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Protecting Groups (protecting + groups)
Selected AbstractsOxime Carbonates: Novel Reagents for the Introduction of Fmoc and Alloc Protecting Groups, Free of Side ReactionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2010Sherine N. Khattab Abstract Fmoc and Alloc protecting groups represent a consistent alternative to classical Boc protection in peptide chemistry. The former was established in the last decades as the ,-amino protecting group of choice, whereas the latter allows a fully orthogonal protection strategy with Fmoc and Boc. Usually, the introduction of the Fmoc and Alloc moieties takes place through their halogenoformates, azides, or activated carbonates. This rather simple reaction is accompanied by several side reactions, specially the formation of Fmoc/Alloc dipeptides and even tripeptides. The present work describes new promising Fmoc/Alloc-oxime reagents, which are easy to prepare, stable, and highly reactive crystalline materials that afford almost contaminant-free Fmoc/Alloc-amino acids in high yields by following a conventional procedure. Amongst the Fmoc-oxime derivatives, the N -hydroxypicolinimidoyl cyanide derivative (N -{[(9H-fluoren-9-yl)methoxy]carbonyloxy}picolinimidoyl cyanide) gave the best results for the preparation of Fmoc-Gly-OH, which is the most predisposed to give side reactions. The same Alloc-oxime analogue afforded the preparation of Alloc-Gly-OH in good yield, purity, and extremely low dipeptide formation, as analyzed by reverse-phase HPLC and NMR spectroscopy. [source] Conformationally Biased Selective Alkylation of trans -Cyclohexane-1,2-bis(sulfonamide) Assisted by Solvent-Tuned Protecting Groups: Applications to the Synthesis of a Large Optically Active Polyazamacrocycle,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2006Carmen Peña Abstract The selective alkylation of (R,R)-cyclohexane-1,2-bis(sulfonamide) with trityl bromoalkyl ethers has been studied in detail. The major formation of either mono- or dialkylated compounds clearly depends on the right combination of protecting groups and the reaction solvent. An exhaustive study suggests that this effect can be reasonably explained by the conformational preferences of the monoalkylated compounds, which also depend on the reaction medium, solvophobic effects and weak intramolecular interactions. Structural analysis by NOE measurements showed the presence of folded conformations in solution for all the tested examples. Monte Carlo conformational searches supported this proposal, showing a very good correlation between the fraction of folded species and the selectivity towards monoalkylation. Finally, tuning of the reaction conditions, leading to either extended or folded conformations of the monoalkylated synthetic intermediates, was exploited for the efficient synthesis of a large optically active polyazamacrocycle. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Bacillus subtilis Esterase (BS2) and its Double Mutant Have Different Selectivity in the Removal of Carboxyl Protecting GroupsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 14-15 2009Efrosini Barbayianni Abstract An esterase from Bacillus subtilis (BS2) and its double mutant E188W/M193C quickly hydrolyze n -butyl, n -propyl, methoxyethyl and allyl esters. The wild-type BS2 preferentially removes such esters from the ,-position of glutamate diesters, while the engineered enzyme has a reversed selectivity removing esters from the ,-position of glutamate diesters. Automated docking and molecular dynamic simulations were performed to understand the molecular reason for the different regioselectivity. [source] Enzymatic Removal of Carboxyl Protecting Groups.CHEMINFORM, Issue 24 2007Part 3. Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Solvolysis of Benzyl Alcohols and Ethers in 1,2-Diols and Application to a Deprotection of Benzyl Ether-Type Protecting Groups.CHEMINFORM, Issue 52 2006Hideyoshi Miyake Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Enzymatic Removal of Carboxyl Protecting Groups.CHEMINFORM, Issue 11 2006Part 2. Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Chemoselective Deprotection of Acid Labile Primary Hydroxyl Protecting Groups under CBr4 -Photoirradiation Conditions.CHEMINFORM, Issue 14 2005Ming-Yi Chen Abstract For Abstract see ChemInform Abstract in Full Text. [source] Selective Removal of 2,2,2-Trichloroethyl- and 2,2,2-Trichloroethoxycarbonyl Protecting Groups with Zn,N-Methylimidazole in the Presence of Reducible and Acid-Sensitive Functionalities.CHEMINFORM, Issue 11 2005Laszlo Somsak Abstract For Abstract see ChemInform Abstract in Full Text. [source] Efficient and Selective Removal of Methoxy Protecting Groups in Carbohydrates.CHEMINFORM, Issue 5 2005Alicia Boto Abstract For Abstract see ChemInform Abstract in Full Text. [source] Selective tert-Butyl Ester Deprotection in the Presence of Acid Labile Protecting Groups with Use of ZnBr2.CHEMINFORM, Issue 1 2005Ramesh Kaul Abstract For Abstract see ChemInform Abstract in Full Text. [source] Development of Tyrosinase Labile Protecting Groups for Amines.CHEMINFORM, Issue 52 2004Helen M. I. Osborn Abstract For Abstract see ChemInform Abstract in Full Text. [source] The Effect of Protecting Groups on Thallium(III)-Promoted Ring Contraction of 3-Alkenols.CHEMINFORM, Issue 39 2002Helena M. C. Ferraz Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Fluorinated Analogues of tert-Butyl Alcohol as Novel Protecting Groups for Use in Fluorous Synthesis.CHEMINFORM, Issue 16 2002Juan Pardo Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Precipitons,Functional Protecting Groups to Facilitate Product Separation: Applications in Isoxazoline Synthesis.CHEMINFORM, Issue 33 2001Todd Bosanac Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Overcoming the Demons of Protecting Groups with Amphoteric MoleculesCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2007Andrei Abstract Synthetic organic chemists have long depended on protecting group manipulations when faced with the challenges of chemoselectivity and functional group incompatibility. Overcoming this dependence will improve the overall efficiency of chemical synthesis. By taking advantage of orthogonally reactive functional groups, amphoteric molecules can afford access not only to more efficient and strategic syntheses but also to the development of novel chemical transformations. [source] Oxime Carbonates: Novel Reagents for the Introduction of Fmoc and Alloc Protecting Groups, Free of Side ReactionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2010Sherine N. Khattab Abstract Fmoc and Alloc protecting groups represent a consistent alternative to classical Boc protection in peptide chemistry. The former was established in the last decades as the ,-amino protecting group of choice, whereas the latter allows a fully orthogonal protection strategy with Fmoc and Boc. Usually, the introduction of the Fmoc and Alloc moieties takes place through their halogenoformates, azides, or activated carbonates. This rather simple reaction is accompanied by several side reactions, specially the formation of Fmoc/Alloc dipeptides and even tripeptides. The present work describes new promising Fmoc/Alloc-oxime reagents, which are easy to prepare, stable, and highly reactive crystalline materials that afford almost contaminant-free Fmoc/Alloc-amino acids in high yields by following a conventional procedure. Amongst the Fmoc-oxime derivatives, the N -hydroxypicolinimidoyl cyanide derivative (N -{[(9H-fluoren-9-yl)methoxy]carbonyloxy}picolinimidoyl cyanide) gave the best results for the preparation of Fmoc-Gly-OH, which is the most predisposed to give side reactions. The same Alloc-oxime analogue afforded the preparation of Alloc-Gly-OH in good yield, purity, and extremely low dipeptide formation, as analyzed by reverse-phase HPLC and NMR spectroscopy. [source] Total Synthesis of Silyl-Protected Early Intermediates of Polyketide Biosynthesis,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 16 2010Karsten Krohn Abstract The ketal- or dithioketal-protected isocoumarins 15,18 gave the corresponding 1-naphthols 21,26 in their reactions with the acetoacetate (10) or pentane-2,4-dione (19) dianions and the acetone monoanion. Subjection of the dithioketal-protected ester 28 to Baker,Venkataraman reaction conditions led to the 8-deoxy tautomeric, protected forms 29/30 of the early decaketide antibiotic intermediate 2b. However, the dithioketal protecting groups could not be removed without destruction of the molecule. Consequently the silyl-protected unstable early tri- and tetracyclic decaketide biosynthesis intermediates 37a, 37b, and 38a (precursors of angucycline and anthracycline antitumor antibiotics) were prepared through silylation of 33a and 33b, to afford 34a and 34b, and subsequent treatment with acetylacetone dianion. The ultimate synthetic goal, the silyl-protected 2,3-dialkylated naphthol derivative 41, was achieved by selective elongation of the bottom chain of the bis-silyl-protected methyl ester 36 with acetylacetone dianion. [source] A Practical Method for Selective Cleavage of a tert -Butoxycarbamoyl N -Protective Group from N,N -Diprotected ,-Amino Acid Derivatives Using Montmorillonite K-10,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 30 2007J. Nicolás Hernández Abstract A new, practical, and mild procedure for the selective cleavage of a tert -butoxycarbonyl group (Boc) in N -Boc- N -acyl-diprotected amines is described. When applied to ,-amino acids, complete integrity of the stereochemistry was observed. The use of N,N -di-Boc-,-amino-,- and ,-hydroxy esters provided both ,- and ,-lactones in very good yields. The method is based on the use of Montmorillonite K-10 either in CH2Cl2 at room temperature or in toluene at 65 °C and is compatible with the presence of a large range of functional and other protecting groups in the substrates. In most cases virtually pure samples are obtained after filtration and removal of solvents. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2006M. Belén Cid Abstract The glycosylation of 1,2- trans -diequatorial diols derived from tetrabenzoylated and tetrabenzylated D - and L - chiro -inositol with several glycosyl donors has been investigated. An unprecedented dependence of the regioselectivity on the absolute configuration of the acceptor has been found. However this trend is also modulated by the nature of the protecting groups on both the donor and acceptor, with benzoylated acceptors affording higher levels of regioselectivity. Most of the results have been rationalized by DFT calculations which indicate that stereoelectronic factors and hydrogen bonding between the donor and acceptor govern their relative orientation and determine the regiochemical outcome of the process. These studies also highlight the role of the acyl group adjacent to the OH to be glycosylated in facilitating the glycosylation reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Solution Synthesis of Two Orthogonally Protected Lactosides as Tetravalent Disaccharide-Based ScaffoldsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 13 2004Sergio Castoldi Abstract Two tetravalent lactosidic scaffolds have been synthesised in solution from commercial lactose. Careful manipulation of the protecting groups allowed us to orthogonally protect four OH groups for their use as diversity sites for the development of broad screening libraries of sugar mimics. The selective access to each of these hydroxy groups has been demonstrated on scaffold 2 by deprotection and functionalisation with p -fluorophenyl isocyanate. Finally, the 6-OH derivative of compound 2 was covalently attached to a polymeric support. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] On the Synthesis and Selective Deprotection of Low-Generation Dendrons with Orthogonally Protected Peripheral Amine Groups and a Possible Impact of the Deprotection Conditions on the Stability of Dendronized Polymers' SkeletonsHELVETICA CHIMICA ACTA, Issue 11 2006Rabie Al-Hellani Abstract The synthesis of first- and second-generation dendrons with defined ratios of orthogonally protected amine groups in the periphery ((benzyloxy)carbonyl (Cbz) and (tert -butoxy)carbonyl (Boc) protection) and the degree to which they can be selectively removed are described. The reaction conditions required for these deprotections were applied to methacrylic acid (=,2-methylprop-2-enoic acid) based dendronized polymers carrying the same peripheral protecting groups to investigate whether they have any detrimental interference with the polymer skeleton. Specifically it was explored whether dendrons attached to the backbone could possibly be cleaved off as a whole (de-dendronization). Finally it was investigated how de-dendronizations can be used for quantifying both the dendron-structure perfection and the polymer-backbone configurations. [source] A New 2H -Azirin-3-amine as a Synthon for 2-MethylaspartateHELVETICA CHIMICA ACTA, Issue 11 2005Kathrin The synthesis of a novel 2,2-disubstituted 2H -azirin-3-amine 3a as a building block for racemic Asp(2Me) is described. This synthon contains an ester group in the side chain. The reaction of 3a with thiobenzoic acid and the amino acid Z-Val-OH yielded the racemic monothiodiamide 10a and the dipeptide 11 as a mixture of diastereoisomers, respectively (Scheme,2). In 11, each of the protecting groups was removed selectively (Scheme,3). First attempts toward the preparation of enantiomerically pure synthons for Asp(2Me) with a chiral auxiliary group in the side chain are described. Synthons 3b with a 1-(naphthalen-1-yl)ethyl ester group and 3c with a menthyl ester group were prepared and reacted with