- Synthesis of the marine sponge cycloheptapeptide phakellistatin 51
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Phakellistatin 5 (1), a constituent of The Federated States of Micronesia (Chuuk) marine sponge Phakellia costada, was synthesized by solution-phase and solid-phase techniques. Because the linear peptide bearing (R)-Asn resisted cyclization, the synthesis of this peptide was repeated using the PAL resin attachment proceeding from N-Fmoc-D-Asp-α-OCH2CH=CH2. After addition of the final unit (Ala), the allyl ester was removed under neutral conditions with Pd°[P(C6H5)3l4. Removal of the final Fmoc- protecting group and cyclization with PyAOP provided (R)-Asn-phakellistatin 5 (2) in 28% overall yield. The same synthetic route from (S)-Asp led to natural phakellistatin 5 (1) in 15% overall recovery. The solution-phase and solid-phase synthetic products derived from (S)-Asp were found to be chemically but not biologically identical with natural phakellistatin 5 (1). This important fact suggested that a trace, albeit highly cancer-cell growth inhibitory, constituent accompanied the natural product or that there is a subtle conformational difference between the synthetic and natural cyclic peptides.
- Pettit, George R.,Toki, Brian E.,Xu, Jun-Ping,Brune, Daniel C.
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- α-Sila-Dipeptides: Synthesis and Characterization
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The first two α-sila-dipeptides, 7 and cyclo-sila-dipeptide 8, were synthesized and characterized by several methods, including X-ray crystallography. Bulky t-BuMe2Si substituents provide some kinetic stabilization to the synthesized molecules. 7 and 8 are the first examples of a “Si for C switch” in the central α-position of an amino acid or a peptide, in which silicon is bonded to both the amino and the carbonyl groups.
- Minkovich, Boris,Ruderfer, Ilya,Kaushansky, Alexander,Bravo-Zhivotovskii, Dmitry,Apeloig, Yitzhak
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- Structure, Total Synthesis, and Biosynthesis of Chloromyxamides: Myxobacterial Tetrapeptides Featuring an Uncommon 6-Chloromethyl-5-methoxypipecolic Acid Building Block
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Soil-living microbes are an important resource for the discovery of new natural products featuring great structural diversity that are reflective of the underlying biosynthetic pathways as well as incorporating a wide range of intriguing small-molecule building blocks. We report here the full structural elucidation, total synthesis, and biosynthesis of chloromyxamides, a new class of tetrapeptides that display an unprecedented 6-chloromethyl-5-methoxypipecolic acid (CMPA) substructure. Chemical synthesis—including an approach to access the CMPA unit—was pursued to confirm the structure of the chloromyxamides and enabled determination of the absolute configuration in the CMPA ring. A model for the nonribosomal assembly of chloromyxamides was devised on the basis of the combined evaluation of the biosynthetic gene cluster sequence and the feeding of stable isotope-labeled precursors. This provided insight into the formation of the various chloromyxamide derivatives and the biogenesis of the CMPA unit.
- Gorges, Jan,Panter, Fabian,Kjaerulff, Louise,Hoffmann, Thomas,Kazmaier, Uli,Müller, Rolf
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- A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters
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A stereo-divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium-catalyzed N-allylation of α-amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)-2-penten-4-yl carbonate in the presence of only 1 mol% of a catalyst, prepared in-situ from the C2-symmetric diphosphine iPr-MediPhos and [Pd(allyl)Cl]2. Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N-allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N-Boc-protection.
- Albat, Dominik,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
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supporting information
p. 2099 - 2102
(2021/07/22)
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- Continuous Flow Synthesis of ACE Inhibitors From N-Substituted l-Alanine Derivatives
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A strategy for the continuous flow synthesis of angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs in the range of ≈0.5 g h?1, all while avoiding both isolation of reactive intermediates and process intensive reaction conditions. The process was further developed by preparing enalapril, a World Health Organization (WHO) essential medicine, in an industrially relevant flow platform that scaled throughput to ≈1 g h?1.
- Breen, Christopher P.,Jamison, Timothy F.
