- SYNTHESIS OF (2Z,6Z,10Z,14E,18E)-FARNESYLFARNESOL
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Nine-step synthesis of the title triterpenol from (E,E)-farnesol using a two-stage cis-C5-homologation procedure is described.
- Moiseenkov, Alexander M.,Polunin, Evgeni V.,Semenovsky, Alexei V.
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- A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway
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A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C20 to C35 in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction. Copyright
- Radetich, Branko,Corey
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- Synergistic factors ensue high expediency in the synthesis of menaquinone [K2] analogue MK-6: Application to access an efficient one-pot protocol to MK-9
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Here we report a practical and efficient method for the synthesis of menaquinone vitamin (K2) analog MK-6 in all trans forms through “1 + 5 convergent synthetic approach” of pentaprenyl chloride with monoprenyl menadione derivative. In the synergistic factors, less efficient leaving group/more efficient nucleophile (Cl) in the substrate makes it more prominent reaction by eliminating all Sn2’ side reaction products. Further, the addition of acetic acid in the last step (desulfonation) of reaction sequence removes the limitations of the reactions in terms of cyclized side product (multiple reactions of pentaprenyl alcohol with Et3B), byproduct (Et3B, incendiary compound) formations and their interruption in the tricky purification processes. The utility of this method was further extended to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis. This approach is economical and efficient and avoids the awkward chromatographic separation processes.
- Yerramsetti, Nanaji,Dampanaboina, Lavanya,Mendu, Venugopal,Battula, Satyanarayana
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- Biosynthesis of sesterterpenes, head-to-tail triterpenes, and sesquarterpenes in Bacillus clausii: Identification of multifunctional enzymes and analysis of isoprenoid metabolites
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We performed functional analysis of recombinant enzymes and analysis of isoprenoid metabolites in Bacillus clausii to gain insights into the biosynthesis of rare terpenoid groups of sesterterpenes, head-to-tail triterpenes, and sesquarterpenes. We have identified an (all-E)-isoprenyl diphosphate synthase (E-IDS) homologue as a trifunctional geranylfarnesyl diphosphate (GFPP)/hexaprenyl diphosphate (HexPP)/heptaprenyl diphosphate (HepPP) synthase. In addition, we have redefined the function of a tetraprenyl-β-curcumene synthase homologue as that of a trifunctional sesterterpene/triterpene/sesquarterpene synthase. This study has revealed that GFPP, HexPP, and HepPP, intermediates of two isoprenoid pathways (acyclic terpenes and menaquinones), are biosynthesized by one trifunctional E-IDS. In addition, GFPP/HexPP and HepPP are the primary substrates for the biosynthesis of acyclic terpenes and menaquinone-7, respectively. Multifunctional terpene biosynthetic enzymes: Geranylfarnesyl diphosphate (GFPP), hexaprenyl diphosphate (HexPP), and heptaprenyl diphosphate (HepPP) are intermediates in two isoprenoid pathways and are biosynthesized by one trifunctional (all-E)-isoprenyl diphosphate synthase. GFPP/HexPP and HepPP are mainly utilized for the biosynthesis of acyclic terpenes and menaquinone-7, respectively.
- Ueda, Daijiro,Yamaga, Hiroaki,Murakami, Mizuki,Totsuka, Yusuke,Shinada, Tetsuro,Sato, Tsutomu
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p. 1371 - 1377
(2015/06/16)
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- Staphylococcus aureus penicillin-binding protein 2 can use depsi-lipid ii derived from vancomycin-resistant strains for cell wall synthesis
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Vancomycin-resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide-containing modified cell-wall precursors for the biosynthesis of peptidoglycan. Transglycosylase is responsible for the polymerization of the peptidoglycan, and the penicillin-binding protein 2 (PBP2) plays a major role in the polymerization among several transglycosylases of wild-type S. aureus. However, it is unclear whether VRSA processes the depsipeptide-containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi-lipid I, a cell-wall precursor of VRSA. By using this chemistry, we prepared a depsi-lipid II analogue as substrate for a cell-free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi-lipid II intermediate as efficiently as its normal substrate. Moreover, the system was successfully used to demonstrate the difference in the mode of action of the two antibiotics moenomycin and vancomycin. Copyright
- Nakamura, Jun,Yamashiro, Hidenori,Miya, Hiroto,Nishiguchi, Kenzo,Maki, Hideki,Arimoto, Hirokazu
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p. 12104 - 12112
(2013/09/23)
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- Synthesis of a comprehensive polyprenol library for the evaluation of bacterial enzyme lipid substrate specificity
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Polyprenols, a universal class of glycan-carrier lipids, play important roles in glycan biosynthesis in wide variety of living organisms. The chemical synthesis of natural polyisoprenols such as undecaprenol and dolichols, and even more so the synthesis o
- Wu, Baolin,Woodward, Robert,Wen, Liuqing,Wang, Xuan,Zhao, Guohui,Wang, Peng George
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p. 8162 - 8173
(2014/01/06)
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- GERANYLGERANYLACETONE DERIVATIVES
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Provided herein are geranylgeranylacetone derivatives and methods of using them.
