- Total Synthesis of γ-Hydroxy-α,β-Unsaturated Aldehydic Esters of Cholesterol and 2-Lysophosphatidylcholine
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Free radical-induced oxidation of polyunsaturated fatty esters in low-density lipoproteins (LDLs) generates 2-lysophosphatidylcholine (PC) and cholesterol esters of γ-hydroxy-α,β-unsaturated aldehydic acids that covalently modify LDL protein, and protein adducts of the corresponding acids are found in human blood. The chemistry and structures of these compounds resemble those of (E)-4-hydroxy-2-nonenal (HNE), previously considered the most cytotoxic aldehyde released during peroxidation of linoleate and arachidonate esters. The present report details total syntheses of 2-lyso-PC and cholesteryl esters of (E)-9-hydroxy-12-oxododec-10-enoic and (E)-5-hydroxy-8-oxooct-6-enoic acid that presumably are derived in vivo from linoleate and arachidonate esters, respectively. The syntheses depend on the use of a 3,3-dimethyl-2,4-dioxolanyl moiety as a latent aldehyde from which the chemically sensitive γ-hydroxy-α,β-unsaturated aldehyde array can be generated in the final step. For the cholesteryl esters, generation of the aldehyde group by oxidative cleavage of a vicinal diol could be accomplished in very good yields with periodate. However, for esters of 2-lyso-PC, the target aldehydes were not obtained upon treatment of vicinal diol precursors with periodate owing to a novel oxidative cleavage of the γ-hydroxy-α,β-unsaturated aldehydes by periodate. Fortunately, treatment of the vicinal diol precursors with Pb(OAc)4 at -80 deg C delivered good yields (82-85 percent) of the desired phospholipid aldehydes.
- Deng, Yijun,Salomon, Robert G.
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- Structure-activity relationship studies of symmetrical cationic bolasomes as non-viral gene vectors
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Compared to traditional cationic lipids, bola-type lipids have received much less attention despite their advantages including the ability to form more stable and regular-shaped liposomes. In this report, a series of novel symmetric cationic bolalipids based on lysine or cyclen headgroups were designed and synthesized. Structure-activity relationships including the effect of the hydrophobic chain length and cationic headgroup on liposome formation, DNA binding, the physical property of bolasomes, and gene transfection were systematically studied. Results reveal that an appropriate hydrophobic chain length is essential to form nano-sized bolasomes with good DNA binding and condensation ability. MTS-based cell viability assays showed low cytotoxicity of these bolasome/DNA complexes. Lys-14-10, which has a 36-atom-length hydrophobic chain, exhibited the best transfection efficiency in the two cell lines. Flow cytometry and confocal laser microscopy assays reveal that the bolaplexes formed from bolalipids with such a chain might induce the highest cellular uptake. For the cationic headgroup, lysine is more suitable than cyclen for such a bola-type vector. Although the TEs of these bolalipids are still lower than commercially used non-bola lipid lipofectamine 2000, this study may give us some clues for the design of novel bolalipids with higher TE and biocompatibility.
- Huang, Zheng,Zhang, Yi-Mei,Cheng, Qian,Zhang, Ji,Liu, Yan-Hong,Wang, Bing,Yu, Xiao-Qi
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- Synthesis and determination of absolute configuration of α-pyrones isolated from penicillium corylophilum
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The first total synthesis of (S)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one, 4-hydroxy-3-methyl-6-((2S,4R)-2,4,11-trihydroxyundecyl)-2H-pyran-2-one, and its unnatural 2R,4R-isomer starting from commercially available 1,8-octanediol is described. The synthesis led to the revision of the proposed structural assignment of the natural product as (R)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one. The key steps include chiral auxiliary mediated asymmetric acetate aldol reaction, dianion addition, and base mediated cyclization to form an α-pyrone ring.
- Yadav,Ganganna,Dutta, Palash,Singarapu, Kiran K.
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Read Online
- Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites
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Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than pa
- Dietzen, Noah M.,Arcario, Mark J.,Chen, Lawrence J.,Petroff, John T.,Moreland, K. Trent,Krishnan, Kathiresan,Brannigan, Grace,Covey, Douglas F.,Cheng, Wayland W. L.
