- An efficient synthetic route tol-γ-methyleneglutamine and its amide derivatives, and their selective anticancer activity
-
In cancer cells, glutaminolysis is the primary source of biosynthetic precursors, fueling the TCA cycle with glutamine-derived α-ketoglutarate. The enhanced production of α-ketoglutarate is critical to cancer cells as it provides carbons for the TCA cycle to produce glutathione, fatty acids, and nucleotides, and contributes nitrogens to produce hexosamines, nucleotides, and many nonessential amino acids. Efforts to inhibit glutamine metabolism in cancer using amino acid analogs have been extensive.l-γ-Methyleneglutamine was shown to be of considerable biochemical importance, playing a major role in nitrogen transport inArachisandAmorphaplants. Herein we report for the first time an efficient synthetic route tol-γ-methyleneglutamine and its amide derivatives. Many of thesel-γ-methyleneglutamic acid amides were shown to be as efficacious as tamoxifen or olaparib at arresting cell growth among MCF-7 (ER+/PR+/HER2?), and SK-BR-3 (ER?/PR?/HER2+) breast cancer cells at 24 or 72 h of treatment. Several of these compounds exerted similar efficacy to olaparib at arresting cell growth among triple-negative MDA-MB-231 breast cancer cells by 72 h of treatment. None of the compounds inhibited cell growth in benign MCF-10A breast cells. Overall,N-phenyl amides andN-benzyl amides, such as3,5,9, and10, arrested the growth of all three (MCF-7, SK-BR-3, and MDA-MB-231) cell lines for 72 h and were devoid of cytotoxicity on MCF-10A control cells;N-benzyl amides with an electron withdrawing group at theparaposition, such as5and6, inhibited the growth of triple-negative MDA-MB-231 cells commensurate to olaparib. These compounds hold promise as novel therapeutics for the treatment of multiple breast cancer subtypes.
- Hossain, Md Imran,Thomas, Ajit G.,Mahdi, Fakhri,Adam, Amna T.,Akins, Nicholas S.,Woodard, Morgan M.,Paris, Jason J.,Slusher, Barbara S.,Le, Hoang V.
-
p. 7115 - 7128
(2021/02/26)
-
- L-Y-METHYLENEGLUTAMINE COMPOUNDS AND METHODS OF USE
-
Disclosed are substantially pure L-y-methyleneglutamine, L-y- methyleneglutamic acid, and/or amide derivatives, and methods of use thereof. In particular, the presently disclosed subject matter relates to L-y-methyleneglutamine, L-y-methyleneglutamic acid, and/or amide derivatives thereof, and methods of treating cancer. The method comprises administering one or more substantially pure L-y-methyleneglutamine, L-y-methyleneglutamic acid, and/or amide derivatives to a subject in need thereof.
- -
-
Paragraph 0085-0087
(2021/02/12)
-
- MASP INHIBITORY COMPOUNDS AND USES THEREOF
-
The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.
- -
-
Page/Page column 227-228
(2020/11/23)
-
- A Stereoselective Synthesis of the ACE Inhibitor Trandolapril
-
A conceptually novel and stereoselective synthesis of the enantiopure octahydroindole building block and its conversion into the ACE inhibitor trandolapril was achieved. Key steps include the α-allylation of a protected l -pyroglutamic acid derivative, a highly diastereoselective Hosomi-Sakurai reaction and a Ru-catalyzed ring-closing metathesis of a 4,5-diallylated proline. This way, the synthesis of trandolapril was efficiently achieved in 25% overall yield (12 steps).
