- Stereoselective synthesis of the a-ring of armatol a from a bromo-substituted chiral building block based on Ireland-claisen rearrangement and ring-closing olefin metathesis
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The stereoselective synthesis of the A-ring of armatol A, a natural polycyclic ether triterpene from the red alga Chondria armata, was achieved in a non-biomimetic way. The synthesis employed Ireland-Claisen rearrangement of an ester, prepared from a bromo-substituted chiral building block, for the construction of C6 and C7 stereocenters and a relay ring-closing olefin metathesis for the seven-membered ring formation.
- Hirose, Yuta,Fujiwara, Kenshu,Saito, Takafumi,Katoono, Ryo,Suzuki, Takanori
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Read Online
- Synthetic studies on the sporolides: Exploration of the Enediyne route
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Synthetic studies towards the construction of the cyclopenta[a]indene fragment of the heptacyclic marine metabolite sporolide are reported based on a hypothetical biosynthesis. The key step of this biogenetic proposal includes a Bergman cyclization of an enediyne precursor. The enediyne target of this synthetic study was prepared by Sonogashira cross-coupling of two fragments, of which the cyclopentane fragment was prepared from cyclopentenone, Morita-Baylis-Hillman reaction, and enantioselective Sharpless dihydroxylation. Georg Thieme Verlag Stuttgart · New York.
- Bonazzi, Simone,Binaghi, Massimo,Fellay, Cindy,Wach, Jean-Yves,Gademann, Karl
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Read Online
- Chemoenzymatic Access to Chiral Tetrols Produced by Thiamine Diphosphate Dependent Benzaldehyde Lyase
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Highly functionalized polyol building blocks have been synthesized by means of stereoselective chemoenzymatic C–C bond formation followed by stereoselective reduction. Catalysis by thiamine diphosphate (ThDP) dependent benzaldehyde lyase (BAL) with glyceraldehyde acetonide as acceptor substrate gave highly stereoenriched polyols such as (1S,2S,3R)-1-phenylbutane-1,2,3,4-tetrol (1), the 3,4-protected anti-1,2-diol 5, and the precursor of both compounds, 2-hydroxyketone 4.
- Zecevic, Damir,Germer, Philipp,Walter, Lydia,Gauchenova, Ekaterina,Müller, Michael
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Read Online
- MONOBACTAM COMPOUNDS AND USE THEREFOR
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Monobactam compounds and a use therefor. Specifically provided are chemical compounds represented by formula (I) or isomers, pharmaceutically acceptable salts, solvates, crystals, or prodrugs thereof, preparation methods therefor, pharmaceutical compositions containing said compounds, and a use of said compounds or compositions in treating bacterial infection. The present compounds feature excellent antibacterial activity, and have great hopes of becoming a therapeutic agent for bacterial infection.
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- Total Synthesis of Euonymine and Euonyminol Octaacetate
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Euonymine (1) and euonyminol octaacetate (2) share the core structure of euonyminol (3), the most hydroxylated member of the dihydro-β-agarofuran family. In 2, eight of the nine hydroxy groups of 3 are acetylated, and 1 has six acetyl groups and a 14-membered bislactone comprising a pyridine dicarboxylic acid with two methyl groups. The different acylation patterns provide distinct biological activities: 1 and 2 display anti-HIV and P-glycoprotein inhibitory effects, respectively. The 11 contiguous stereocenters and 9 oxygen functionalities of the ABC-ring system of 1 and 2 represent a formidable challenge, which is further heightened by the macrocyclic structure of 1. Here we disclose an efficient synthetic strategy for enantioselective total synthesis of 1 and 2. Starting from (R)-glycerol acetonide, we constructed the B-ring by an Et3N-accelerated Diels-Alder reaction, the C-ring by intramolecular iodoetherification, and the A-ring by ring-closing olefin metathesis. The 10 stereocenters were installed through a series of substrate-controlled stereoselective C-C and C-O bond formations by exploiting the three-dimensional structures of judiciously designed substrates. These newly developed reaction sequences led to protected euonyminol 5, which served as a common intermediate for assembling 1 and 2. Global deprotection of 5 and subsequent acetylation produced 2. Alternatively, the discriminative protective groups of 5 allowed for site-selective bis-esterification to generate bislactone. Combining [3 + 2]-cycloaddition and reductive desulfurization introduced the last remaining stereocenters of the two methyl groups on the macrocycle. Finally, deprotection and acetylation gave rise to fully synthetic 1 for the first time.