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supporting information
p. 14527 - 14531
(2019/11/03)
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- Total synthesis of wewakazole B
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Wewakazole B is a novel cyclodecapeptide with highly potent cytotoxic activity isolated from a sample of M. producens collected from the Red Sea. It contains nine common and three modified amino acid residues. The first total synthesis of Wewakazole B was successfully achieved on a gram scale, unambiguously confirming its structure. Notable features include the careful choice of amino acid-protecting groups and the construction of three different substituted oxazoles present in this natural product.
- Long, Bohua,Zhang, Jingzhao,Tang, Xudong,Wu, Zhengzhi
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supporting information
p. 9712 - 9715
(2016/10/31)
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- Ring-Strain Effects in Base-Induced Sommelet–Hauser Rearrangement: Application to Successive Stereocontrolled Transformations
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The base-induced Sommelet–Hauser (S–H) rearrangement of azetidine-2-carboxylic acid ester-derived ammonium salts into 2-aryl-substituted derivatives was demonstrated. The ring-strain of four-membered N-heterocycles enables efficient generation of the desired ylide intermediate and enhances the rate of the S–H rearrangement. The asymmetric version of the rearrangement was characterized by excellent levels of successive chirality transmissions. The regio- and stereo-controlled nucleophilic ring opening of the rearrangement products produced quaternary α-aryl amino acid esters with excellent enantiopurities.
- Tayama, Eiji,Watanabe, Kazutoshi,Matano, Yoshihiro
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supporting information
p. 3631 - 3641
(2016/07/29)
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- Stereoselective Synthesis of Tricyclic Diproline Analogues that Mimic a PPII Helix: Structural Consequences of Ring-Size Variation
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Polycyclic proline-derived scaffolds (ProMs) have recently demonstrated their value as conformationally defined dipeptide analogs for the modular construction of secondary structure mimetics, specifically interfering with PPII helix-mediated protein-protein interactions. We disclose the stereoselective synthesis of two new tricyclic amino acid scaffolds (ProM-4 and ProM-8) that differ from the first generation scaffold ProM-1 by the size of ring A. Conformational preferences and subtle structural differences of the three homologous scaffolds were analyzed by X-ray crystallography, computational calculations, and NMR spectroscopy. N-tert-butoxycarbonyl(Boc)-3-(1-propenyl)azetidine-2-carboxylic acid was prepared from L-aspartic acid through β-lactam intermediates. The corresponding piperidine-based building block rac-N-Boc-3-vinylpipecolic acid was synthesized by Cu-catalyzed 1,4-addition of vinyl-MgBr to methyl N-Boc-2,3-dehydropipecolate. Target molecules were prepared through peptide coupling of the respective ring A building blocks with cis-5-vinylproline tert-butyl ester and subsequent ring-closing metathesis. Selective deprotection of a tert-butyl carbamate (N-Boc protecting group) in the presence of a tert-butyl ester was achieved with trifluoroacetic acid at 0 C. Two new tricyclic amino acid scaffolds, which differ from the first generation scaffold by the size of ring A, were stereoselectively synthesized. The conformational analysis of the three homologous scaffolds was revealed by NMR spectroscopy.
- Soicke, Arne,Reuter, Cédric,Winter, Matthias,Neud?rfl, J?rg-Martin,Schl?rer, Nils,Kühne, Ronald,Schmalz, Hans-Günther
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supporting information
p. 6467 - 6480
(2016/02/18)
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- Stereoselective synthesis of cyclic amino acids via asymmetric phase-transfer catalytic alkylation
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An asymmetric synthesis of cyclic amino acids having piperidine and azepane core structures was realized starting from readily available glycine and alanine esters by combination of phase-transfer catalyzed asymmetric alkylation and subsequent reductive a
- Kano, Taichi,Kumano, Takeshi,Sakamoto, Ryu,Maruoka, Keiji
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supporting information
p. 271 - 278
(2013/02/25)
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- Solution-phase synthesis and evaluation of tetraproline chiral stationary phases
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A protocol was developed for the solution-phase synthesis of multigram amounts of two 9-fluorenylmethoxycarbonyl (Fmoc)-protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution-phase-synthesized tetraproline CSPs with that prepared by stepwise solid-phase synthesis revealed that all three had similar chromatographic performance for resolving 53 model analytes. This suggests that the solution-phase synthesis of oligoprolines, which allows for the specific benefits of good batch reproducibility, selector homogeneity, and possibly low cost, is a feasible alternative to the solid-phase synthesis of oligoproline CSPs. Copyright
- Dai, Zhi,Ye, Guozhong,Pittman Jr., Charles U.,Li, Tingyu
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p. 329 - 338
(2012/05/20)
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- Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition
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The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus Diheterospora chlamydosphoria, consists of α-aminoisobutyric acid, l-phenylalanine, d-proline and an unusual amino acid (S)-2-amino-8-((S)-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.
