- Identification of the Amipurimycin Gene Cluster Yields Insight into the Biosynthesis of C9 Sugar Nucleoside Antibiotics
-
Feeding studies indicate a possible synthetic pattern for the N-terminal cis-aminocyclopentane carboxylic acid (ACPC) and suggest an unusual source of the high-carbon sugar skeleton of amipurimycin (APM). The biosynthetic gene cluster of APM was identified and confirmed by in vivo experiments. A C9 core intermediate was discovered from null mutants of ACPC pathway, and an ATP-grasp enzyme (ApmA8) was reconstituted in vitro for ACPC loading. Our observations allow a first proposal of the APM biosynthetic pathway.
- Kang, Wen-Jia,Pan, Hai-Xue,Wang, Shengyang,Yu, Biao,Hua, Huiming,Tang, Gong-Li
-
-
Read Online
- Chemoenzymatic synthesis of both enantiomers of cispentacin
-
Based on the lipase-catalysed kinetic resolution of the silyloxyalcohol (1RS,2SR)-5 by transesterification with vinyl acetate in the presence of lipase from Pseudomonas cepacia a synthesis of both enantiomers of the β-amino acid cispentacin (1R,2S)-1 and (1S,2R)-1 using simple functional group interconversions is described.
- Theil, Fritz,Ballschuh, Sibylle
-
-
Read Online
- The N-Hydroxymethyl Group as a Traceless Activating Group for the CAL-B-Catalysed Ring Cleavage of β-Lactams: A Type of Two-Step Cascade Reaction
-
An efficient enzymatic two-step cascade procedure has been devised for rapid access to diverse amino acids from N-hydroxymethyl-β-lactams; representative amino acids include the antifungal agent cispentacin, intermediates for the taxol side-chain, and assorted cathepsin inhibitors. When CAL-B-catalysed hydrolyses of racemic N-hydroxymethyl-β-lactams were performed with H2O (0.5 equiv.) in iPr2O at 60 °C, relatively quick (vs. non-activated counterparts) and enantioselective (E > 200) ring cleavage reactions took place. As the ring-opened amino acids formed, the hydroxymethyl group, as a traceless activating group, underwent spontaneous in situ degradation. Consequently, the desired β-amino acid and unreacted N-hydroxymethyl-β-lactam enantiomers (ee > 95 %) were formed. The formation of polymers, induced by liberation of formaldehyde, was successfully restricted by the addition of benzylamine as a capture agent, to the enzymatic reactions. An efficient enzymatic two-step cascade procedure was devised for CAL-B-catalysed hydrolysis of racemic N-hydroxymethyl-β-lactams. Conditions in which the hydroxymethyl group serves as a traceless activating group (E > 200), giving desired β-amino acid along with unreacted starting lactam enantiomers (ee > 95 %) were identified; polymerization was controlled by addition benzylamine addition.
- Forró, Enik?,Galla, Zsolt,Fül?p, Ferenc
-
p. 2647 - 2652
(2016/06/09)
-
- CYCLOALKYL-FUSED TETRAHYDROQUINOLINES AS CRTH2 RECEPTOR MODULATORS
-
The invention provides certain cycloalkyl-fused tetrahydroquinolines of the Formula (I), and their pharmaceutically acceptable salts and esters, wherein R1, R2, R7, R8, R8a, E, Y, Z, n, u, and t are a
- -
-
Page/Page column 53
(2013/02/28)
-
- Hairpin folding behavior of mixed α/β-peptides in aqueous solution
-
The invention of new strategies for the design of protein-mimetic oligomers that manifest the folding encoded in natural amino acid sequences is a significant challenge. In contrast to the α-helix, mimicry of protein β-sheets is less understood. We report
- Lengyel, George A.,Frank, Rebecca C.,Horne, W. Seth
-
p. 4246 - 4249
(2011/06/21)
-
- Enantiomeric discrimination of cyclic β-amino acids using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent
-
(18-Crown-6)-2,3,11,12-tetracarboxylic acid is an excellent chiral NMR solvating agent for cyclic β-amino acids with cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, bicyclo[2.2.1]heptane, and bicyclo[2.2.1]heptene rings. The crown ether was added to the neutral β-amino acids in methanol-d4. A neutralization reaction between the crown ether and β-amino acid forms the ammonium ion needed for favorable association. Enantiomeric discrimination of the two hydrogen atoms α to the amine and carboxylic acid moieties of the β-amino acid was observed with every substrate studied. Trends in the order of the enantiomeric discrimination of certain hydrogen atoms for substrates of similar structures correlate with the absolute configuration.
