- Synthesis and Enzymatic Studies of Isoprenoid Thiolo Bisubstrate Analogues
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Chain elongation prenyltransferases catalyze the addition of the hydrocarbon moiety of allylic isoprenoid diphosphates to the carbon-carbon double bond in isopentenyl diphosphate (IPP) in the primary building reactions in the isoprenoid biosynthetic pathway. Bis-O-diphosphate analogues 3-OPP/OPP, 4-OPP/OPP, and 5-OPP/OPP and bis-thiolodiphosphate bisubstrate analogues 3-SPP/SPP, 4-SPP/SPP, and 5-SPP/SPP were synthesized. The analogues 4-OPP/OPP, 5-OPP/OPP, 4-SPP/SPP, and 5-SPP/SPP were excellent competitive inhibitors of avian farnesyl diphosphate synthase with KI = 1.0 ± 0.12 μM, KI = 0.5 ± 0.2 μM, KI = 0.7 ± 0.3 μM, and KI = 2.9 ± 0.27 μM, respectively, whereas, analogues 3-OPP/OPP and 3-SPP/SPP displayed mixed type inhibition with KI = 1.4 μM and KI = 5.5 μM, respectively.
- Ramamoorthy, Gurusankar,Phan, Richard M.,Poulter, C. Dale
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- Synthesis and characterization of 5-alkoxycarbonyl-4-hydroxymethyl-5-alkyl- pyrroline N-oxide derivatives
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The syntheses, analytical properties, and spin trapping behavior of four novel EMPO derivatives, namely 5-ethoxycarbonyl-4-hydroxymethyl-5-methyl- pyrroline N-oxide (EHMPO), 5-ethoxycarbonyl-5-ethyl-4-hydroxymethyl-pyrroline N-oxide (EEHPO), 4-hydroxymethyl-5-methyl-5-propoxycarbonyl-pyrroline N-oxide (HMPPO), and 4-hydroxymethyl-5-methyl-5-iso-propoxycarbonyl-pyrroline N-oxide (HMiPPO), towards different oxygen- and carbon-centered radicals are described.
- Patel, Anjan,Rohr-Udilova, Natascha,Rosenau, Thomas,Stolze, Klaus
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- Synthesis of 1,2-Dihydropyridines, 2,3-Dihydro-4(1H)-pyridinone, and 1,2,3,4-Tetrahydropyridines via N-Acyl N,O-Hemiacetal Formation
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New procedures are described for the synthesis of α,β-ethylenic and acetylenic aldehydes from 2-butene- and 2-butyne-1,4-diol, respectively (see Scheme 1).These are applied to the preparation of a particular δ-acetylamino-α,β-ethylenic aldehyde ((E)-5) as well as of its acetylenic analogue 15.On heating in the presence of a silyl enol ether, the former undergoes a complete dehydrative cyclization affording the N-acetyl-1,2-dihydropyridine 19.The addition of HCl to aldehyde (E)-5 results in the production of the 4-chloro-1,2,3,4-tetrahydropyridine 22 which is hydrolyzed to the corresponding alcohol 23 on silica gel.Similarly, the addition of HCl or HBr to the δ-acetylamino-α,β-acetylenic aldehyde 15 leads to the previously unknown 4-halo-1,2-dihydropyridines 26; these are easily hydrolyzed to the 2,3-dihydro-4(1H)-pyridinone 27.The ring-forming process involves a N-acyl N,O-hemiacetal as intermediate which is eventually dehydrated.
- Roduit, Jean-Paul,Wyler, Hugo
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- Synthetic studies towards N-substituted 3-vinyl-4-piperidineacetic acid derivatives
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The synthesis and full characterization of two new (E)-2-butenyl)-5-amino-2-pentenoates, (Z)-4-[N-(3-buten-1-yl)benzamido]-2-buten-1-ol, and (Z)-1-chloro-4-[N-(3-buten-l-yl)benzamido]-2-butene are reported. These were designed as substrates for a projected thermal ene cyclization leading to the N-substituted 3-vinyl-4-piperidineacetic acid scaffold. Although conditions for this ene-cyclization have not yet been uncovered, the ease of preparation of these ene-cyclization substrates gives promise for their future use.