- Islam, Md. Shahidul,Bhuiyan, Mohammed P. I.,Islam, Md. Nurul,Nsiama, Tienabe Kipassa,Oishi, Naoto,Kato, Tamaki,Nishino, Norikazu,Ito, Akihiro,Yoshida, Minoru
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body text
p. 2103 - 2110
(2012/08/29)
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- (9H-fluoren-9-yl)methanesuIfonyl (Fms): An amino protecting group complementary to Fmoc
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A sulfonamide-based protecting group (PG), (9H-fluoren-9yl)methanesulfonyl (Fms), which can be used in a similar way to the well-established Fmoc PG, was developed. The advantages of this new PG were demonstrated in the successful formation of a phosphonamide between an N-Fmsprotected a-phosphonoalanine monoester and secondary alkylamines, including (R)-2-phenylethylamine, (S)-phenylalanine iert-butyl ester (H-Phe-OtBu), H-Pro-Gly-OtBu, and H-Phe-Phe-OtBu, without formation of oxazaphospholine, which is a serious problem associated with the Fmoc PG. The success should pave the way to the solid-phase synthesis of unnatural peptides substituted with a-amino phosphonic acid (AP) at essentially any arbitrary position without significant modification of the Fmoc-based chemistry that has been accumulated since Carpino's report in 1970. The N-Fms-AP monomer would attract much attention in the field of peptide mimetics.
- Ishibashi, Yoshitaka,Miyata, Kengo,Kitamura, Masato
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experimental part
p. 4201 - 4204
(2010/10/02)
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- Direct electrochemical α-cyanation of N-protected cyclic amines
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α-Cyanation of N-protected cyclic amines was achieved using a direct electrochemical method. Unsubstituted N-protected cyclic amines were easily cyanated at the α-position using an undivided cell in high yields; moreover, α-cyanation of α′-substituted pyrrolidine and α′-,β′- or γ-substituted piperidines smoothly proceeded in high yield and with high to excellent diastereoselectivity. α-Substituted N-cyano-pyrrolidines and -piperidines were also cyanated at the more substituted position (the α-position) using a divided cell with high yield and high regioselectivity.
- Libendi, Samuel Shikuku,Demizu, Yosuke,Onomura, Osamu
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experimental part
p. 351 - 356
(2009/03/12)
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- Asymmetric [1,2] Stevens rearrangement of (S)-N-benzylic proline-derived ammonium salts under biphasic conditions
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The Stevens rearrangement of (S)-N-benzylic proline-derived ammonium salt with cesium hydroxide in 1,2-dichloroethane is shown to proceed with a high degree of the N-to-C chirality transmission to afford the α-substituted proline derivatives in high enantio-purities. Copyright
- Tayama, Eiji,Nanbara, Shintaro,Nakai, Takeshi
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p. 478 - 479
(2007/10/03)
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- Catalytic removal of N-allyloxycarbonyl groups using the [CpRu(IV)(π-C3H5)(2-quinolinecarboxylato)]PF 6 complex. A new efficient deprotecting method in peptide synthesis
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A variety of amines including even sterically less demanding and highly nucleophilic secondary amines have been efficiently deprotected without decarboxylative N-allylation from the corresponding N-allyloxycarbonyl (N-AOC) compounds by using a catalytic amount of [CpRu-(IV)(π-C3H 5)(2-quinolinecarboxylato)]PF6 in the presence of 1 molar amount of trifluoromethanesulfonic acid, the general utility of which has been demonstrated by the efficient synthesis of a collagen protein unit tripeptide, Pro-Pro-Gly.