- Chisholm, Cora D.,Fueloep, Ferenc,Forro, Eniko,Wenzel, Thomas J.
-
experimental part
p. 2289 - 2294
(2010/11/05)
-
- Vapour-assisted enzymatic hydrolysis of β-lactams in a solvent-free system
-
A new, solvent-free, vapour-assisted method, developed for the synthesis of carbocyclic cis β-amino acid enantiomers through the Candida antarctica lipase B-catalysed enantioselective (E >200) hydrolysis of β-lactams with 0.5 equiv of H2O at 70 °C, has been demonstrated to be applicable on a preparative scale to produce (±)-2 (the starting racemate for cispentacin), (±)-3 (the starting racemate for 4-tert-butylcispentacin, a new cispentacin analogue) and (±)-7 (the starting racemate for 1,4-ethylene-bridged cispentacin).
- Forro, Eniko,Fueloep, Ferenc
-
p. 1005 - 1009
(2008/09/21)
-
- 2,4-diamino-pyrimidines as aurora inhibitors
-
The present invention encompasses compounds of general formula (1) wherein R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a pharmaceutical composition having the above-mentioned properties.
- -
-
Page/Page column 18
(2008/06/13)
-
- Lipase-catalyzed enantioselective ring opening of unactivated alicyclic-fused beta-lactams in an organic solvent.
-
[reaction: see text] A highly efficient and very simple method was developed for the synthesis of enantiopure beta-amino acids (e.g. cispentacin) and beta-lactams through the enzyme-catalyzed enantioselective ring opening of unactivated alicyclic beta-lac
- Forro, Eniko,Fueloep, Ferenc
-
p. 1209 - 1212
(2007/10/03)
-
- Novel antifungal β-amino acids: Synthesis and activity against Candida albicans
-
A series of novel β-amino acids has been synthesized and tested for their in vitro antifungal activity against Candida albicans. A steep SAR was observed. β-Amino acid 21 (BAY 10-8888/PLD-118) revealed the most favourable activity-tolerability profile and was selected for clinical studies as a novel antifungal for the oral treatment of yeast infections.
- Mittendorf, Joachim,Kunisch, Franz,Matzke, Michael,Militzer, Hans-Christian,Schmidt, Axel,Schoenfeld, Wolfgang
-
p. 433 - 436
(2007/10/03)
-
- The use of enantiomerically pure ketene dithioacetal bis(sulfoxides) in highly diastereoselective intramolecular nitrone cycloadditions. Application in the total synthesis of the beta-amino acid (-)-cispentacin and the first asymmetric synthesis of cis-(3R,4R)-4-amino-pyrrolidine-3-carboxylic acid.
-
Intramolecular 1,3-dipolar nitrone cycloaddition onto an enantiomerically pure ketene dithioacetal dioxide using a three-carbon tether gave the corresponding 5,5-disubstituted isoxazolidine as a single diastereomer in good yield. This reaction has been used as the key step in an asymmetric synthesis of the naturally occurring antibiotic, (-)-cispentacin. An asymmetric synthesis of 4-amino-pyrrolidine-3-carboxylic acid has also been carried out using the intramolecular nitrone cycloaddition as the stereocontrolling step.
- Aggarwal, Varinder K,Roseblade, Stephen,Alexander, Rikki
-
p. 684 - 691
(2007/10/03)
-
- An alkaloid-mediated desymmetrization of meso-anhydrides via a nucleophilic ring opening with benzyl alcohol and its application in the synthesis of highly enantiomerically enriched β-amino acids
-
The cinchona alkaloid-mediated opening of prochiral cyclic anhydrides in the presence of benzyl alcohol leading to optically active hemiesters is described. Structurally diverse anhydrides are converted into their corresponding benzyl monoesters with either enantiomer being obtained with up to 99 percent e.e. by using quinine or quinidine as the directing additive. A simple aqueous work-up protocol permits the isolation of the products in analytically pure form and the recovery of the alkaloids almost quantitatively. These hemiesters can be converted to N-protected β-amino esters by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of both protecting groups by a single reaction step leads to the free β-amino acids in excellent yields. The efficiency of this procedure is demonstrated by the short asymmetric synthesis of the fungicide cis-pentacin delivering the amino acid with >99.7 percent enantiomeric excess.