- Chiha, Slim,Spilles, Matthias,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
-
supporting information
p. 813 - 816
(2019/04/25)
-
- Design and Synthesis of Building Blocks for PPII-Helix Secondary-Structure Mimetics: A Stereoselective Entry to 4-Substituted 5-Vinylprolines
-
In the course of our studies towards the synthesis of proline-based secondary-structure mimetics, we developed a straightforward methodology for the diastereoselective preparation of 4-alkyl-5-vinyl-substituted proline derivatives. Starting from N-Boc-protected tert-butyl pyroglutamate, α-alkylation, lactam reduction and acid-catalyzed methanolysis afforded 4-alkyl-5-methoxyproline derivatives. After BF3-induced formation of an N-acyl-iminium intermediate, the introduction of the 5-vinyl side chain was achieved with high diastereoselectivity by using vinylmagnesium bromide in the presence of AlCl3 or CuBr·SMe2 to afford either the cis- or the trans-product, respectively. The utility of the method was demonstrated in the rapid and efficient construction of new diproline mimetics rigidified in a polyproline-type II helix (PPII) conformation.
- Chiha, Slim,Soicke, Arne,Barone, Matthias,Müller, Matthias,Bruns, Judith,Opitz, Robert,Neud?rfl, J?rg-Martin,Kühne, Ronald,Schmalz, Hans-Günther
-
supporting information
p. 455 - 460
(2018/02/09)
-
- INHIBITORS FOR INHIBITING TUMOR METASTASIS
-
The present invention relates to chemical compounds that can in particular be used as structural mimetics of proline-rich peptides. The compounds of the present invention are capable of selectively inhibiting ena/VASP-EVH1-mediated protein-protein interactions. The invention further relates to the use of said compounds as pharmaceutical agents and to the use of the pharmaceutical agents to treat tumor diseases. The chemical compounds of the present invention can significantly inhibit the chemotaxis and motility of invasive tumor cells and can therefore be used in the treatment and/or prevention of tumor metastases.
- -
-
Paragraph 0073
(2017/11/30)
-
- HETEROARYL PYRIDONE AND AZA-PYRIDONE AMIDE COMPOUNDS
-
Heteroaryl pyridone and aza-pyridone amide compounds of Formula (I) are provided, and various substituents including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk, and for treating cancer and immune disorders such as inflammation mediated by Btk. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
- -
-
Page/Page column 101
(2015/01/16)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: (structurally represented), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Page/Page column 70
(2015/02/25)
-
- The revisited synthesis of tert-butyl pyroglutamate derivatives
-
The very common protection reactions of scaffolds by introduction of Boc or tert-butyl groups on lactams or acids in the pyroglutamic series have been revisited in a green perspective. Particularly, reaction conditions allowing a quantitative yield in substitution of bromine in tert-butyl bromide were discovered for the first time, allowing the synthesis of tert-butyl pyroglutamate 4. This synthesis of tert-butyl ester by nucleophilic substitution, realized without using concentrated perchloric or sulfuric acid, could be of interest for acid sensitive compounds. On the other hand, we demonstrated that non toxic N-methylimidazole and tert-butanol can pleasantly replace the problematic toxic 4-dimethylaminopyridine (DMAP) and dichloromethane utilized for the N-carbamoylation of lactam 4. This environmentally improved route to compound 4 allowed the development of a multi-gram supply of protected N-aminoethyl and N-hydroxyethyl γ-glutamine 1 and 2.
- Claverie, Christelle,Ghinet, Alina,Gautret, Philippe,Vuong, Chi-Thanh,Rigo, Beno?t
-
p. 6821 - 6825
(2013/07/26)
-
- Crotonase catalysis enables flexible production of functionalized prolines and carbapenams
-
The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.
- Hamed, Refaat B.,Henry, Luc,Gomez-Castellanos, J. Ruben,Mecinovic, Jasmin,Ducho, Christian,Sorensen, John L.,Claridge, Timothy D. W.,Schofield, Christopher J.
-
p. 471 - 479
(2012/03/07)
-
- INDUCTION OF ALPHA HELIX CONFORMATIONS IN PROTEINS AND PEPTIDES
-
Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.