- Tanaka, Shinji,Saburi, Hajime,Murase, Takanori,Yoshimura, Masahiro,Kitamura, Masato
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p. 4682 - 4684
(2007/10/03)
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- Synthesis of (ε-13C-,ε-15N)-enriched L-lysine - Establishing schemes for the preparation of all possible 13C and 15N isotopomers of L-lysine, L-ornithine, and L-proline
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In this paper we describe a simple synthetic strategy that, with the right rational adaptation, gives direct access to any 13C/15N isotopomer of L-glutamate, L-ornithine, L-proline, L-lysine, and L-α, amino adipic acid. This strategy also allows access to nonproteinogenic amino acids like L-citrulline in high yields and optical purity. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Siebum, Arjan H. G.,Tsang, Robert K. F.,Van Der Steen, Rob,Raap, Jan,Lugtenburg, Johan
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p. 4391 - 4396
(2007/10/03)
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- A new protocol for selective deprotection of N-tert-butoxycarbonyl protective group (t-Boc) with Sn(OTf)2
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A simple and efficient method for the selective removal of N-Boc group by employing tin(II) trifluoromethanesulfonate [Sn(OTf)2] in CH2Cl2 or solvent-free conditions was developed. The scope of this procedure is explored for the deprotection of a variety of amines, including amino acid derivatives.
- Bose, D. Subhas,Kumar, K. Kiran,Reddy, A.V. Narsimha
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p. 445 - 450
(2007/10/03)
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- Efficient deprotection of N-benzyloxycarbonyl group from amino acids by hydroxyapatite-bound Pd catalyst in the presence of molecular hydrogen
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Hydroxyapatite-bound Pd catalyst was found to be highly effective for the deprotection of N-benzyloxycarbonyl group from amino acids in the presence of molecular hydrogen. The catalyst was also applicable to the hydrogenolysis of a sterically encumbered core-Z-protected poly(amido amine) dendrimer, affording the dendritic amino compound in 99% yield.
- Murata, Makoto,Hara, Takayoshi,Mori, Kohsuke,Ooe, Masahiko,Mizugaki, Tomoo,Ebitani, Kohki,Kaneda, Kiyotomi
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p. 4981 - 4984
(2007/10/03)
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- Synthesis of phakellistatin 11: A Micronesia (Chuuk) marine sponge cyclooctapeptide
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The cyclic octapeptide phakellistatin 11 (1), a constituent of The Federated States of Micronesia (Chuuk) marine sponge Phakellia sp., was synthesized using solid-phase techniques. An initial solution-phase synthesis proved to be inadequate owing to spontaneous deprotection of the Fmoc group at the heptapeptide stage. Using the PAL resin attachment and proceeding from Fmoc-Glu-α-allyl ester, linear elongation of the octapeptide was performed until the final unit Pro was added. The allyl ester was removed using Pd0[P(C6H5)3]4. Cleavage of the final Fmoc group and cyclization with PyAOP provided phakellistatin 11 (1) in 17% overall yield. The synthetic specimen of phakellistatin 11 (1) was found to be chemically but not biologically (cancer cell lines) identical to the natural product. The result suggested a conformational difference or more likely the presence of a trace amount of a highly active antineoplastic agent that binds noncovalently to the natural cyclic octapeptide 1.
- Pettit,Lippert III,Taylor,Tan,Williams
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p. 883 - 891
(2007/10/03)
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- D-proline derivatives
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New compounds have the formula: wherein R, R1, X and Y have the meanings described herein. Methods are set forth for synthesizing these compounds and using these compounds to treat diseases associated with amyloidosis, such as Alzheimer's disease, maturity onset diabetes mellitus, familial amyloid polyneuropathy, scrapie, and Kreuzfeld-Jacob disease.