- Zhang, Mingbao,Zhu, Lei,Ma, Xin
-
p. 3455 - 3468
(2007/10/03)
-
- Highly Diastereoselective Nitrone Cycloaddition onto a Chiral Ketene Equivalent: Asymmetric Synthesis of Cispentacin
-
matrix presented A highly diastereoselective intramolecular nitrone cycloaddition onto a chiral ketene equivalent, obtained by Horner-Wadsworth-Emmons olefination of either enantiomer of bis-sulfinyl phosphonate 6, is described. Cycloaddition gave 5,5-disubstituted isoxazolidine 10 in good yield as a single diastereomer. Catalytic hydrogenolysis of 10 furnished either enantiomer of optically pure cis-2-aminocyclopentane-1-carboxylic acid.
- Aggarwal, Varinder K.,Roseblade, Stephen J.,Barrell, Juliet K.,Alexander, Rikki
-
p. 1227 - 1229
(2007/10/03)
-
- Efficient and highly enantioselective process for the preparation of enantiomerically pure cyclopentane-β-amino acids
-
The process according to the invention for the preparation of enantiomerically pure cyclopentane-β-amino acids of the general formula (I) STR1 in which A and D have the meanings given in the description, is characterized in that meso-dicarboxylic acid anhydrides are first converted by asymmetric alcoholysis with allyl alcohols and in the presence of a chiral amine base present in enantiomerically pure form, in inert solvents, via the intermediate enantiomerically pure salt stage, into the enantiomerically pure dicarboxylic acid monoesters, in a further step these dicarboxylic acid monoesters are intermediately converted, in the sense of a Curtius rearrangement by reaction with azides, into the corresponding acid azides, and are subsequently converted into the corresponding rearranged isocyanates and the isocyanates are then reacted with allyl alcohols to give the compounds of the general formula (VII), and finally the cyclopentane-β-amino acids of the general formula (I) are obtained by splitting off the urethane and ester function.
- -
-
-
- Asymmetric Synthesis of (-)-(1R,2S)-Cispentacin and Related cis- and trans-2-Amino Cyclopentane- and Cyclohexane-1-carboxylic Acids
-
The antifungal antibiotic (-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid (cispentacin) 8 and its cyclohexane homologue 14 have been prepared utilizing the highly stereoselective conjugate addition of homochiral lithium N-benzyl-N-α-methylbenzylamide 5.
- Davies, Stephen G.,Ichihara, Osamu,Lenoir, Isabelle,Walters, Iain A. S.
-
p. 1411 - 1416
(2007/10/02)
-
- Synthesis of racemic and optically active cispentacin (FR109615) using intramolecular nitrone-olefin cycloaddition
-
Synthesis of racemic and optically active cispentacin ((-)-1) is described. Intramolecular nitrone-olefin cycloaddition of the alkenyl nitrone 7 gave cis-isoxazolidine (±)-8, which was transformed into (±)-1 by sequential reactions involving catalytic hyd
- Konosu,Oida
-
p. 1012 - 1018
(2007/10/02)
-
- Whole Cell Catalysed Kinetic Resolution of 6-Azabicyclohept-3-en-7-one: Synthesis of (-)-Cispentacin (FR 109615)
-
Enantioselective hydrolysis of the β-lactam (+/-)2 using Rhodococcus equi provided (1R,5S)-6-azabicyclohept-3-en-7-one (+)-2, a precursor of the antifungal agent cispentacin.
- Evans, Chris,McCague, Ray,Roberts, Stanley M.,Sutherland Alan G.,Wisdom, Richard
-
p. 2276 - 2277
(2007/10/02)
-
- Probing a Molecular Model of Taste Utilizing Peptidomimetic Stereoisomers of 2-Aminocyclopentanecarboxylic Acid Methyl Ester
-
On the basis of the preferred conformations of L-aspartyl dipeptide derivatives containing α-amino acids at the second position and their retro-inverso analogues deduced by a combination of X-ray crystallography, 1H NMR spectroscopy, and molecular mechani
- Yamazaki, Toshimasa,Zhu, Yun-Fei,Probstl, Albert,Chadha, Raj K.,Goodman, Murray
-
p. 6644 - 6655
(2007/10/02)
-