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Terms modified by Boc Selected AbstractsEvidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancerHUMAN MUTATION, Issue 2 2001Francesco Baudi Abstract Several genes have been involved in the pathogenesis of hereditary breast/ovarian cancer (BOC), but mutations in the BRCA1 gene are by far the most recurrent. In this study, we report the identification of a founder mutation in a geographically and historically homogeneous population from Calabria, a south Italian region. A screening performed on 24 patients from unrelated families highlighted the high prevalence of a 5083del19 alteration in the BRCA1 gene, which accounts for 33% of the overall gene mutations. The same mutation was also detected in 4 patients, all of Calabrian origin, referred to us by research centres from the north of Italy. Allelotype analysis, performed on probands and unaffected family members revealed the presence a common allele, therefore suggesting a founder effect due to a common ancestor. Our findings underscore the importance of ethnic background homogeneity in patients' selection and highlight the usefulness of founder mutations as a potential tool for optimisation of preclinical diagnosis in gene carriers and therapeutic approaches in affected individuals. Hum Mutat 18:163,164, 2001. © 2001 Wiley-Liss, Inc. [source] Low-complexity unambiguous acquisition methods for BOC-modulated CDMA signalsINTERNATIONAL JOURNAL OF SATELLITE COMMUNICATIONS AND NETWORKING, Issue 6 2008Elena Simona Lohan Abstract The new M-code signals of GPS and the signals proposed for the future Galileo systems are of split-spectrum type, where the pseudorandom (PRN) code is multiplied with rectangular sub-carriers in one or several stages. Sine and cosine binary-offset-carrier (BOC) modulations are examples of modulations, which split the signal spectrum and create ambiguities in the envelope of the autocorrelation function (ACF) of the modulated signals. Thus, the acquisition of split-spectrum signals, based on the ambiguous ACF, poses some challenges, which might be overcome at the expense of higher complexity (e.g. by decreasing the step in searching the timing hypotheses). Recently, two techniques that deal with the ambiguities of the ACF have been proposed, and they were referred to as ,sideband (SB) techniques' (by Betz, Fishman et al.) or ,BPSK-like' techniques (by Martin, Heiries et al.), since they use SB correlation channels and the obtained ACF looks similar to the ACF of a BPSK-modulated PRN code. These techniques allow the use of a higher search step compared with the ambiguous ACF situation. However, both these techniques use SB-selection filters and modified reference PRN codes at the receivers, which affect the implementational complexity. Moreover, the ,BPSK-like' techniques have been so far studied for even BOC-modulation orders (i.e. integer ratio between the sub-carrier frequency and the chip rate) and they fail to work for odd BOC-modulation orders (or equivalently for split-spectrum signals with significant zero-frequency content). We propose here three reduced-complexity methods that remove the ambiguities of the ACF of the split-spectrum signals and work for both even and odd BOC-modulation orders. Two of the proposed methods are extensions of the previously mentioned techniques, and the third one is introduced by the authors and called the unsuppressed adjacent lobes (UAL) technique. We argue via theoretical analysis the choice of the parameters of the proposed methods and we compare the alternative methods in terms of complexity and performance. Copyright © 2008 John Wiley & Sons, Ltd. [source] Conventional Tetrakis(triphenylphosphine)palladium-Copper(I) Iodide-Catalyzed Sonogashira Coupling of Free and BOC- Protected Propargylic Amines "On Water"ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2009Bartomeu Soberats Abstract Alkynylation of aryl iodides with propargylic amines has been achieved by means of a Sonogashira coupling using "on water" methods. The use of less than 0.2,mol% of tetrakis(triphenylphosphine)palladium [Pd(PPh3)4] and 1.5,mol% copper(I) iodide [CuI] in the presence of diisopropylethylamine (DIPEA) allows the coupling to proceed at 95,°C yielding moderate to good yields of mono-, bis-, and tris-aminoalkynylbenzene derivatives. [source] m/p -Cresol,based t -BOC protected alternating "high ortho" copolymer as a possible e-beam resist: Characterization using multidimensional NMR spectroscopy,JOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2009Maneesh Sharma Abstract Synthesis of a m/p -cresol,based novolac resin and its subsequent esterification using di- tert -butyl dicarbonate (t -BOC) is described. The product has been characterized using techniques of FTIR spectroscopy, one dimensional 1H NMR, 13C NMR, and DEPT-135 spectra. Two dimensional NMR experiments like, COSY, HSQC, and HMBC have been used for exhaustive probing of the microstructural details of the derivatized copolymer. