- 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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- 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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- Stereoselective synthesis and antiproliferative activity of the isomeric sphinganine analogues
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A flexible synthetic approach to biologically active sphingoid base-like compounds with a 3-amino-1,2-diol framework was achieved through a [3,3]-sigmatropic rearrangement and late stage olefin cross-metathesis as the key transformations. The stereochemistry of the newly created stereogenic centre was assigned via a single crystal X-ray analysis of the (4S,5R)-5-(hydroxymethyl)-4-vinyloxazolidine-2-thione. In order to rationalise the observed stereoselectivity of the aza-Claisen rearrangement, DFT calculations were carried out. The targeted isomeric sphingoid bases were screened in vitro for anticancer activity on a panel of seven human malignant cell lines. Cell viability experiments revealed that C17-homologues are more active than their C12 congeners.
- ?onková, Miroslava,Martinková, Miroslava,Gonda, Jozef,Jacková, Dominika,Pilátová, Martina Bago,Kupka, Daniel,Jáger, Dávid
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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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- 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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- Total synthesis of branimycin: An evolutionary approach
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The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization. Competitive approach: The first total synthesis of the macrolactone antibiotic branimycin is described (see figure). The dehydrodecalin core was targeted via five competing approaches featuring various kinds of chiral elements and ring-closing methodology. In this "Darwinian" struggle the most successful route emerged and led to the completion of the synthesis. Copyright
- Enev, Valentin S.,Felzmann, Wolfgang,Gromov, Alexey,Marchart, Stefan,Mulzer, Johann
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p. 9651 - 9668
(2012/09/21)
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- Synthesis and evaluation of eight- and four-membered iminosugar analogues as inhibitors of testicular ceramide-specific glucosyltransferase, testicular β-glucosidase 2, and other glycosidases
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Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve ring-closing metathesis and Sharpless asymmetric dihydroxylation and for the four-membered analogues Sharpless epoxidation, epoxide ring-opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6) was moderately active against rat-derived ceramide-specific glucosyltransferase, and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3S,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25) displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase, and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC50 of 600 nM and β-glucosidase (almond) with an IC50 of 20 μM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied.
- Lee, Jae Chul,Francis, Subhashree,Dutta, Dinah,Gupta, Vijayalaxmi,Yang, Yan,Zhu, Jin-Yi,Tash, Joseph S.,Schoenbrunn, Ernst,Georg, Gunda I.
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experimental part
p. 3082 - 3098
(2012/05/31)
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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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- Design, synthesis, and X-ray structure of substituted bis-tetrahydrofuran (bis-THF)-derived potent HIV-1 protease inhibitors
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We investigated substituted bis-THF-derived HIV-1 protease inhibitors in order to enhance ligand-binding site interactions in the HIV-1 protease active site. In this context, we have carried out convenient syntheses of optically active bis-THF and C4-substituted bis-THF ligands using a [2,3]-sigmatropic rearrangement as the key step. The synthesis provided convenient access to a number of substituted bis-THF derivatives. Incorporation of these ligands led to a series of potent HIV-1 protease inhibitors. Inhibitor 23c turned out to be the most potent (Ki = 2.9 pM; IC50 = 2.4 nM) among the inhibitors. An X-ray structure of 23c-bound HIV-1 protease showed extensive interactions of the inhibitor with the protease active site, including a unique water-mediated hydrogen bond to the Gly-48 amide NH in the S2 site.
- Ghosh, Arun K.,Martyr, Cuthbert D.,Steffey, Melinda,Wang, Yuan-Fang,Agniswamy, Johnson,Amano, Masayuki,Weber, Irene T.,Mitsuya, Hiroaki
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body text
p. 298 - 302
(2011/06/21)
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- An improved two-step synthetic route to primary allylic alcohols from aldehydes
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An improved two-step synthetic route to allylic alcohols from aldehydes has been developed. A modification of the HWE reaction in H2O-2-PrOH (1 : 1) and a convenient protocol to prepare AlH3 in THF from LiAlH 4 and n-BuBr are the key factors in the improvement.