thiobenzoic acid to form monothiodiamides 10b and 10c (Scheme,2). However, the diastereoisomers of the synthons 3b and 3c could not be separated by chromatography. [source] Catalytic, Asymmetric Vinylogous Mukaiyama Aldol Reactions of Pyrrole- and Furan-Based Dienoxy Silanes: How the Diene Heteroatom Impacts StereocontrolADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2010Claudio Curti Abstract Denmark's chiral bisphosphoramide/silicon tetrachloride system performs as an excellent Lewis base-Lewis acid catalyst for the vinylogous Mukaiyama aldol reaction of pyrrole- and furan-based dienoxy silanes with aromatic and heteroaromatic aldehydes. This asymmetric methodology provides a powerful synthetic entry to a variety of ,-hydroxylated ,-butenolide-type frameworks with high efficiency and valuable margins of regio-, diastereo-, and enantioselectivity. Notably, the nature of the heteroatom within the vinylogous dienoxy silane donor heavily impacts the diastereocontrol, with syn -configured aldol adducts emerging from pyrroles bearing electron-withdrawing N -protecting groups (Boc, Ts, and Cbz) and anti -configured adducts prevailing when furan- or N -alkyl/alkenylpyrrole donors are involved. [source] Direct B -Alkyl Suzuki,Miyaura Cross-Coupling of Trialkyl- boranes with Aryl Bromides in the Presence of Unmasked Acidic or Basic Functions and Base-Labile Protections under Mild Non-Aqueous ConditionsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 3 2009Bing Wang Abstract An efficient and chemoselective palladium-catalyzed direct B -alkyl Suzuki,Miyaura cross-coupling of trialkylboranes with diversely functionalized aryl bromides is described. A wide variety of unmasked acidic or basic functions are tolerated. The mild non-aqueous conditions are compatible with aldehydes, ketones, nitriles, chloro substitution as well as base-labile phenolic Piv and TBS protecting groups. The anhydrous conditions were found to be advantageous for aryl bromide substrates. A potent CEPT inhibitor was efficiently synthesised using this protocol. [source] Aminolysis of methoxy groups in pyrimidine derivatives.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2002Activation by 5-nitroso The nucleophilic substitution of 2-mefhoxy groups in pyrimidine derivatives was strongly activated by introduction of a 5-nitroso group on to the pyrimidine ring. The aminolysis of several 2-methoxy-5-nitrosopyrimidine derivatives was performed at room temperature in hydroxylic as well as in non-hydroxylic media with different primary amines in short time and good yields. The aminolysed substrates include 6-[(per- O -acetyl)glycosyl]aminopyrimidines which afforded the corresponding 2-aminopyrimidines without harming the acetyl protecting groups of the sugar moiety. [source] Synthesis of morphine-[N -methyl- 14C]-6- , - D -glucuronideJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2002John R. Ferguson Abstract Protected morphine-6-glucuronide was converted into morphine-[N -methyl- 14C]-6-glucuronide by a three-step procedure. Methyl (3-pivaloylmorphin-6-yl 2,3,4-tri- O -isobutyryl- , -D-glucopyranosid)uronate was N-demethylated by treatment with 1-chloroethyl chloroformate to afford protected normorphine-6-glucuronide as its hydrochloride salt. The normorphine-6-glucuronide derivative was alkylated with iodomethane-[14C] in the presence of potassium carbonate to produce C-14 labelled protected morphine-6-glucuronide. Finally, hydrolysis of the protecting groups using 5% sodium hydroxide solution gave morphine-[N -methyl- 14C]-6- , -D-glucuronide with a specific activity of 41.8 mCi mmol,1 and radiochemical purity of 99.2% (HPLC). Copyright © 2002 John Wiley & Sons, Ltd. [source] Synthesis of cyclooctapeptides: constraints analogues of the peptidic neurotoxin, ,-agatoxine IVB,an experimental point of viewJOURNAL OF PEPTIDE SCIENCE, Issue 3 2008Ewelina Minta Abstract ,-AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q-type calcium channels. The best route to achieve the analogues possessing the three-dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza-tryptophane and alanine were synthesized. The synthesis was carried out on various acid-labile resins (BARLOS chlorotrityl, Rink amide, PEG-based or Wang resins), by Fmoc strategy. In this paper, we describe optimization of the peptide cyclization with various protecting groups, and on resin or in solution cyclization experimental parameters. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Studies on deprotection of cysteine and selenocysteine side-chain protecting groupsJOURNAL OF PEPTIDE SCIENCE, Issue 2 2007Katharine M. Harris Abstract We present here a simple method for deprotecting p -methoxybenzyl groups and acetamidomethyl groups from the side-chains of cysteine and selenocysteine. This method uses the highly elecrophilic, aromatic disulfides 2,2,-dithiobis(5-nitropyridine) (DTNP) and 2,2,-dithiodipyridine (DTP) dissolved in TFA to effect removal of these heretofore difficult-to-remove protecting groups. The dissolution of these reagents in TFA, in fact, serves to ,activate' them for the deprotection reaction because protonation of the nitrogen atom of the pyridine ring makes the disulfide bond more electrophilic. Thus, these reagents can be added to any standard cleavage cocktail used in peptide synthesis. The p -methoxybenzyl group of selenocysteine is easily removed by DTNP. Only sub-stoichiometric amounts of DTNP are required to cause full removal of the p -methoxybenzyl group, with as little as 0.2 equivalents necessary to effect 70% removal of the protecting group. In order to remove the p -methoxybenzyl group from cysteine, 2 equivalents of DTNP and the addition of thioanisole was required to effect removal. Thioanisole was absolutely required for the reaction in the case of the sulfur-containing amino acids, while it was not required for selenocysteine. The results were consistent with thioanisole acting as a catalyst. The acetamidomethyl group of cysteine could also be removed using DTNP, but required the addition of > 15 equivalents to be effective. DTP was less robust as a deprotection reagent. We also demonstrate that this chemistry can be used in a simultaneous cyclization/deprotection reaction between selenocysteine and cysteine residues protected by p -methoxybenzyl groups to form a selenylsulfide bond, demonstrating future high utility of the deprotection method. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Site-specific synthesis of Amadori-modified peptides on solid phaseJOURNAL OF PEPTIDE SCIENCE, Issue 6 2006Andrej Frolov Abstract Glycation of peptides and proteins is a slow chemical reaction of reducing sugars modifying the amino groups. The first intermediates of this nonenzymatic glycosylation are the Amadori products that can undergo further chemical reactions, finally leading to advanced glycation end products (AGEs). The formation of AGEs was not only linked to aging of tissues and organs in general but also to several diseases such as diabetes mellitus and Alzheimer's disease. Because of the importance of these modifications and their potential use as diagnostic markers, a global postsynthetic approach on solid phase was developed. The peptides were synthesized by Fmoc/tBu-chemistry, with the lysine residue to be modified being protected with the very acid-labile methyltrityl group. Incubation of the peptides with D -glucose in DMF at elevated temperatures resulted in product yields of 35%. Neighboring residues with bulky protecting groups reduced the yields only slightly. The major by-products were the unmodified peptide and an oxidation product. Whereas the unmodified peptide eluted before the glycated peptide, all other by-products eluted later in RP-HPLC, allowing simple purification. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis of linear and cyclic phosphopeptides as ligands for the N -terminal SH2-domain of protein tyrosine phosphatase SHP-1JOURNAL OF PEPTIDE SCIENCE, Issue 7 2005Dr Diana Imhof Abstract Linear and cyclic phosphopeptides related to the pY2267 binding site of the epithelial receptor tyrosine kinase Ros have been synthesized as ligands for the amino-terminal SH2 (src homology) domain of protein tyrosine phosphatase SHP-1. The synthesis was accomplished by Fmoc-based solid-phase methodology using side-chain unprotected phosphotyrosine for the linear and mono-benzyl protected phosphotyrosine for the cyclic peptides. According to molecular modelling, the incorporation of a glycine residue between Lys (position pY,1 relative to phosphotyrosine) and Asp or Glu (position pY+2) was recommended for the cyclic candidates. The preparation of these peptides was successfully performed by the incorporation of a Fmoc-Xxx(Gly-OAll)-OH (Xxx = Asp, Glu) dipeptide building block that was prepared in solution prior to SPPS. The cyclization was achieved with PyBOP following Alloc/OAll-deprotection. This study demonstrates the usefulness of allyl-type protecting groups for the generation of side-chain cyclized phosphopeptides. Alloc/OAll-deprotection and cyclization are compatible with phosphorylated tyrosine. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||