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 [source] Photoreaction Between Benzoylthiophenes and N -BOC-Tryptophan Methyl Ester,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2006Julia Pérez-Prieto ABSTRACT Drug-induced photoallergy requires as the first step formation of covalent drug-protein photoadducts. One of the key amino acids involved in this process is tryptophan (Trp). In this context, several diaryl ketones, including 2-benzoylthiophene (BT), [2-(5-benzoyl-5-thienyl)]-2-methylpropanoic methyl ester (TPA methyl ester) and 4-(2-thienylcarbonyl)phenyl]-2-methylpropanoic methyl ester (SUP methyl ester) have been irradiated in the presence of N -BOC-(L)-tryptophan methyl ester. Laser flash photolysis has allowed to detect three neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal hydrogen-atom abstraction. This correlates well with the isolation of homodimers, as well as with cross-coupling products, in the preparative irradiation. The main cross-coupling products were in all cases lactones arising from the reaction of the Trp-derived skatolyl radicals with the corresponding ketyl radicals. These lactones were obtained as the (4R) stereoisomers with remarkable diasteroselectivity. No coupling products through the phenyl p -position of BT or TPA methyl ester were found. By contrast, ketone homodimers and cross-coupling products arising from reaction through the thienyl 5-position were obtained when using BT and SUP methyl ester; this is very interesting, because stable LAT-derived products are difficult to isolate. [source] Immunohistochemical characterization of guided bone regeneration at a dehiscence-type defect using different barrier membranes: an experimental study in dogsCLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2008Frank Schwarz Abstract Objectives: The aim of the present study was to evaluate immunohistochemically the pattern of guided bone regeneration (GBR) using different types of barrier membranes. Material and methods: Standardized buccal dehiscence defects were surgically created following implant bed preparation in 12 beagle dogs. Defects were randomly assigned to six different GBR procedures: a collagen-coated bone grafting material (BOC) in combination with either a native, three cross-linked, a titanium-reinforced collagen membrane, or expanded polytetrafluorethylene (ePTFE), or BOC alone. After 1, 2, 4, 6, 9, and 12 weeks of submerged healing, dissected blocks were processed for immunohistochemical (osteocalcin , OC, transglutaminase II , angiogenesis) and histomorphometrical analysis [e.g., bone-to-implant contact (BIC), area of new bone fill (BF)]. Results: In general, angiogenesis, OC antigen reactivity, and new bone formation mainly arose from open bone marrow spaces at the bottom of the defect and invaded the dehiscence areas along the implant surface and BOC. At 4 weeks, membranes supporting an early transmembraneous angiogenesis also exhibited some localized peripheral areas of new bone formation. However, significantly increasing BIC and BF values over time were observed in all groups. Membrane exposure after 10,12 weeks was associated with a loss of the supporting alveolar bone in the ePTFE group. Conclusion: Within the limits of the present study, it was concluded that (i) angiogenesis plays a crucial role in GBR and (ii) all membranes investigated supported bone regeneration on an equivalent level. [source] A survey of the frequency and impact of Behaviours of Concern in dementia on residential aged care staffAUSTRALASIAN JOURNAL ON AGEING, Issue 2 2007Katrina Cubit Objectives:,To investigate staff perceptions of the frequency of Behaviours of Concern (BoC) exhibited by residents with dementia; to rank order the BoC causing most disruption to the everyday running of facilities, and the most personal distress to staff. Methods:,A cross-sectional survey was conducted in 2005, across staff in 15 residential aged care facilities in Tasmania, using a self-administered questionnaire. Results:,Over 80% of staff reported residents' repetitive actions, wandering and verbal disruption as occurring more than once a day BoC. The three highest ranked BoC reported as being the most disruptive to the running of the unit were verbal disruption, wandering and repetitive actions. Residents' physical