- Hagiwara, Koichi,Inoue, Masayuki,Nagai, Toshiya,Wang, Yinghua,Watanabe, Itsuki
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supporting information
p. 21037 - 21047
(2021/12/17)
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- NOVEL PROCESSES FOR PREPARATION OF TEZACAFTOR
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The present invention generally relates to processes for preparation of Tezacaftor and pharmaceutical composition comprising the same. The present invention also encompasses novel intermediates of tezacaftor, processes for its preparation and use of said intermediates in the preparation of tezacaftor.
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Page/Page column 84
(2021/08/14)
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- Preparation method of intermediate of antitumor drug gemcitabine hydrochloride
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The invention relates to a preparation method of a intermediate of antitumor drug gemcitabine hydrochloride. According to the method, D-isoascorbic acid is used as a starting raw material and reacts with 2,2-dimethylpropane under the catalysis of p-toluenesulfonic acid in the presence of acetone serving as a solvent to protect hydroxyl groups at 5 and 6 sites to obtain T1; then, hydrogen peroxideis used for carrying out oxidation under the alkaline condition to obtain T2; the T2 is oxidized by sodium hypochlorite to obtain T3; the T3 and ethyl bromodifluoroacetate are subjected to a Reformatsky reaction to obtain T4; then the T4 is subjected to deprotection and cyclization under the catalysis of trifluoroacetic acid to obtain T5; the T5 and benzoyl chloride are subjected to an esterification reaction under the catalysis of DMAP to obtain T6, and a synthetic route II is shown in the specification.
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- Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis
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In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters (“cord factor”) form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn-methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material.
- Buter, Jeffrey,Fodran, Peter,Jayaraman, Dhineshkumar,Minnaard, Adriaan J.,Moody, D. Branch,Ocampo, Tonatiuh A.,Tahiri, Nabil,Van Rhijn, Ildiko,Witte, Martin D.
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supporting information
p. 7555 - 7560
(2020/03/23)
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- NHC-Catalyzed Dual Stetter Reaction: A Mild Cascade Annulation for the Syntheses of Naphthoquinones, Isoflavanones, and Sugar-Based Chiral Analogues
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The N-heterocycle carbene (NHC)-catalyzed dual Stetter cascade reaction is discovered through coupling of β-nitrostyrene with phthalaldehyde under mild conditions to furnish valuable aryl-naphthoquinones. The generality of the new reaction is validated through the development of a C-C and O-C bond forming Stetter cascade reaction using salicylaldehydes to obtain functionalized dihydroisoflavanones. The mild NHC organocatalysis is successfully employed for the construction of optically pure sugar-based naphthoquinones and dihydroisoflavanones. Herein, NHC is found as a unique and powerful organocatalyst to construct homoatomic C-C cross-coupling, heteroatomic O-C bond formation, and cascade cyclization utilizing NO2 as a leaving group at ambient temperature. A mechanistic pathway of the new metal-free catalysis is predicted on the basis of our ESI-MS study of the ongoing reaction and literature.
- Mitra, Rajendra N.,Show, Krishanu,Barman, Debabrata,Sarkar, Satinath,Maiti, Dilip K.
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supporting information
p. 42 - 52
(2019/01/10)
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- Comprehensive evaluation of antioxidant effects of Japanese Kampo medicines led to identification of Tsudosan formulation as a potent antioxidant agent
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Oxidative stress due to the overproduction of reactive oxygen species plays an important role in the pathogenesis of various diseases. In the present study, we comprehensively evaluated the antioxidant activities of 147 oral formulations of Japanese traditional herbal medicines (Kampo medicines), representing the entire panel of oral Kampo medicines listed in the Japanese National Health Insurance Drug List, using in vitro radical scavenging assays, including the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay, the superoxide anion scavenging activity assay, and the oxygen radical absorption capacity assay. Three of the formulations tested, namely, Tsudosan, Daisaikoto, and Masiningan, showed the most potent in vitro antioxidant activities and were selected for further investigation of their intracellular and in vivo antioxidant effects. The results of the 2′,7′-dichlorodihydrofluorescin diacetate assay demonstrated that all three Kampo medicines significantly inhibited hydrogen peroxide-induced oxidative stress in human hepatocellular liver carcinoma HepG2 cells. In addition, Tsudosan significantly increased the serum biological antioxidant potential values when orally administrated to mice, indicating that it also had in vivo antioxidant activity. The potent antioxidant activity of Tsudosan may be one of the mechanisms closely correlated to its clinical usage against blood stasis.
