10569-72-9Relevant articles and documents
A new enantioselective synthesis of β-amino acids
Saylik, Dilek,Campi, Eva M.,Donohue, Andrew C.,Jackson,Robinson, Andrea J.
, p. 657 - 667 (2001)
Enantioselective hydrogenation of some α,β-unsaturated nitriles and their corresponding methyl esters bearing a phthalimidomethyl substituent at the α-carbon using Rh-DuPHOS catalysts afforded β-amino acid precursors with modest e.e.s of up to 48%. Hydrogenation of the α,β-unsaturated methyl esters using a Ru-BINAP catalyst gave higher e.e.s of up to 84%. Method development for the determination of the enantiomeric excesses of these derivatives using chiral HPLC is also reported.
Diastereoselective total synthesis and structural confirmation of surugamide F
Kuranaga, Takefumi,Fukuba, Atsuki,Ninomiya, Akihiro,Takada, Kentaro,Matsunaga, Shigeki,Wakimoto, Toshiyuki
, p. 637 - 641 (2018)
Surugamide F is a linear decapeptide (1) isolated along with the cyclic octapeptides surugamides A–E (2–6), from a marine-derived Streptomyces species. The linear peptide 1 is produced by two nonribosomal peptide synthetases (NRPSs) encoded in adjacent open reading frames, which are further flanked by an additional pair of NRPS genes responsible for the biosyntheses of the cyclic peptides 2–6. While the cyclic peptides 2–6 were identified to be cathepsin B inhibitors, the biological activity of the new metabolite 1 still remained unclear. In order to elucidate its unique biosynthetic pathway and biological activity in detail, we planned to develop an efficient synthetic route toward 1. Here we report the diastereoselective total synthesis of 1, utilizing 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis. During this study, we found that the structural correction of 1 was required, due to the mislabeling of the commercially obtained 3-amino-2-methylpropionic acid, and the true structure of 1 was corroborated by the chemical synthesis and chromatographic comparison.
New biocatalytic route for the production of enantioenriched β-alanine derivatives starting from 5- and 6-monosubstituted dihydrouracils
Martínez-Gómez, Ana Isabel,Clemente-Jiménez, Josefa María,Rodríguez-Vico, Felipe,Kanerva, Liisa T.,Li, Xiang-Guo,Heras-Vázquez, Francisco Javier Las,Martínez-Rodríguez, Sergio
, p. 2090 - 2096 (2012)
Taking advantage of the catalytic promiscuity of pyrimidine-catabolism enzymes (dihydropyrimidinase (E.C. 3.5.2.2), N-carbamoyl-β-alanine amidohydrolase (E.C. 3.5.1.6)), the production of different β-alanine derivatives starting from 5- and 6-monosubstituted dihydrouracils has been evaluated using a mimesis approach. In this work, the S-enantioselective character of dihydropyrimidinase from Sinorizhobium meliloti toward 6-monosubstituted dihydrouracil derivatives has been shown. An inverted R-/S-enantioselectivity of N-carbamoyl-β-alanine amidohydrolase from Agrobacterium tumefaciens toward two different N-carbamoyl-β-amino acids has been proved. Our results have shown for the first time that this mimetic tandem constitutes an interesting biotechnological tool for the preparation of different β-alanine derivatives in an environmentally friendly way, allowing the production of enantioenriched (R)-α-phenyl-β-alanine (e.e. > 95%) and (R)-α-methyl-β-alanine (e.e. > 90%).
Modular Enzymatic Cascade Synthesis of Vitamin B5 and Its Derivatives
Abidin, Mohammad Z.,Saravanan, Thangavelu,Zhang, Jielin,Tepper, Pieter G.,Strauss, Erick,Poelarends, Gerrit J.
, p. 17434 - 17438 (2018)
Access to vitamin B5 [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B5 [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3-dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three-step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL), aspartate-α-decarboxylase (ADC), β-methylaspartate-α-decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B5 and both diastereoisomers of α-methyl-substituted vitamin B5, which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug-resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B5 derivatives by modifying the pantoyl or β-alanine moiety.
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Pollack
, p. 1335 (1943)
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Stereoselective α-alkylation of new chiral auxiliaries: An access to enantiomerically pure α- and α,β-substituted β-amino acids
Agami, Claude,Cheramy, Sandrine,Dechoux, Luc
, p. 1838 - 1840 (1999)
New bicyclic heterocycles 5, which are potentially useful for the enantioselective synthesis of substituted β-amino acids, have been synthesized. A study on the α-alkylation of these chiral auxiliaries is presented. An optically pure β-amino acid was obtained in excellent yield from its masked chiral derivative 6a.
The Formation of Amino Acids by the Reactions of Singlet NH with Several Carboxylic Acids
Tsunashima, Shigeru,Kitamura, Takashi,Sato, Shin
, p. 2869 - 2871 (1981)
The photolysis of hydrogen azide was studied in liquid acetic acid, propionic acid, and isobutyric acid at room temperature.The formation of amino acids was confirmed by the color reactions with ninhydrin and with chromotropic acid and by the NMR spectra.From the propionic acid, α- and β-alanine were formed in the ratio of 1.5.In the case of isobutyric acid, α- and β-aminoisobutyric acids were formed in the ratio of about 5.These results are explained by the insertion reaction of NH(a1Δ) into the C-H bonds of carboxylic acids.
METHODS AND MATERIALS FOR ASSESSING AND TREATING OBESITY
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, (2021/03/13)
This document relates to methods and materials for assessing and/or treating obese mammals (e.g., obese humans). For example, methods and materials for using one or more interventions (e.g., one or more pharmacological interventions) to treat obesity and/or obesity-related comorbidities in a mammal (e.g., a human) identified as being likely to respond to a particular intervention (e.g., a pharmacological intervention) are provided.
β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP
Kosson, Piotr,Lipiński, Piotr F. J.,Misicka, Aleksandra,Tymecka, Dagmara
, (2020/08/11)
TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.