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- Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I
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The stereoselective total synthesis of strongylodiol H and I has been accomplished. The synthetic procedure comprised the stereoselective reduction of a ketone functionality in an ene–yne–one employing CBS as a catalyst and a Cadiot–Chodkiewicz coupling r
- Gangadhar, Pamarthi,Ramakrishna, Sayini,Venkateswarlu, Ponneri,Srihari, Pabbaraja
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supporting information
p. 2313 - 2320
(2018/09/14)
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- Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes
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Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture broth of Streptomyces sp. KP-197. They have a unique structural motif, including a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched but non-branched in the case of jietacin C. During a drug discovery program, we found that jietacins display potent anthelmintic activity against parasitic nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300 mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that jietacins have potential for drug discovery research. In order to create a novel anthelmintic agent, we performed design, synthesis, and biological evaluation of jietacin derivatives against parasitic nematodes. Of these derivatives, we found that a fully synthesized simplified derivative exhibited better anthelmintic activity against three parasitic nematodes than natural jietacins. In addition, it had a better efficacy in vivo through oral administration against a mouse nematode. This indicated that the azoxy motif could prove useful as a template for anthelmintic discovery, possibly creating a class of anthelmintic with novel skeletons, a potential new mode of action, and providing further insight for rational drug design.
- Sugawara, Akihiro,Kubo, Masahiko,Hirose, Tomoyasu,Yahagi, Kyoichi,Tsunoda, Noriaki,Noguchi, Yoshihiko,Nakashima, Takuji,Takahashi, Yoko,Welz, Claudia,Mueller, Dennis,Mertens, Christina,Koebberling, Johannes,ōmura, Satoshi,Sunazuka, Toshiaki
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p. 524 - 538
(2018/01/17)
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- IMINOSUGARS USEFUL FOR THE TREATMENT OF VIRAL DISEASES
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Formula IA, ad their use for treating viral infections.
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Page/Page column 41; 43
(2016/06/01)
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- Efficient preparation of apically substituted diamondoid derivatives
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We present an effective three-step chromatography-free sequence for the preparation of apical monohydroxy derivatives of diamantane, triamantane, and [121]tetramantane from the corresponding bis-apical diols utilizing tert-butyldimethylsilyl chloride as t
- Kahl, Paul,Tkachenko, Boryslav A.,Novikovsky, Anatoliy A.,Becker, Jonathan,Dahl, Jeremy E. P.,Carlson, Robert M. K.,Fokin, Andrey A.,Schreiner, Peter R.
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p. 787 - 798
(2014/04/03)
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- Synthesis and properties of fluorous benzoquinones and their application in deprotection of silyl ethers
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1,4-Benzoquinone derivatives bearing trifluoromethyl, perfluorobutyl and perfluorohexyl groups were prepared and employed in the deprotection of silyl ethers. The fluorous character of these compounds was examined by measuring the partition coefficient between the fluorous and organic solvents. The benzoquinone derivatives showed significant fluorous character, indicating that they can be recovered from the reaction mixtures using a fluorous/organic biphasic system. The oxidising ability of the fluorous benzoquinones was estimated by cyclic voltammetry, and these compounds were found to be strong oxidisers. The fluorous benzoquinones were utilised in the oxidative desilylation of silyl ethers to afford the deprotected alcohols in high yield. In addition, the reduced fluorous benzoquinones were recovered from the reaction mixtures in good yields using a fluorous/organic biphasic system. This journal is the Partner Organisations 2014.
- Matsubara, Hiroshi,Maegawa, Takahiko,Kita, Yasuaki,Yokoji, Takato,Nomoto, Akihiro
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supporting information
p. 5442 - 5447
(2014/07/21)
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- Stereoselective total synthesis of crucigasterins A, B and D through a common intermediate
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The first stereoselective total synthesis of the marine-derived antimicrobial amino-alcohols, crucigasterins A, B and D has been accomplished through a common intermediate starting from pent-3-en-1-ol. The method involves the Sharpless asymmetric aminohyd
- Kumar, Jayprakash Narayan,Das, Biswanath
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p. 3865 - 3867
(2013/07/19)
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- Construction of carbo- And heterocycles using radical relay cyclizations initiated by alkoxy radicals
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An efficient method for the rapid construction of carbo- and heterocycles has been developed using radical relay cyclizations initiated by alkoxy radicals. Linear substrates were cyclized to form a wide range of cyclopentane, pyrrolidine, tetrahydropyran, and tetrahydrofuran derivatives in excellent yields. This methodology was utilized as a key step in the synthesis of the tetrahydrofuran fragment in (-)-amphidino-lide K.