- -
-
Page/Page column 13-14
(2012/07/14)
-
- Discovery of a novel class of potent and orally bioavailable sphingosine 1-phosphate receptor 1 antagonists
-
A series of subtype selective sphingosine 1-phosphate receptor 1 (S1P 1) antagonists are disclosed. Our high-throughput screening campaign revealed hit 1 for which an increase in potency and mouse oral exposure was achieved with minor modifications to the chemical scaffold. In vivo efficacy revealed that at high doses compounds 12 and 15 inhibited tumor growth. Further optimization of our lead series led to the discovery of proline derivatives 37 (XL541) and 38 which had similar efficacy as our first generation analogues at significantly lower doses. Analogue 37 displayed excellent pharmacokinetics and oral exposure in multiple species.
- Ibrahim, Mohamed A.,Johnson, Henry W. B.,Jeong, Joon Won,Lewis, Gary L.,Shi, Xian,Noguchi, Robin T.,Williams, Matthew,Leahy, James W.,Nuss, John M.,Woolfrey, John,Banica, Monica,Bentzien, Frauke,Chou, Yu-Chien,Gibson, Anna,Heald, Nathan,Lamb, Peter,Mattheakis, Larry,Matthews, David,Shipway, Aaron,Wu, Xiang,Zhang, Wentao,Zhou, Sihong,Shankar, Geetha
-
experimental part
p. 1368 - 1381
(2012/04/04)
-
- Insights into the reaction mechanism of the prolyl - Acyl carrier protein oxidase involved in anatoxin-a and homoanatoxin-a biosynthesis
-
Anatoxin-a and homoanatoxin-a are two potent cyanobacterial neurotoxins. We recently reported the identification of the gene cluster responsible for the biosynthesis of these toxins as well as the in-vitro reconstitution of the first steps of this biosynthesis. We now report experimental evidence supporting the proposed reaction mechanism of AnaB, a flavoprotein homologous to acyl-CoA dehydrogenase. AnaB catalyzes the two-electron oxidation of prolyl-AnaD, which is proline linked to the acyl carrier protein holo-AnaD, to dehydroprolyl-AnaD using oxygen as the second substrate. AnaB is thus an oxidase. By using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we have identified and characterized dehydroprolyl-AnaD, the AnaB product. We estimated an apparent catalytic constant of 1 min- 1 for AnaB catalysis. We synthesized several deuterium-labeled prolines and enzymatically transformed them into their corresponding prolyl-AnaD. These deuterium-labeled prolyl-AnaDs were oxidized in the presence of AnaB, and the deuterium labeling in the remaining substrate and in the product was determined by LC-MS/MS. The data supported a reaction mechanism starting with a rapid enolization followed by a slow oxidation to give the conjugated imine, which in turn was isomerized to pyrroline-5-carboxyl-AnaD. We also showed that cis- and trans-4-fluoro-l-prolyl- AnaD and 3,4-dehydro-l-prolyl-AnaD were transformed into pyrrole-2-carboxyl-AnaD by AnaB. Thus, the 4-fluoro-analogues experienced a β-elimination supporting the AnaB-catalyzed aza - allylic isomerization. We identified by sequence alignment the AnaB active site base, Glu244. We produced, purified, and characterized the E244A AnaB mutant, which is inactive, supporting the catalytic role of E244 as a base.
- Mann, Stephane,Lombard, Berangere,Loew, Damarys,Mejean, Annick,Ploux, Olivier
-
experimental part
p. 7184 - 7197
(2012/07/02)
-
- STRUCTURAL MIMETICS OF PROLINE-RICH PEPTIDES AND THE PHARMACEUTICAL USE THEREOF
-
The invention relates to compounds of general formula (I), which can be used particularly as structural mimetics of proline-rich peptides and are therefore capable of binding PRM binding domains (proline-rich motif binding domains) of proteins. The invention also relates to the use of said compounds as pharmaceutical active agents and the use of these pharmaceutical active agents for treating bacterial diseases, neurodegenerative diseases and tumours.