aggression, verbal disruptions and wandering were ranked 1, 2 and 3, respectively, as causing staff the most personal distress. Conclusions:,Although occurring infrequently physical aggression is the BoC perceived by staff to cause them the greatest amount of personal distress. [source] "Tail,Tail Dimerization" of Ferrocene Amino Acid DerivativesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 25 2010Daniel Siebler Abstract Acid anhydrides of N-protected 1,-aminoferrocene-1-carboxylic acid (Fca) have been prepared and spectroscopically characterized (protection group Boc, Fmoc, Ac; 4a,4c). The structure of the Boc-derivative 4a has been determined by single-crystal X-ray crystallography. An intramolecular N,H···O hydrogen bond involving the carbamate units results in a ring structure containing the two ferrocene units, the anhydride moiety, and the hydrogen bond. In the crystal, the individual molecules are connected by intermolecular N,H···O hydrogen bonds of the carbamate unit. Experimental and theoretical studies suggest that the ring motif is also a dominant species in solution. Electronic communication across the anhydride moiety is found to be very weak as judged from electrochemical, spectroscopic, and theoretical experiments. [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] Switchable Fluorescent and Solvatochromic Molecular Probes Based on 4-Amino- N -methylphthalimide and a Photochromic DiaryletheneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2008Sergey F. Yan Abstract New fluorescent photochromic compounds (1 -H and 1 -Boc) have been synthesized and characterized in different solvents. The fluorescence emission can be switched "on" and "off" with visible light and UV, respectively, by means of the photochromic reaction. The emission wavelength and efficiency strongly depend on the polarity of the solvent. The compounds show a positive solvatochromic effect in the emission maxima, and their fluorescence quantum yield decreases as the solvent's polarity increases (from cyclohexane to dioxane). In solvents more polar than dioxane the emission is too weak and therefore undetectable, and thus 1 -H and 1 -Boc behave as "normal" photochromic compounds. The photochromic reaction is also sensitive to the environment. A decrease of more than an order of magnitude was found for the quantum yield of the colouring reaction (,OF,CF) for 1 -H in ethanol compared with cyclohexane, and an about threefold decrease in ,OF,CF was observed for the compound 1 -Boc in polar solvents (compared with apolar solvents). For both compounds the ring-opening reaction was found not to dependent on the solvent. The novel fluorescent molecular switches 1 -H and 1 -Boc are able to probe the polarity of their microenvironment. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [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] Synthesis of Novel Nucleo-,-Amino Acids and Nucleobase-Functionalized ,-PeptidesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2003Arndt M. Brückner Abstract Four novel ,-amino acids bearing the canonical nucleobases guanine, cytosine, adenine, and thymine in the side chain, are synthesized starting from Boc- L -aspartic acid 4-benzyl ester. The syntheses are accomplished in six steps by the nucleophilic substitution of (S)-,-(tert -butoxycarbonylamino)-,-bromopentanoic acid benzyl ester with the corresponding nucleobase derivative as the key step. The guaninyl and cytosinyl ,-amino acids were built into ,-peptides that were studied by temperature-dependent CD and UV spectroscopy. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Val-Ala Dipeptide Isosteres by Hydrocyanation of ,,-Amino ,,,-Unsaturated Ketones , Control of Stereoselectivity by the N -Protecting GroupEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2003Fabio Benedetti Abstract Three diastereoisomeric hydroxyethylene isosters of the Val-Ala dipeptide were synthesized from ,,,-unsaturated ketones 1 derived from N -Boc- and N,N -dibenzyl- L -valine. The enones were hydrocyanated with diethylaluminum cyanide to give the corresponding ,-cyano ketones with the stereoselectivity depending on the protecting group. N -Boc protected enone 1a gave a 1:1 mixture of anti and syn adducts 4a, 5a while the corresponding N,N -dibenzyl compound 1c gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride reduction of the resulting cyano ketones is also controlled by the protecting group, resulting in opposite stereoselectivities for N -Boc and N,N -dibenzyl compounds. The cyano alcohols thus obtained were converted, in several steps, into two series of enantiomerically pure hydroxyethylene isosters