- Liu, Zheng,Gong, Yaqiong,Byun, Hoe-Sup,Bittman, Robert
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experimental part
p. 470 - 475
(2010/06/14)
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- One-pot, fluoride-promoted wittig reaction
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A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl -bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced ,-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl -bromopropionate, -bromo acetonitrile, and -bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected ,-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.
- Fumagalli, Tiziano,Sello, Guido,Orsini, Fulvia
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experimental part
p. 2178 - 2195
(2009/12/01)
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- Diazo reagents in copper(I)-catalyzed olefination of aldehydes
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The olefination of aldehydes to synthesize unsaturated ketones, esters, amides and phosphonates using diazo reagents and triphenylphosphine in the presence of copper(I) iodide as catalyst, is described. Good to excellent E:Z selectivities as well as yields were obtained for a large variety of aliphatic, aromatic and heteroaromatic aldehydes. The reaction showed also an excellent functional group compatibility and aldehydes were selectively reacted in the presence of ketone, nitro, amine, ether, acetal, thioether and halide groups. The use of a cost-effective copper salt as a catalyst is advantageous compared to previously reported expensive transition metal complexes. The method was used in the total synthesis of the scutifoliamide A, a biologically active compound that exhibits antifungal activity.
- Lebel, Helene,Davi, Michael
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supporting information; experimental part
p. 2352 - 2358
(2009/10/02)
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- The formal synthesis of isofebrifugine using stereoselective intramolecular Michael addition
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The formal synthesis of isofebrifugine, a bioactive alkaloid, was achieved via a stereoselective intramolecular Michael addition reaction from d-mannitol.
- Sudhakar, Neela,Srinivasulu, Gannoju,Rao, Ganipisetti Srinivas,Rao, Batchu Venkateswara
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experimental part
p. 2153 - 2158
(2009/04/05)
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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 5
(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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- 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 21
(2008/06/13)
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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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- Stereoselective synthesis of chiral tetrahydrofurans with potent 5-LO inhibitory activity
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Chiral glyceraldehydes have been exploited for the design of convenient and scalable synthetic approaches to chiral tetrahydrofurans, which have potential as potent 5-lipoxygenase (5-LO) inhibitors. The synthesis of all four possible stereoisomers by a general methodology is reported; wherein the chirons derived from the glyceraldehyde derivatives on reaction with homopropargyl ether, cyclization and further reactions gave the targets.
- Sharma,Punna, Sreenivas,Krishna, Palakodety Radha,Chorghade, Mukund S.,Ley, Steven V.
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p. 1125 - 1133
(2007/10/03)
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- Stereoselective syntheses of pharmaceutically relevant chiral tetrahydrofurans from (S)- and (R)-glyceraldehyde derivatives
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A practically simple and flexible method of making chiral tetrahydrofurans of therapeutic relevance is reported from glyceraldehyde derivatives as chiral synthons. One of the stereocentres is derived from glyceraldehyde derivatives, while the other one is introduced by Sharpless asymmetric epoxidation using either (+)- or (-)-DIPT.
- Sharma,Punna, Sreenivas,Rajendra Prasad,Krishna, Palakodety Radna,Chorghade, Mukund S.,Ley, Steven V.
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p. 1113 - 1123
(2007/10/03)
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- Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted tetrahydrofurans using a sulfoxonium ylide
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Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects. Copyright
- Schomaker, Jennifer M.,Pulgam, Veera Reddy,Borhan, Babak
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p. 13600 - 13601
(2007/10/03)
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- Crude D-(+)-Glyceraldehyde Obtained from D-Mannitol-Diacetonide by Oxidative Cleavage with Sodium Periodate: Its Reactions with Nucleophilic Species
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The oxidative cleavage of D-(+)-mannitol-diacetonide with sodium periodate lead to a mixture of D-(+)-glyceraldehyde, its hydrate and oligomeric derivatives. In spite of the low concentration of free glyceraldehyde (estimated in ~20%, by NMR), good yields were obtained in nucleophilic additions involving this mixture and a variety of nucleophiles (amines, phosphonates, phosphoranes, nitronates, organometallic compounds).