- -
-
Page/Page column 30
(2011/02/26)
-
- Synthesis of amino acid conjugates to 2-imino-3-methylene-5-carboxypyrrolidine and 2-imino-3-methylene-6-carboxypiperidine
-
The four stereomers of 2-imino-3-methylene-5-l(carboxy-l-valyl)pyrrolidine, a bacterial metabolite that is inhibitory to the fire blight bacterium Erwinia amylovora, were synthesised and compared for antibacterial activity. Several alternative amino acid conjugates with l,l-stereochemistry were also prepared, and the synthesis was extended to 3-methylenepiperidine-6-l-carboxylic acid and a selection of 2-imino-3-methylenepiperidine-6-l-carboxy-l-amino acid conjugates. All synthetic amino acid conjugates (l,l-stereomers) were inhibitory to the growth of E. amylovora. The likely participation of the conjugated iminomethylene moiety as a Michael acceptor is implicated.
- Mitchell, Robin E.
-
scheme or table
p. 1910 - 1912
(2010/07/06)
-
- PREPARATION OF ALKYL ESTERS OF N-PROTECTED OXO-AZACYCLOALKYLCARBOXYLIC ACIDS
-
A process for the preparation of alkyl esters of N-protected oxo-azacycloalkylcarboxylic acids of Formula III: comprises contacting a ketosulfoxonium ylide of Formula II: with an iridium catalyst to obtain Compound III, wherein PG1 is an amine protective group group; k is 0, 1, or 2; and RU, R1, R2, and R3 are defined herein. An embodiment of the process further com rises contacting a compound of Formula I: with a sulfoxonium halide of formula (RU)3S(O)Z, wherein Z is halide, in the presence of a strong base to obtain Compound II. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6- diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.
- -
-
Page/Page column 28; 29
(2010/11/17)
-
- SPHINGOSINE-1-PHOSPHATE RECEPTOR ANTAGONISTS
-
This disclosure relates to sphingosine-1 -phosphate (SlP) receptor antagonists, compositions comprising the SlP receptor antagonists and methods for using and processes for making the SlP receptor antagonists. In particularly, this disclosure relates to sphingosine-1 -phosphate 1 (SlPl) receptor antagonists, compositions comprising the SlPl receptor antagonist and methods for using the SlPl receptor antagonist, such as in the treatment of cancer, and processes for making the SlPl receptor antagonists.
- -
-
Page/Page column 90-91
(2010/04/30)
-
- Addressing protein-protein interactions with small molecules: A pro-pro dipeptide mimic with a PPII helix conformation as a module for the synthesis of PRD-binding ligands
-
X marks the spot: The synthetic tricyclic amino acid X (see structure; C gray, H cyan, N blue, O red, double bond yellow) can be incorporated, without loss of binding ability, as a Pro-Pro substitute into two peptides that bind to the proline-rich motif-recognizing domains Fyn-SH3. The dipeptide analogue X, which is locked in a polyproline type II helix conformation, is created by stereoselective introduction of a vinylidene bridge into a diproline unit.
- Zaminer, Jan,Brockmann, Christoph,Huy, Peter,Opitz, Robert,Reuter, Cedric,Beyermann, Michael,Freund, Christian,Mueller, Matthias,Oschkinat, Hartmut,Schmalz, Hans-Guenther,Kuehne, Ronald
-
supporting information; experimental part
p. 7111 - 7115
(2010/12/18)
-
- A unified strategy targeting the thiodiketopiperazine mycotoxins exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin a and aranotin
-
A unified synthetic strategy directed towards mycotoxins belonging to the thiodiketopiperazine family is reported. The building blocks for a number of natural products-including exserohilone, gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin-have been synthesised stereoselectively from a common precursor. This key intermediate was constructed through an efficient and highly diastereoselective[2+2] cycloaddition between a ketene and an enecarbamate derived from l-pyroglutamic acid. The annelation of the second ring was accomplished through ring-closing metathesis and enol ether-olefin ring-closing metathesis to provide both cis-and trans-annelated azabicyclic cyclohexenones, as well as an annelated sevenmembered cyclic enol ether. A Pd-catalysed elimination of allyl acetate gave rise to the cyclohexadienol structure of gliotoxin. Dimerisation of one building block to afford the diketopiperazine core was demonstrated.
