70935-35-2Relevant academic research and scientific papers
Synthesis method of L-prolinamide
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Paragraph 0030; 0032; 0035; 0037; 0040; 0042; 0045; 0047, (2019/01/16)
The invention belongs to the field of organic synthesis, and discloses a synthesis method of L-prolinamide. The method comprises steps of S1, dissolving an initial material, L-proline, in water and then reacting with acetic anhydride, after reaction, extracting and drying to prepare N-acetyl-L-proline; S2, in a solvent system, performing a reaction on a raw material, N-acetyl-L-proline prepared inS1 and thionyl chloride, then concentrating and drying to obtain a compound; S3, dripping aqueous ammonia in the compound prepared in S2 as a raw material so as to react, filtering and preparing 1-acetyl-2-pyrrolidinecarboxamide; and S4, dripping HC1 into the 1-acetyl-2-pyrrolidinecarboxamide prepared in S3 as a raw material, so as to react, then concentrating, filtering and drying to prepare L-prolinamide. In the reaction process of the synthesis method provided by the invention, common reagent raw materials are used, the costs are low, the reaction conditions are mild, the chiral purity ishigh, the yield is high, the environment pressure is low, and the synthesis method is suitable for large-scale production.
α-Sila-Dipeptides: Synthesis and Characterization
Minkovich, Boris,Ruderfer, Ilya,Kaushansky, Alexander,Bravo-Zhivotovskii, Dmitry,Apeloig, Yitzhak
supporting information, p. 13261 - 13265 (2018/09/21)
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.
Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents
Malik, Sachin,Khan, Suroor A.
, p. 505 - 516 (2014/08/05)
A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a-5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED50 value of 6.20mg/kg (oral/rat) and a protective index (PI=ED50/TD50) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5b, 5c, 5i and 5o, their influence on sodium channel was evaluated in vitro.
Synthesis and evaluation of aza-peptidyl inhibitors of the lysosomal asparaginyl endopeptidase, legumain
Lee, Jiyoun,Bogyo, Matthew
supporting information; experimental part, p. 1340 - 1343 (2012/04/04)
Legumain or asparaginly endopeptidase (AEP) is a lysosomal cysteine protease with a high level of specificity for cleavage of protein substrates after an asparagine residue. It is also capable of cleaving after aspartic acids sites when in the acidic environment of the lysosome. Legumain expression and activity is linked to a number of pathological conditions including cancer, atherosclerosis and inflammation, yet its biological role in these pathologies is not well-understood. Highly potent and selective inhibitors of legumain would not only be valuable for studying the functional roles of legumain in these conditions, but may have therapeutic potential as well. We describe here the design, synthesis and in vitro evaluation of selective legumain inhibitors based on the aza-asparaginyl scaffold. We synthesized a library of aza-peptidyl inhibitors with various non-natural amino acids and different electrophilic warheads, and characterized the kinetic properties of inactivation of legumain. We also synthesized fluorescently labeled inhibitors to investigate cell permeability and selectivity of the compounds. The inhibitors have second order rate constants of up to 5 × 104 M-1 s-1 and IC50 values as low as 4 nM against recombinant mouse legumain. In addition, the inhibitors are highly selective toward legumain and have little or no cross-reactivity with cathepsins. Overall, we have identified several valuable new inhibitors of legumain that can be used to study legumain function in multiple disease models.
Stereoselective synthesis of 2-aminocyclobutanols via photocyclization of α-amido alkylaryl ketones: Mechanistic implications for the Norrish/Yang reaction
Griesbeck, Axel G.,Heckroth, Heike
, p. 396 - 403 (2007/10/03)
A series of chiral N-acylated α-amino p-methylbutyrophenone derivatives 1a-1h was synthesized from α-amino acids via a three-step procedure. These substrates were photolyzed in benzene and gave Norrish II and Norrish I cleavage products as well as the N-acylated 2-aminocyclobutanols that derive from γ-hydrogen abstraction and 1,4-triplet biradical combination (Yang cyclization). The products were formed with characteristic Yang/cleavage ratios. The quantum yields for the photodecomposition of the N-acetyl-protected substrates 1b,e,f were moderate (12-26%); the diastereoselectivities of the cyclobutanol formation were remarkably high for all substrates. High diastereospecificity was observed for the isoleucine derivatives (2S,3S)-1g and allo-(2S,3R)-1g; the Yang reaction dominated the photochemistry of allo-1g, whereas 1g gave preferentially Norrish II cleavage. The role of hydrogen bonding as one of the stereo-directing effects was demonstrated by comparison of the cyclization efficiency of the valine derivative 1e with 1h,i,j. Also, aromatic β-keto esters gave the Yang cyclization products in low yields. The diastereoselectivity of the cyclobutanol formation was rationalized by a three-step mechanism where every step is connected with one distinct stereochemical induction mechanism: (a) diastereoselective hydrogen abstraction, (b) conformational equilibration of the 1,4-tetramethylene biradicals (as calculated by semiempiric methods) controlled by hydrogen bonding, and (c) diastereoselective biradical combination (versus cleavage) influenced by spin-orbit coupling controlled intersystem crossing geometries.
Transmutation of 1,3-dipoles. The conversion of α-diazo ketones into azomethine ylides via carbonyl ylides
Padwa, Albert,Dean, Dennis C.,Zhi, Lin
, p. 593 - 601 (2007/10/02)
A series of N-acyl-2-(1-diazoacetyl)pyrrolidines, when treated with a catalytic quantity of a rhodium(II) carboxylate, were found to afford tricyclic dihydropyrrolizines derived from an azomethine ylide intermediate. The initial reaction involves generati