- Domingos, Jorge L. De O.,Vilela, Guilherme V. M. De A.,Costa, Paulo R. R.,Dias, Ayres G.
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p. 589 - 598
(2007/10/03)
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- Synthesis of (-)-tetrodotoxin: Preparation of an advanced cyclohexenone intermediate
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The preparation of an advanced intermediate toward the enantioselective synthesis of tetrodotoxin is outlined. The enantiomerically pure cyclopentene 15 was generated from ketone 14 by alkylidene carbene insertion with retention of absolute configuration. An ozonolysis/aldol sequence first produced the trans cyclohexenone, which upon epimerization gave the more stable cis enone 18.
- Taber, Douglass F.,Storck, Pierre H.
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p. 7768 - 7771
(2007/10/03)
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- Utilization of 1-Oxa-2,2-(dimesityl)silacyclopentane acetals in the stereoselective synthesis of polyols
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We have developed a route for the stereoselective synthesis of 1-oxa-2,2-(dimesityl)silacyclopentane acetals, intermediates in the synthesis of highly functionalized 1,3-diols. This route involves a diastereoselective conjugate addition reaction of a hydrosilyl anion, a subsequent diastereoselective enolate alkylation, and a fluoride-catalyzed intramolecular hydrosilylation reaction to afford the oxasilacyclopentane acetal. A highly selective nucleophilic substitution reaction, followed by oxidation of the C-Si bond, leads to the desired polyol. Copyright
- Powell, Sharon A.,Tenenbaum, Jason M.,Woerpel
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p. 12648 - 12649
(2007/10/03)
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- Substituted oxygen alicyclic compounds, including methods for synthesis thereof
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The invention provides new methods for preparation of cyclic oxygen compounds, including 2,5-disubstituted tetahydrofurans, 2,6-disubstituted tetrahydropyrans, 2,7-disubstituted oxepanes and 2,8-oxocanes. The invention also provides new cyclic oxygen compounds and pharmaceutical compositions and therapeutic methods that comprise such compounds.
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- Methods for synthesis of substituted tetrahydrofuran compound
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The invention includes inter alia new methods for preparation of the pharmaceutically active compound 2-(4-fluorophenoxymethyl)-5-(4-N-hydroxyureidyl-1-butynyl)-tetrahydrofuran and precursors thereof.
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- Stereoselective synthesis of highly oxygenated cyclohexanes through a [3+3] annulation approach
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The synthesis of highly oxygenated cyclohexanes has been achieved through a Michael-Wittig protocol via a [3+3] annulation of the enal that is derived from 2,3-O-isopropylidene-(R)-glyceraldehyde. The γ-alkoxy enal system is responsible for the stereosele
- Sharma,Prasad, Rajendra T.,Krishna, Palakodety Radha,Krishnudu,Ramana Rao,Kunwar
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p. 4499 - 4507
(2007/10/03)
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- Manganese dioxide can oxidise unactivated alcohols under in situ oxidation-Wittig conditions
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The in situ alcohol oxidation-Wittig reaction using manganese dioxide as the oxidant has been applied to semi-activated and, for the first time, unactivated alcohols to furnish the corresponding α,β-unsaturated esters.
- Blackburn, Leonie,Wei, Xudong,Taylor, Richard J. K.
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p. 1337 - 1338
(2007/10/03)
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- Stereoselective synthesis of 1-hydroxymethyl-4-phenylsulfonylbutadienes
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Stereoselective syntheses of 1-hydroxymethyl-4-phenylsulfonylbutadienes were achieved from unsaturated sulfones which were easily obtained from D-Mannitol.
- Urones, Julio G.,Marcos, Isidro S.,Garrido, Narciso M.,Basabe,Bastida, Angel J.,San Feliciano, Sonia G.,Díez, David,Goodman, Jonathan M.