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- Design, synthesis, and dopamine receptor modulating activity of diketopiperazine peptidomimetics of L-prolyl-L-leucylglycinamide
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The diketopiperazine 'C5' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG, 1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N- terminal 'C5' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [3H]spiroperidol/N- propylnorapomorphine (NPA) D2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidemimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal 'C5' conformation may play a role in the potency of the γ- lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 ± 13.96% (p 0.001, n = 7) increase in rotations compared to apomorphine administered alone.
- Baures, Paul W.,Ojalar, William H.,Costain, Willard J.,Ott, Michael C.,Pradhan, Ashish,Gleason, William B.,Mishra, Ram K.,Johnson, Rodney L.
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p. 3594 - 3600
(2007/10/03)
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- Synthesis of the cyclic heptapeptides Axinastatin 2 and Axinastatin 3
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Practical total syntheses of axinastatins 2 2b and 3 2c were completed by employing Fmoc protection for the N-terminal, and tert-butyl ester blocking for the C-terminal, units of the amlno add and peptide intermediates. Generally, diethyl phosphorocyanidate proved effective for formation of the peptide bond, and in the one exception, asparagine, the o-nitrophenyl active ester proved to be useful. For the final cyclization reaction BOP-Cl was found especially effective. Copyright 1996 by the Royal Society of Chemistry.
- Pettit, George R.,Holman, Jeffrey W.,Boland, Gerard M.
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p. 2411 - 2416
(2007/10/03)
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- Photochemical deprotection of 3′,5′-dimethoxybenzoin (DMB) carbamates derived from secondary amines
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Treatment of secondary amines with a (dimethoxybenzoin)carbonylimidazolium salt provides dimethoxybenzoin carbamates that can be deprotected photochemically.
- Pirrung, Michael C.,Huang, Chia-Yu
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p. 5883 - 5884
(2007/10/02)
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- Design, synthesis, X-ray analysis, and dopamine receptor-modulating activity of mimics of the 'C5' hydrogen-bonded conformation in the peptidomimetic 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1- pyrrolidineacetamide
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3(R)-(7a(S)-Hexahydro-1-oxo-3,3-dimethyl-1H-pyrrolo[1,2-c]imidazol-2-yl)- 2-oxo-1-pyrrolidine-acetamide (2) and 3(R)-[1-(2,5-dioxopyrrolidino[3,4- c]piperazino)]-2-oxo-1-pyrrolidineacetamide (3) were designed and prepared as mimics of the 'C5' hydrogen-bonded structure found in the crystal structure of 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacetamide (1). Both compounds effectively restrict the ψ1 torsional angle to very near the value found in the X-ray structure of 1 as seen in the X-ray crystallographic determination of 2 and methyl 3(R)-[1-(2,5-dioxopyrrolidino[3,4- c]piperazino)]-2-oxo-1-pyrrolidineacetate (11), a diketopiperazine intermediate in the synthesis of 3. These analogs were tested for their ability to enhance the binding of the dopamine D2 receptor agonist N- propylnorapomorphine (NPA) in the absence and presence of 5'- guanylylimidodiphosphate (Gpp(NH)p). Both compounds enhanced [3H]-NPA binding in a dose-dependent manner by increasing both the binding affinity of the agonist and the number of high-affinity sites available for binding. Both 2 and 3 also attenuated the Gpp(NH)p-induced conversion of D2 receptor high- affinity states to the low-affinity states.
- Baures,Ojala,Gleason,Mishra,Johnson
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p. 3677 - 3683
(2007/10/02)
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- Process for the preparation of 1,1-dioxo-7-substituted cephems
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The present invention relates to an improved process for the preparation of the compounds of formula (I) STR1 which involve the direct oxidation without N-protection of the compound of the formula (II) STR2
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- Asymmetric Catalytic Hydrogenations of N-Pyruvoyl-(S)-proline Esters
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Asymmetric catalytic hydrogenations of the entitled compounds were carried out over palladium on charcoal in various solvents to afford N--(S)-proline esters with a d.e.(=diastereoisomeric excess) of up to 59percent.The stereochemistry of the catalytic hydrogenation was explained by the "chelation mechanism." And the effects of temperature and bulkiness of the ester groups on the asymmetric induction were also described.
