6027-21-0Relevant articles and documents
Combining Aldolases and Transaminases for the Synthesis of 2-Amino-4-hydroxybutanoic Acid
Hernandez, Karel,Bujons, Jordi,Joglar, Jesús,Charnock, Simon J.,Domínguez De María, Pablo,Fessner, Wolf Dieter,Clapés, Pere
, p. 1707 - 1711 (2017/08/15)
Amino acids are of paramount importance as chiral building blocks of life, for drug development in modern medicinal chemistry, and for the manufacture of industrial products. In this work, the stereoselective synthesis of (S)- and (R)-2-amino-4-hydroxybutanoic acid was accomplished using a systems biocatalysis approach comprising a biocatalytic one-pot cyclic cascade by coupling of an aldol reaction with an ensuing stereoselective transamination. A class II pyruvate aldolase from E. coli, expressed as a soluble fusion protein, in tandem with either an S- or R-selective, pyridoxal phosphate dependent transaminase was used as a catalyst to realize the conversion, with formaldehyde and alanine being the sole starting materials. Interestingly, the class II pyruvate aldolase was found to tolerate formaldehyde concentrations of up to 1.4 M. The cascade system was found to reach product concentrations for (S)- or (R)-2-amino-4-hydroxybutanoic acid of at least 0.4 M, rendering yields between 86% and >95%, respectively, productivities of >80 g L-1 d-1, and ee values of >99%.
Deracemization of amino acids by coupling transaminases of opposite stereoselectivity
Park, Eul-Soo,Shin, Jong-Shik
, p. 3505 - 3509 (2015/02/19)
Biocatalytic deracemization of amino acids without relying on oxidase-based deamination of an unwanted enantiomer was demonstrated by coupling a-and w-transaminases displaying opposite stereoselectivity. This strategy employs isopropylamine and a keto acid as cosubstrates and is free of generation of hydrogen peroxide which is troublesome in the conventional oxidase-based methods.
Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography
Prasad, Vysakh Pushpa,Wagner, Stefan,Keul, Petra,Hermann, Sven,Levkau, Bodo,Sch?fers, Michael,Haufe, Günter
, p. 5168 - 5181 (2015/02/19)
Sphingosine-1-phosphate (S1P) receptors play major roles in cardiovascular, immunological and neurological diseases. The recent approval of the sphingolipid drug Fingolimod (Gilenya), a sphingosine-1-phosphate agonist for relapsing multiple sclerosis, in 2010 exemplifies the potential for targeting sphingolipids for the treatment of human disorders. Moreover, non-invasive in vivo imaging of S1P receptors that are not available till now would contribute to the understanding of their role in specific pathologies and is therefore of preclinical interest. Based on fluorinated analogues of the S1P1receptor antagonist W146 showing practically equal in vitro potency as the lead structure, the first S1P receptor antagonist [18F]-radiotracer has been synthesized and tested for in vivo imaging of the S1P1receptor using positron emission tomography (PET). Though the tracer is serum stable, initial in vivo images show fast metabolism and subsequent accumulation of free [18F]fluoride in the bones.
Chemical approach for interconversion of (S)- and (R)-α-amino acids
Sorochinsky, Alexander E.,Ueki, Hisanori,Ace?a, José Luis,Ellis, Trevor K.,Moriwaki, Hiroki,Sato, Tatsunori,Soloshonok, Vadim A.
, p. 4503 - 4507 (2013/08/23)
Here we report a general method for the preparation of unnatural (R)-α-amino acids via complexation of α-(phenyl)ethylamine derived chiral reagent (S)-3 with various (S)-α-amino acids. The reactions proceed with synthetically useful chemical yields and thermodynamically controlled diastereoselectivity. Chiral reagent (S)-3 can be conveniently recovered and reused without any loss of enantiomeric purity and reactivity. The Royal Society of Chemistry 2013.
PROCESSES FOR PREPARING AMINO-SUBSTITUTED GAMMA-LACTAMS
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Page/Page column 27; 28, (2010/10/03)
The present application describes general process for the preparation of amino-substitued gamma-lactams involving the reaction of synthons of the general Formulae (I) and (VI): with amines. The processes are amenable to solid phase synthetic techniques and therefore allow the efficient incorporation of amino-substitued gamma-lactams into a wide variety of structural scaffolds, including, in particular peptides.
