- Self-assembly and anion-response of azobenzene-based L-valinamide derivative
-
An azobenzene-based L-valinamide derivative was synthesized, and its gelation ability and self-assembly in organic solvents were investigated. Results suggested that it is an excellent gelator and formed organogels in many solvents, such as 3-pentanone, aniline, o-dichlorobenzene (ODCB), CH2Cl2, THF, ethanol, DMSO, and DMF. Its self-assembly in ODCB gel was studied. Transmission electron microscopic observation suggested that the gelator can self-assemble into one-dimensional nanofibers in the gel, and this phenomenon is driven by hydrogen bonding between amide units and π-π interaction between azobenzene moieties. With the increase in gelator concentration, the gel-to-sol phase transition temperature increased and the gelation time of the solvent shortened. Moreover, the gel exhibit anion response. A gel-to-sol phase transition was found after fluoride anion was added, exhibiting selective response to F?.
- Li, Kechang,Xue, Pengchong
-
-
Read Online
- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
-
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
-
supporting information
p. 8297 - 8302
(2021/03/01)
-
- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
-
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
-
p. 1080 - 1090
(2020/05/25)
-
- COMPOUNDS, COMPOSITIONS, METHODS, AND USES FOR TREATING CANCER AND IMMUNOLOGICAL DISORDERS
-
The present disclosure provides novel polypeptide-therapeutic compound or hormone-therapeutic compound conjugates using cleavable or non-cleavable linkers, whereby the polypeptide or hormone serves to target specific cells using receptor expression on the targeted cell to bind the ligand (polypeptide or hormone) carrying the therapeutic compound unlike antibody drug conjugates. Upon binding, the ligand and the therapeutic compound (multiples of the therapeutic compound in some embodiments) enter the cell by receptor-mediated endocytosis, and release drugs conjugated to the ligand by linkers, to interact with intracellular components to enhance, restore, or block a signal transduction process. The ligands for the polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: cytokines, growth factors and hormones among other proteins with corresponding cell surface specific receptors. The disorders targeted by such polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: immunological disorders (e.g., allergy and autoimmune disorders) and cancer.
- -
-
Paragraph 0546; 0551-0552
(2020/02/06)
-
- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
-
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
-
p. 30720 - 30728
(2019/10/28)
-
- Determination of Chemical and Enantiomeric Purity of α-Amino Acids and their Methyl Esters as N-Fluorenylmethoxycarbonyl Derivatives Using Amylose-derived Chiral Stationary Phases
-
Liquid chromatographic enantiomer separation and simultaneous determination of chemical and enantiomeric purity of α-amino acids and their methyl esters as N-fluorenylmethoxycarbonyl (FMOC) derivatives was performed on three covalently bonded type chiral stationary phases (CSPs) derived from amylose derivatives. The enantiomer separation of α-amino acid esters as N-FMOC derivatives was better than that of the corresponding acids, especially for CSP 1 and 2. Chemical impurities as the corresponding racemic acids present in several commercially available racemic amino acid methyl esters were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L-amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α-amino acids and/or esters as N-FMOC derivatives using amylose-derived CSPs.
- Islam, Md. Fokhrul,Adhikari, Suraj,Paik, Man-Jeong,Lee, Wonjae
-
p. 332 - 338
(2019/04/13)
-
- Fmoc-Amox, A Suitable Reagent for the Introduction of Fmoc
-
Synthesis of most peptides is achieved using solid-phase peptide synthesis employing the Fmoc/tert-butyl strategy. However, the introduction of Fmoc in N-unprotected amino acids seems to be challenging due to the formation of dipeptides and sometimes tripeptides as impurities and β-alanyl impurities when Fmoc-OSu is used as well. Herein, we report an efficient and successful method using Fmoc-Amox, which is an oxime based derivative, toward the synthesis of Fmoc-glycine with no traces of side reactions. Fmoc-Amox is inexpensive, and Amox can be easily removed after the reaction, thus affording pure Fmoc-Gly-OH devoid of any detrimental impurities or contamination, mainly dipeptide or Amox itself, as shown by high-performance liquid chromatography and NMR, respectively.