- Zhu, Hai,Wickenden, Jason G.,Campbell, Natalie E.,Leung, Joe C. T.,Johnson, Kayli M.,Sammis, Glenn M.
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supporting information; experimental part
p. 2019 - 2022
(2009/09/08)
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- Cyclization reactions through DDQ-mediated vinyl oxazolidinone oxidation
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Vinyl oxazolidinones react with DDQ to form α,β-unsaturated acyliminium ions in a new method for forming electrophiles under oxidative conditions. Appended nucleophiles undergo 1,4-addition reactions with these intermediates to form cyclic vinyl oxazolidinones with good levels of diastereocontrol, highlighting a new approach to utilizing oxidative carbon-hydrogen bond functionalization to increase molecular complexity.
- Liu, Lei,Floreancig, Paul E.
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supporting information; scheme or table
p. 3152 - 3155
(2009/12/05)
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- Novel monodisperse PEG-grafted polystyrene resins: synthesis and application in gel-phase 13C NMR spectroscopy
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A series of novel polystyrene-oligo(oxyethylene) graft copolymers containing monodisperse PEG units (n = 2-12) have been synthesized and examined concerning their applicability for gel-phase 13C NMR spectroscopy. A strong correlation between the graft length and the line widths in the gel-phase spectra was observed. By grafting a PEG chain with only eight units, it was possible to obtain results similar to TentaGel resin. Additionally, TOF-SIMS images were recorded in order to evaluate the homogeneity of the resin.
- Braunshier, Christian,Hametner, Christian,Fr?hlich, Johannes,Schn?ller, Johannes,Hutter, Herbert
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scheme or table
p. 7103 - 7105
(2009/04/10)
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- Synthesis of 5-(7-hydroxyheptyl)-1,2-dithiolan-3-one 1-oxide, a core functionality of antibiotic leinamycin
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5-(7-Hydroxyheptyl)-1,2-dithiolan-3-one 1-oxide was designed and synthesized in our laboratories that contain the heterocycle of 1,2-dithiolan-3-one 1-oxide, a reactive core of antibiotic leinamycin. In addition, the activated ester of 5-(7-hydroxyheptyl)-1,2-dithiolan-3-one 1-oxide was prepared, which presumably is useful for coupling this DNA-cleaving functionality to certain DNA-binding agents.
- Lee, Alex H. F.,Chen, Jian,Chan, Albert S. C.,Li, Tianhu
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p. 1163 - 1174
(2007/10/03)
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- Stereoselective transannular radical cyclization of unsaturated cyclic iodoacetals yielding medium-sized carbocycles
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Iodoacetalization of (Z)-allylic alcohols 1a-1c in high dilution followed by transannular radical cyclization gave cis-fused bicyclic acetals 5a-5c and 6a-6c with high diastereoselectivities (84-93% de) and in 54-62% yields. The reaction of 2a gave 5a and 6a with 77% de, but in low yield. However, the sequential reaction of the higher homologue 1d and (E)-allylic alcohols 2b-2d showed poor diastereoselectivities.
- Nagano,Tada,Isobe,Yajima
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p. 1193 - 1195
(2007/10/03)
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- Selective deprotection of t-butyldiphenylsilyl ethers in the presence of t-butyldimethylsilyl ethers by tetrabutylammonium fluoride, acetic acid, and water
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The selective deprotection of t-butyldiphenylsilyl ethers in the presence of t-butyldimethylsilyl ethers by tetrabutylammonium fluoride, acetic acid, and water has been realize.
- Higashibayashi,Shinko,Ishizu,Hashimoto,Shirahama,Nakata
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p. 1306 - 1308
(2007/10/03)
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- Total synthesis of the threo, trans, threo-mono-tetrahydrofuran annonaceous acetogenin longifolicin
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An enantioselective synthesis of the C35 threo, trans, threo-mono-tetrahydrofuran annonaceous acetogenin longifolicin through use of chiral long-chain α-and γ-OMOM allylic stannanes and (E)-ethyl 3-formyl-2-propenoate as the starting materials
- Marshall, James A.,Jiang, Hongjian
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p. 1493 - 1496
(2007/10/03)
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- Enantiomeric synthesis of the key synthon of the oviposition-deterring pheromone of Rhagoletis cerasi L.
