- Synthesis and conformation of backbone N-aminated peptides
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The chemical modification of peptides is a promising approach for the design of protein-protein interaction inhibitors and peptide-based drug candidates. Among several peptidomimetic strategies, substitution of the amide backbone maintains side-chain functionality that may be important for engagement of biological targets. Backbone amide substitution has been largely limited to N-alkylation, which can promote cis amide geometry and disrupt important H-bonding interactions. In contrast, N-amination of peptides induces distinct backbone geometries and maintains H-bond donor capacity. In this chapter we discuss the conformational characteristics of designed N-amino peptides and present a detailed protocol for their synthesis on solid support. The described methods allow for backbone N-amino scanning of biologically active parent sequences.
- Rathman, Benjamin M.,Rowe, Jennifer L.,Del Valle, Juan R.
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- Cobalt Used as a Novel and Reusable Catalyst: A New and One-Pot Synthesis of Isatin-Derived N, S -Acetals Using Substituted Isatins and Thiols
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The synthesis of isatin-derived N, S -acetals using cobalt as a recyclable heterogeneous catalyst in batch and continuous flow is reported for the first time. The present protocol produced high yields, which can be observed from the reaction between ketimines and thiols. Such reactions can also be applied to a gram-scale. In addition, the catalyst is recyclable, economically-viable, and nontoxic as well as easy to prepare. The remarkable features of this new methodology are high conversion and cleaner reaction profiles.
- Albuquerque, Tábata B.,Da Silva, Caren D. G.,Domingues, Nelson L. C.,Dos Santos, Beatriz F.,Katla, Ramesh,Kupfer, Vicente L.,Rinaldi, Andrelson W.,Tavares Junior, José M. C.
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supporting information
p. 4014 - 4022
(2019/10/28)
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- The enantioselective addition of 1-fluoro-1-nitro(phenylsulfonyl)methane to isatin-derived ketimines
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An asymmetric organocatalytic addition of fluorinated phenylsulfonylnitromethane to isatin-derived ketimines was developed. The reaction was efficiently catalyzed by a chiral tertiary amine, cinchonine. This methodology provides a new type of optically active compound with two adjacent quaternary carbon stereocenters in good yield (up to 96%), with moderate diastereoselectivity (up to 5.7:1 dr) and excellent enantioselectivity (up to 98/96% ee).
- Urban,Franc,Hofmanová,Císa?ová,Vesely
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p. 9071 - 9076
(2017/11/14)
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- Access to Enantiopure α-Hydrazino Acids for N-Amino Peptide Synthesis
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Backbone N-methylation of α-peptides has been widely employed to enhance the bioavailability and bioactivity of parent sequences. Heteroatomic peptide amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 canonical proteinogenic amino acids and demonstrate their use in the solid-phase synthesis of N-amino peptide derivatives.
- Kang, Chang Won,Sarnowski, Matthew P.,Elbatrawi, Yassin M.,Del Valle, Juan R.
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supporting information
p. 1833 - 1841
(2017/02/10)
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- Method for producing hematopoietic stem cells using pyrazole compounds
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An expanding agent for hematopoietic stem cells and/or hematopoietic progenitor cells useful as a therapy for various hematopoietic diseases and useful for improvement in the efficiency of gene transfer into hematopoietic stem cells for gene therapy is provided. A method of producing hematopoietic stem cells and/or hematopoietic progenitor cells, which comprises expanding hematopoietic stem cells by culturing hematopoietic stem cells ex vivo in the presence of a compound represented by the formula following (I), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof (wherein R1 to R8 are as defined in the description).
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- PYRAZOLE COMPOUNDS HAVING THERAPEUTIC EFFECT ON MULTIPLE MYELOMA
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Novel therapeutic agents for myeloma are provided. A therapeutic agent for multiple myeloma containing a pyrazole compound represented by the formula (1): wherein R1 is C1-C6 alkyl, C1-C6 alkyl substituted with R17, C1-C6 haloalkyl, phenyl, phenyl substituted with a R11's or the like, R2 is a hydrogen atom, C1-C6 alkyl, phenyl or phenyl optionally substituted with e R21's or the like, R3 is a hydrogen atom or the like, X is a single bond or —(CR6, R7)n—, each of R4 and R5 is independently C1-C6 alkyl or the like, R6 and R7 are hydrogen atoms or C1-C6 alkyl, R8 is phenyl, phenyl optionally substituted with k R81's or the like, a tautomer of the compound or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient.
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- Oxaziridine-mediated amination of primary amines: Scope and application to a one-pot pyrazole synthesis
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(Chemical Equation Presented) Electrophilic amination of primary aliphatic and aromatic amines is reported using a diethylketomalonate-derived oxaziridine to afford the corresponding N-Boc hydrazines in good to excellent yields. The method allows a one-pot synthesis of pyrazoles from primary amines.
- Armstrong, Alan,Jones, Lyn H.,Knight, Jamie D.,Kelsey, Richard D.
