The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Yoshiaki Kiso - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of human C-type natriuretic peptide 22 using chlorotrityl resin and tetrafluoroboric acid deprotection.
Chemical & pharmaceutical bulletin, 1996Co-Authors: Yoichi Fujiwara, Kenichi Akaji, Junichi Yokotani, Yoshiaki KisoAbstract:Human C-type natriuretic peptide 22 (hCNP22), the third member of the natriuretic peptide family, was efficiently synthesized by Fmoc-based peptide chain construction on a 2-chlorotrityl (Clt) resin, followed by deprotection using tetrafluoroboric acid (HBF4). The use of Clt resin was effective in suppressing racemization at the C-terminal cysteine residue caused by the base treatment for Fmoc-cleavage. The disulfide bond of hCNP22 was constructed using the Silyl Chloride-sulfoxide method to avoid oxidation at the Met residue. Using amino acid- and dipeptide-resin derivatives, the effects of bases, protecting groups and resin supports on the racemization at the C-terminal Cys residue were examined in detail.
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SYNTHESIS OF HUMAN ENDOTHELIN-1 BY REGIOSELECTIVE DISULFIDE FORMATION USING THE Silyl Chloride-SULFOXIDE SYSTEM
Tetrahedron Letters, 1995Co-Authors: Kenichi Akaji, Hajime Nishiuchi, Yoshiaki KisoAbstract:Abstract Human endothelin-1, a 21-amino acid peptide having two intramolecular disulfide bonds, has been synthesized by successive oxidation with iodine and methyltrichlorosilane-diphenylsulfoxide. Acetamidomethyl and tert-butyl groups were employed as the orthogonal thiol protecting groups. The indole ring of the C-terminal Trp residue was protected during the oxidation reaction with the formyl group that was introduced-using the formic acid-HCl mixture after the peptide-chain construction.
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Synthesis of rat brain natriuretic peptide 45 using tetrafluoroboric acid deprotection and Silyl Chloride disulfide formation.
Chemical & pharmaceutical bulletin, 1993Co-Authors: Kenichi Akaji, Yoichi Fujiwara, Yoshihito Nakagawa, Kenji Fujino, Yoshiaki KisoAbstract:A newly isolated rat brain natriuretic peptide 45 (rBNP45) was synthesized using the 9-fluorenylmethyloxy-carbonyl (Fmoc)-based solid-phase method. Tetrafluoroboric acid (HBF4) deprotection was successfully applied for this synthesis, while the conventional trifluoroacetic acid (TFA)-thioanisole method gave unsatisfactory results. The disulfide bond of rBNP45 was constructed by using the Silyl Chloride method within 10min, which was extremely advantageous to avoid the formation of Met(O)-rBNP45. The chick rectum relaxant activity of the synthetic rBNP45 was three times as potent as that of α-rat atrial natriuretic peptide (α-rANP).
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Total synthesis of human insulin by regioselective disulfide formation using the Silyl Chloride-sulfoxide method
Journal of the American Chemical Society, 1993Co-Authors: Kenichi Akaji, Kenji Fujino, T. Tatsumi, Yoshiaki KisoAbstract:Total synthesis of human insulin, a two:chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. The key reaction in the synthesis is separate regioselective formation of three disulfide bonds using a Silyl Chloride method developed by us. Prior to the insulin synthesis, it was confirmed by the syntheses of double-disulfide peptides, conotoxin M1, β-hANP, and an unnatural parallel dimer of α-hANP, that no disulfide exchange occurred during the Silyl Chloride treatment. Using three orthogonal thiol-protecting groups, Trt, Acm, and t-Bu, the three disulfide bonds of human insulin were efficiently constructed by successive reactions using thiolysis, iodine oxidation, and the Silyl Chloride method
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Disulfide Bond Formation Using the Silyl Chloride-Sulfoxide System for the Synthesis of a Cystine Peptide
Journal of the American Chemical Society, 1992Co-Authors: Kenichi Akaji, Yoichi Fujiwara, T. Tatsumi, Makoto Yoshida, Tooru Kimura, Yoshiaki KisoAbstract:An efficient method for disulfide bond formation in peptides by the Silyl Chloride-sulfoxide system is described. Methyltrichlorosilane in trifluoroacetic acid, in the presence of diphenyl sulfoxide, is found to cleave various S-protecting groups of cysteine to form cystine directly within 10-30 min. No side reactions were observed with nucleophilic amino acids such as Met, His, or Tyr, except for Trp, under the reaction conditions of the Silyl Chloride-sulfoxide treatment. A chlorination of the indole moiety of unprotected Trp, rather than sulfur-sulfur bond formation, is a dominant reaction when the peptide containing unprotected Trp is treated with the chlorosilane-sulfoxide. However, the disulfide bond can be formed efficiently with no modification at the indole ring by treatment of the peptide having a formyl-protect ed Trp residue with the Silyl Chloride-sulfoxide system. The formyl group is removed by a brief treatment at basic pH without affecting the disulfide bond formed by the Silyl Chloride-sulfoxide treatment. This new disulfide bond forming reaction in trifluoroacetic acid is successfully applied to the syntheses of oxytocin, human brain natriuretic peptide, and somatostatin without any solubility problem.