- Johnson, David A.,Gribble, Gordon W.
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p. 178 - 195
(2019/05/15)
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- Total synthesis and antibacterial testing of the A54556 cyclic acyldepsipeptides isolated from streptomyces hawaiiensis
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The first total synthesis of all six known A54556 acyldepsipeptide (ADEP) antibiotics from Streptomyces hawaiiensis is reported. This family of compounds has a unique mechanism of antibacterial action, acting as activators of caseinolytic protease (ClpP). Assembly of the 16-membered depsipeptide core was accomplished via a pentafluorophenyl ester-based macrolactamization strategy. Late stage amine deprotection was carried out under neutral conditions by employing a mild hydrogenolysis strategy, which avoids the formation of undesired ring-opened depsipeptide side products encountered during deprotection of acid-labile protecting groups. The free amines were found to be significantly more reactive toward late stage amide bond formation as compared to the corresponding ammonium salts, giving final products in excellent yields. A thorough NMR spectroscopic analysis of these compounds was carried out to formally assign the structures and to aid with the spectroscopic assignment of ADEP analogues. The identity of two of the structures was confirmed by comparison with biologically produced samples from S. hawaiiensis. An X-ray crystallographic analysis of an ADEP analogue reveals a conformation similar to that found in cocrystal structures of ADEPs with ClpP protease. The degree of antibacterial activity of the different compounds was evaluated in vitro using MIC assays employing both Gram-positive and Gram-negative strains and a fluorescence-based biochemical assay.
- Goodreid, Jordan D.,Wong, Keith,Leung, Elisa,McCaw, Shannon E.,Gray-Owen, Scott D.,Lough, Alan,Houry, Walid A.,Batey, Robert A.
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supporting information
p. 2170 - 2181
(2014/12/11)
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- One-pot oxidation/isomerization of Z-allylic alcohols with oxygen as stoichiometric oxidant
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A method for generating (E)-α,β-unsaturated aldehydes from Z-allylic alcohols or E/Z-mixtures is described. The one-pot procedure involves a Cu-catalyzed oxidation followed by an organocatalytic Z/E-isomerization with N,N-dimethylaminopyridine (DMAP).
- Koenning, Daniel,Hiller, Wolf,Christmann, Mathias
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supporting information
p. 5258 - 5261
(2013/01/15)
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- Total synthesis of Japanese Hop Ether using an efficient intramolecular Pauson-Khand reaction
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The naturally occurring monoterpene Japanese Hop Ether has been synthesised in 14 steps in an overall yield of 29%. The key step of the synthesis, an intramolecular Pauson-Khand reaction, has been shown to proceed in good to excellent yield under mild N-oxide promotion conditions and with complete retention of alkene stereochemistry (for both cis- and trans-alkenes) in the product cyclopentenone. Georg Thieme Verlag Stuttgart.
- Caldwell, John J.,Cameron, Iain D.,Christie, Steven D. R.,Hay, Alastair M.,Johnstone, Craig,Kerr, William J.,Murray, Anthony
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p. 3293 - 3296
(2007/10/03)
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- HETEROCYCLIC COMPOUND DERIVATIVES AND MEDICINES
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The present invention provides a compound which is useful as a PGI2 receptor agonist, and a pharmaceutical composition. The present invention is directed to a pharmaceutical composition comprising a compound represented by the following formula [1]: (R1 and R2 are the same or different and each represents optionally substituted aryl, Y represents N or CH, Z represents N or CH, A represents NH, NR5, O, S, or ethylene, R5 represents alkyl, D represents alkylene or alkenylene, E represents phenylene or single bond, G represents O, S, or CH2, R3 and R4 are the same or different and each represents hydrogen or alkyl, Q represents carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, or N-(alkylsulfonyl)carbamoyl), or a pharmaceutically acceptable salt thereof as an active ingredient.
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- Ring-closing metathesis: Development of a cyclisation-cleavage strategy for the solid-phase synthesis of cyclic sulfonamides
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A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation-cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5-5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.
- Moriggi, Jean-Dominique,Brown, Lynda J.,Castro, Jose L.,Brown, Richard C. D.
