134235-83-9Relevant articles and documents
Total Synthesis of Mannopeptimycins α and β
Wang, Bo,Liu, Yunpeng,Jiao, Rui,Feng, Yiqing,Li, Qiong,Chen, Chen,Liu, Long,He, Gang,Chen, Gong
, p. 3926 - 3932 (2016)
The mannopeptimycins are a class of glycopeptide natural products with unusual structures and potent antibiotic activity against a range of Gram-positive multidrug-resistant bacteria. Their cyclic hexapeptide core features a pair of unprecedented β-hydroxyenduracididines (l- and d-βhEnd), an O-glycosylated d-Tyr carrying an α-linked dimannose, and a β-methylated Phe residue. The d-βhEnd unit also carries an α-linked mannopyranose at the most hindered N of its cyclic guanidine ring. Herein, we report the first total synthesis of mannopeptimycin α and β with fully elaborated N- and O-linked sugars. Critically, a gold-catalyzed N-glycosylation of a d-βhEnd substrate with a mannosyl ortho-alkynylbenzoate donor enabled the synthesis of the most challenging N-Man-d-βhEnd unit with excellent efficiency and stereoselectivity. The l-βMePhe unit was prepared using a Pd-catalyzed C-H arylation method. The l-βhEnd, d-Tyr(di-Man), and l-βMePhe units were prepared in gram quantities. A convergent assembly of the cyclic peptide scaffold and a single global hydrogenolysis deprotection operation provided mannopeptimycin α and β.
Stereoinversion of β- and γ-substituted α-amino acids using a chemo-enzymatic oxidation-reduction procedure
Enright, Alexis,Alexandre, Francois-Rene,Roff, Geoffrey,Fotheringham, Ian G.,Dawson, Michael J.,Turner, Nicholas J.
, p. 2636 - 2637 (2003)
Both D- and L-β- and γ-substituted α-amino acids can be interconverted to their respective L- and D- diastereoisomers by treatment with an enantioselective amino acid oxidase and a chemical reducing agent.
Development of a Model for the δ Opioid Receptor Pharmacophore. 2. Conformationally Restricted Phe3 Replacements in the Cyclic δ Receptor Selective Tetrapeptide Tyr-cOH (JOM-13)
Mosberg, Henry I.,Omnaas, John R.,Lomize, Andrei,Heyl, Deborah L.,Nordan, Ian,et al.
, p. 4384 - 4391 (1994)
The in vitro pharmacological properties and conformational features of analogs of the δ opioid receptor selective tetrapeptide Tyr-cOH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of β-methylphenylalanine (β-MePhe) were investigated.Both analogs in which the α carbon of the Phe3 replacement has L-stereochemistry display high affinity for δ receptors with the (2S,3S)-MePhe3 analog exhibiting approximately 8-fold higher affinity than the (2S,3R)-MePhe3 diastereomer.Surprisingly, one analog with D-stereochemistry in residue 3, the (2R,3R)-MePhe3 analog, also display high affinity for the δ receptor and is extraordinarily selective for this receptor.All analogs were agonists in the mouse vas deferens (MVD) and guinea pig ileum (GPI) smooth muscle bioassays, displaying MVD and GPI potencies consistent with their δ and μ opioid receptor affinities, respectively.The use of β-MePhe as a replacement for Phe3 was based upon the desire to reduce the conformational flexibility of the Phe3 side chain by imposing a steric rotational constraint in the form of the β-methyl substituent and to thus deduce the residue 3 side chain orientation in the δ receptor-bound conformation from the correlation between δ receptor binding affinities and conformational preferences.Molecular mechanics computations revealed, however, that the conformational constraints imposed by the β-methyl group in the (2S,3S)-MePhe3 and (2S,3R)-MePhe3 analogs were too modest to allow unequivocal determination of δ receptor-bound residue 3 side chain conformation.However, analysis of the high-affinity (2R,3R)-MePhe3 analog revealed a strong preference for a single side chain conformer (χ1 ca 60 deg).Low-energy conformers of this analog could only be effectively superimposed with low-energy conformers of the parent peptide in which the Phe3 side chain conformation was limited to χ1 ca -60 deg.This observation eliminates the last remaining uncertainty regarding conformational features of the pharmacophore elements in the δ receptor-bound state, allowing the proposal of a complete model.
SB-203207 and SB-203208, two novel isoleucyl tRNA synthetase inhibitors from a Streptomyces sp. I. Fermentation, isolation and properties
Stefanska, Anna L.,Cassels, Robert,Ready, Sarah J.,Warr, Stephen R.