- Sato, Naoko,Li, Wei,Takemoto, Hiroaki,Takeuchi, Mio,Nakamura, Ai,Tokura, Emi,Akahane, Chie,Ueno, Kanako,Komatsu, Kana,Kuriyama, Noriko,Onoda, Toshihisa,Higai, Koji,Koike, Kazuo
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supporting information
p. 163 - 172
(2018/11/06)
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- Microwave-induced synthesis of enantiopure beta lactams from L-glyceraldehyde
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Microwave-induced asymmetric synthesis of β-lactams from L-glyceraldehyde derived imines is achieved following a reaction with acid chlorides in the presence of a tertiary base. An exclusive formation of the cis enantiomer (3S,4R) is observed. The whole process is highly efficient and it completed within 2 h.
- Yadav, Ram Naresh,Banik, Indrani,Banik, Bimal Krishna
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p. 1393 - 1396
(2020/06/27)
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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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- Stereoselective Synthesis of a Highly Oxygenated δ-Lactone Related to the Core Structure of (-)-Enterocin
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The title compound was prepared in a concise route starting from an appropriately protected (S)-glyceraldehyde. A highly diastereoselective (d.r. >95:5) Mukaiyama aldol reaction of an acetoacetate-derived silyl enol ether served as the initial step of the synthetic sequence. It was found that protection of the glyceraldehyde as a butane-2,3-dione acetal is required to achieve the desired diastereoselectivity. Upon lactonization, a Tsuji-Trost allylation and a subsequent one-pot reaction cascade including an ozonolysis and an α-hydroxylation gave diastereoselective access to the desired α-hydroxy-β-oxo-δ-lactone. Alternative synthetic approaches are discussed and proof for the configuration of the product is presented.
- Wegmann, Marcus,Bach, Thorsten
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supporting information
p. 209 - 217
(2016/12/24)
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- PROCESS FOR THE PREPARATION OF [(1 S,2R)-3-[[(4-AMINOPHENYL)SULFONYL] (2-METHYLPROPYL)AMINO]-2-HYDROXY-1 -(PHENYLMETHYL)PROPYL]-CARBAMIC ACID (3R,3AS,6AR)HEXAHYDRO FURO[2,3-B]FURAN-3-YL ESTER AND ITS AMORPHOUS FORM
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The present invention relates to an improved process for the preparation of [(1 S,2R)-3-[ [(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy- 1 -(phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl ester compound of formula- 1 represented by the following structural formula:
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- Diastereoselective synthesis of β-lactams via Kinugasa reaction of acyclic chiral nitrones
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An approach to β-lactams via a Kinugasa reaction between chiral copper acetylides and chiral acyclic nitrones bearing either 1,3-dioxane or 1,3-dioxolane moieties is reported. The stereochemical preferences observed in these reactions are discussed. The reaction provides access to a variety of interesting β-lactam structures. Electronic circular dichroism in combination with NMR spectroscopy was shown to be a useful and effective method for the reliable determination of the absolute configuration of all components of a complex mixtures of azetidinones. The effectiveness of the chiral analysis of complex mixtures was demonstrated for HPLC coupled on-line with electronic circular dichroism detection as well.
- Mucha, ?ukasz,Parda, Kamil,Staszewska-Krajewska, Olga,Stecko, Sebastian,Ulikowski, Artur,Frelek, Jadwiga,Suszczyńska, Agata,Chmielewski, Marek,Furman, Bart?omiej
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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; 0049
(2017/06/02)
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- 2′-fluoronucleosides
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2′-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein Base is a purine or pyrimidine base;R1 is OH, H, OR3, N3, CN, halogen, CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy;R2 is H, phosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving benzyl, a lipid, an amino acid, peptide, or cholesterol; andR3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group; or a pharmaceutically acceptable salt thereof.
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Page/Page column 48; 49
(2015/11/30)
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- Ruthenium-catalyzed asymmetric N -demethylative rearrangement of isoxazolidines and its application in the asymmetric total syntheses of (-)-(1 r,3 s)-hpa-12 and (+)-(1 s,3 r)-hpa-12
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An asymmetric N-demethylative rearrangement of 1,2-isoxazolidines catalyzed by ruthenium is described. Enantioenriched syn-1,3-aminoalcohols as well as cis-1,3-oxazinanes, which are useful building blocks, can be efficiently prepared stereospecifically by this reaction in good yields, via the isoxazolidine intermediates in situ generated from a nitrone bearing a chiral auxiliary and styrenes. This asymmetric reaction was also applied in the asymmetric total syntheses of both (-)-(1R,3S)-HPA-12 and (+)-(1S,3R)-HPA-12.