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p. 835 - 844
(2007/10/03)
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- A simple and efficient method for selective deprotection of t- butyldimethylsilyl ethers by zinc tetrafluoroborate in water
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Selective deprotection of t-butyldimethylsilyl ethers has been achieved under mild conditions using an aqueous solution of zinc tetrafluoroborate.
- Ranu, Brindaban C.,Jana, Umasish,Majee, Adinath
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p. 1985 - 1988
(2007/10/03)
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- A mild, efficient, inexpensive, and selective cleavage of primary tert-butyldimethylsilyl ethers by oxone in aqueous methanol
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(formula presented) The use of a 50% aqueous methonolic solution of Oxone is described for the selective cleavage of primary tert-butyldimethylsilyl and aryl ethers at room temperature. This method enables one to deprotect tert-butyldimethylsilyl ethers of primary alcohols in the presence of tertbutyldimethylsilyl ethers of secondary and tertiary alcohols and phenols. The silyl ethers of phenols were deprotected at longer reaction times.
- Sabitha, Gowravaram,Syamala, Mandali,Yadav
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p. 1701 - 1703
(2008/02/11)
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- Stannous chloride dihydrate: A new catalyst for the tetrahydropyranylation of alcohols
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Catalytic Stannous chloride dihydrate in polar aprotic solvents like chloroform efficiently catalyse the tetrahydropyranylation of alcohols in a short time under mild conditions.
- Joju Davis,Bhalerao,Vittal Rao
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p. 1679 - 1686
(2007/10/03)
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- Selective monotetrahydropyranylation of symmetrical diols catalyzed by ion-exchange resins
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Primary and secondary symmetrical diols with 2-10 carbon atoms gave selectively monotetrahydropyranyl ethers in the reaction catalyzed by wet sulfonic acid-type ion-exchange resins in 3,4-dihydro-2H-pyran (DHP)/toluene or DHP/hexane. The yields of the monoethers were higher than 80% while those of the corresponding diethers were lower than 5%. In these reactions the rate of the formation of the diethers did not increase much even after most of the diols had been consumed. In the reaction of 1,10-decanediol in DHP/hexane, the yields of the monoether were increased by the addition of DMF or DMSO. Each diol was found to have a particular DHP/hydrocarbon ratio that gave the highest selectivity for the monoether. Generally, the larger the number of carbon atoms of the diols, the smaller the ratio of DHP in the solvents to give high selectivity for the monoether. This method of the selective etherification is quite simple and practical.
- Nishiguchi, Takeshi,Fujisaki, Shizuo,Kuroda, Masahumi,Kajisaki, Kohtaro,Saitoh, Masahiko
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p. 8183 - 8187
(2007/10/03)
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- Reductive decomplexation of biscobalthexacarbonyl acetylenes into olefins
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The decomplexation of acetylene biscobalthexacarbonyl complexes can usually be achieved under oxidative condition. We had found other reductive conditions with endo-cyclic complexes, and recently other reductive conditions with both endo- and exo-cyclic complexes using either tributyltin hydride or triethylsilane. The original acetylene derivatives were transformed selectively either into the corresponding cis olefins or cis- vinylsilanes.
- Hosokawa, Seijiro,Isobe, Minoru
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p. 2609 - 2612
(2007/10/03)
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- S-adenosyl methionine decarboxylase inhibitors
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The adenosine derivatives represented by the following formula: STR1 and the pharmaceutically acceptable salts thereof wherein R is H or C1 -C7 alkyl, Q is the moiety of the formula STR2 wherein V is H or --COOH X is H, F, Cl, Br, and Z is H, F, Cl, or Br. These compounds are inhibitors of S-adenosylmethione decarboxylase and are useful for treating parasitic infections.
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- Highly Selective Monotetrahydropyranylation of Symmetrical Diols Catalysed by a Strongly Acidic Ion-exchange Resin
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Several primary and secondary symmetrical diols, ranging from propane-1,3-diol to decane-1,10-diol, are selectively monoprotected by monotetrahydropyranyl ether formation catalysed by a strongly acidic ion-exchange resin (Dowex 50x x 2, 50-100 mesh) in a 3,4-dihydro-2H-pyran-hydrocarbon mixture.