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- Synthesis and NMR characterization of (Z, Z, Z, Z, E, E,ω)- heptaprenol
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We describe a practical, multigram synthesis of (2Z,6Z,10Z,14Z,18E,22E)-3, 7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-ol [(Z 4,E2,ω)-heptaprenol, 4] using the nerol-derived sulfone 8 as the key intermediate. Su
- Hesek, Dusan,Lee, Mijoon,Zajicek, Jaroslav,Fisher, Jed F.,Mobashery, Shahriar
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supporting information; experimental part
p. 13881 - 13888
(2012/10/08)
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- Modular synthesis of diphospholipid oligosaccharide fragments of the bacterial cell wall and their use to study the mechanism of moenomycin and other antibiotics
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We present a flexible, modular route to GlcNAc-MurNAc-oligosaccharides that can be readily converted into peptidoglycan (PG) fragments to serve as reagents for the study of bacterial enzymes that are targets for antibiotics. Demonstrating the utility of these synthetic PG substrates, we show that the tetrasaccharide substrate lipid IV (3), but not the disaccharide substrate lipid II (2), significantly increases the concentration of moenomycin A required to inhibit a prototypical PG-glycosyltransferase (PGT). These results imply that lipid IV and moenomycin A bind to the same site on the enzyme. We also show the moenomycin A inhibits the formation of elongated polysaccharide product but does not affect length distribution. We conclude that moenomycin A blocks PG-strand initiation rather than elongation or chain termination. Synthetic access to diphospholipid oligosaccharides will enable further studies of bacterial cell wall synthesis with the long-term goal of identifying novel antibiotics.
- Gampe, Christian M.,Tsukamoto, Hirokazu,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
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p. 9771 - 9778
(2012/02/15)
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- Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan
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The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse d-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical d-amino acids can be introduced into the bacterial cell wall.
- Lupoli, Tania J.,Tsukamoto, Hirokazu,Doud, Emma H.,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
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p. 10748 - 10751
(2011/09/13)
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- Solid-phase organic synthesis of polyisoprenoid alcohols with traceless sulfone linker
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(Chemical Equation Presented) Solid-phase organic synthesis of polyprenols with a traceless sulfone linker is described. The polymerbound benezenesulfinate is first linked with the "tail" building blocks of isoprenyl chlorides via S-alkylation. With use of dimsyl anion as an appropriate base, the polymer-bound α-sulfonyl carbanion is generated and coupled with other "body" building blocks in an efficient manner. After repeated processes and a global palladium-catalyzed desulfonation with LiEt3BH as the reducing agent, the desired polyprenols with various chain lengths and geometrical configurations are obtained in 32-59% overall yields. The solid-phase synthesis offers the advantage in facile isolation of polyprenols without tedious operation or time-consuming purification.
- Chang, Yi-Fan,Liu, Chen-Yu,Guo, Chih-Wei,Wang, Yen-Chih,Fang, Jim-Min,Cheng, Wei-Chieh
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experimental part
p. 7197 - 7203
(2009/05/09)
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- General preparation and controlled cyclization of acyclic terpenoids
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A general preparation method of the all-(E)-polyprenols 12 has been developed from readily available geranyl sulfone by the chain-extension process utilizing the C5 unit 5 and the chain-termination process utilizing the C5 unit 10 to
- Kuk, Jinchul,Beom, Soo Kim,Jung, Heejung,Choi, Seyoung,Park, Jung-Youl,Koo, Sangho
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p. 1991 - 1994
(2008/09/18)
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- Alkene substituents for selective activation of endo-regioselective polyepoxide oxacyclizations
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(Chemical equation presented) The presence of an alkenyl substituent on the terminal epoxide of a polyepoxide substrate enhances the yield of all-endo-regioselective tandem oxacyclization to trans-syn-trans-fused polycyclic ethers. For a substrate in which the epoxide and alkene functional groups are separated by two methylene substituents, a novel bromonium ion-induced endo-regioselective cyclization to bromooxepane is also described.