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p. 713 - 716
(2007/10/03)
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- Synthesis of arylglycines by reaction of diethyl N-Boc-iminomalonate with organomagnesium reagents
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Diethyl N-Boc-iminomalonate (3), prepared on multigram scale, served as a stable and highly reactive electrophilic glycine equivalent which reacted with organomagnesium compounds affording substituted aryl N-Boc-aminomalonates. Subsequent hydrolysis produced arylglycines.
- Calí,Begtrup
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- N-alkyloxycarbonyl-3-aryloxaziridines: Their preparation, structure, and utilization as electrophilic amination reagents
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This paper reports the synthesis of a series of N-protected oxaziridines (N-Moc, Boc, Z or Fmoc) and discusses their ability to deliver their N-alkoxycarbonyl fragment to amines, enolates, sulfur, and phosphorus nucleophiles (electrophilic amination). These oxaziridines are prepared by oxidation of the corresponding imines with oxone or anhydrous MCPBA lithium salt as the source of oxygen. They transfer their N-protected fragment to primary and secondary amines to give protected hydrazines in fair to excelent yield. The nitrogen transfer to free amino acids (in form of their R4N+ salts) is particularly fast, even at low temperature, providing L (or D) N-protected α-hydrazino acids. Enolates are C-aminated to give N-protected α-amino ketones, esters, or amides in modest yield, due to a side aldol reaction of the unreacted enolate with the released benzaldehyde. With tertiary amines (Et3N), sulfides (PhSMe), and phosphines (Ph3P), amination and oxidation proceed in a parallel way; the amount of amination product increases when the temperature is lowered (kinetic control). Some of the factors that can orient the oxaziridine reactivity towards amination or oxidation of nucleophiles are considered.
- Vidal, Joelle,Damestoy, Stephanie,Guy, Laure,Hannachi, Jean-Christophe,Aubry, Andre,Collet, Andre
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p. 1691 - 1709
(2007/10/03)
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- Electrophilic Amination: Preparation and Use of N-Boc-3-(4-cyanophenyl)oxaziridine, a New Reagent That Transfers a N-Boc Group to N- and C-Nucleophiles
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We describe the preparation of the title compound 2b via aza-Wittig reaction of N-Boc-triphenyliminophosphorane (6) with 4-cyanobenzaldehyde followed by Oxone oxidation of the resulting imine 5b.Oxaziridine 2b is a stable, crystalline solid, which transfers under mild conditions its N-Boc fragment to primary and secondary amines (to give Nβ-Boc-hydrazines) and enolates (to give N-Boc-amino drivatives).
- Vidal, Joelle,Guy, Laure,Sterin, Sebastien,Collet, Andre
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p. 4791 - 4793
(2007/10/02)
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- Reactions of cobaltacyclopentadiene complexes with organic azides directed toward synthesis of highly substituted pyrroles
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The reactions of the cobaltacyclopentadiene complexes (η5-C5H5)(PPH3)-Co(-CR1=CR2-CR3=CR4)- (I) with organic azides were investigated.The complex Ia (R1)=R2=R3=R4=Ph) reacts with phenyl azide at 80 degC to give 1,2,3,4,5-pentaphenylpyrrole in 73percent yeld.Similarly, the reactions of Ia with benzoyl and t-butoxycarbonyl azides give 1-benzoyl- and 1-(t-butoxycarbonyl)-2,3,4,5-tetraphenylpyrroles in 41 and 64percent yields, respectively, but reaction with p-toluenesulfonyl azide gives 2,3,4,5-tetraphenylpyrrole and 3,4,5,6-tetraphenylpyridazine in 35 and 45percent yields, respectively, in place of the expected 1-(p-toluenesulfonyl)-2,3,4,5-tetraphenylpyrrole.The reaction of Ic (R1=R4=Ph, R2=R3=CO2CH3) with phenyl azide at 130 degC gives 1,2,5-triphenyl-3,4-bis(methoxycarbonyl)pyrrole (IIc)and 2,5-diphenyl-3,4-bis(methoxcarbonylpyrrole (Vb) in 22 and 15percent yields, respectively.The reaction of Ic with benzenesulfonyl azide gives only Vb in 57percent yield.In the reaction of Id (R1=R3=Ph, R2=R4=CO2CH3) with benzenesulfonyl azide, Vb was unexpectedly obtained in 26percent yield, together with 2,4-diphenyl-3,5-bis(methoxycarbonyl)pyrrole (Vc, 30percent), which suggests that a skeletal rearrangement of the metallacycle IXd to IXc occurs during the reaction.The reaction of Ic or Id with benzoyl azide at 130 degC gives the 2(1H)-pyridinone derivatives VIIIa (82percent) and VIIIb (53percent), which are the products of the reaction of the corresponding cobaltacyclpentadiene with phenyl isocyanate generated by the rearrangement of benzoyl nitrene, in place of the expected, corresponding pyrrole.
- Hong, Pangbu,Yamazaki, Hiroshi
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p. 133 - 142
(2007/10/02)
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