- Kumar, Ashish,Sharma, Anamika,Haimov, Elvira,El-Faham, Ayman,De La Torre, Beatriz G.,Albericio, Fernando
-
p. 1533 - 1541
(2017/10/25)
-
- Fmoc-OPhth, the reagent of Fmoc protection
-
Fmoc-OSu has been widely used for Fmoc protection of amino groups, especially amino acids, in solid phase peptide synthesis. However, it has been recognized that Fmoc-βAla-OH is formed as a by-product via the Lossen rearrangement during the reaction. Since we reconfirmed the formation of Fmoc-βAla-OH during the preparation of Fmoc-AA-OH by Fmoc-OSu, Fmoc-OPhth was designed and synthesized as a new Fmoc reagent to avoid the formation of Fmoc-βAla-OH. Furthermore, Fmoc protection by Fmoc-OPhth and Fmoc-SPPS were evaluated. The various Fmoc-amino acids prepared by Fmoc-OPhth were carried out in good yields and these are applicable in Fmoc-SPPS.
- Yoshino, Ryo,Tokairin, Yoshinori,Kikuchi, Mari,Konno, Hiroyuki
-
supporting information
p. 1600 - 1603
(2017/04/03)
-
- Chiral oxazoline NNP type ligands as well as synthesis method and application thereof
-
The invention relates to chiral oxazoline NNP type ligands as well as a synthesis method and an application thereof. The ligands adopt the structure shown in general formula 1 or 2. During preparation, a chiral ligand 1 and a chiral ligand 2 are prepared from Fmoc-Cl and a chiral amino acid compound 3 used as initial raw materials through multi-step reactions. The ligands can be applied to catalytic synthesis of chiral beta ketone ester fluoride and synthesis of propanedione derivatives and chiral malonate derivatives through palladium-catalyzed asymmetric allyl substitution reactions. Compared with the prior art, the reaction condition is mild, operation is easy, repeatability is good, mass preparation can be realized, and the prepared catalyst has higher ee value and yield when applied to beta ketone ester fluoridation and palladium-catalyzed asymmetric allyl substitution reactions.
- -
-
Paragraph 0092; 0093; 0094; 0095
(2017/08/28)
-
- Caged xanthones: Potent inhibitors of global predominant MRSA USA300
-
Total of 22 caged xanthones were subjected to susceptibility testing of global epidemic MRSA USA300. Natural morellic acid showed the strongest potency (MIC of 12.5 μM). However, its potent toxicity diminishes MRSA therapeutic potential. We synthetically modified natural morellic acid to yield 13 derivatives (3a-3m). Synthetically modified 3b retained strong potency in MRSA growth inhibition, yet the toxicity was 20-fold less than natural morellic acid, permitting the possibility of using caged xanthones for MRSA therapeutic.
- Chaiyakunvat, Pongkorn,Anantachoke, Natthinee,Reutrakul, Vichai,Jiarpinitnun, Chutima
-
supporting information
p. 2980 - 2983
(2016/06/13)
-
- Total Synthesis and Biological Evaluation of Natural and Designed Tubulysins
-
A streamlined total synthesis of N14-desacetoxytubulysin H (Tb1) based on a C-H activation strategy and a short total synthesis of pretubulysin D (PTb-D43) are described. Applications of the developed synthetic strategies and technologies to the synthesis of a series of tubulysin analogues (Tb2-Tb41 and PTb-D42) are also reported. Biological evaluation of the synthesized compounds against an array of cancer cells revealed a number of novel analogues (e.g., Tb14), some with exceptional potencies against certain cell lines [e.g., Tb32 with IC50 = 12 pM against MES SA (uterine sarcoma) cell line and 2 pM against HEK 293T (human embryonic kidney) cell line], and a set of valuable structure-activity relationships. The highly potent cytotoxic compounds discovered in this study are highly desirable as payloads for antibody-drug conjugates and other drug delivery systems for personalized targeted cancer chemotherapies.