, p. 357 - 363 (2000)
Two novel inhibitors of isoleucyl tRNA synthetase designated SB-203207 and SB-203208 have been detected in the culture of a new Streptomyces species. The fermentation, isolation and some properties of the inhibitors are described.
Stereoselective Synthesis of β-Branched Aromatic α-Amino Acids by Biocatalytic Dynamic Kinetic Resolution**
Chen, Jason S.,Li, Fuzhuo,Renata, Hans,Yang, Li-Cheng,Zhang, Jingyang
supporting information, p. 17680 - 17685 (2021/07/07)
β-Branched noncanonical amino acids are valuable molecules in modern drug development efforts. However, they are still challenging to prepare due to the need to set multiple stereocenters in a stereoselective fashion, and contemporary methods for the synthesis of such compounds often rely on the use of rare-transition-metal catalysts with designer ligands. Herein, we report a highly diastereo- and enantioselective biocatalytic transamination method to prepare a broad range of aromatic β-branched α-amino acids. Mechanistic studies show that the transformation proceeds through dynamic kinetic resolution that is unique to the optimal enzyme. To highlight its utility and practicality, the biocatalytic reaction was applied to the synthesis of several sp3-rich cyclic fragments and the first total synthesis of jomthonic acid A.
Preparation method of (2R, 3R)-3-methyl-3-phenylalanine
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, (2021/06/23)
The invention relates to a preparation method of (2R, 3R)-3-methyl-3-phenylalanine. The technical problems that an existing preparation method is long in route, expensive in used reagent, incapable of achieving large-scale production and the like are mainly solved. According to the technical scheme, the preparation method of the (2R, 3R)-3-methyl-3-phenylalanine comprises the following steps: condensing 2-acetamidomalonic acid diethyl ester and 1-bromoethyl benzene under the action of alkali to obtain 2-acetamido-2-(1-phenylethyl) malonic acid diethyl ester; heating and hydrolyzing in concentrated hydrochloric acid, concentrating and crystallizing to obtain erythro 3-methyl-3-phenylalanine; then performing acylation to obtain the erythro 2-acetamido-3-methyl 3-phenylalanine; splitting under the action of acetamido transferase, and obtaining (2R, 3R)-2-acetamido-3-methyl 3-phenylalanine; and finally, heating and hydrolyzing by using hydrochloric acid to obtain the product (2R, 3R)-3-methyl-3-phenylalanine (hydrochloride).
Site-Selective γ-C(sp3)?H and γ-C(sp2)?H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group
Lin, Hua,Wang, Chao,Bannister, Thomas D.,Kamenecka, Theodore M.
, p. 9535 - 9541 (2018/07/14)
The first selective PdII-catalysed γ-C(sp3)?H and γ-C(sp2)?H arylation of free amino esters using a commercially available catalytic transient directing group. A variety of free amino esters, including α-amino esters and β-amino esters, amino monoesters and amino bis-esters, are shown to react with a diverse range of simple aryl and heteroaryl iodide reagents.
Immunomodulatory peptides
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, (2014/12/12)
The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.
(2R,1'S,2'R)- And (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl] alanines and their incorporation into hormaomycin analogues
De Meijere, Armin,Kozhushkov, Sergei I.,Yufit, Dmitrii S.,Grosse, Christian,Kaiser, Marcel,Raev, Vitaly A.
supporting information, p. 2844 - 2857 (2015/02/19)
Efficient and scalable syntheses of enantiomerically pure (2 R ,1' S ,2' R )- and (2 S ,1' S ,2' R )-3-[2-mono(di,tri)fluoromethylcyclopropyl] alanines 9a - c , as well as allo-D-threonine ( 4 ) and ( 2 S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S )- and (R )-2-[( N-benzylprolyl)amino]benzophenone [(S)- and (R)-10 ] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin ( 1 ) with (fluoromethylcyclopropyl) alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity.
Stereoselective synthesis of β-alkylated α-amino acids via palladium-catalyzed alkylation of unactivated methylene C(sp3)-H Bonds with Primary Alkyl Halides
Zhang, Shu-Yu,Li, Qiong,He, Gang,Nack, William A.,Chen, Gong
, p. 12135 - 12141 (2013/09/02)
We report a new set of reactions based on the Pd-catalyzed alkylation of methylene C(sp3)-H bonds of aliphatic quinolyl carboxamides with α-haloacetate and methyl iodide and applications in the stereoselective synthesis of various β-alkylated α-amino acids. These reactions represent the first generally applicable method for the catalytic alkylation of unconstrained and unactivated methylene C-H bonds with high synthetic relevance. When applied with simple isotope-enriched reagents, they also provide a convenient and powerful means to site-selectively incorporate isotopes into the carbon scaffolds of amino acid compounds.