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p. 1361 - 1363
(2007/10/03)
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- Synthesis of unsaturated esters from aldehydes: An inexpensive, practical alternative to the Horner-Emmons reaction under neutral conditions
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A practical, efficient, and mild process is described for the synthesis of unsaturated esters from aldehydes in good yields and diastereoselectivities. All of the reagents used in the protocol are commercially available at a nominal price: N2CHCO2Et, catalytic (1 mol%) ReOCl3(PPh3)2, and (EtO)3P. Additionally, the reaction process can be carried out successfully in good yields (85%) and diastereoselectivities (>20:1) with reagent-grade solvent without prior purification of the reagents.
- Ledford, Brian E.,Carreira, Erick M.
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p. 8125 - 8128
(2007/10/03)
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- Cycloaddition Reaction of 2,2-Dimethyl-3,4-dihydro-2H-pyrrole N-Oxide With Unsaturated Sugar Lactones and Esters
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Intermolecular asymmetric 1,3-dipolar cycloaddition of 2,2-dimethyl-3,4-dihydro-2H-pyrrole N-oxide with optically active α,β-unsaturated esters 1,2 gave the diastereomers 8,9,10 and with sugar lactones 3 and 6 gave stereoselectively the cycloadduct 11 and 12.The stereochemistry of the products has been established using high field nmr techniques.The major adducts 11 and 12 arise from an exo transition state and anti-approach, indicating the dominance of steric factors over secondary orbital interactions.
- Baskaran, S.,Trivedi, Girish.K.
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p. 1853 - 1864
(2007/10/03)
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- Stereoselective Synthesis of Enantiopure 4,5-Dihydroxy-2-Alkene Esters from Simple Allylic Alcohols
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A general stereoselective synthesis of 4,5-dihydroxy-2-alkene esters is developed using the photo-induced rearrangement of α,β-epoxy diazomethyl ketones.Starting with readily available enantiopure allylic alcohols that contain a chiral center at C4, i.e. a protected secondary alcohol function, a neighboring stereogenic center is introduced by irradiation of the mentioned diazo ketones.The configuration of this newly introduced center is determined by the chiral inductor used in the Sharpless epoxidation of the allylic alcohol and therefore can be selected at will.
- Aar, Marcel P. M. van,Thijs, Lambertus,Zwanenburg, Binne
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p. 9699 - 9712
(2007/10/02)
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- New routes to isomerically pure cyclopentanes. Synthesis of (3S,4S)-3,4-bis(benzoyloxymethyl)cyclopentan-1-ol using palladium-catalyzed [2 + 3] cycloaddition
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Two different routes to the enantiomerically pure (3S,4S)-3,4-bis(benzoyloxymethyl)cyclopentan-1-ol (6), a useful intermediate for the synthesis of a number of natural products, are described. Formation of the chiral five-membered ring was achieved using a palladium-catalyzed [2 + 3] cycloaddition between 2-(acetoxymethyl)-3-(trimethylsilyl)propene and optically active methyl (E)-3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-α-D-xylo-hept-5- enofuranuronate or ethyl (4R,Z)-4,5-(isopropylidenedioxy)pent-2-enoate.
- Janson,Kvarnstrom,Svensson,Classon,Samuelsson
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p. 129 - 133
(2007/10/02)
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- Conformational Diagnosis of Diethyl (4S,5S)-4,5-Bis(tert-butyldimethylsiloxy)-2E,6E-octadienedioate Based on the Stereochemical Outcomes of Representative Reactions As Compared with Those of Its 4,5-O-Isopropylidene Derivatives and on a Dichroic Exciton C
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In order to gain more insight into the conformation of diethyl (4S,5S)-4,5-bis(tert-butyldimethylsiloxy)-2E,6E-octadienedioate (1) experimentally, some appropriate reactions of 1 and its derivative (S,S)-3, which bears isopropylidene protecting groups, ha
- Saito, Seiki,Narahara, Osamu,Ishikawa, Teruhiko,Asahara, Masahiro,Moriwake, Toshio,et al.