- Nicolaou,Yin, Jun,Mandal, Debashis,Erande, Rohan D.,Klahn, Philipp,Jin, Michael,Aujay, Monette,Sandoval, Joseph,Gavrilyuk, Julia,Vourloumis, Dionisios
-
supporting information
p. 1698 - 1708
(2016/02/20)
-
- Ureidopeptide-based Bronsted bases: Design, synthesis and application to the catalytic enantioselective synthesis of β-amino nitriles from (arylsulfonyl)acetonitriles
-
The addition of cyanoalkyl moieties to imines is a very attractive method for the preparation of β-amino nitriles. We present a highly efficient organocatalytic methodology for the stereoselective synthesis of β-amino nitriles, in which the key to success is the use of ureidopeptide-based Bronsted base catalysts in combination with (arylsulfonyl)acetonitriles as synthetic equivalents of the acetonitrile anion. The method gives access to a variety of β-amino nitriles with good yields and excellent enantioselectivities, and broadens the stereoselective Mannich-type methodologies available for their synthesis. Learning from peptides: A concise route for the catalytic enantioselective synthesis of β-amino nitriles has been achieved by using ureidopeptide-based Bronsted bases as catalysts in the Mannich reaction of N-Boc imines and (arylsulfonyl)acetonitriles (see scheme; Boc=tert-butoxycarbonyl, napht=naphthyl, TMS=trimethylsilyl).
- Diosdado, Saioa,Lopez, Rosa,Palomo, Claudio
-
p. 6526 - 6531
(2014/06/09)
-
- Catalytic enantioselective synthesis of tertiary thiols from 5h-thiazol-4-ones and nitroolefins: Bifunctional ureidopeptide-based bronsted base catalysis
-
Fully loaded: The ureidopeptide-based bifunctional Bronsted base 1 efficiently promotes the first direct catalytic Michael reaction of α-mercapto carboxylate surrogates with nitroolefins involving a fully substituted α-carbon atom construction. Copyright
- Diosdado, Saioa,Etxabe, Julen,Izquierdo, Joseba,Landa, Aitor,Mielgo, Antonia,Olaizola, Iurre,Lopez, Rosa,Palomo, Claudio
-
p. 11846 - 11851
(2013/11/19)
-
- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
-
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
-
p. 10575 - 10582
(2013/02/22)
-
- Siloxyl ether functionalized resins for chemoselective enrichment of carboxylic acids
-
Although the carboxylic acid moiety is prevalent in many biologically produced molecules, including natural products and proteins, methods to chemoselectively target this functional group have remained elusive. Generally, strategies that utilize carboxylate nucleophilicity also promote reactions with other nucleophiles such as amines and hydroxyls. A reagent was sought to facilitate the selective isolation of carboxylic acid containing compounds from complex mixtures. Here, the development of siloxyl ether functionalized solid supports is described.
- Trader, Darci J.,Carlson, Erin E.
-
supporting information; experimental part
p. 5652 - 5655
(2011/12/04)
-
- Liquid-chromatography quantitative analysis of 20 amino acids after derivatization with FMOC-CI and its application to different origin Radix isatidis
-
We developed a simple, rapid and reliable method for determination of 20 common amino acids based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-CI) and RP-LC/UV, this method was first introduced into quantitative analysis of amino acids. The amino groups of amino acids were trapped with FMOC-CI to form amino acid-FMOC-Cl adducts which can be suitable for LC-UV. Chromatographic separation was performed on a C18 column with a mobile phase gradient consisting of acetonitrile and sodium acetate solution. This method was shown to be sensitive for 20 common amino acids. In the intra-day precisions assay, the range of RSDs was 3.21-7.67% with accuracies of 92.34-102.51%; for the inter-day precisions assay, the range of RSDs was 5.82-9.19% with accuracies of 90.25-100.63%. The results also indicated that solutions of amino acids-FMOC-Cl can be kept at room temperature for at least 24 h without showing significant losses in the quantified values. The validated method was successfully applied to the determination of major four kinds of amino acids in R. isatidis samples (Arg, Pro, Met and Val). The total content of amino acids in different origin R. isatidis was 13.32-19.16 mg/g. The differences between R. isatidis samples were large using HCA.
