- Synthesis of 2-hydroxy acid from 2-amino acid by Clostridium butyricum
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Cultures of Clostridium butyricum type strain in synthetic medium supplemented with various L-2-amino acids revealed the presence of the corresponding 2-hydroxy acid. This metabolite is able to produce the polyester poly(2-hydroxyalkanoic acid). The bioconversion is not stereoselective since D-2-amino acids were also converted. Chiral GC analysis demonstrated that only D-enantiomer is formed from L-leucine.
- Khelifa, Nasser,Butel, Marie-Jose,Rimbault, Alain
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- Structure revision of isocereulide A, an isoform of the food poisoning emetic Bacillus cereus toxin cereulide
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The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A-G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an L-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESITOF- MS, as well as MSn sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the L-O-Leu as assumed to date, one L-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(D-O-Leu-D-Ala-L-O-Val-L-Val)2(DO- Leu-D-Ala-L-O-Ile-L-Val)].
- Ehling-Schulz, Monika,Hofmann, Thomas F.,Kranzler, Markus,Stark, Timo D.,Walser, Veronika
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supporting information
(2021/05/31)
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- Efficient Synthesis of D-Phenylalanine from L-Phenylalanine via a Tri-Enzymatic Cascade Pathway
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D-phenylalanine is an important intermediate in food and pharmaceutical industries. Here, to enable efficient D-phenylalanine biosynthesis from L-phenylalanine, a tri-enzymatic cascade was designed and reconstructed in vivo. The activity of Proteus vulgaris meso-diaminopimelate dehydrogenase (PvDAPDH) toward phenyl pyruvic acid was identified as the limiting step. To overcome, the tension in the phenyl pyruvic acid side-chain, PvDAPDH was engineered, generating PvDAPDHW121A/R181S/H227I, whose catalytic activity of 6.86 U mg?1 represented an 85-fold increase over PvDAPDH. Introduction of PvDAPDHW121A/R181S/H227I, P. mirabilis L-amino acid deaminase, and Bacillus megaterium glucose dehydrogenase in E. coli enabled the production of 57.8 g L?1 D-phenylalanine in 30 h, the highest titer to date using 60 g L?1 L-phenylalanine as starting substrate, which meant a 96.3 % conversion rate and >99 % enantioselectivity on a 3-L scale. The proposed tri-enzymatic cascade provides a novel potential bio-based approach for industrial production of D-phenylalanine from cheap amino acids.
- Lu, Cui,Zhang, Sheng,Song, Wei,Liu, Jia,Chen, Xiulai,Liu, Liming,Wu, Jing
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p. 3165 - 3173
(2021/06/09)
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- Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis
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Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the calcium channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel. Through genome sequencing and targeted gene disruption, a noniterative nonribosomal peptide synthetase was found to be involved in the biosynthesis of leualacin. A comparison of the structures of leualacin and its analogues indicated that the A2 and A4 domains of the leualacin synthetase are substrate specific, while A1, A3, and A5 can accept alternative precursors to yield new molecules.
- Zhang, Shuwei,Qiu, Yixing,Kakule, Thomas B.,Lu, Zhenyu,Xu, Fuchao,Lamb, John G.,Reilly, Christopher A.,Zheng, Yong,Sham, Shing Wo Simon,Wang, Wei,Xuan, Lijiang,Schmidt, Eric W.,Zhan, Jixun
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p. 363 - 370
(2017/03/08)
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- Asymmetric Assembly of All-Carbon Tertiary/Quaternary Nonadjacent Stereocenters through Organocatalytic Conjugate Addition of α-Cyanoacetates to a Methacrylate Equivalent
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An efficient, highly diastereo- and enantioselective assembly of acyclic carbonyl fragments possessing nonadjacent all-carbon tertiary/quaternary stereoarrays is reported based on a Br?nsted base catalyzed Michael addition/α-protonation sequence involving α-cyanoacetates and 2,4-dimethyl-4-hydroxypenten-3-one as novel methacrylate equivalent.
- Iriarte, Igor,Vera, Silvia,Badiola, Eider,Mielgo, Antonia,Oiarbide, Mikel,García, Jesús M.,Odriozola, José M.,Palomo, Claudio
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supporting information
p. 13690 - 13696
(2016/09/13)
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- Medusamide a, a panamanian cyanobacterial depsipeptide with multiple β-amino acids
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From a collection of marine cyanobacteria made in the Coiba National Park along the Pacific coast of the Republic of Panama a novel cyclic depsipeptide, given the trivial name medusamide A, has been isolated and fully characterized. Medusamide A contains four contiguous β-amino acid (2R,3R)-3-amino-2-methylhexanoic acid (Amha) residues. This is the first report of multiple Amha residues and contiguous β-amino acid residues within a single cyclic peptide-type natural product. Stereochemical assignment of the Amha residues was completed following the synthesis of reference standards for this β-amino acid and the subsequent derivatization with Marfey's reagent and LC-MS analysis.