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A convenient and enantioselective synthesis of ethyl (8RS,15R)-6-acetoxy-15-hydroxyhexadecanoate 15 via a chemoenzymatic approach has been described.The salient features of the synthesis were operational simplicity, use of easily accessible materials, and
- Sharma, Anubha,Chattopadhyay, Subrata
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p. 4020 - 4026
(2007/10/03)
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- A remarkably simple process for monoprotecting diols
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Lipase from pig pancreas (PPL) has been shown to catalyse selectively the hydrolysis of alkane-1,n-diol bis-acetates into the corresponding monoacetate.
- Houille, Olivier,Schmittberger, Thierry,Uguen, Daniel
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p. 625 - 628
(2007/10/02)
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- Synthesis of (9Z,12Z,15E)- and (9E,12Z,15Z)-octadecatrienoic acids and their -radiolabelled analogs
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In order to study the effect of the double bonds geometry of linolenic acid (18:3 n-3) on its biological activities, (9Z,12Z,15E)- and (9E,12Z,15Z)-octadecatrienoic acids, found in many refined vegetable oils, were made by total synthesis. Synthesis of 18
- Eynard, Thierry,Vatele, Jean-Michel,Poullain, Didier,Noeel, Jean-Pierre,Chardigny, Jean-Michel,Sebedio, Jean-Louis
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p. 175 - 184
(2007/10/02)
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- Symmetrical Alkoxysilyl Ethers. A New Class of Alcohol-Protecting Groups. Preparation of tert-Butoxydiphenylsilyl Ethers
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The preparation and evaluation of a new class of alcohol-protecting groups, the alkoxydiphenylsilyl ethers, are described.In particular, tert-butoxydiphenylsilyl ethers, which can be formed from primary, secondary, or tertiary alcohols and tert-butoxydiphenylsilyl chloride, offer the useful synthetic properties of acid stability and high fluoride reactivity.Opportunities for selective silyl group cleavage are highlighted.
- Gillard, John W.,Fortin, Rejean,Morton, Howard E.,Yoakim, Christiane,Quesnelle, Claude A.,at al.
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p. 2602 - 2608
(2007/10/02)
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- DISTANNOXANE-CATALYZED CLEAVAGE OF ACETALS AND SILYL ETHERS
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Deprotection of acetals including tetrahydropyranyl ethers and silyl ethers can be achieved under neutral conditions by use of a distannoxane catalyst in excellent yields.
- Otera, Junzo,Nozaki, Hitosi
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p. 5743 - 5746
(2007/10/02)
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- tert-BUTYLMETHOXYPHENYLSILYL ETHER - A NEW SELECTIVE, STABLE ALCOHOL PROTECTING GROUP WITH REMARKABLE LABILITY TO FLUORIDE.
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tert-Butylmethoxyphenylsilyl ethers, which can be formed from primary, secondary or tertiary alcohols and tert-butylmethoxyphenylsilyl bromide, are selectively cleaved by fluoride in the presence of other silyl ethers.
- Guindon, Yvan,Fortin, Rejean,Yoakim, Christiane,Gillard, John W.
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p. 4717 - 4720
(2007/10/02)
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- Dimethylboron Bromide and Diphenylboron Bromide: Cleavage of Acetals and Ketals
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The cleavage of various acetal and ketal derivatives by the use of dialkyl- and diarylboron halides is described.Acetals and ketals readily react with dimethylboron bromide or diphenylboron bromide at -78 deg C to give the corresponding carbonyl compounds in excellent yield.Under similar reaction conditions MEM, MOM, and MTM ethers are smoothly converted to alcohols.Acetonides are also cleaved with dimethylboron bromide while THP and THF ethers and methyl glycosides react at room temperature.Mechanistic considerations of the cleavage reactions are presented.The chemoselective virtues of dimethylboron bromide are summarized.
- Guindon, Yvan,Yoakim, Christiane,Morton, Howard E.
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p. 3912 - 3920
(2007/10/02)
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