Kenichi Akaji - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of human C-type natriuretic peptide 22 using chlorotrityl resin and tetrafluoroboric acid deprotection.
Chemical & pharmaceutical bulletin, 1996Co-Authors: Yoichi Fujiwara, Kenichi Akaji, Junichi Yokotani, Yoshiaki KisoAbstract:Human C-type natriuretic peptide 22 (hCNP22), the third member of the natriuretic peptide family, was efficiently synthesized by Fmoc-based peptide chain construction on a 2-chlorotrityl (Clt) resin, followed by deprotection using tetrafluoroboric acid (HBF4). The use of Clt resin was effective in suppressing racemization at the C-terminal cysteine residue caused by the base treatment for Fmoc-cleavage. The disulfide bond of hCNP22 was constructed using the Silyl Chloride-sulfoxide method to avoid oxidation at the Met residue. Using amino acid- and dipeptide-resin derivatives, the effects of bases, protecting groups and resin supports on the racemization at the C-terminal Cys residue were examined in detail.
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Studies on development of disulfide bond forming reaction and the application to regioselective disulfide formation
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 1996Co-Authors: Kenichi AkajiAbstract:An efficient method for the disulfide bond formation in peptides by the SilylChloride-sulfoxide system is described. Methyltrichlorosilane in trifluoroacetic acid, in the presence of diphenylsulfoxide, is found to cleave various S-protecting groups of cysteine to form cystine directly within 10 to 30 min. No side reactions were observed with nucleophilic amino acids such as Met, His, or Tyr, except for Trp, under the reaction conditions of the SilylChloride-sulfoxide treatment. A chlorination of the indole moiety of unprotected Trp, rather than the sulfur-sulfur bond formation, is a dominant reaction when the peptide containing unprotected Trp is treated with the chlorosilane-sulfoxide. However, the disulfide bond can be formed efficiently with no modification at the indole ring by the treatment of the peptide having formyl-protected Trp residue with the SilylChloride-sulfoxide system. The formyl group is removed by a brief treatment at basic pH without affecting the disulfide bond formed by the SilylChloride-sulfoxide treatment. Total synthesis of human insulin, a two chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. The key reaction in the synthesis is regioselective formation of three disulfide bonds separately using the Silyl Chloride method described above. Prior to the insulin synthesis, it was confirmed by the syntheses of double-disulfide peptides: b-hANP, unnatural parallel dimer of a-hANP, and human endothelin-1 that no disulfide exchange occurred during the Silyl Chloride treatment. Using three orthogonal thiol protecting groups, Trt, Acm, and But, three disulfide bonds of human insulin were efficiently constructed by the successive reactions using thiolysis, iodine oxidation, and the sily1 Chloride method. Each reaction for the stepwise disulfide formation proceeded within 15 to 60 min with no polymeric product and no solubility problem. The synthetic human insulin had the correct structure and was indistinguishable from natural human insulin.
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SYNTHESIS OF HUMAN ENDOTHELIN-1 BY REGIOSELECTIVE DISULFIDE FORMATION USING THE Silyl Chloride-SULFOXIDE SYSTEM
Tetrahedron Letters, 1995Co-Authors: Kenichi Akaji, Hajime Nishiuchi, Yoshiaki KisoAbstract:Abstract Human endothelin-1, a 21-amino acid peptide having two intramolecular disulfide bonds, has been synthesized by successive oxidation with iodine and methyltrichlorosilane-diphenylsulfoxide. Acetamidomethyl and tert-butyl groups were employed as the orthogonal thiol protecting groups. The indole ring of the C-terminal Trp residue was protected during the oxidation reaction with the formyl group that was introduced-using the formic acid-HCl mixture after the peptide-chain construction.