- Fenner, Amanda M.,Engene, Niclas,Spadafora, Carmenza,Gerwick, William H.,Balunas, Marcy J.
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p. 352 - 355
(2016/02/19)
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- Biocontrolled formal inversion or retention of L -α-amino acids to enantiopure (R)- or (S)-hydroxyacids
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Natural L-α-amino acids and L-norleucine were transformed to the corresponding α-hydroxy acids by formal biocatalytic inversion or retention of absolute configuration. The one-pot transformation was achieved by a concurrent oxidation reduction cascade in aqueous media. A representative panel of enantiopure (R)- and (S)-2-hydroxy acids possessing aliphatic, aromatic and heteroaromatic moieties were isolated in high yield (67-85 %) and enantiopure form (>99 % ee) without requiring chromatographic purification.
- Busto, Eduardo,Grischek, Barbara,Kroutil, Wolfgang,Richter, Nina
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p. 11225 - 11228,4
(2015/01/07)
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- Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides
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The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).
- Kang, Chang Won,Ranatunga, Sujeewa,Sarnowski, Matthew P.,Del Valle, Juan R.
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supporting information
p. 5434 - 5437
(2015/02/19)
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- Photoreaction of rac-Leucine in ice by circularly polarized synchrotron radiation: Temperature-induced mechanism switching from Norrish type II to deamination
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The delivery of extraterrestrial organics to primitive Earth is considered to have triggered the origin and subsequent evolution of life. Indeed, enantiomerically enriched amino acids of nonterrestrial origin have been found in carbonaceous meteorites, and enantioselective photodecomposition by circularly polarized light (CPL) in outer space has been proposed to have played some role in the initial enantiomeric bias. To experimentally examine this possibility and elucidate the photoreaction mechanisms, we have studied the photolysis of racemic leucine (rac-Leu) in acidic and neutral ice/water media at 21-298 K with left- and right-CPL in an attempt to detect enantiomerically enriched D- and L-Leu, respectively. Comprehensive product analyses revealed that the CPL-induced deracemization of Leu proceeds in both acidic and neutral ice matrices even at 21 K, and that the main mechanism switches from Norrish-type II γ-hydrogen abstraction to SNi deamination on lowering the temperature. The potential role of the CPL-induced photodecomposition of amino acids as a source of the enantiomer imbalance in meteorites is discussed. ET arrives! Enantioselective photoreaction of rac-leucine by circularly polarized synchrotron radiation proceeds in both neutral and acidic ices at temperatures down to 21 K, with the main mechanism switching from Norrish type II γ-hydrogen abstraction to SNi deamination by lowering the irradiation temperature (see figure). Copyright
- Nishino, Hideo,Hosaka, Masahito,Katoh, Masahiro,Inoue, Yoshihisa
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p. 13929 - 13936
(2013/10/22)
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- Synthesis, characterization and activity of new phosphonate dipeptides as potential inhibitors of VanX
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VanX, a Zn(II)-dependent D-ala-D-ala dipeptidase, is essential for vancomycin resistance in Enterococcus faecium. The enzymatic activity of VanX was previously found to be inhibited competitively by 2-{[(1-aminoethyl) (hydroxy) phosphoryl]oxy} propanoic acid (1B). Here we report the synthesis and characterization of seven phosphonate dipeptide analogs of D-ala-D-ala with various substituent, the activity evaluation indicated that six of these phosphonate analogs inhibit VanX with IC50 of 0.48-8.21 mM. These data revealed a structure-activity relationship which is that the large substituent group on β-carbon resulted in low binding affinity of the phonphonate analog to VanX. This information will be helpful to guide the design and synthesis of the tightly-binding inhibitors for VanX.
- Jia, Chao,Yang, Ke-Wu,Liu, Cheng-Cheng,Feng, Lei,Xiao, Jian-Min,Zhou, Li-Sheng,Zhang, Yi-Lin
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supporting information; experimental part
p. 482 - 484
(2012/03/11)
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- Cyclodepsipeptides, sesquiterpenoids, and other cytotoxic metabolites from the filamentous fungus Trichothecium sp. (MSX 51320)
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Two new cyclodepsipeptides (1 and 2), two new sesquiterpenoids (3 and 4), and the known compounds guangomide A (5), roseotoxin S, and three simple trichothecenes were isolated from the cytotoxic organic extract of a terrestrial filamentous fungus, Trichothecium sp. The structures were determined using NMR spectroscopy and mass spectrometry. Absolute configurations of the cyclodepsipeptides were established by employing chiral HPLC, while the relative configurations of 3 and 4 were determined via NOESY data. The isolation of guangomide A was of particular interest, since it was reported previously from a marine-derived fungus.
- Sy-Cordero, Arlene A.,Graf, Tyler N.,Adcock, Audrey F.,Kroll, David J.,Shen, Qi,Swanson, Steven M.,Wani, Mansukh C.,Pearce, Cedric J.,Oberlies, Nicholas H.