- Gross, Ulrike,Nieger, Martin,Br?se, Stefan
-
supporting information; experimental part
p. 11624 - 11631
(2010/11/17)
-
- Parallel solution-phase synthesis of (2S,4E)-4-(arylaminomethylidene) pyroglutamic acids
-
A library of twelve N(4')-substituted di-tert-butyl (2S,4E)-4- arylaminomethylidene-5-oxopyrrolidine-1,2-dicarboxylates 6/6'a-l were prepared in 47-90% yield by parallel acid-catalysed treatment of di-tert-butyl (2S,4E)-4-[(dimethylamino)methylidene]-5-oxopyrrolidine-1,2-dicarboxylate (4) with anilines 5a - j, ethyl glycinate (5k), and ethyl β-alaninate (31). Acidolytic deprotection of compounds 6a - c, e - j afforded the corresponding (2S,4E)-4-arylaminomethylidene-5-oxopyrrolidine-2-carboxylic acids 7a - c, e - j in 39-99% yield. The configuration around the C=C double bond in the enaminones 6 and 7 was determined by NMR spectroscopy.
- Svete, Jurij,Groselj, Uros,Baskovc, Jernej,Dahmann, Georg,Stanovnik, Branko
-
scheme or table
p. 811 - 820
(2011/01/10)
-
- Stereoselective synthesis of the epicoccin core
-
A short, convergent, and asymmetric synthesis of the epicoccin core was achieved using a phosphite-promoted one-step condensation of a complex proline-type amino acid. Key features of the assembly of this amino acid were a double-bond isomerlzation/vlnylation/ring-closing metathesis strategy as well as an efficient, highly deastereoselective [2 + 2] cycloaddition of a ketene to an enecarbamate, derived from L-pyroglutamic acid.
- Gross, Ulrike,Nieger, Martin,Braese, Stefan
-
supporting information; experimental part
p. 4740 - 4742
(2009/12/22)
-
- Synthesis of alexine-like compounds from chiral five-membered endocyclic enecarbamates
-
Stereoselective syntheses of enantiomerically enriched trihydroxy pyrrolizidine and indolizidines were accomplished from a common chiral endocyclic enecarbamate. The synthetic strategy features an efficient [2+2] cycloaddition of ketenes to the endocyclic enecarbamate and a highly regioselective Baeyer-Villiger oxidation of the intermediate azabicyclic-cyclobutanones. These new heterocycles are compounds structurally related to the alexines.
- Valle, Marcelo Siqueira,Retailleau, Pascal,Correia, Carlos Roque Duarte
-
p. 1957 - 1960
(2008/09/19)
-
- Substrate-dependent dihydroxylation of substituted cyclopentenes: Toward the syntheses of carbocyclic sinefungin and noraristeromycin
-
Carbocyclic nucleosides are of considerable interest for the development of new therapeutic agents. A key reaction in the preparation of many such nucleoside analogues is dihydroxylation of appropriately substituted cyclopentenes. Although often considered a routine reaction, in this paper, we report the dramatic influence of substituents on the facial selectivity of dihydroxylations. The substituted cyclopentene substrates are derived from acylnitroso cycloaddition reactions of cyclopentadiene, followed by N-O reduction and efficient enzymatic resolution. The results are directly utilized in a very efficient asymmetric synthesis of an antiviral carbocyclic nucleoside, noraristeromycin 5. Extensions toward the synthesis of carbocyclic sinefungin 7 document the importance of realizing the substituent dependence of the dihydroxylation reaction.
- Jiang, May Xiao-Wu,Jin, Bohan,Gage, Jennifer L.,Priour, Alain,Savela, Gordon,Miller, Marvin J.
-
p. 4164 - 4169
(2007/10/03)
-
- NOVEL CYANOPYRROLIDIDES, METHODS FOR THE PRODUCTION THEREOF, AND USE OF THE SAME AS MEDICAMENTS
-
The invention relates to compounds of formula (I) wherein the radicals have the designations cited in the text. The invention also relates to the stereoisomer forms and the physiologically compatible salts thereof, the physiologically functional derivatives thereof, and methods for producing the same. The inventive compounds are suitable for treating illnesses of the metabolism such as type 2 diabetes.