- Zhou, Wei,Zhang, Xiao-Yan,Duan, Geng-Li
-
experimental part
p. 509 - 515
(2012/01/04)
-
- Derivates of Polyethylene Glycol Modified Thymosin Alpha 1
-
Pharmaceutical compositions that include thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol, and their pharmaceutical acceptable salts, are generally disclosed. Also, new methods used to prepare these thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol are generally provided. The presently disclosed compounds and their salts can be prepared administered to humans to treat immune disease and can also be used in adjuvant treatment.
- -
-
-
- Efficient procedure for the preparation of oligomer-free N-fmoc amino acids
-
A two-step method is presented for the peptide-free, high-purity, and high-yield synthesis of N-Fmoc amino acids. The first step involves the preparation of stable dicyclohexylammonium-amino acid ionic adduct in acetone. Subsequently, the ionic adducts, on reaction with Fmoc-Nosu under mild alkaline conditions, give dipeptide-free N-Fmoc amino acids. The positive charge of the dicyclohexylammonium counterion in the ionic salt has a longer radius, moderating the nucleophilicity of the carboxylate ion of the amino acid and preventing by-products by arresting the formation of mixed anhydrides, the precursors of oligopeptide impurities.
- Nowshuddin, Shaik,Rao,Reddy, A. Ram
-
experimental part
p. 2022 - 2031
(2009/11/30)
-
- METHOD OF LABELING WITH ISOTOPE OF OXYGEN
-
The present invention provides methods for labeling one or two oxygen atom(s) in a carboxyl group of a carboxyl-containing compound with an oxygen isotope selected from oxygen-17 ( 17 O) or oxygen-18 ( 18 O). The methods of the present invention are characterized in that an activated ester of the carboxyl-containing compound (carboxylic acid) is reacted with H 2 17 O or H 2 18 O in the presence of an activator. In the methods of the present invention, the reaction between the activated ester of a carboxylic acid and H 2 17 O or H 2 18 O can be allowed to proceed without including drastic conditions such as strongly acidic conditions or alkaline hydrolysis because an activator is used.
- -
-
Page/Page column 7
(2010/11/25)
-
- A convenient, general synthesis of 1,1-dimethylallyl esters as protecting groups for carboxylic acids
-
(Chemical Equation Presented) Carboxylic acids were converted in high yield to their 1,1-dimethylallyl (DMA) esters in two steps. Palladium-catalyzed deprotection of DMA esters was shown to be compatible with tert-butyl, benzyl, and Fmoc protecting groups, and Fmoc deprotection could be carried out selectively in the presence of DMA esters. DMA esters were also shown to be resistant to nucleophilic attack, suggesting that they will serve as alternatives to tert-butyl esters when acidic deprotection conditions need to be avoided.
- Sedighi, Minoo,Lipton, Mark A.
-
p. 1473 - 1475
(2007/10/03)
-
- A novel and efficient method for cleavage of phenacylesters by magnesium reduction with acetic acid
-
(Equation Presented) In the present study, we use magnesium turnings as a new deprotection reagent for the phenacyl group during orthogonal organic synthesis in the presence of other esters and sensitive protecting groups. By applying the new magnesium turnings/acetic acid deprotection method, phenacyl group can be more easily combined with other protecting groups that are not compatible with the zinc/acetic acid method.
- Kokinaki, Stella,Leondiadis, Leondios,Ferderigos, Nikolas
-
p. 1723 - 1724
(2007/10/03)
-
- Antiangiogenic peptides
-
Mammalian kringle 5 fragments and kringle 5 fusion proteins are disclosed as a compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.
- -
-
-
- Treatment of obesity
-
A method for the treatment of obesity in an animal such as a human, comprises administering to the animal an effective amount of a peptide which comprises an analogue of the carboxyl-terminal sequence of a growth hormone, particularly an analogue of the carboxyl-terminal sequence of human growth hormone containing amino acid residues 177-191. A pharmaceutical composition for use in the treatment of obesity is also disclosed.
- -
-
-
- Employing the structural diversity of nature: Development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones
-
A library of novel dipeptideanalogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected a-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [{RuCl2(p-cymene)}2 and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98% ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on Damino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.
