- Synthesis of N-Fmoc-O-(N′-boc-N′-methyl)-aminohomoserine, an amino acid for the facile preparation of neoglycopeptides
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The synthesis of N-Fmoc-O-(N′-Boc-N′-methyl)- aminohomoserine in 35% overall yield from L-homoserine is described. This amino acid can be efficiently incorporated into peptides using Fmoc-chemistry-based solid-phase peptide synthesis, and the resulting peptides can be chemo-selectively glycosylated at the aminooxy side chains to generate neoglycopeptides. The synthesis of this derivative greatly expands the availability of a previously developed neoglycopeptide synthesis strategy.
- Carrasco, Michael R.,Brown, Ryan T.,Serafimova, Iana M.,Silva, Oscar
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Read Online
- Synthesis and Hydrolytic Stability of N- and O-Methyloxyamine Linkers for the Synthesis of GlycoconjugatesSynthesis and Hydrolytic Stability of N- and O-Methyloxyamine Linkers for the Synthesis of Glycoconjugates
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A comparison of the merits of N- and O-methyloxyamines as linkers for carbohydrates is presented for the first time. In particular, optimized synthetic routes for each linker type are given, and the ease of glycan conjugation is described. The hydrolytic stabilities of the respective oxyamine glycoconjugates under a variety of different conditions are reported. This provides insight into the factors that influence hydrolysis rates, and sheds light on the acid-catalysed hydrolysis mechanism.
- Munneke, Stefan,Hill, Jaimé C.,Timmer, Mattie S. M.,Stocker, Bridget L.
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Read Online
- Synthesis of N-Alkyl Anilines from Arenes via Iron-Promoted Aromatic C-H Amination
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We report both an intermolecular C-H amination of arenes to access N-methylanilines and an intramolecular variant for the synthesis of tetrahydroquinolines. A newly developed, highly electrophilic aminating reagent was key for the direct synthesis of unprotected N-methylanilines from simple arenes. The reactions display a broad functional group tolerance and employ catalytic amounts of a benign iron salt under mild reaction conditions.
- Falk, Eric,Gasser, Valentina C. M.,Morandi, Bill
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supporting information
p. 1422 - 1426
(2021/03/08)
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- A Metal-Free Direct Arene C?H Amination
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The synthesis of aryl amines via the formation of a C?N bond is an essential tool for the preparation of functional materials, active pharmaceutical ingredients and bioactive products. Usually, this chemical connection is only possible by transition metal-catalyzed reactions, photochemistry or electrochemistry. Here, we report a metal-free arene C?H amination using hydroxylamine derivatives under benign conditions. A charge transfer interaction between the aminating reagents TsONHR and the arene substrates enables the chemoselective amination of the arene, even in the presence of various functional groups. Oxygen was crucial for an effective conversion and its accelerating role for the electron transfer step was proven experimentally. In addition, this was rationalized by a theoretical study which indicated the involvement of a dioxygen-bridged complex with a “Sandwich-like” arrangement of the aromatic starting materials and the aminating agents at the dioxygen molecule. (Figure presented.).
- Wang, Tao,Hoffmann, Marvin,Dreuw, Andreas,Hasagi?, Edina,Hu, Chao,Stein, Philipp M.,Witzel, Sina,Shi, Hongwei,Yang, Yangyang,Rudolph, Matthias,Stuck, Fabian,Rominger, Frank,Kerscher, Marion,Comba, Peter,Hashmi, A. Stephen K.
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supporting information
p. 2783 - 2795
(2021/04/05)
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- Regioselective Radical Arene Amination for the Concise Synthesis ofortho-Phenylenediamines
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The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactiveN-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the areneorthoposition. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly toortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuableortho-phenylenediamines, this work demonstrates the potential for utilizing noncovalent interactions to control positional selectivity in radical reactions.
- Gillespie, James E.,Morrill, Charlotte,Phipps, Robert J.
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supporting information
p. 9355 - 9360
(2021/07/19)
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- Development of a multifunctional neoglycoside auxiliary for applications in glycomics research
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A novel, multifunctional, tetrazine-containing neoglycoside auxiliary has been synthesized in three steps and 28% overall yield. The oxyamine was conjugated with unprotected carbohydrates under aqueous conditions (pH = 4.7), with DMF as a cosolvent, to provide neoglycosides in yields ranging between 51% and 68%. This auxiliary displayed broad advantages in the isolation and purification of complex carbohydrate mixtures, compatibility during extension by glycosyltransferases, and direct conjugation to chemical probes. Furthermore, the auxiliary can be removed in 96% yield under acidic conditions (0.25% TFA in H2O) that leave glycosidic linkages intact. Thereby, the tetrazine-containing neoglycoside auxiliary can serve to facilitate future glycomics investigations.