- Xiao, Zu-Feng,Yao, Chuan-Zhi,Kang, Yan-Biao
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supporting information
p. 6512 - 6514
(2015/02/19)
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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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- One-pot synthesis of trichloromethyl carbinols from primary alcohols
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Versatile trichloromethyl carbinols can be prepared in one pot from primary alcohols by treatment with Dess-Martin periodinane (DMP) in CHCl3 followed by introduction of commercially available 1,5,7-triazabicyclo[4.4.0] dec-5-ene (TBD). A modification of the method was used to convert chiral primary alcohol (R)-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol to the corresponding trichloromethyl carbinol with complete stereochemical fidelity, despite the reactant proceeding through a base-sensitive aldehyde intermediate.
- Gupta, Manoj K.,Li, Zhexi,Snowden, Timothy S.
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experimental part
p. 4854 - 4860
(2012/07/30)
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- Practical one-pot synthesis of protected l-glyceraldehyde derivatives
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A large-scale, simple, economic, and safe procedure for the preparation of l-glyceraldehyde acetonide under conditions, which allow its direct transformation (one-pot) into the desired products (acetylene, imine, nitrone, unsaturated ester) is reported. l-Glyceraldehyde acetonide is obtained from the corresponding ester, which is readily available from l-serine. Georg Thieme Verlag Stuttgart New York.
- Stecko, Sebastian,Michalak, Micha,Stodulski, MacIej,Muchal, Lukasz,Parda, Kamil,Furman, Bartlomiej,Chmielewski, Marek
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p. 2695 - 2698
(2012/11/07)
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- Total synthesis of brevenal
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This Article describes the total synthesis of the marine ladder toxin brevenal utilizing a convergent synthetic strategy. Critical to the success of this work was the use of olefinic-ester cyclization reactions and the utilization of glycal epoxides as precursors to C-C and C-H bonds.
- Zhang, Yuan,Rohanna, John,Zhou, Jie,Iyer, Karthik,Rainier, Jon D.
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supporting information; experimental part
p. 3208 - 3216
(2011/04/25)
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- Synthesis of key fragments of amphidinolide Q - A cytotoxic 12-membered macrolide
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β-Hydroxy aldehyde and alkyl ketone moieties were effectively synthesized as key intermediates of amphidinolide Q, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp.. The asymmetric center of the former derivative was produced by Sharpless asymmetric epoxidation, followed by E-selective 1,4-addition to give the sp2 methyl group. Derivatization of the L-ascorbic acid derivative by Evans asymmetric alkylation and Peterson olefination provided the latter intermediate. The coupling reaction of the segments was examined.
- Kawa, Kohei,Hara, Akihiro,Ishikawa, Yuichi,Nishiyama, Shigeru
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p. 5422 - 5436
(2011/09/20)
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- Synthesis of the C7-26 fragment of amphidinolides G and H
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A new approach to the synthesis of the C7-26 fragment of amphidinolides G and H was developed. In the sequence, the C7-18 portion of this fragment was synthesized using an acetylide coupling protocol, while an Evans alkylation and Sharpless asymmetric dihydroxylation were employed as key steps in construction of the C19-26 subfragment. Finally, both of these units were joined by utilizing an aldol coupling reaction to produce the target C7-26 fragment in good yield.
- Hara, Akihiro,Morimoto, Ryo,Ishikawa, Yuichi,Nishiyama, Shigeru
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supporting information; experimental part
p. 4036 - 4039
(2011/10/04)
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- Access to functionalized steroid side chains via modified Julia olefination
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Various functionalized steroidal side chains were conveniently accessed by a modified Julia olefination strategy using a common sulfone donor and an appropriate α-branched aldehyde acceptor. For the coupling of these hindered classes of reaction partners (and in contrast to typically observed trends), the benzothiazolyl(BT)-sulfone anion gave superior outcomes compared to the phenyltetrazolyl(PT)-sulfone anion.
- Izgu, Enver Cagri,Burns, Aaron C.,Hoye, Thomas R.
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supporting information; scheme or table
p. 703 - 705
(2011/04/26)
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- Efficient asymmetric synthesis of (2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)- siloxy]ethyl}-4-oxoazetidin-2-yl acetate
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(2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)siloxy]ethyl}-4-oxoazetidin-2-yl acetate was efficiently prepared from l-ascorbic acid. The key steps were the a highly diastereoselective [2 + 2] cycloaddition of diketene with an (S)-glyceraldehyde-derived ald?imine to give the ketone, stereoselective titanium tetrachloride mediated asymmetric reduction to give the corrsponding S-configured alcohol, and Mitsunobu inversion of the latter to give the desired R-configured alcohol. Georg Thieme Verlag Stuttgart ? New York.