- Nishiguchi, Takeshi,Kuroda, Masahumi,Saitoh, Masahiko,Nishida, Akiko,Fujisaki, Shizuo
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p. 2491 - 2492
(2007/10/03)
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- 5'-amine substituted adenosine analogs as immunosuppressants
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The present invention relates to a method of effecting immunosuppression in a patient in need thereof comprising administering to said patient an effective immunosuppressive amount of certain 5'-amine substituted adenosine analogs.
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- Stereocontrolled construction of 1, 7-dimethyl A.B.C.[6.6.6] tricycles. Part I. transannular Diels-Alder reactions of 14-membered macrocycles containing frans-dienophiles
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Transannular Diels-Alder reactions of 14-membered macrocyclic trienes possessing a methyl substituent on both the diene and dienophile moiety have been investigated. Macrocyclic structures la, lb, and lc having cis-trans-trans (CTT), trans-cis-trans (TCT), and trans-trans-trans (TTT) geometries could be stereoselectively constructed by coupling appropriately functionalized dienes 5 and dienophile 4 following an intramolecular displacement of an allylic halide by the anion of an appropriately located dimethyl malonate unit. The transannular Diels-Alder reaction performed on la led to a mixture of four major tricyclic products, including 34 possessing the unexpected trans-anti-cis (TAC) stereochemistry. When heated at 300°C, macrocycle lb underwent an unique conversion via an ene-retroene, Diels-Alder process, producing the unexpected tricycle 41 (racemic form) containing five contiguous chiral centers. A rationale for the above experimental facts is presented. In contrast to the previous results, the transannular Diels-Alder reaction of macrocycle lc was straightforward, producing a 95% isolated yield of trans-anti-cis (TAC) tricycle 34. This investigation demonstrates a general methodology for the stereocontrolled synthesis of 1, 2-dimethyl A.B.C[6.6.6] tricyclic compounds, which are potential precursors to polycyclic natural products such as steroids and terpenes.
- Xu, Yao-Chang,Roughton, Andrew L.,Plante, Raymond,Goldstein, Solo,Deslongchamps, Pierre
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p. 1152 - 1168
(2007/10/02)
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- Synthesis and transannular Diels-Alder reaction of a 13-membered macrocyclic triene. A synthetic approach towards the tricyclic part A.B.C.[6.6.5] of the veratrum alkaloids
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The syntheses of the acyclic triene cis-trans-trans (3Z,9Z,11E)-13-chloro-3-methoxy-1,1,7,7-tetrakis(methoxycarbonyl)-4- methyltrideca-3,9,11-triene (25), and the corresponding trans-cis-trans (3Z,9E,11E) isomer 37, and trans-trans-trans (3Z,9E,11E) isomer, 46, are described. Compounds 25 and 37 furnished in good yield 13-membered macrocyclic compounds (3Z,9Z,11E)- and (3Z,9E,11Z)-3-methoxy-1,1,7,7-tetrakis(methoxycarbonyl)-4- methylcyclotride-ca-3,9,11-triene (26) and (38) which led to tricyclic compound (cis-anti-cis)-2-methoxy-4,4,11,11-tetrakis(methoxycarbonyl)-1- methyl-tricyclo[7.4.0.02,6]tridec-7-ene (27) by transannular Diels-Alder reaction. Macrocyclization of trans-trans-trans chloride 46 was not successful.
- Quimpere,Ruest,Deslongchamps
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p. 132 - 140
(2007/10/02)
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- S-Adenosylmethionine decarboxylase inhibitors
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This invention relates to novel chemical compounds useful as S-adenosylmethionine decarboxylase inhibitors, of the formula, , H2N-Q- wherein R1 is H or F, n is 1 or 2, V1 is H or CH3, V2 is H or COOH, and each of W, X, Y, and Z are H, F, Cl or Br. To the processes useful for their preperation and to their use in the treatment of a variety of condition and disease states associated with a rapid proliferation of cell growth.