- Brichacek, Matthew,Cheewawisuttichai, Thamrongsak
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supporting information
p. 6613 - 6617
(2021/08/12)
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- Design and Scalable Synthesis of N-Alkylhydroxylamine Reagents for the Direct Iron-Catalyzed Installation of Medicinally Relevant Amines**
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Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine-derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug-like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.
- Delcaillau, Tristan,Falk, Eric,Gürtler, Laura,Makai, Szabolcs,Morandi, Bill
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supporting information
p. 21064 - 21071
(2020/09/21)
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- Phosphonodiamidate prodrugs of N-alkoxy analogs of a fosmidomycin surrogate as antimalarial and antitubercular agents
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A series of N-alkoxy analogs of a L-leucine ethyl ester phosphonodiamidate prodrug of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. These compounds originate b
- Courtens, Charlotte,Risseeuw, Martijn,Caljon, Guy,Cos, Paul,Martin, Anandi,Van Calenbergh, Serge
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supporting information
p. 1051 - 1053
(2019/03/23)
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- Double prodrugs of a fosmidomycin surrogate as antimalarial and antitubercular agents
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A series of eleven double prodrug derivatives of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. A pivaloyloxymethyl (POM) phosphonate prodrug modification was c
- Courtens, Charlotte,Risseeuw, Martijn,Caljon, Guy,Maes, Louis,Cos, Paul,Martin, Anandi,Van Calenbergh, Serge
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p. 1232 - 1235
(2019/03/21)
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- OXADIAZEPINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF HEPATITIS B INFECTIONS
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Provided herein are compounds of formula (IA) and (III) useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Page/Page column 343
(2018/02/28)
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- Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides
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Selective C-H amidation of 1H-indoles at the C3 position is reported as a direct entry to biologically important 3-aminoindoles. This transformation is achieved using novel N-[(benzenesulfonyl)oxy]amides as electrophilic nitrogen agents in the presence of ZnCl2. Interestingly, analogous reactions in the absence of ZnCl2 resulted in the formation of indole aminal products.
- Ortiz, Gerardo X.,Hemric, Brett N.,Wang, Qiu
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supporting information
p. 1314 - 1317
(2017/03/23)
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- Glyco-functionalized dinuclear rhenium(i) complexes for cell imaging
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The design, synthesis and photophysical characterization of four new luminescent glycosylated luminophores based on dinuclear rhenium complexes, namely Glyco-Re, are described. The derivatives have the general formula [Re2(μ-Cl)2(CO)
- Palmioli, Alessandro,Aliprandi, Alessandro,Septiadi, Dedy,Mauro, Matteo,Bernardi, Anna,De Cola, Luisa,Panigati, Monica
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p. 1686 - 1699
(2017/02/23)
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- Enantioselective NHC-Catalyzed Redox [2+2] Cycloadditions with Perfluoroketones: A Route to Fluorinated Oxetanes
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The N-heterocyclic carbene (NHC) catalyzed redox formal [2+2] cycloaddition between α-aroyloxyaldehydes and perfluoroketones, followed by ring-opening in situ delivers a variety of perfluorinated β-hydroxycarbonyl compounds in good yield, and excellent diastereo- and enantioselectivity. Through a reductive work-up and subsequent cyclization, this protocol offers access to highly substituted fluorinated oxetanes in two steps and in high ee.
- Davies, Alyn T.,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 18944 - 18948
(2016/01/26)
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- Enantioselective direct α-amination of aldehydes via a photoredox mechanism: A strategy for asymmetric amine fragment coupling
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The direct, asymmetric α-amination of aldehydes has been accomplished via a combination of photoredox and organocatalysis. Photon-generated N-centered radicals undergo enantioselective α-addition to catalytically formed chiral enamines to directly produce stable α-amino aldehyde adducts bearing synthetically useful amine substitution patterns. Incorporation of a photolabile group on the amine precursor obviates the need to employ a photoredox catalyst in this transformation. Importantly, this photoinduced transformation allows direct and enantioselective access to α-amino aldehyde products that do not require postreaction manipulation.
- Cecere, Giuseppe,Koenig, Christian M.,Alleva, Jennifer L.,MacMillan, David W. C.
