui-Long
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p. 1465 - 1467
(2007/10/03)
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- A novel stereoselective total synthesis of (+)-5-epi-cytoxazone
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Stereoselective synthesis of a potent cytokine modulator cytoxazone isomer has been achieved from 2,3-O-isopropylidene D-glyceraldehyde involving Grignard reaction, subsequent formation of an azide followed by reduction to the aminodiol, and finally cyclization of the N-Boc diol. Copyright
- Swamy, Navath Raghavendra,Krishnaiah, Pendem,Reddy, Natala Srinivasa,Venkateswarlu, Yenamandra
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p. 217 - 222
(2007/10/03)
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- Mild and facile procedure for clay-catalyzed acetonide protection and deprotection of N(Boc)-amino alcohols and protection of 1,2-diols
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The application of clay as a catalyst for acetonide protection of N(Boc)-amino alcohols and 1,2-diols to obtain good to excellent yields of the acetonide derivatives is described. Acetonide deprotection to obtain the parent amino alcohol was carried out using a similar catalyst in the presence of methanol as solvent. The reaction takes place at room temperature within 2h to give the parent amino alcohol in quantitative yield keeping the N(Boc) group intact.
- Shaikh, Nadim S.,Bhor, Santosh S.,Gajare, Anil S.,Deshpande, Vishnu H.,Wakharkar, Radhika D.
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p. 5395 - 5398
(2007/10/03)
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- N-(4-substituted phenyl)-anthranilic acid hydroxamate esters
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The present invention relates to oxygenated esters of 4-substituted-phenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.
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- Formal total synthesis of shikonin via D?tz benzannulation
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The D?tz benzannulation reaction provides mild conditions for the construction of highly functionalized aromatic compounds. We have utilized this method for the formal total synthesis of shikonin. The key step in our approach is the application of the D?tz benzannulation reaction between Fischer a chromium carbene complex and an optically active alkyne for the construction of the aromatic skeleton. This is followed by protecting group manipulation and formation of the epoxide moiety using the Sharpless procedure.
- Pulley, Shon R.,Czakó, Barbara
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p. 5511 - 5514
(2007/10/03)
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- Indium-mediated allylation reaction in aqueous media: Synthetic studies towards the total synthesis of dysiherbaine
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A stereospecific route to the key intermediate 4 for the total synthesis of dysiherbaine has been successfully developed based on the indium-mediated allylation reaction in aqueous media. Further manipulation to the advanced intermediate 28 has resulted in the discovery of a series of highly stereoselective processes.
- Huang, Jing-Mei,Xu, Kai-Chen,Loh, Teck-Peng
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p. 755 - 764
(2007/10/03)
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- A divergent approach to apoptolidin and FD-891: Asymmetric preparation of a common intermediate
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Biologically active Apoptolidin and FD-891 have structural similarity in their macrocyclic cores. Asymmetric preparation of a common intermediate in the total synthesis of these two macrolides is presented. A modified Masuyama Sn-allylation was employed to control the relative stereochemistry in the synthesis of the intermediate.
- Chng, Shu-Sin,Xu, Jia,Loh, Teck-Peng
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p. 4997 - 5000
(2007/10/03)
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- N-(4-substituted phenyl)-anthranilic acid hydroxamate esters
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The present invention relates to oxygenated esters of 4-substituted-phenylamino benzhydroxamic acid derivatives, pharmaceutical compositions, and methods of use thereof.
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Page/Page column 11
(2010/02/06)
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- Direct access to furanosidic eight-membered ulosonic esters from cis-α,β-epoxy aldehydes
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Direct access to bicyclic precursors of octulosonic acids is achieved by treatment of differentially (or not) protected γ,δbis(silyloxy) cis-α,β-epoxy aldehydes with ethyl 2-(trimethylsilyloxy)-2-propenoate in the presence of boron trifluoride-diethyl ether. An X-ray crystallographic structure of a bicycle (compound 33a) was obtained and used to determine the absolute configurations of the different stereogenic centers and thus the diastereoselective preference of the aldol reaction (syn) and the regioselectivity of the epoxide ring-opening (C-6 atom). Functionalization and opening of the bicyclic compound to afford octulosonic analogues in their furanoside forms was studied. An octulosonic 8-phosphate analogue has been synthesized. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Sugisaki, Claudia H.,Ruland, Yvan,Baltas, Michel
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p. 672 - 688
(2007/10/03)
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- Nucleophilic reaction of glycidol tosylate and the corresponding cyclic sulfate with various nucleophiles: A comparative study
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The nucleophilic reaction of glycidol tosylate and the corresponding cyclic sulfate tosylate have been carried out with a number of nucleophiles to study the possible attack of nucleophiles at C1, C2 or C3 positions. The regioselectivity and reactivity of both the substrates i.e. epoxide tosylate 1 and the corresponding cyclic sulfate 2 have been compared and established that under similar conditions cyclic sulfate counterpart shows better regioselectivity and better reactivity than the corresponding epoxide.
- Lohray,Rajesh,Bhushan
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p. 586 - 592
(2007/10/03)
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- Reactivity Enhancement for Chiral Dirhodium(II) Tetrakis (Carboxamidates)
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Difluorinated ligands from azetidinone-4-carboxylates and pyrrolidinone-5-carboxylate have been prepared, substituted onto dirhodium(II), and the reactivities and selectivities of the resulting catalysts have been examined. The fluorinated catalysts exhibit enhanced reactivity towards diazo decomposition but diminished enantioselectivities for cyclopropanation. Selectivity for ylide formation and rearrangement or Si-H insertion is enhanced or similar to that with unfluorinated analogues.
- Doyle, Michael P.,Hu, Wenhao,Phillips, Iain M.,Moody, Christopher J.,Pepper, Adrian G.,Slawin, Alexandra M. Z.
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p. 112 - 117
(2007/10/03)
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- New protecting groups for 1,2-diols (boc- and moc-ethylidene). Cleavage of acetals with bases
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1,2-Diols react at rt with alkyl propynoates, in the presence of 4-dimethylaminopyridine, to give cyclic acetals which are quite stable to acid-catalyzed hydrolysis or methanolysis. 1,3-Diols and 1,4-diols do not form acetals with alkyl propynoates under the same conditions. Deprotection is accomplished with bases (via elimination and addition/elimination steps).
- Ariza, Xavier,Costa, Anna M.,Faja, Montserrat,Pineda, Oriol,Vilarrasa, Jaume
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p. 2809 - 2811
(2007/10/03)
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