- -
-
Page/Page column 16; 33
(2010/02/10)
-
- Hetero-Diels-Alder and pyroglutamate approaches to (2S,4R)-2-methylamino-5- hydroxy-4-methylpentanoic acid
-
The stereoselective syntheses of fully protected (2S,4R)-2-methylamino-5- hydroxy-4-methylpentanoic acid, a non-coded amino acid of cyclomarin A, and its diastereomer are reported. A pyroglutamate template was employed in the key diastereoselective alkylation used for introducing the 4-methyl stereochemistry. In addition, the first diastereoselective intramolecular hetero-Diels-Alder of a 2-cyano-1-azadiene with an electron deficient dienophile is described. Graphical Abstract
- Tarver Jr., James E.,Terranova, Kristen M.,Joullié, Madeleine M.
-
p. 10277 - 10284
(2007/10/03)
-
- A study of polychlorinated leucine derivatives: Synthesis of (2S,4S)-5,5-dichloroleucine
-
The first total synthesis of (2S,4S)-5,5-dichloroleucine has been achieved in 11 steps from L-pyroglutamic acid. A key step is the dichlorination process on the hydrazone of aldehyde 13 with CuCl2 in triethylamine.
- Ardá, Ana,Jiménez, Carlos,Rodríguez, Jaime
-
p. 3241 - 3243
(2007/10/03)
-
- NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
-
The present invention discloses novel peptide compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such peptides as well as methods of using them to treat disorders associated with the HCV protease.
- -
-
-
- Synthesis of 1,2-dithiolane analogues of leucine for potential use in peptide chemistry.
-
[reaction: see text]1,2-Dithiolanes present several points of interest for both peptide and medicinal chemistry, yet no chiral alpha-amino acids containing this five-membered heterocyclic system are available. We report here the first synthesis of N- and C-protected derivative of (S)-2-amino-3-(1,2-dithiolan-4-yl)propionic acid (Adp) and its 1,3-dithiolic form.
- Morera, Enrico,Pinnen, Francesco,Lucente, Gino
-
p. 1139 - 1142
(2007/10/03)
-
- Stereospecific synthesis of (2S,4R)-[5,5,5-2H3]leucine
-
The first stereospecific chemical synthesis of a sample of the amino acid (2S)-leucine labelled in one of the diastereotopic methyl groups has been achieved using (2S)-pyroglutamic acid as a chiral template. This has been used to develop a method for assigning resonances to the diastereotopic methyl groups of the leucine residues in the 1H NMR spectra of proteins.
- August, Ryan A.,Khan, Jeffrey A.,Moody, Claire M.,Young, Douglas W.
-
p. 507 - 514
(2007/10/03)
-
- Synthesis of (2S,4S)- And (2S,4R)-5,5′-dihydroxy[5,5-2H2]leucine by two independent routes
-
In studies directed at discovering the absolute stereochemistry of the reaction catalysed by the enzyme glutamate γ-carboxylase, two independent stereoselective syntheses of (2S,4S)-5,5′-dihydroxy[5,5- 2H2]-leucine 4a and its (2S,4R)-diastereoisomer 4b have been developed. The first synthesis uses (2S)-pyroglutamic acid as starting material and provides (2S,4S)-5,5′-dihydroxy[5,5-2H2]leucine 4a, while the second starts with (2S,4R)-4-hydroxyproline and provides (2S,4R)-5,5′-dihydroxy[5,5-2H2]leucine 4b.
- Durand, Xavier,Hudhomme, Pietrick,Khan, Jeffrey A.,Young, Douglas W.
-
p. 1131 - 1139
(2007/10/03)
-
- Synthesis of [6-13C]-L-lysine
-
A short and efficient enantioselective synthesis of [6-13C]-L-lysine from commercially available N-benzyloxycarbonyl-L-glutamic acid α-methyl ester is described using [13C]-sodium syanide as the source of isotopic label.