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- Synthesis and transannular Diels-Alder reaction of a 13-membered macrocyclic triene having a tetrasubstituted enol ether as dienophile
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The syntheses of the acyclic triene trans-trans-cis 27 and trans-trans-trans 31 are described.Macrocyclization and concomitant transannular Diels-Alder reaction were performed with the chloride derivative obtained from the trans-trans-cis triene alcohol 27 yielding a mixture of the tricyclic compounds trans-syn-trans 33 and cis-syn-cis 34.On the other hand, macrocyclization of the chloride derived from trans-trans-trans triene 31 was not successful.
- Berube, Gervais,Deslongchamps, Pierre
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p. 404 - 411
(2007/10/02)
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- USE OF AN ALLYLIC ANCHOR GROUP AND OF ITS PALLADIUM CATALYZED HYDROSTANNOLYTIC CLEAVAGE IN THE SOLID PHASE SYNTHESIS OF PROTECTED PEPTIDE FRAGMENTS
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The allylic handle -O-CH2-CH=CH-CH2-O-CH2-CO- has been used in the synthesis of protected peptide fragments on aminomethyl polystyrene.The palladium-catalyzed hydrostannolytic cleavage of the peptide fragments from the resin occurs under very mild conditions.
- Guibe, F.,Dangles, O.,Balavoine, G.,Loffet, A.
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p. 2641 - 2644
(2007/10/02)
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- Palladium-Catalyzed Allylic Sulfinate-Sulfone Rearrangements
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Upon treatment with a zero-valent palladium catalyst, tetrakis(triphenylphosphine)palladium, in tetrahydrofuran under mild conditions allylic p-toluenesulfinates underwent α- or γ-rearrangements of the sulfonyl group via ionic intermediates to give allylic sulfones.The regiochemistry of the rearrangements depends on the character of the intermediary allylic cationic carbons generated and the steric hindrance involved therein.Keywords - allylic sulfinate; allylic sulfone; palladium catalyst; sulfinate-sulfone rearrangement; regiochemistry; tetrakis(triphenylphosphine)palladium.
- Hiroi, Kunio,Makino, Kunitaka
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p. 1727 - 1737
(2007/10/02)
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- A simple and direct method of cyclization for the synthesis of 10-membered rings
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Ten-membered rings containing two unsaturations are produced without the use of high dilution techniques by the intramolecular malonate anion displacement of an allylic chloride.
- Deslongchamps, Pierre,Lamothe, Serge,Lin, Ho-Shen
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p. 1298 - 1307
(2007/10/02)
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- INTRAMOLECULAR CARBOPALLADATION OF ALLYLIC AMINES AND SULFIDES
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β-Malonyl allyl sulfides and amines have been found to cyclize in the presence of lithium tetrachloropalladate and base to regiospecifically and stereospecifically provide fused bicyclic palladocycles which are converted to cyclopentanes upon hydrogenation.The cyclization may be extended to generate six- and seven-membered rings in high yield.Cyclization to provide cyclic ketones also occurs in high yield.
- Holton, Robert A.,Zoeller, Joseph R.
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p. 2124 - 2131
(2007/10/02)
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- NOC Approach to Spiroketals. A Total Synthesis of (+/-)-Talaromycin B
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A total synthesis of the unqiue spiroketal natural product talaromycin B (1) is reported.This molecule, produced in nature by the toxicogenic fungus Talaromyces stipitatus, was constructed in the laboratory from the isoxazoline 6 generated (formula) on reacting the oxime 4 with the olefin 5 in the presence of NaOCl/Et3N/H20/CH2Cl2.The synthesis scheme is sufficiently flexible and efficient so as to be of practical use in the preparation of suitable quantities of this material for biological evaluation.
- Kozikowski, Alan P.,Scripko, James G.
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p. 353 - 355
(2007/10/02)
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- A simple and direct method of cyclization for the synthesis of a 10-membered ring
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The malonate anion displacement of allylic chloride in a ten-carbon aliphatic chain containing one additional unsaturation center yields 10-membered cyclic compounds.
- Deslongchamps, Pierre,Lamothe, Serge,Lin, Ho-Shen
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p. 2395 - 2398
(2007/10/02)
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