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p. 6292 - 6302
(2007/10/02)
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- Stereoselective synthesis of 3-azido-2,3-dideoxy-D-ribose derivatives and its utilization for the synthesis of anti-HIV nucleosides [1]
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Detail account of the synthesis of 3'-azido nucleosides utilizing 3- azido-2,3-dideoxy-D-ribose derivative 7 as the key intermediate was described. The key intermediate 7 was synthesized from D-mannitol in 8 steps in a preparative scale. The Michael reaction of the azide group with α,β- unsaturated-γ-butyrolactone 4 was affected by the steric bulkiness of the substituent at the 5-O position. A bulky t-butyldiphenylsilyl substitution at 5-O gave almost exclusively the α-azido adduct 5b, while unsubstitution at 5-O produced I:1 mixture of α-and β-adducts. The ratio of α to β anomers in the condensation between azido acetate 7a and pyrimidine bases for the preparation of AZT and AZDU was greatly influenced by the solvent and the Lewis acid catalyst used. In the synthesis of 12(AZDU, CS-87), the combination of dichloroethane and trimethylsilyl triflate gave an optimal result, while in the case of 14(AZT), various conditions gave similar ratio of α,β anomers. The azido intermediate 7b was also utilized for the synthesis of several 3'-azido purine-like nucleosides 16-27. The glycosylation was also affected by the Lewis acid catalyst. Boron trifluoride etherate gave the desired N1-glycosylated compounds in which the α-anomer was major, but other catalysts such as trimethylsilyl triflate or stannic chloride produced N2-glycosylated compounds as the major products. The newly synthesized purine-like compounds have been tested against HIV, however, none of them showed any significant activity.
- Jeong,Beach,Chu
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p. 1445 - 1452
(2007/10/02)
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- Asymmetric dihydroxylation of acrolein acetals: Synthesis of stable equivalents of Enantiopure glyceraldehyde and glycidaldehyde
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Asymmetric dihydroxylation (ADH) of acrolein acetals afforded optically active glyceraldehyde equivalents. Enantiopure 3-(1,2-dihydroxyethyl)-1,5-dihydro-3H-2,4-benzodioxepine 3, a protected glyceraldehyde, was obtained from the corresponding acrolein acetal 2 by ADH and subsequent recrystallization. Enantiopure 3-(1,2-epoxyethyl)-1,5-dihydro-3H-2,4-benzodioxepine 5, a protected glycidaldehyde, was produced in two steps from 3.
- Oi, Ryu,Sharpless, K. Barry
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p. 2095 - 2098
(2007/10/02)
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- The Synthesis of Optically Pure Epoxyalkyl β-D-Glucosides and β-Cellobiosides as Active-Site Directed Inhibitors of Some β-Glucan Hydrolases
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(2R)- and (2S)-2,3-Epoxypropyl, (3R)- and (3S)-3,4-epoxybutyl and (4S)-4,5-epoxypentyl β-D-glucopyranoside, together with the (3R)- and (3S)-3,4-epoxybutyl β-cellobioside, have been prepared by condensation of a glycosyl bromide with the appropriate enantiomer of a chiral alcohol containing a diol protected as an isopropylidene acetal, and subsequent manipulation of the unmasked diol to the epoxide function.As well, in an improvement to the whole process, both diastereoisomers of the various epoxypropyl and epoxybutyl glycosides were available, from just the one enantiomer of the alcohol by an alternative manipulation of the diol.Finally, precursors to 2,3-epoxy-4-hydroxybutyl β-D-glucosides and β-cellobiosides were prepared in high optical purity by Sharpless asymmetric epoxidation of the appropriate 4-hydroxybutyl-2-enyl glycosides.
- Rodriguez, Evelyn B.,Scally, Gavin D.,Stick, Robert V.