Structure of the O-antigen of Acinetobacter lwoffii EK30A; Identification of d-homoserine, a novel non-sugar component of bacterial polysaccharides
Arbatsky, Nikolay P.,Kondakova, Anna N.,Shashkov, Alexander S.,Drutskaya, Marina S.,Belousov, Pavel V.,Nedospasov, Sergei A.,Petrova, Mayya A.,Knirel, Yuriy A.
experimental part, p. 3571 - 3577 (2010/08/21)
We established a peculiar structure of the O-specific polysaccharide (O-antigen) of a psychrotrophic strain of Acinetobacter lwoffii, EK30A, isolated from a 1.6-1.8 million-year-old Siberian permafrost subsoil sediment sample. The polysaccharide was released by mild acid degradation of the lipopolysaccharide and studied using chemical analyses, Smith degradation, 1H and 13C NMR spectroscopy and mass spectrometry. It was found to contain d-homoserine, which is N-linked to 4-amino-4,6-dideoxy-d- glucose (Qui4N) and is N-acylated itself with acetyl in about half of the repeating units or (S)-3-hydroxybutanoyl group in the other half. The following is the structure of the tetrasaccharide repeating unit of the polysaccharide: →3)-β-d-Quip4NAcyl-(1→6)-α-d-Galp-(1→4) -α-d-GalpNAc-(1→3)-α-d-FucpNAc-(1→ where Acyl stands for either N-acetyl- or N-[(S)-3-hydroxybutanoyl]-d-homoseryl. The Royal Society of Chemistry 2010.
Positional scanning for peptide secondary structure by systematic solid-phase synthesis of amino lactam peptides
Jamieson, Andrew G.,Boutard, Nicolas,Beauregard, Kim,Bodas, Mandar S.,Ong, Huy,et al.
supporting information; experimental part, p. 7917 - 7927 (2009/10/16)
Incorporation of amino lactams into biologically active peptides has been commonly used to restrict conformational mobility, enhance selectivity, and increase potency. A solid-phase method using a Fmoc-protection strategy has been developed for the systematic synthesis of peptides containing configurationally defined α- and β-amino γ-lactams. N-Alkylation of N-silyl peptides with five- and six-member cyclic sulfamidates 9 and 8 minimized bis-alkylation and provided N-alkyl peptides,which underwent lactam annulation under microwave heating. Employing th is solid-phase protocol on the growth hormone secretagogue GHRP-6, as well as on the allosteric modulator of the IL-1 receptor 101.10, has furnished 16 lactam derivatives and validated the effectiveness of this approach on peptides bearing aliphatic, aromatic, branched, charged, and heteroatomic side chains. The binding affinity IC 50 values of the GHRP-6 lactam analogues on both the GHS-R1a and CD36 receptors are reported as well as inhibition of thymocyte proliferation measurements for the 101.10 lactam analogues. In these cases, lactam analogues were prepared exhibiting similar or improved properties compared with the parent peptide. Considering the potential for amino lactams to induce peptide turn conformations, the effective method described herein for their supported construction on growing peptides, and for the systematical amino lactam scan of peptides, has proven useful for the rapid identification of the secondary structure necessary for peptide biological activity.
Isoxazolinium salts in asymmetric synthesis. 1. Stereoselective reduction induced by a 3′-alkoxy stereocentre. A new approach to polyfunctionalized β-amino acids
Henneb?hle, Marco,Le Roy, Pierre-Yves,Hein, Matthias,Ehrler, Rudolf,J?ger, Volker
, p. 451 - 467 (2007/10/03)
A new approach to optically active N-methylamino acids is presented, relying on stereoselective reduction of N-methylisoxazolinium salts with a dioxyethyl side-chain. The diastereoselectivity of the reduction step is studied systematically, in comparison with that of respective isoxazolines. A two-step transformation of isoxazolinium salts - with NaBH3(OAc) and subsequent catalytic hydrogenation as well as a one-pot reduction by catalytic hydrogenation led to high (95:5 and 87:13) diastereomeric ratios of protected erythro-N-methylaminopentanetriols. The hydroxyethyl side-chain is elaborated by oxidation to afford the β-N-methylamino acid 37, exemplifying the potential of this strategy.
Reversal of diastereofacial selectivity in the nucleophilic addition reaction to chiral N-sulfinimine and application to the synthesis of indrizidine 223AB
Koriyama, Yuji,Nozawa, Akihiro,Hayakawa, Ryuuichirou,Shimizu, Makoto
, p. 9621 - 9628 (2007/10/03)
Diastereoselective addition reaction of ester enolates and Grignard reagents to optically active N-sulfinimines was examined. Reversal of the diastereofacial selectivity was realized by using appropriate metal species, solvents and additives, and the β-amino esters (up to >98% de) and the homoallylic amines (up to >98% de) were obtained in good yields. β-Amino esters thus obtained were converted to the useful β-amino acids involving (R)-homoserine. Application to the synthesis of indrizidine alkaloids was also described.
Optical resolution by preferential crystallization of (RS)-α-amino-γ-butyrolactone hydrochloride
Shiraiwa, Tadashi,Miyazaki, Hideya,Ohta, Atsushi,Waki, Yukitaka,Yasuda, Masahiro,Morishita, Toshimitsu,Kurokawa, Hidemoto
, p. 2322 - 2325 (2007/10/03)
(RS)-α-Amino-γ-butyrolactone hydrochloride [(RS)-ABL·HCl] was found to exist as a conglomerate based on the infrared spectrum, solubility, and melting point. Optical resolution by preferential crystallization of (RS)-ABL·HCl was achieved to yield (R)- and (S)-ABL·HCl. The obtained (R)- and (S)-ABL·HCl were recrystallized, taking into account the solubility of (RS)-ABL·HCl to give optically pure (R)- and (S)-ABL·HCl.