- Bravo, Fernando,McDonald, Frank E.,Neiwert, Wade A.,Hardcastle, Kenneth I.
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p. 4487 - 4489
(2007/10/03)
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- A convergent approach to coenzyme Q
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Syntheses of coenzyme Q3-8 are described, as well as related systems such as plastoquinone-5. Preparation of the higher homologues of the ubiquinones relies on two new conjunctive reagents, or "linchpins", each of which ultimately corresponds to two or three prenyl units. These allow for attachment of a polyprenyl halide at one end, followed by a Ni(0)-catalyzed cross-coupling at the other terminus with a chloromethylated p-quinone.
- Lipshutz, Bruce H.,Bulow, Gerd,Fernandez-Lazaro, Fernando,Kim, Sung-Kyu,Lowe, Richard,Mollard, Paul,Stevens, Kirk L.
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p. 11664 - 11673
(2007/10/03)
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- Superacidic low-temperature cyclization of terpenols and their acetates
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The superacidic low-temperature cyclization of terpenols and their acetates be fluorosulfonic acid represents a highly efficient chemo- and structurally selective and stereospecific process.Homoallylic alcohols (α-isomers of cycloterpenols) are the products of cyclization of terpenols; the configuration of the hydroxymethyl group in the products is predetermined by the configuration of the allylic double bond in aliphatic or partially cyclized precursors.The cyclization of terpenyl acetates yields monoacetates of fully cyclized diastereomeric primary-tertiary γ-diols.Their stereochemistry also depends on the configuration of the allylic double bond in the starting substrates. - Key words: terpenols; terpenyl acetates; cyclization, fluorosulfonic acid, drimanes, isoagathanes, scarlanes.
- Vlad, P. F.,Ungur, N. D.,Nguen Van Hung,Perutsky, V. B.
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p. 2391 - 2403
(2007/10/03)
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- A simple synthetic process for the elaboration of oligoprenols by stereospecific coupling of di-, tri-, or oligoisoprenoid units
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An effective method of allyl-allyl coupling which is position and stereospecific leads in a simple way to oligoprenols from E-allylic halides.
- Corey,Shieh
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p. 6435 - 6438
(2007/10/02)
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- SYNTHESIS OF DOLICHOL-TYPE (S)-HEXA- AND (S)-HEPTAPRENOLS
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(R)-1-Phenylsulfonyl-2-methylbutan-4-ol has been used as starting material for the stepwise synthesis of the dolichol-related hexa- and heptaprenols (S)-3,7,11,15,19,23-hexymethyltetraicosa-6Z,10Z,14E,18E,22-pentaene1-ol and (S)-3,7,-11,15,19,23,27-heptamethyloctaicosa-6Z,10Z,14E,18E,22E,26-hexaen-1-ol.
- Veselovskii, V. V.,Koptenkova, V. A.,Novikova, M. A.,Moiseenkov, A. M.
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p. 1887 - 1891
(2007/10/02)
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- β,γ-dihydropolyprenyl alcohol derivatives and pharmaceutical composition containing a polyprenyl compound
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A β,γ-dihydropolyprenyl alcohol derivative having the formula: STR1 wherein n is an integer of 5 to 7 and R is hydrogen, a lower alkyl group or an aliphatic or aromatic acyl group, is new and useful as a phylactic agent against human and animal infectious diseases. Other disclosed polyprenyl compounds are also useful as such agents.
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- GENERAL METHOD OF STEREOSPECIFIC SYNTHESIS OF NATURAL POLYPRENOLS. SYNTHESIS OF BETULAPRENOL-6, -7, -8, AND -9
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A stereoselective synthesis of (Z,Z,Z)-12-benzyloxy-1-chloro-2,6,10-trimethyldodeca-2,6,10-triene was achieved starting from (Z,Z)-farnesol.All the components of betulaprenols were synthesized using the C15 block 3 and its lower homologue (C10 block) as t
- Sato, Kikumasa,Miyamoto, Osamu,Inoue, Seiichi,Furusawa, Fumio,Matsuhasi, Yasusuke
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p. 1105 - 1108
(2007/10/02)
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