- Huang, Jian-Ping,Zhao, Lei,Gu, Shuang-Xi,Wang, Zhong-Hua,Zhang, Hao,Chen, Fen-Er,Dai, Hui-Fang
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experimental part
p. 555 - 562
(2011/04/15)
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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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- Asymmetric synthesis of (4S,5S)-2-oxo-4-phenyloxazolidine-5-carboxylic acid using a 1,2-addition of PhMgBr to an N-sulfinimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA
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We report an asymmetric synthesis of (4S,5S)-2-oxo-4-phenyloxazolidine-5- carboxylic acid via stereoselective addition of phenylmagnesium bromide (PhMgBr) to an N-sulfinimine derived from (R)-glyceraldehyde acetonide. (S)- and (R)-Glyceraldehyde acetonides, important chiral synthons in synthetic organic chemistry, are prepared from the corresponding epichlorohydrin using an identical synthetic methodology.
- Babu, K. Chandra,Vysabhattar, Raman,Srinivas,Nigam, Satish,Madhusudhan,Mukkanti
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experimental part
p. 2619 - 2624
(2011/01/05)
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- Synthesis of a functionalized 7,6-bicyclic spiroimine ring fragment of the spirolides
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The asymmetric synthesis of a functionalized 7,6-spiroimine related to the spirolides is described. Intermolecular Diels-Alder cycloaddition of a chiral trisubstituted dienophile and Danishefsky's diene enabled simultaneous installation of the C7 and C29 stereocenters. Further transformations and late-stage aza-Wittig cyclization afforded the spiroimine in good yield. During this study, an unprecedented 14-membered dialdimine was also obtained.
- Gueret, Stephanie M.,Furkert, Daniel P.,Brimble, Margaret A.
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supporting information; experimental part
p. 5226 - 5229
(2011/02/23)
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- Studies toward the total synthesis of armatol F: Stereoselective construction of the C6 and C7 stereocenters and formation of the A-ring skeleton
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Armatol F, isolated from the red alga Chondria armata as a polyether triterpene, has a solitary oxepane (A-ring) and a fused tricyclic ether moiety (BCD-ring). The A-ring features a rare cis-relationship between the hydroxy group at the quaternary carbon C6 and the carbon chain at C7. As part of our program toward the total synthesis of armatol F, a new stereoselective method for the construction of the C6 and C7 stereocenters has been developed based on chirality-transferring Ireland-Claisen rearrangement. The A-ring skeleton has also been synthesized from the rearrangement product by a process including ring-closing olefin metathesis.
- Fujiwara, Kenshu,Hirose, Yuta,Sato, Daisuke,Kawai, Hidetoshi,Suzuki, Takanori
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scheme or table
p. 4263 - 4266
(2010/09/07)
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- A pyrrolysine analogue for protein click chemistry
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(Chemical Equation Presented) Ignoring the STOP sign: A pyrrolysine analogue bearing a terminal alkyne was site-specifically incorporated into recombinant calmodulin (CaM) through a UAG codon. The resulting protein was labeled with an azide-containing dye using a copper(I)-catalyzed click reaction. Subsequent application of an orthogonal cysteine tagging method yielded a CaM labeled with two distinct fluorophores that enabled its study by FRET spectroscopy.
- Fekner, Tomasz,Li, Xin,Lee, Marianne M.,Chan, Michael K.
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supporting information; experimental part
p. 1633 - 1635
(2009/06/30)
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- On the stereochemistry of palmerolide A
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Degradative studies of the anticancer macrolide palmerolide A have resulted in re-assignment of the C-7, C-10, and C-11 stereocenters.
- Lebar, Matthew D.,Baker, Bill J.
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p. 8009 - 8010
(2008/03/18)
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- An efficient and green oxidation of vicinal diols to aldehydes using polymer-supported (diacetoxyiodo)benzene as the oxidant
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An operationally simple and clean oxidation of a variety of vicinal diols to aldehydes using polymer-supported (diacetoxyiodo)benzene (PSDIB) has been developed in high to excellent yields. Protecting groups such as OAc, OR, OBn, OBz and isopropylidene in the substrates were found to be stable under these reaction conditions. The regenerated PSDIB could be reused for the same reaction, affording oxidation products in high yield and purity. Georg Thieme Verlag Stuttgart.