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Synthesis of rat brain natriuretic peptide 45 using tetrafluoroboric acid deprotection and Silyl Chloride disulfide formation.
Chemical & pharmaceutical bulletin, 1993Co-Authors: Kenichi Akaji, Yoichi Fujiwara, Yoshihito Nakagawa, Kenji Fujino, Yoshiaki KisoAbstract:A newly isolated rat brain natriuretic peptide 45 (rBNP45) was synthesized using the 9-fluorenylmethyloxy-carbonyl (Fmoc)-based solid-phase method. Tetrafluoroboric acid (HBF4) deprotection was successfully applied for this synthesis, while the conventional trifluoroacetic acid (TFA)-thioanisole method gave unsatisfactory results. The disulfide bond of rBNP45 was constructed by using the Silyl Chloride method within 10min, which was extremely advantageous to avoid the formation of Met(O)-rBNP45. The chick rectum relaxant activity of the synthetic rBNP45 was three times as potent as that of α-rat atrial natriuretic peptide (α-rANP).
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Total synthesis of human insulin by regioselective disulfide formation using the Silyl Chloride-sulfoxide method
Journal of the American Chemical Society, 1993Co-Authors: Kenichi Akaji, Kenji Fujino, T. Tatsumi, Yoshiaki KisoAbstract:Total synthesis of human insulin, a two:chain peptide containing three disulfide bonds, was achieved unambiguously by sequential and selective formation of disulfide bonds in the protein for the first time. The key reaction in the synthesis is separate regioselective formation of three disulfide bonds using a Silyl Chloride method developed by us. Prior to the insulin synthesis, it was confirmed by the syntheses of double-disulfide peptides, conotoxin M1, β-hANP, and an unnatural parallel dimer of α-hANP, that no disulfide exchange occurred during the Silyl Chloride treatment. Using three orthogonal thiol-protecting groups, Trt, Acm, and t-Bu, the three disulfide bonds of human insulin were efficiently constructed by successive reactions using thiolysis, iodine oxidation, and the Silyl Chloride method
Nikos Hadjichristidis - One of the best experts on this subject based on the ideXlab platform.
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well defined comb star comb and comb on comb polybutadienes by anionic polymerization and the macromonomer strategy
Macromolecules, 2005Co-Authors: Giorgos Koutalas, David J Lohse, Hermis Iatrou, Nikos HadjichristidisAbstract:Stryrenic macromonomers of polybutadienes (sMMB) were synthesized by selective reaction of living polybutadienes with the Silyl Chloride group of 4-(chlorodimethylSilyl)styrene. Anionic copolymerization of sMMBs with butadiene, in the presence of a randomizer (potassium 2,3-dimethyl-3-pentoxide randomizer), led to living random comb polybutadienes (PBCs). Taking advantage of the living character of the PBCs, a number of well-defined comb, star−comb, and comb-on-comb polybutadienes were synthesized by using high-vacuum techniques. All samples prepared were characterized by size exclusion chromatography (SEC) with DRI detector and SEC with two-angle laser light scattering detector (SEC-TALLS).
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Well-Defined Comb, Star−Comb, and Comb-on-Comb Polybutadienes by Anionic Polymerization and the Macromonomer Strategy
Macromolecules, 2005Co-Authors: Giorgos Koutalas, David J Lohse, Hermis Iatrou, Nikos HadjichristidisAbstract:Stryrenic macromonomers of polybutadienes (sMMB) were synthesized by selective reaction of living polybutadienes with the Silyl Chloride group of 4-(chlorodimethylSilyl)styrene. Anionic copolymerization of sMMBs with butadiene, in the presence of a randomizer (potassium 2,3-dimethyl-3-pentoxide randomizer), led to living random comb polybutadienes (PBCs). Taking advantage of the living character of the PBCs, a number of well-defined comb, star−comb, and comb-on-comb polybutadienes were synthesized by using high-vacuum techniques. All samples prepared were characterized by size exclusion chromatography (SEC) with DRI detector and SEC with two-angle laser light scattering detector (SEC-TALLS).
Gamil A. Guirgis - One of the best experts on this subject based on the ideXlab platform.