- Pastor, Isidro M.,Vaestilae, Patrik,Adolfsson, Hans
-
p. 4031 - 4045
(2007/10/03)
-
- A new polymer-supported reagent for the Fmoc-protection of amino acids
-
A new polymer-supported Fmoc-OSu (Fmoc-P-OSu) has been prepared from polymer-bound N-hydroxysuccinimide (P-HOSu), and used as a solid-supported reagent for the Fmoc-protection of amino groups. The residual P-HOSu generated after the protection reaction can be separated by simple filtration and reused.
- Chinchilla, Rafael,Dodsworth, David,Nájera, Carmen,Soriano, José
-
p. 7579 - 7581
(2007/10/03)
-
- Methods and compositions for treating rheumatoid arthritis
-
The present invention provides compositions and methods for the treatment of rheumatoid arthritis in a subject wherein one or more compounds of Formula I as defined herein alone or in combination with one or more other antiarthritic drugs provide suppression of rheumatoid arthritis.
- -
-
-
- Apparatus and methods for detecting antibodies
-
A single, unitary, solid phase support apparatus having a planar surface divided into a plurality of separate zone functions to detect antibodies. Each zone has bonded to it, a different peptide through its C-terminal end. The zones are incubated with the analyte sample and observed for reaction, indicating the virus-specific or bacteria specific presence or absence.
- -
-
-
- Convenient protection of amines as carbamates using polymer-bound HOBT as catalyst
-
A method for the facile protection of primary and secondary amines as carbamate (Cbz, Fmoc and t-Boc) derivatives using polymer bound 1-hydroxybenzotriazole (HOBT) is reported.
- Dendrinos, Kleanthis G.,Kalivretenos, Aristotle G.
-
p. 1463 - 1464
(2007/10/03)
-
- Angiopeptin cyclopeptide compounds
-
The invention relates to a compound selected from those of formula (I) (SEQ ID NO:1): STR1 in which R1, R2, X1 and X2 are as defined in the description, useful as inhibitor of the proliferation component of vascular smooth muscle cells.
- -
-
-
- Amino acid protecting groups
-
This invention relates to compounds of the formula a compound of the formula STR1 wherein X is O, CR7 R8, S or NR9 wherein R7 and R8 are independently hydrogen, or lower alkyl, and R9 is lower alkyl; n is 0 or 1; R1 and R2 are independently hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, aryl, or nitro; R3 is hydrogen, lower alkyl, monoorganosilyl, diorganosilyl, triorganosilyl, halogen, 9-fluorenylalkyl, cycloalkyl, aryl or aralkyl; R4 and R5 are independently hydrogen, lower alkyl, or aryl or one of R4 and R5 is 9-fluorenyl; R6 is H or COZ wherein Z is an amino acid, a peptide residue or a leaving group; and with the provisos that when n is 0 and R3 is hydrogen, R1 and R2 are not hydrogen, halogen or nitro; that when n is 0 and R3 is lower alkyl, R1 and R2 are not hydrogen; and that when X is O or CR7 R8 wherein R7 and R8 are H, that R1, R2, R3, R4, R5, and R6 are not all simultaneously H. The compounds of the present invention are useful in peptide synthesis as blocking or protecting groups for reactive groups. The present invention is also directed to a method of protecting a reactive group of an organic molecule during a reaction which modifies a portion of the molecule other than the protected group.
- -
-
-
- A New Synthesis of Thymosin α1
-
Thymosin α1, an N-acetylated octacosa thymus peptide, isolated first from thymosin fraction 5, is synthesized by the solid phase method using the p-benzyloxybenzyl alcohol/polystyrene/divinylbenzene resin, Nα-Fmoc-amino acids and those with tert-butyl or Boc side chain protection.All couplings are performed with the Bop reagent.The peptide is purified by a combination of gel chromatography and preparative HPLC, its purity checked by amino acid analysis and analytical HPLC, and the biological activity tested by the E-rosette assay.