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supporting information
p. 11521 - 11524
(2013/09/02)
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- Labeled Alginate Conjugates for Molecular Imaging Applications
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Described are bifunctional NOTA-based derivatives capable of conjugating with alginate and with metal ions, as well as NOTA-alginate conjugates which can be labeled with stable or radioactive metal ions. Also described are conjugation methods of the bifun
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Paragraph 0107
(2013/06/27)
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- Chemoselective and microwave-assisted synthesis of glycopeptoids
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The chemoselective glycosylation of N-alkylaminooxy side chains with unprotected reducing sugars has proven useful for the synthesis of glycopeptides. Herein, we extend the N-alkylaminooxy strategy to the synthesis of glycopeptoids. A N-methylaminooxy sub
- Seo, Jiwon,Michaelian, Nairie,Owens, Shawn C.,Dashner, Scott T.,Wong, Amanda J.,Barron, Annelise E.,Carrasco, Michael R.
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supporting information; experimental part
p. 5210 - 5213
(2010/03/01)
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- ENHANCED IMMUNOGENICITY OF TUMOR ASSOCIATED ANTIGENS BY ADDITION OF ALPHAGAL EPITOPES
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The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. The present invention describes prophylactic or therapeutic cancer vaccines based on purified TAA proteins or TAA-derived synthetic peptides altered by chemical, enzymatic or chemo-enzymatic methods to introduce αGal epitopes or αGal glycomimetic epitopes, in order to allow for enhanced opsonization of the antigen by natural anti-αGal antibodies to stimulate TAA capture and presentation, thereby inducing a humoral and cellular immune response to the TAA expressed by a tumor. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.
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Page/Page column 4/7
(2008/12/05)
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- Direct α-oxytosylation of carbonyl compounds: One-pot synthesis of heterocycles
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N-Methyl-O-tosylhydroxylamine is an effective reagent for the direct α-oxytosylation of carbonyl compounds. The reactions proceed smoothly at room temperature in the presence of both moisture and air and functional group tolerance in the substrate is good. With nonsymmetrical substrates regioselectivity for primary over secondary centers is observed and complete regiospecificity for primary over tertiary centers is obtained. Addition of a bis-heteronucleophile directly to the crude reaction mixture in a one-pot process leads to the corresponding heterocyclic product.
- John, Oliver R. S.,Killeen, Niall M.,Knowles, Deborah A.,Yau, Sze Chak,Bagley, Mark C.,Tomkinson, Nicholas C. O.
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p. 4009 - 4012
(2008/02/11)
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- A general method for the α-acyloxylation of carbonyl compounds
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(Chemical Equation Presented) A simple, one-pot method for the α-acyloxylation of carbonyl compounds that proceeds at room temperature in the presence of both moisture and air has been developed. Treatment of a variety of aldehydes and both cyclic and acy
- Beshara, Cory S.,Hall, Adrian,Jenkins, Robert L.,Jones, Kerri L.,Jones, Teyrnon C.,Killeen, Niall M.,Taylor, Paul H.,Thomas, Stephen P.,Tomkinson, Nicholas C. O.
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p. 5729 - 5732
(2007/10/03)
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- SYNTHESIS OF L-β-(ISOXAZOLIN-5-ONE-2-YL)-ALANINE: A NOVEL METHOD FOR THE SYNTHESIS OF N-SUBSTITUTED 3,4-UNSUBSTITUTED ISOXAZOLIN-5-ONES
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A mild new general method for the synthesis of the isoxazolin-5-one-2-yl ring system (4) via a favoured 5-endo-dig cyclisation is described; this methodology has been successfully applied for the first chemical enantio-efficient synthesis of L-β-(isoxazol
- Baldwin, Jack E.,Adlington, Robert M.,Birch, David J.
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p. 5931 - 5934
(2007/10/02)
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- O-Arenesulfonyl-N-alkylhydroxylamines as Aminating Reagents
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O-(p-Toluenesulfonyl)-N-methyl-, -N-ethyl-, and -N-isopropil-hydroxylamines and O-mesitylenesulfonyl-N-methylhydroxylamine were prepared.The N-methyl and N-ethyl derivatives were found to react with tertiary amines and triphenylphosphine to give the corresponding N-(alkylamino)ammonium salts and P-(alkylamino)phosphonium salts, but the N-isopropyl derivative was less reactive, probably due to steric effects.These reagents also reacted with tri-n-butylborane to give the corresponding alkyl-n-butylamines.Keywords-- electrophilic aminating reagent; tert-butoxycarbonylation; di-tert-butyl dicarbonate; N-(methylamino)ammonium salts; P-(methylamino)triphenylphosphonium salt; N-(methylamino)pyridinium salt; secondary amines
- Tamura, Yasumitsu,Ikeda, Hiroyuki,Morita, Iwao,Tsubouchi, Hidetsugu,Ikeda, Masazumi
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p. 1221 - 1224
(2007/10/02)
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- 2-Imino-3-aminothiazolidines and indoleamine-N-methyltransferase inhibition
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2-Imino-3-aminothiazolidines are inhibitors of indoleamine-N-methyl transferase in vivo.
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