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The molecular structure of methyl(difluoro)Silyl Chloride as determined by broadband microwave spectroscopy
Journal of Molecular Structure, 2012Co-Authors: Nathan A. Seifert, Gamil A. Guirgis, Brooks H. PateAbstract:Abstract The rotational spectrum of methyl(difluoro)Silyl Chloride, CH 3 SiF 2 Cl, has been obtained using chirped-pulse Fourier transform microwave spectroscopy. The spectrum is complicated by hyperfine structure contributed by the chlorine, as well as transition doubling by the internal rotation of the methyl group. The spectrum was analyzed by simultaneously fitting both the hyperfine and internal rotation contributions using the Internal Axis Method (IAM), and the resulting fit rotational constants are A = 3780.570(6), B = 2423.8177(16), and C = 2317.9254(13) MHz. Additionally, the singly-substituted isotopologue spectra corresponding to 13 C, 37 Cl, 29 Si and 30 Si, as well as the 37 Cl/ 29 Si and 37 Cl/ 30 Si double isotopologues, were observed. This abundance of isotopic data enabled calculation of both an experimental substitution structure ( r s ) and an effective ground state fit structure ( r 0 ) for CH 3 SiF 2 Cl in excellent agreement with the ab initio results. The ab initio structure was calculated using the MP2/aug-cc-pVTZ level of theory and a potential energy surface was calculated for the methyl rotor using the MP2/6–311++g(d,p) level of theory. These calculations predict a torsional barrier of 435.835 cm −1 , in agreement with the experimental barrier height of 468(3) cm −1 .
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Infrared and Raman spectra, conformational stability, vibrational assignment and ab initio calculations of methylvinyl Silyl Chloride
Spectrochimica acta. Part A Molecular and biomolecular spectroscopy, 2003Co-Authors: James R. Durig, Seung Won Hur, Gamil A. GuirgisAbstract:Abstract The infrared spectra (3200–50 cm −1 ) of gaseous and solid and Raman spectra (3200–10 cm −1 ) of the liquid and solid methylvinyl Silyl Chloride, CH 2 CHSiH(CH 3 )Cl, and the Si-d isotopomer have been recorded. The three expected stable conformers (the three different groups eclipsing the double bond) have been identified in the fluid phase, but it was not possible to obtain an annealed solid with a single conformer. Variable temperature (−105 to −150 °C) studies of the infrared spectra of the sample dissolved in liquid krypton has been carried out. From these data the enthalpy differences between the most stable conformer with the hydrogen atom (HE) eclipsing the double bond to that with the chlorine atom (ClE) and the methyl group (ME) eclipsing the double bond have been determined to be 17±4 cm −1 (203±48 J mol −1 ) and 80±12 cm −1 (957±144 J mol −1 ), respectively. However in the liquid state the ME conformer is the most stable form with enthalpy differences of 13±4 and 27±7 cm −1 to the HE and ClE rotamers, respectively. It is estimated that there is 39% of the HE conformer, 35% of the ClE conformer, and 26% of the ME conformer present at ambient temperature. A complete vibration assignment is proposed for the HE conformer which is based on infrared band contours and group frequencies, which is supported by normal coordinate calculations utilizing the force constants from ab initio MP2/6-31G(d) calculations. Additionally, several of the fundamentals for the other two conformers have been assigned. The optimal geometries, conformational stabilities, harmonic force fields, infrared intensities, Raman activities, depolarization ratios, and vibrational frequencies are reported for all three conformers from MP2/6-31G(d,p) ab initio calculations with full electron correlation. Optimized geometrical parameters and conformational stabilities have been obtained from MP2/6-311+G(d,p) calculations. At this highest level of calculations, the HE conformer is predicted to be more stable by 62 and 84 cm −1 than the ME and ClE conformers, respectively. The coefficients from the potential function governing the conformational interchange have been obtained from the MP2/6-31G(d) ab initio calculations. By utilizing the frequency of the SiH stretching mode, the r 0 SiH distance has been determined to be 1.481 A for the HE conformer. The ab initio calculated quantities are compared to the experimentally determined values where applicable, as well as to some corresponding results for some similar molecules.