- Sutherland,Willis
-
-
- C-glycosylation of cyclic N-acyliminium ions with trimethylsilyloxyfuran
-
C-glycosylation of 2-methoxy-5-alkoxycarbonyl pyrrolidines with trimethylsilyloxyfuran allows us to obtain the corresponding pyrrolidines contigus to a α,β-unsaturated butyrolactone.
- Pichon, Marianne,Figadere, Bruno,Cave, Andre
-
p. 7963 - 7966
(2007/10/03)
-
- A convenient N-protection of pyroglutamate derivatives
-
Esters of pyroglutamic acid were N-protected by conventional protective groups (Z. Boc, and COOMe) in high yield, without racemization, using LiHMDS in THF at -78°C and ZCl, Boc2O, and ClCOOMe, respectively.
- Li,Sakamoto,Kato,Kikugawa
-
p. 4045 - 4052
(2007/10/03)
-
- Stereospecific Synthesis of (2S,4R)--Leucine
-
The first fully stereospecific synthesis of a sample of the amino acid (2S)-leucine labelled in only one of the diastereotopic methyl groups has been achieved using (2S)-pyroglutamic acid as a chiral template. Key Words: leucine; stereospecific synthesis; amino acid; isotopic labelling; bio-organic
- August, Ryan A.,Khan, Jeffrey A.,Moody, Claire M.,Young, Douglas W.
-
p. 4617 - 4620
(2007/10/02)
-
- A NEW SYNTHETIC EQUIVALENT OF THE GLUTAMIC ACID γ-ANION AND ITS APPLICATION TO THE SYNTHESIS OF S-(+)-γ-CARBOXYGLUTAMIC ACID
-
Protected S-pyroglutamic acid can be deprotonated specifically at the γ-position.The resulting enolate can be converted into γ-carboxyglutamic acid in optically pure form.
- Attwood, Michael R.,Carr, Maria G.,Jordan, Steven
-
p. 283 - 284
(2007/10/02)
-
- Amino Acid Synthesis Using (L)-Pyroglutamic Acid as a Chiral Starting Material
-
Deprotonation of protected pyroglutamates 1(c), 1(d), and 1(e) with lithium di-isopropylamine (LDA) or lithium hexamethyldisilazide (LiHDMS) in THF, followed by reaction with electrophiles, leads to the formation of 4-substituted pyroglutamates in good yield.This approach has been used for the synthesis of the novel amino acid (4).Key Words: pyroglutamic acid; chiral amino acid synthesis
- Baldwin, Jack E.,Miranda, Tania,Moloney, Mark,Hokelek, Tuncer
-
p. 7459 - 7468
(2007/10/02)
-
- A Novel Synthesis of L-Pyroglutamic Acid Derivatives from L-Proline: Utility of N-Protecting Groups for Ruthenium Tetroxide Oxidation of Cyclic α-Amino Acids
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The utility of four urethane type N-protecting groups, benzyloxycarbonyl (Z), p-nitrobenzyloxycarbonyl , trichloroethoxycarbonyl (Troc) and tert-butoxycarbonyl (Boc) groups, was tested in the ruthenium tetroxide (RuO4) oxidation of N-protected L-proline esters.Three groups, but not the Z group, which was decomposed by RuO4, were found to be stable during the oxidation and afforded high yields of the corresponding L-pyroglutamic acid esters.Removal of the protecting groups from the oxidation products was carried out successfully in the usual manner to give N-unsubstituted (NH-type) L-pyroglutamic acid derivatives without racemization.The first transformation of L-proline into L-pyroglutamic acid and its derivatives has been accomplished.Keywords - oxidation; ruthenium tetroxide oxidation; lactam synthesis; L-pyroglutamic acid synthesis; carboxamide N-protection; ruthenium tetroxide; L-proline; L-pyroglutamic acid; twophase method.
- Yoshifuji,Shigeyuki,Tanaka, Ken-ichi,Kawai, Tomoyuki,Nitta, Yoshihiro
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p. 3873 - 3878
(2007/10/02)
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