- Chen, Fen-Er,Xie, Bin,Zhang, Ping,Zhao, Jian-Feng,Wang, Hui,Zhao, Lei
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p. 619 - 622
(2007/10/03)
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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 12; 14
(2010/11/27)
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- Diastereomeric enols and enol derivatives of 8-fluoro-5,11-dihydro-10H- dibenzo[a,d]cyclohepten-10-one with a chiral 11-substituent
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Aldol condensation of 8-fluoro-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10- one and (4S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde provides access to the corresponding (E,Z)-α,β-unsaturated ketones with a (4R)-chiral 11-substituent. Subsequent hydrogenation affords a mixture of (11R)/ (11S)-epimeric ketones, which undergoes base-catalysed equilibration resulting in selective crystallisation of the (11R) epimer. The enol intermediate and acyclic enol derivatives are shown to exist as two slowly interconverting conformers with a high inversion barrier of the 10,11-disubstituted ring. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Compernolle, Frans,Toppet, Suzanne,Brossette, Thierry,Mao, Hua,Koukni, Mohamed,Kozlecki, Tomasz,Medaer, Bart,Guillaume, Michel,Lang, Yolande,Leurs, Stef,Hoornaert, Georges J.
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p. 1586 - 1592
(2007/10/03)
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- Process for preparing alpha, beta - unsaturated ester
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A process for preparing an α,β-unsaturated ester of the compound (4), wherein R7 and R8 are the same or different and hydrogen atom, C1-6alkyl group or phenyl group, which comprises oxidizing a glycerol derivative (2), wherein R7 and R8 are the same as defined above, in the presence of a nitroxyl radical compound and a co-oxidant to prepare a glyceraldehyde and then reacting the compound with a phosphonoacetic acid alkyl ester or a (triphenylphosphoranylidene)acetic acid alkyl ester to give the compound (4).
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Page/Page column 6
(2008/06/13)
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- 4-Formylazetidin-2-ones, synthon for the synthesis of (2R,3S) and (2S,3R)-3-amino-2-hydroxydecanoic acid (AHDA)
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An efficient synthesis of 3-amino-2-hydroxydecanoic acid (AHDA), a nonproteinogenic amino acid, using enantiopure 3-benzyloxy-4-formylazetidin-2-one as a building block is described. Both the enantiomers of AHDA have been synthesized from the corresponding enantiomer of 3-benzyloxy-4-formylazetidin-2-one in good yield and optical purity.
- Shirode, Nilesh M.,Deshmukh, Abdul Rakeeb A.S.
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p. 4615 - 4621
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF GLYCERALDEHYDE ACETONIDE
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The invention relates to a process for the preparation of glyceraldehyde acetonide by oxidation of 2,2-dimethyl-1,3-dioxolane-4-methanol by an oxidizing agent, wherein the 2,2-dimethyl-1,3-dioxolane-4-methanol is oxidized by an organic N-chloro compound in the presence of an inert base and TEMPO or a TEMPO-derivative. In one embodiment of the invention enantiomerically enriched glyceraldehyde acetonide is prepared from the corresponding enantiomerically enriched 2,2-dimethyl-1,3-dioxolane-4-methanol. Preferably, the organic N-chloro compount is trichloroisocyanuric acid or dichlorodimethyl hydantoin. Preferably, the inert base is sodium acetate or sodium bicarbonate.
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Page/Page column 19-20
(2008/06/13)
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- Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3- b]furan-3-ol
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(Chemical Equation Presented) Two short and efficient synthesis routes have been developed for bis-THF-alcohol 2, a key building block of the investigational HIV protease inhibitor TMC114 (1). Using S-2,3-O- isopropylideneglyceraldehyde (4) as the source of chirality, both routes are based on a diastereoselective Michael addition of nitromethane to give predominantly the syn congeners 6 followed by a Nef oxidation and cyclization to afford lactone acetals 8, which are reduced and cyclized to give 2.
- Quaedflieg, Peter J. L. M.,Kesteleyn, Bart R. R.,Wigerinck, Piet B. T. P.,Goyvaerts, Nicolaas M. F.,Vijn, Robert Jan,Liebregts, Constantinus S. M.,Kooistra, Jaap H. M. H.,Cusan, Claudia
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p. 5917 - 5920
(2007/10/03)
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- METHODS FOR THE PREPARATION OF (3R,3aS,6aR) HEXAHYDRO-FURO[2,3-b]FURAN-3-OL
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The present invention relates to methods for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol (6) as well as a novel intermediate, (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one (4) for use in said methods. More in particular the invention relates to a stereoselective method for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol, as well as methods for the crystallization of (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan- 2-one and for the epimerization of (3aR,4R,6aS) 4-methoxy-tetrahydro-furo[3,4-b]-furan-2-one to (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one.