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Conformational Stability of Chloromethyl Silyl Chloride from Temperature-Dependent FT-IR Spectra of Krypton Solutions
Structural Chemistry, 2001Co-Authors: Gamil A. Guirgis, Chunhua Pan, Shiyu Shen, James R. DurigAbstract:The Raman spectra (3200–30 cm^−1) of liquid and solid, and infrared spectra of gaseous and solid chloromethyl Silyl Chloride, ClCH_2SiH_2Cl, have been recorded. Variable temperature (−105–−150°C) studies of the infrared spectra of the sample dissolved in liquid krypton have been carried out. From these data, the enthalpy difference is 177 ± 35 cm^−1 (2.12 ± 0.42 kJ/mol), with the more stable form being the trans conformer, which is consistent with the prediction from ab initio calculations at both the Hartree–Fock level and with electron correlation by the perturbation method to second order. It is estimated that 56% of the sample is in the trans form at ambient temperature. A complete vibrational assignment is proposed for both the trans and gauche conformers based on infrared band contours, relative intensities, depolarization values, and group frequencies, which is supported by normal coordinate calculations utilizing the force constants from the ab initio MP2/6-31G(d) calculations. The optimized geometries have also been obtained from ab initio calculations utilizing several different basis sets with full electron correlation by the perturbation method up to MP2/6-311+G(2d,2p). The results are discussed and compared to some corresponding results for several related molecules.
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Spectra and structure of silicon containing compounds. XXVI. Raman and infrared spectra, ro structural parameters, conformational stability, vibrational assignment, and ab initio calculations of vinyl Silyl Chloride
Journal of Molecular Structure, 2000Co-Authors: James R. Durig, Yasser E. Nashed, Mohammad A. Qtaitat, Gamil A. GuirgisAbstract:Abstract Variable temperature (−55 to −150°C) studies of the infrared spectra between 4000 and 400 cm −1 of vinyl Silyl Chloride, CH 2 CHSiH 2 Cl, dissolved in liquid xenon and krypton have been recorded. From the xenon data, the enthalpy difference has been determined to be 78±11 cm −1 ( 0.93±0.13 kJ/mol ) with the gauche conformer the more stable form. However, in the krypton solution the conformational stability could not be determined. The Raman spectra (3500–20 cm −1 ) of liquid and solid, as well as the infrared spectra of the gaseous and solid vinyl Silyl-d 2 Chloride, have been recorded. Utilizing the isolated silicon-hydrogen stretching frequencies from the CH 2 CHSiHDCl molecule the Si–H distances of 1.479 A were obtained for both conformers. Vibrational assignments are provided for the CH 2 CHSiD 2 Cl molecule for both conformers. Complete equilibrium geometries have been determined for both rotamers using ab initio calculations employing the 6-31G(d), 6-311+G(d,p) and 6-311+G(2d,2p) basis sets at the levels of restricted Hartree–Fock and/or with full electron correlation by the perturbation method, Moller–Plesset, to the second order. Irrespective of the size of the basis set used, the gauche conformer is predicted to be the more stable conformer, which is in agreement with the experimental results. Utilizing previously reported microwave rotational constants for both conformers along with the ab initio predicted structural values, r o parameters have been obtained for both the cis and gauche conformers. The spectroscopic and theoretical results are discussed and compared to the corresponding quantities for some similar molecules.
Tamio Hayashi - One of the best experts on this subject based on the ideXlab platform.
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Reactions of bis(Silyl)palladium(II) complexes with allyl halides. Synthesis of mono(Silyl)palladium(II) halides and X-ray structure of trans-PdCl(SiF2Ph)(PMe2Ph)2
Inorganica Chimica Acta, 1999Co-Authors: Fumiyuki Ozawa, Mitsuru Sugawara, Koh Hasebe, Tamio HayashiAbstract:Abstract Reactions of trans -Pd(SiF 2 Ph) 2 L 2 (L=PMe 3 ( 1a ), PMe 2 Ph ( 1b ), PMePh 2 ( 1c )) with allyl bromide readily proceeded in CH 2 Cl 2 at −20°C to form CH 2 CHCH 2 SiF 2 Ph and the corresponding bromo(Silyl)palladium complexes, trans -PdBr(SiF 2 Ph)L 2 ( 2a – 2c ) in high selectivities. Treatment of 1a – 1c with dry HCl in CH 2 Cl 2 at −20°C gave Silyl Chloride complexes, trans -PdCl(SiF 2 Ph)L 2 ( 3a – 3c ), respectively. Complexes 2a – 2c and 3a – 3c were isolated and characterized by NMR spectroscopy and/or elemental analysis. One of the complexes, trans -PdCl(SiF 2 Ph)(PMe 2 Ph) 2 ( 3b ), was identified also by X-ray diffraction study. Relevance of bis-Silyl complexes to catalytic Silylation of allylic compounds with disilanes is discussed.