- Munegumi, Toratane,Fujita, Manabu,Maruyama, Tetsuya,Shiono, Shozo,Takasaki, Michiaki,Harada, Kaoru
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p. 249 - 254
(2007/10/02)
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- Studies of Unusual Amino Acids and Their Peptides. XVII. The Synthesis of Peptides Containing N-Carboxymethyl Amino Acids. II.
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The synthetic routes were investigated to four kinds of tetrapeptides made up of three usual amino acid residues and one N-carboxymethyl (Cm-) amino acid residue.The application of vacuum distillation made the isolation of a Cm-amino acid diester more convenient and efficient compared with the chromatographic methods which had been used previously.The efficiency of peptide bond formation at the imino group of a Cm-amino acid by the acid chloride method was remarkably improved under suitable reaction conditions.In the elongation of the peptide chain from a peptide containing a Cm-amino acid at the C-terminal position, the coupling efficiency was usually poorer than that in the case of the corresponding peptide composed only of the usual amino acid residues, and it depended greatly on the coupling methods, the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-1-hydroxybenzotriazole method being generaly the most desirable.
- Miyazawa, Toshifumi,Hiramatsu, Shin'ichi,Tsuboi, Yasuhiro,Yamada, Takashi,Kuwata, Shigeru
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p. 1976 - 1982
(2007/10/02)
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- 4-Methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr): a New Amino and Imidazole Protecting Group in Peptide Synthesis
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The 4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr) group was introduced as a protecting group for the amino function, especially the ε-amino function of lysine, and the imidazole ring of histidine.The Nε-Mtr group was removable by dilute methanesulfonic acid-containing trifluoroacetic acid-thioanisole, but was stable to trifluoroacetic acid or catalytic hydrogenation.The Nim-Mtr group was removable by trifluoroacetic acid-dimethylsulfide or 1-hydroxybenzotriazole, but was more stable than the Nim-Tos or the Nim-Mbs group with triethylamine.To examine the usefulness of the Mtr group as a protecting group for use in peptide synthesis, mastoparan X and chicken gastrin releasing peptide (c-GRP) were synthesized, and this group was found to be very convenient for general solution synthesis.In particular, the introduction of Lys(Mtr) made possible a new strategy in peptide synthesis.Keywords-4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr); Nε-4-methoxy-2,3,6-trimethylbenzenesulfonyllysine; Nim-4-methoxy-2,3,6-trimethylbenzenesulfonylhistidine; methanesulfonic acid-trifluoroacetic acid-thioanisole deprotection; trifluoroacetic acid-dimethylsulfide deprotection; mastoparan X; chicken gastrin releasing peptide
- Wakimasu, Mitsuhiro,Kitada, Chieko,Fujino, Masahiko
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p. 2766 - 2779
(2007/10/02)
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- HYDROXYCARBAMOYLALKYLACYLPIPECOLIC ACID COMPOUNDS
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New hydroxycarbamoylalkylacyl derivatives of pipecolic acid which have the general formula STR1 are useful as angiotensin converting enzyme inhibitors.
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- PROLINE DERIVATIVES AND RELATED COMPOUNDS
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New proline derivatives and related compounds which have the general formula STR1 are useful as angiotensin converting enzyme inhibitors.
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- CARBOXYACYLPROLINE DERIVATIVES
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New carboxyalkylacylamino acids which are derivatives of proline, pipecolic acid and azetidine-2-carboxylic acid and have the general formula STR1 are useful as angiotensin converting enzyme inhibitors.
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- N-acyl and desamino human calcitonin and analogs thereof
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The new hypocalcaemically active peptides of formula I and corresponding compounds in which one or more of the asparagine and glutamic acid radicals are replaced by the aspartic acid or glutamic acid radical and/or the aspartic acid radical is replaced by the asparagine radical, their dimers, especially those in which 2 identical peptide sequences (1-32 and 1'-32') are joined in an anti-parallel arrangement via the cysteine radicals 1,7' and 7,1' by means of a disulfide bond, and derivatives are useful as hypocalcaemic agents and are prepared by splitting off groups protecting at least one amino or one carboxyl group or oxidizing the corresponding sulfides to the disulfides or condensing together adequate peptides.
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