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Page/Page column 39
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF (S)-GLYCERALDEHYDE ACETONIDE
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The invention relates to a process for the preparation of (S)-glyceraldehyde acetonide in aqueous solution from 3,4-O--isopropylidene-L-threonic acid or a salt thereof in aqueous solution, and hypochlorite in aqueous solution wherein the aqueous hypochlorite solution has a pH > 7.5 and wherein during addition of at least 0.1 molar equivalents of hypochlorite based on the amount of 3,4-O-isopropylidene--L-threonic acid, an acid solution is not simultaneously added. The invention also relates to a process according to the invention, wherein 3,4-O-isopropylidene-L-threonic acid or a salt thereof is prepared from 5,6-O-isopropylidene-L-ascorbic acid or a salt thereof in the presence of H2O2 and a base in a manner known per se, wherein excess H2O2 is optionally removed by catalase. The invention also relates to a process according to the invention, wherein 5,6-O-isopropylidene-L-ascorbic acid or a salt thereof is prepared by reacting L-ascorbic acid or a salt thereof with an acetonide forming agent, preferably in the presence of an acid catalyst.
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Page/Page column 9-10
(2008/06/13)
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- Production method of 2-deoxy-L-ribose compound
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An aldehyde compound represented by the formula (1) is reacted with an organometallic compound represented by the formula (2) to give an alcohol compound represented by the formula (3), which is then subjected to deprotection of a hydroxyl group and production of aldehyde by acid hydrolysis. wherein R1 and R2 are each independently a hydroxyl-protecting group or R1 and R2 in combination show a hydroxyl-protecting group, R3 and R4 are each independently an alkyl group, an aralkyl group, an aryl group or a silyl group or R3 and R4 in combination show a cyclic alkyl group.
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Page/Page column 16
(2010/02/13)
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- NEW PROCESS FOR THE PREPARATION OF RACEMIC ([2S[2R*[R[R*]]]] and ([2R[2S*[S[S*]]]]-(±)- α,α' -[imino-bis(methylene)]bis[6-fluoro-chroman-2-methanol] AND ITS PURE [2S[2R*[R[R*]and
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Process for the preparation of racemic ([2S[2R*[R[R*]]]]- and ([2R[2S*[S[S*]]]]-(±)- α,α' -[imino-bis(methylene)]bis[6-fluoro-chroman-2-methanol] of the compound of the formula (I) and its pure ([2S[2R*[R[R*]]]]- and ([2R[2S*[S[S*]]]]- enantiomer compounds characterized in that the products are prepared from 4--fluoro-phenole or 4-fluoro-anisole via crystalline, optically active intermediates.
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- A concise asymmetric synthesis of the ADE fragment of nakadomarin A
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(Chemical equation presented) The ADE fragment of nakadomarin A has been synthesized in nine linear steps from commercial material. The key transformation is an asymmetric azomethine ylide [1,3]-dipolar cycloaddition to establish the AD-spirocyclic system containing three of the four stereocenters of the natural product.
- Ahrendt, Kateri A.,Williams, Robert M.
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p. 4539 - 4541
(2007/10/03)
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- On the selectivity of oxynitrilases towards α-oxygenated aldehydes
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Different α-alkoxy and α,β-di-alkoxy substituted aldehydes have been submitted to the catalytic action of the oxynitrilases from almond (PaHNL) or from Hevea brasiliensis (HbHNL), in order to explore the possibility of using these enzymes for the preparation of complex cyanohydrins. The selectivity of both enzymes towards these compounds was found to be largely dependent on the substitutents, being low with the aldehydes carrying the sterically more demanding phenyl substituent. Contrary to the chemical addition of HCN, which always occurs with a slight preference for the formation of the anti diastereoisomers, the enzymatic cyanuration - occurring with a facial preference, Si or Re according to the biocatalyst used - gave a mixture of cyanohydrins that, depending on the starting enantiomeric aldehyde, can be enriched in the syn diastereoisomers.