of the Val-Ala dipeptide. In the first series the hydroxy group and the N -terminal of the isoster are internally protected through the formation of an oxazolidine; in the second series the hydroxy group and the C-terminal are protected as lactone. Two oxazolidines (28, 29), corresponding to syn,syn and syn,anti 4-hydroxy-5-amino acid isosters, and three lactones (23,25), corresponding to syn,syn, syn,anti, and anti,anti isosters were obtained by this approach. (© Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2003) [source] Synthesis of Novel Amino Acids and Dehydroamino Acids Containing the Benzo[b]thiophene MoietyEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2003Ana S. Abreu Abstract Several novel amino acids and dehydroamino acids containing the benzo[b]thiophene moiety were prepared by Michael addition or sequential Michael addition and palladium-catalyzed C,C or C,N cross couplings. The substrates for Michael addition were the methyl esters of N,N -bis(tert -butyloxycarbonyl)dehydroalanine [Boc2,,Ala,OMe] and N -(4-toluenesulfonyl)- N -(tert -butyloxycarbonyl)dehydroalanine [Tos,,Ala(N -Boc),OMe], and the nucleophiles were aromatic thiols and 3-iodobenzylamine. The addition of mercaptobenzo[b]thiophenes directly to Tos,,Ala(N -Boc),OMe gave stereoselectively, in good yields, the E -isomer of the corresponding dehydrocysteine. When thiophenols and 3-iodobenzylamine were used as nucleophiles the presence of an additional function (halogen or amine) allowed a subsequent palladium-catalyzed cross-coupling reaction with functionalized benzo[b]thiophenes (boronic acids, a halogen or an amine). Using this strategy, several racemic amino acid and dehydroamino acid derivatives, which are linked to the benzo[b]thiophene moiety by an aromatic spacer, were obtained in good yields. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] O -Glycosyl Amino Acids by 2-Nitrogalactal Concatenation , Synthesis of a Mucin-Type O -GlycanEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2003Gottfried A. Winterfeld Abstract Base-promoted Michael-type addition of N -Boc- and N -Fmoc-protected serine and threonine esters to 2-nitrogalactal derivatives 2 and 26 led highly selectively to ,-glycosides 4a,d and 27a,c, respectively. Ensuing transformation of threonine derivative 4d and serine derivatives 4a,b resulted in compounds useful as lysine and dipeptide mimetics. 6- O -Desilylation of 27a,c, then 6- O -sialylation, and transformation of the nitro group of the galactose moiety into a 2-acetamido functionality, afforded N -Boc-protected serine and threonine tert -butyl esters 31a,c carrying the O -protected STN -antigen at the hydroxy group. The threonine derivative 31c was then transformed into the N -Fmoc-protected amino acid building block 33, which was employed for the synthesis of mucin repeating unit partial structure Ac-GS(STN)-TAPPAHG-NH2 (1). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADHFEBS JOURNAL, Issue 9 2002Nobuya Itoh Phenylacetaldehyde reductase (PAR) produced by styrene-assimilating Corynebacterium strain ST-10 was used to synthesize chiral alcohols. This enzyme with a broad substrate range reduced various prochiral aromatic ketones and ,-ketoesters to yield optically active secondary alcohols with an enantiomeric purity of more than 98% enantiomeric excess (e.e.). The Escherichia coli recombinant cells which expressed the par gene could efficiently produce important pharmaceutical intermediates; (R)-2-chloro-1-(3-chlorophenyl)ethanol (28 mg·mL,1) from m -chlorophenacyl chloride, ethyl (R)-4-chloro-3-hydroxy butanoate) (28 mg·mL,1) from ethyl 4-chloro-3-oxobutanoate and (S)- N-tert -butoxycarbonyl(Boc)-3-pyrrolidinol from N -Boc-3-pyrrolidinone (51 mg·mL,1), with more than 86% yields. The high yields were due to the fact that PAR could concomitantly reproduce NADH in the presence of 3,7% (v/v) 2-propanol in the reaction mixture. This biocatalytic process provided one of the best asymmetric reductions ever reported. [source] Isolation and X-Ray Structures of Reactive Intermediates of Organocatalysis with Diphenylprolinol Ethers and with ImidazolidinonesHELVETICA CHIMICA ACTA, Issue 11 20085-Repulsion, A Survey, Comparison with Computed Structures, the Geminal-Diaryl Effect at Work, with 1-Acyl-imidazolidinones: The Abstract Reaction of 2-phenylacetaldehyde with the Me3Si ether of diphenyl-prolinol, with removal of H2O, gives a crystalline enamine (1). The HBF4 salts of the MePh2Si ether of diphenyl-prolinol and of 2-(tert -butyl)-3-methyl- and 5-benzyl-2,2,3-trimethyl-1,3-imidazolidin-4-one react with cinnamaldehyde to give crystalline iminium salts 2, 3, and 4. Single