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p. 1391 - 1405
(2007/10/02)
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- Efficient Procedures for in situ Trapping of (R)- and (S)-Glyceraldehyde acetonides by Stabilized Wittig Reagents
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Practical, high yielding procedures are described whereby useful chiral enones and enoates can be prepared from either (R)- or (S)-glyceraldehyde acetonide.The labile aldehydes, formed from their precursors by lead tetraacetate cleavage, are reacted with stabilized Wittig reagents in situ.
- Leonard, John,Mohialdin, Soad,Swain, Philip
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p. 3529 - 3534
(2007/10/02)
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- STEREOSELECTIVE SN2' ADDITIONS OF ORGANOCUPRATES TO HOMOCHIRAL ACYLIC VINYLOXIRANES
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Additions of various methylcopper reagents to the homochiral acylic vinyloxiranes A14, A15, B6-B9, and C5, C6 were performed in order to evaluate E/Z and syn/anti preferences.The unsubstituted oxiranes A14 and A15 gave a mixture of SN2 and SN2' substitution products with the four reagents examined, LiMe2Cu, LiMeCuCN, BrMgMe2Cu, and LiMeCuI*BF3.The more highly substituted systems B6-B9 derived from geraniol and C5, C6 derived from nerol yielded only SN2' products.The (Z)-allylic alcohol derivatives B8 and C6 and LiMeCuCN gave the best anti/syn ratios (99:1 and 97:3, respectively).In both cases the newly formed double bond was exclusively E.
- Marshall, James A.,Trometer, Joseph D.,Cleary, Darryl G.
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p. 391 - 402
(2007/10/02)
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- AN EFFICIENT TOTAL SYNTHESIS OF 3'-AZIDO-3'-DEOXYTHYMIDINE (AZT) AND 3'-AZIDO-2',3'-DIDEOXYURIDINE (AZDDU, CS-87) FROM D-MANNITOL
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An efficient stereoselective total synthesis of 3'-azido-3'deoxythymidine (AZT) and 3'-azido-2',3'-dideoxyuridine (AZDDU, CS-87) from readily available and inexpensive starting material, D-mannitol has been achieved.
- Chu, Chung K.,Beach, J. Warren,Ullas, Giliyar V.,Kosugi, Yoshiyuki
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p. 5349 - 5352
(2007/10/02)
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- A Short Synthesis of (S)-5-Hydroxy-2-penten-4-olide from D-Mannitol via 2,3-O-Isopropylidene-D-glyceraldehyde
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(S)-5-Hydroxy-2-penten-4-olide (5) was synthesized in three steps starting from D-mannitol bis(acetonide) (1), via D-glyceraldehyde acetonide (2) by Z-selective Wittig reaction, acid-catalyzed lactonization and crystallization with a total yield of 40percent.
- Haefele, Brigitte,Jaeger, Volker
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- A Convenient Synthesis of L-(S)-Glyceraldehyde Acetonide from L-Ascorbic Acid
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L-(S)-glyceraldehyde acetonide is easily obtained from L-ascorbic acid by three-step procedure.Since the aldehyde is rather unstable in pure form it is more convenient to use it as an aqueous solution.It was used to synthesize L-(R)-glycerol acetonide, monocyclic-β-lactams, and olefins (by Wittig reaction).
- Hubschwerlen, Christian
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p. 962 - 964
(2007/10/02)
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- Practical Synthesis of Some Versatile Chiral Building Blocks from (D)-Mannitol
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The three chiral building blocks ethyl 4,5-O-isopropylidene-(E)-(S)-4,5-dihydroxy-2-pentenoate , (S)-5-hydroxy-4-pentanolide , and (S)-5-hydroxy-2-penten-4-olide are conveniently prepared from 1,2:5,6-di-O-isopropylidene-D-mannitol (4) via a glycol cleavage and Horner-Emmons reaction sequence.
- Takano, Seiichi,Kurotaki, Ayako,Takahashi, Michiyasu,Ogasawara, Kunio
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p. 403 - 406
(2007/10/02)
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