- Bianchi, Paola,Roda, Gabriella,Riva, Sergio,Danieli, Bruno,Zabelinskaja-Mackova, Antonina,Griengl, Herfried
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p. 2213 - 2220
(2007/10/03)
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- An expedient one-step preparation of (S)-2,3-O-isopropylidene-glyceraldehyde
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One-step PCC oxidation of (R)-2,3-O-isopropylideneglycerol in dichloromethane provides (S)-2,3-O-isopropylideneglyceraldehyde 2 in 30% yield after its separation from ester 3 by careful distillation. The same procedure with (S)-2,3-O-isopropylideneglycerol affords (R)-2,3-O-isopropylideneglyceraldehyde.
- Ermolenko,Sasaki,Potier
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p. 1565 - 1566
(2007/10/03)
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- Aldol Addition of Lithium and Boron Enolates of 1,3-Dioxan-5-ones to Aldehydes. A New Entry into Monosaccharide Derivatives
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Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the α-position. Enantioselective deprotonation of CS symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH-(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21).
- Majewski, Marek,Nowak, Pawel
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p. 5152 - 5160
(2007/10/03)
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- Synthesis of novel L-series 2',3'-dideoxy-3'-hydroxy-methyl-nucleosides and a convenient method for the separation of nucleoside anomers
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Photoinduced addition of methanol to 5(R)-(tert- butyldimethylsilyloxymethyl) -2(5H)-furan-2-one (derived from L-gulono-1,4- lactone) provided the photoadduct 5(R)-(tert-butyldimethylsiloxymethyl)- 4(S)-hydroxymethyl-tetrahydrofuran-2-one, which was converted into two L- series-2',3'-dideoxy-3'-hydroxymethyl-nucleosides. In addition, we describe a new method for the chromatographic separation of cytidine anomers using a N- 2-(4-nitrophenyl)ethyl carbamate derivative.
- Gould, Jayne H.M.,Mann, John
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p. 193 - 213
(2007/10/03)
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- Synthetic study on gymnodimine: Highly stereoselective construction of substituted tetrahydrofuran and cyclohexene moieties
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The synthetic studies on gymnodimine, a shellfish toxin, are described. This marine toxin consists of 16-membered carbocycle, tetrahydrofuran, and spiro-imine moieties. Our synthetic strategy involves the stereoselective allylation of tetrahydrofuran compound and the exo-selective intramolecular Diels-Alder reaction.
- Ishihara, Jun,Miyakawa, Jun,Tsujimoto, Takashi,Murai, Akio
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p. 1417 - 1419
(2007/10/03)
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- Structure-activity relationships of 2'-deoxy-2',2'-difluoro-L-erythro- pentofuranosyl nucleosides
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Following the recent discoveries that some L-nucleosides are more or equal potent than their D-counterparts, we synthesized 2'-deoxy-2',2'- difluoro-L-erythro-pentofuranosyl nucleosides as potential antiviral agents. The target compounds were synthesized via the key intermediates 7a or 7b from L-gulono γ-lactone. Compound 2 was oxidatively cleaved and coupled with ethyl bromodifluoroacetate in the presence of activated zinc under Reformatsky conditions to obtain a diastereomeric mixture of 4(R) and 4(S), in a 4:1 ratio. The major 4(R) isomer was cyclized and treated appropriately to obtain the mesylate 8a or 8b, which was condensed with various silyl- protected pyrimidines. Condensation of the alcohol 7a or 7b with 6- chloropurine under Mitsunobu conditions afforded the 6-chloropurine analogs 53a or 53b and 54a or 54b. Further treatment of the compounds 53a, 54a and 53b, 54b afforded the inosine and adenine derivatives 57-60, respectively. The condensation of 2-amino-6-chloropurine with compound 8a and subsequent treatment with 2-mercaptoethanol/sodium methoxide afforded the guanine analogs 63 and 64. All of the synthesized nucleosides 31-52, 57-60, 63, and 64 were evaluated for antiviral activity and for cellular toxicity. Adenine derivative 57 showed a moderate activity against HIV-1 in PBM cells (3.4 μM). None of the other compounds showed any significant activities against HIV-1, HBV, HSV-1, HSV-2, and toxicity in Veto, CEM, and PBM cell lines up to 100 μM. The X-ray structure of the 5-iodocytosine analog showed a 2'- exo/3'-endo conformation for the carbohydrate moiety, which is different from those of the biologically active compounds (-)-FTC and L-FMAU.
- Kotra, Lakshmi P.,Xiang, Yuejun,Gary Newton,Schinazi, Raymond F.,Cheng, Yung-C.,Chu, Chung K.
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p. 3635 - 3644
(2007/10/03)
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