- Echner, Hartmut,Voelter, Wolfgang
-
p. 1095 - 1098
(2007/10/02)
-
- 5-Norbornene-2,3-dicarboximido Carbonochloridate. A New Stable Reagent for the Introduction of Amino-Protecting Groups
-
The synthesis of activated carbonates, based on a new carbonochloridate derived from N-hydroxy-5-norbornene-2,3-dicarboximide, is reported.These activated carbonic esters are excellent reagents for the introduction of all currently used urethane protecting groups.
- Henklein, Peter,Heyne, Hans-Ulrich,Halatsch, Wolf-Rainer,Niedrich, Hartmut
-
p. 166 - 167
(2007/10/02)
-
- 9-Fluorenylmethyl Pentafluorophenyl Carbonate as a Useful Reagent for the Preparation of N-9-Fluorenylmethyloxycarbonylamino Acids and their Pentafluorophenyl Esters
-
9-Fluorenylmethyl pentafluorophenyl carbonate is a useful reagent for the efficient, side reaction-free introduction of N-9-fluorenylmethyloxycarbonyl protecting group into amino acids and for the subsequent preparation of their pentafluorophenyl esters.Some new compounds of both types are described.
- Schoen, Istvan,Kisfaludy, Lajos
-
p. 303 - 305
(2007/10/02)
-
- On the Use of Five-Membered Heterocycles in Peptide Chemistry
-
N-Acyl derivatives of 2-benzoxazolethiol, 2-benzothiazolethiol and 2-benzimidazolethiol are proposed for use both as efficient acylating agents for the synthesis of N-benzyloxycarbonyl and N-fluorenylmethyloxycarbonyl amino acid derivatives and as activated amides for the synthesis of peptides.
- Romani, S.,Moroder, L.,Bovermann, G.,Wuensch, E.
-
p. 738 - 742
(2007/10/02)
-
- Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates
-
9-Fluorenylmethyl succinimidyl, pentachlorophenyl, and benzotriazole-1-yl carbonates were prepared and their reactivity with L-serine and L-serine benzyl ester was compared.The most efficient reagent, 9-fluorenylmethyl succinimidyl carbonate, was used for the preparation of 9-flourenylmethyloxycarbonyl derivatives of other hydroxyamino acids and hydroxyamino acid esters in high yields.The use of trichloroethyl and benzyl succinimidyl carbonates for an efficient conversion of hydroxyamino acids and their esters into the corresponding N-trichloroethoxycarbonyl and benzyloxycarbonyl derivatives is described.
- Paquet, Alenka
-
p. 976 - 980
(2007/10/02)
-
- Solid phase synthesis without repetitive acidolysis. Preparation of leucyl-alanyl-glycyl-valine using 9-fluorenylmethyloxycarbonylamino acids.
-
The utility of repetitive nonhydrolytic base cleavage of alpha-amino protective groups in solid phase peptide synthesis is shown by a preparation of the model tetrapeptide leucyl-alanyl-glycyl-valine on a p-benzyloxybenzyl ester polystyrene--1% divinylbenzene resin support. Nalpha-9-Fluorenylmethyloxycarbonyl (Fmoc: Carpino & Han, 1970, 1972) amino acids were coupled by the symmetrical anhydride procedure, followed by Fmoc group cleavage using 50% piperidine in methylene chloride. Quantitative removal of the Fmoc-tetrapeptide from the solid support was effected by treatment with 55% trifluoroacetic acid in methylene chloride. Homogeneous free tetrapeptide was obtained in 87% overall yield. The procedure is proposed to offer advantages over present solid phase methods which use acidolysis for repetitive alpha-amino group deblocking.
- Meienhofer,Waki,Heimer,Lambros,Makofske,Chang
-
p. 35 - 42,37,39
(2007/10/06)
-
- Solid phase synthesis with base N alpha-protecting group cleavage
-
An improved solid phase peptide synthesis method is disclosed utilizing base labile Nα-amino acid protecting groups. Such method provides a more efficient synthesis procedure in that it eliminates acid treatment thereby preventing loss of peptide from the support during each deprotection cycle and eliminates a substantial number of wash cycles in each step. A preferred base labile Nα-amino protecting group is the 9-fluorenylmethyloxycarbonyl group (Fmoc) and a preferred base for deprotection is piperidine.
- -
-
-