crystals of the enamine and of two iminium salts, 2 and 3, were subjected to X-ray structure analysis (Figs.,1, 2, and 6), and a 2D-NMR spectrum of the third iminium salt was recorded (Fig.,7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five-membered heterocycles, i.e., D, E (Scheme,2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl-prolinol derivatives (from the Cambridge File CSD; Table,1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig.,4). The iminium ions 3 and 4 are compared with N -acylated imidazolidinones F and G (Figs.,9, 12, and 13, and Table,3), and common structural aspects such as minimalization of 1,5-repulsion (the ,A1,3 -effect'), are discussed. The crystal structures of the simple diphenyl-prolinol,HBF4 salt (Fig.,3) and of Boc- and benzoyl-(tert -butyl)methyl-imidazolidinone (Boc-BMI and Bz-BMI, resp.; Figs.,10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high-level-of-theory DFT calculations (Figs.,5 and 8, and Table,2). Delicate details including pyramidalization of trigonal N-atoms, distortions around iminium CN bonds, shielding of diastereotopic faces, and the , -interaction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations. [source] Preparation of the ,3 -Homoselenocysteine Derivatives Fmoc- ,3hSec(PMB)-OH and Boc- ,3hSec(PMB)-OH for Solution and Solid-Phase-Peptide Synthesis and SelenoligationHELVETICA CHIMICA ACTA, Issue 9 2007Oliver Flögel Abstract The title compounds, 4 and 7, have been prepared from the corresponding , -amino acid derivative selenocystine (1) by the following sequence of steps: cleavage of the SeSe bond with NaBH4, p -methoxybenzyl (PMB) protection of the SeH group, Fmoc or Boc protection at the N-atom and Arndt,Eistert homologation (Schemes,1 and 2). A ,3 -heptapeptide 8 with an N-terminal ,3 -hSec(PMB) residue was synthesized on Rink amide AM resin and deprotected (,in air') to give the corresponding diselenide 9, which, in turn, was coupled with a ,3 -tetrapeptide thiol ester 10 by a seleno-ligation. The product ,3 -undecapeptide was identified as its diselenide and its mixed selenosulfide with thiophenol (Scheme,3). The differences between , - and , -Sec derivatives are discussed. [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] Preparation of ,2 -Amino Acid Derivatives (,2hThr, ,2hTrp, ,2hMet, ,2hPro, ,2hLys, Pyrrolidine-3-carboxylic Acid) by Using DIOZ as Chiral Auxiliary,HELVETICA CHIMICA ACTA, Issue 8 2005Francois Gessier The title compounds were prepared from valine-derived N -acylated oxazolidin-2-ones, 1,3, 7, 9, by highly diastereoselective (,,90%) Mannich reaction (,,4,6; Scheme,1) or aldol addition (,,8 and 10; Scheme,2) of the corresponding Ti- or B-enolates as the key step. The superiority of the ,5,5-diphenyl-4-isopropyl-1,3-oxazolidin-2-one' (DIOZ) was demonstrated, once more, in these reactions and in subsequent transformations leading to various t -Bu-, Boc-, Fmoc-, and Cbz-protected ,2 -homoamino acid derivatives 11,23 (Schemes,3,6). The use of , -bromo-acyl-oxazolidinones 1,3 as starting materials turned out to open access to a variety of enantiomerically pure trifunctional and cyclic carboxylic-acid derivatives. [source] Facile Synthesis of Diastereoisomerically and Optically Pure 2-Substituted Hexahydro-1H -pyrrolizin-3-onesHELVETICA CHIMICA ACTA, Issue 8 2005Romain Siegrist We report a short synthetic route that provides optically active 2-substituted hexahydro-1H -pyrrolizin-3-ones in four steps from commercially available Boc (tert -but(oxy)carbonyl))-protected proline. Diastereoisomers (,)- 11 and (,)- 12 were assembled from the proline-derived aldehyde (,)- 8 and ylide 9via a Wittig reaction and subsequent catalytic hydrogenation (Scheme,3). Cleavage of the Boc protecting group under acidic conditions, followed by intramolecular cyclization, afforded the desired hexahydro-1H -pyrrolizinones (,)- 1 and (+)- 13. Applying the same protocol to ylide 19 afforded hexahydro-1H -pyrrolizinones (,)- 25 and (,)- 26 (Scheme,5). The absolute configuration of the target compounds was determined by a combination of NMR studies (Figs.,1 and 2) and X-ray crystallographic analysis (Fig.,3). [source] Synthesis, CD Spectra, and Enzymatic Stability of ,2 -Oligoazapeptides Prepared from (S)-2-Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and LeuHELVETICA CHIMICA ACTA, Issue 12 2003Gérald Lelais , -Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs.,1 and 2). We report here the synthesis and spectroscopic investigations of ,2 -peptide analogs consisting of (S)-3-aza- , -amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N -benzyl- L - , -amino acids with an oxaziridine (Scheme,1). Couplings and fragment coupling of the 3-benzylaza- ,2 -amino acids and a corresponding tripeptide (N -Boc/C -OMe strategy) with common peptide-coupling reagents in solution led to ,2 -di, ,2 -tri-, and ,2 -hexaazapeptide derivatives, which could be N -debenzylated (4,9; Schemes,2,4). The new compounds were identified by optical rotation, and IR, 1H- and 13C-NMR, and CD spectroscopy (Figs.,4 and 5) and high-resolution mass spectrometry, and, in one case, by X-ray crystallography (Fig.,3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the ,2 -azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N -Boc and C -OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)- 314 -helical structure. The N -Boc- ,2 -tri and N -Boc- ,2 -hexaazapeptide esters, 7 and 9, were shown to be stable for 48,h against the following peptidases: pronase, proteinase,K, chymotrypsin, trypsin, carboxypeptidase,A, and 20S proteasome. [source] The Nonchiral Bislactim Diethoxy Ether as a Highly Stereo-Inducing Synthon for Sterically Hindered, , -Branched , -Amino Acids: A Practical, Large-Scale Route to an Intermediate of the Novel Renin Inhibitor AliskirenHELVETICA CHIMICA ACTA, Issue 8 2003Richard Göschke The diastereoselective synthesis of the sterically hindered, , -branched , -amino acid derivative (2S,4S)- 24a and its N -[(tert -butoxy)carbonyl](Boc)-protected alcohol (2S,4S)- 19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)- 17 was obtained by alkylation of the chiral Schöllkopf dihydropyrazine (R)- 12a with the dialkoxy-substituted alkyl bromide (R)- 11a, which proceeded with explicitly high diastereofacial selectivity (ds ,98%) to give (2S,5R,2,S)- 13a (Scheme,4), followed by mild acid hydrolysis and N -Boc protection (Scheme,5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)- 11a with the enantiomeric (S)- 12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeOC(6) and the bulky residues of (R)- 11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)- 11a was found to provide a 95,:,5 mixture of diastereoisomers (2S,2,S)- 22a and (2R,2,S)- 23a in high yield (Scheme,6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)- 24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)- 28a and (R)- 28b with both (R)- 12a and (S)- 12b as well as with the achiral 21 was investigated (Schemes,7,9). The precursor bromides (R)- 11a, (S)- 11b, (R)- 28a, and (S)- 28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)- 7a and (S)- 7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes,3 and 7). A practical and economical protocol of the preparation of (2S,4S)- 24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N -protected , -branched , -amino acid with (2S) absolute configuration. [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] Microwave-assisted solid-phase peptide synthesis at 60 °C: alternative conditions with low enantiomerization,JOURNAL OF PEPTIDE SCIENCE, Issue 12 2009Carina Loffredo Abstract Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04,0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 °C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L -Ser, L -His, L -Cys and/or L -Met were manually synthesized traditionally, at 60 °C using conventional heating and at 60 °C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L -Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 °C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] A novel solid phase approach to Aia-containing peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 1 2009Debby Feytens Abstract A strategy was developed to directly assemble 4-amino-1,2,4,5-tetrahydro-indolo[2,3- c]-azepin-3-ones on solid-phase-supported peptide sequences. Fmoc- and Boc-based strategies were investigated. The Fmoc-strategy approach strongly depends on the peptide sequence being synthesized while the Boc-based synthesis leads to excellent results for all the selected peptide analogs. The method was applied to prepare Aia-analogs of several bioactive peptides containing one or more Trp-residues which were shown to be important for biological recognition. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] ,O -Acyl isopeptide method' for peptide synthesis: Solvent effects in the synthesis of A,1,42 isopeptide using ,O -acyl isodipeptide unit'JOURNAL OF PEPTIDE SCIENCE, Issue 12 2007Atsuhiko Taniguchi Abstract ,O -Acyl isopeptide method' is an efficient synthetic method for peptides. We designed ,O -acyl isodipeptide units', Boc-Ser/Thr(Fmoc-Xaa)-OH, as important building blocks to enable routine use of the O -acyl isopeptide method. In the synthesis of an A,1,42 isopeptide using O -acyl isodipeptide unit Boc,Ser(Fmoc,Gly),OH, a side reaction, resulting in the deletion of Ser26 in the O -acyl isopeptide structure, was noticed during coupling of the unit. We observed that the side reaction occurred during the activation step and was solvent-dependent. In DMF or NMP, an intramolecular side reaction, originating from the activated species of the unit, occurred during the activation step. In non-polar solvents such as CHCl3 or CH2Cl2, the side reaction was less likely to occur. Using CH2Cl2 as solvent in coupling the unit, the target A,1,42 isopeptide was synthesized with almost no major side reaction. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Conformational study on glycosylated asparagine-oligopeptides by NMR spectroscopy and molecular dynamics calculationsJOURNAL OF PEPTIDE SCIENCE, Issue 8 2005Stefania Mazzini Abstract The conformational properties of the homo oligomers of increasing chain length Boc-(Asn)n -NHMe (n = 2, 4, 5), (GlcNAc-,-Asn)n -NHMe (n = 2, 4, 5, 8) and Boc-[GlcNAc(Ac)3 -,-Asn]n -NHMe (n = 2, 4, 5) were studied by using NOE experiments and molecular dynamic calculations (MD). Sequential NOEs and medium range NOEs, including (i,i+2) interactions, were detected by ROESY experiments and quantified. The calculated inter-proton distances are longer than those characteristic of ,-turn secondary structures. Owing to the large conformational motions expected for linear peptides, MD simulations were performed without NMR constraints, with explicit water and by applying different treatments of the electrostatic interactions. In agreement with the NOE results, the simulations showed, for all peptides, the presence of both folded and unfolded structures. The existence of significant populations of ,-turn structures can be excluded for all the examined compounds, but two families of structures were more often recognized. The first one with sinusoidal or S-shaped forms, and another family of large turns together with some more extended conformations. Only the glycosylated pentapeptide shows in vacuo a large amount of structures with helical shaped form. The results achieved in water and in DMSO are compared and discussed, together with the effect of the glycosylation. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Polypeptide synthesis using an expressed peptide as a building block for condensation with a peptide thioester: Application to the synthesis of phosphorylated p21Max protein(1,101)JOURNAL OF PEPTIDE SCIENCE, Issue 9 2001Toru Kawakami Abstract An expressed peptide proved to be useful as a building block for the synthesis of a polypeptide via the thioester method. A partially protected peptide segment, for use as a C -terminal building block, could be prepared from a recombinant protein; its N -terminal amino acid residue was transaminated to an ,-oxoacyl group, the side-chain amino groups were then protected with t -butoxycarbonyl (Boc) groups, and, finally, the ,-oxoacyl group was removed. On the other hand, an O -phosphoserine-containing peptide thioester was synthesized via a solid-phase method using Boc chemistry. These building blocks were then condensed in the presence of silver ions and an active ester component. During the condensation, epimerization at the condensation site could be suppressed by the use of N,N -dimthylformamide (DMF) as a solvent. Using this strategy, a phosphorylated partial peptide of the p21Max protein, [Ser(PO3H2)2,11]-p21Max(1,101), was successfully synthesized. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Solid-phase synthesis of a dendritic peptide related to a retinoblastoma protein fragment utilizing a combined boc- and fmoc-chemistry approachJOURNAL OF PEPTIDE SCIENCE, Issue 5 2001Vittoria Cavallaro Abstract Dendritic peptides, often presented as multiple antigen peptides (MAPs), are widely used in immunological-based fields of research, although their synthesis can be extremely challenging. In this paper, a tetrameric dendritic MAP-like presentation of the retinoblastoma protein [649-654] sequence (4RB649-654) has been prepared using solid-phase peptide synthesis (SPPS) methods. During the synthesis of this dendritic molecule, numerous modifications to the synthetic protocols were examined. These modifications included the introduction of a combination Boc- and Fmoc-chemistry approach and also the use of 1,8-diazabicyclo[5.4.0]-undec-7-ene as a Fmoc-deprotection agent. The use in combination of Boc- and Fmoc-based synthetic strategies resulted in the production of the desired peptide molecule, 4RB649-654, in high purity and acceptable yields following purification by reversed phase HPLC. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||