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experimental part
p. 2137 - 2142
(2011/12/14)
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- Antineoplastic agents. 571. total synthesis of bacillistatin 2
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The first total synthesis of bacillistain 2 (2) has been achieved in 24 steps and 22.9% overall yield, providing a quite efficient route with maximal convergence. Notable features of this approach include two successful applications of the Mitsunobu reaction during respective assemblies of key intermediates 22 and 27, successful employment of 2-methyl- 6-nitrobenzoic anhydride (MNBA) in the formation by lactonization of a macrocyclic (36-membered) ring, and very flexible access to structural modifications of the bacillistatin-type cyclodepsipeptides.
- Pettit, George R.,Hu, Shougang,Knight, John C.,Chapuis, Jean-Charles
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experimental part
p. 372 - 379
(2009/12/06)
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- Antineoplastic agents. 570. isolation and structure elucidation of bacillistatins 1 and 2 from a marine bacillus silvestris
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Two new cyclodepsipeptides designated bacillistatins 1 (1)and2(2) have been isolated from cultures of a sample of Bacillus silvestris that was obtained from a Pacific Ocean (southern Chile) crab. Each 12-unit cyclodepsipeptide strongly inhibited growth of a human cancer cell line panel, with GI 50's of 10-4-10-5 μg/mL, and each compound was active against antibiotic-resistant Streptococcus pneumoniae. The structures were elucidated by a combination of X-ray diffraction and mass and 2D NMR spectroscopic analyses, together with chemical degradation.
- Pettit, George R.,Knight, John C.,Herald, Delbert L.,Pettit, Robin K.,Hogan, Fiona,Mukku, Venugopal J. R. V.,Hamblin, John S.,Dodson II, Michael J.,Chapuis, Jean-Charles
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experimental part
p. 366 - 371
(2009/12/25)
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- QUINAZOLINES USEFUL AS MODULATORS OF ION CHANNELS
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The present invention relates to compounds useful as inhibitors of voltage-gated sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.
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Page/Page column 135
(2008/06/13)
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- Processes for producing 4-aminoquinazolines
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The present invention relates to methods for preparing compounds of formula I: or suitable salts thereof useful as inhibitors of voltage-gated sodium channels and calcium channels. The invention also relates to methods for preparing intermediates related thereto.
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Page/Page column 29
(2008/06/13)
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- Biocatalytic racemization of aliphatic, arylaliphatic, and aromatic α-hydroxycarboxylic acids
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Biocatalytic racemization of a range of aliphatic, (aryl)aliphatic, and aromatic α-hydroxycarboxylic acids was accomplished by using whole resting cells of a range of Lactobacillus spp. The mild (physiological) reaction conditions ensured an essentially "clean" isomerization in the absence of side reactions, such as elimination or decomposition. Whereas straight-chain aliphatic 2-hydroxy-carboxylic acids were racemized with excellent rates (up to 85% relative to lactate), steric hindrance was observed for branched-chain analogues. Good rates were observed for aryl-alkyl derivatives, such as 3-phenyllactic acid (up to 59%) and 4-phenyl-2-hydroxybutanoic acid (up to 47%). In addition, also mandelate and its o-chloro analogue were accepted at a fair rate (45%). This biocatalytic racemization represents an important tool for the deracemization of a number of pharmaceutically important building blocks.
- Glueck, Silvia M.,Pirker, Monika,Nestl, Bettina M.,Ueberbacher, Barbara T.,Larissegger-Schnell, Barbara,Csar, Katrin,Hauer, Bernhard,Stuermer, Rainer,Kroutil, Wolfgang,Faber, Kurt
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p. 4028 - 4032
(2007/10/03)
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- Synthesis and evaluation of backbone/amide-modified analogs of leualacin
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Leualacin (1), a cyclic depsi-pentapeptide, and its backbone/amidemodified analogs 2-4 were synthesized. Amide analogue 3 exhibited stronger vasodilatory effects. It also strongly inhibited collagen- and arachidonic acid (AA)induced platelet aggregations with IC50s of 0.6 μM and 2.0 μM, respectively.
- Hu, Ming-Kuan,Yang, Fu-Chu,Chou, Chi-Cheun,Yen, Mao-Hsiung
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p. 563 - 568
(2007/10/03)
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- Synthesis of 3-alkoxyazetidin-2-ones: Dipeptide mimics
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Several dipeptide mimics, 3-alkoxyazetidin-2-ones, were prepared in a diastereoselective fashion by the direct displacement of a scalemic triflate with 3-hydroxyazetidin-2-ones. The scope and limitation are presented.
- Qabar, Maher N.,Meara, Joseph P.,Ferguson, Mark D.,Lum, Christopher,Kim, Hwa-Ok,Kahn, Michael
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p. 5895 - 5898
(2007/10/03)
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- Enantioselective synthesis of α-hydroxy carboxylic acids: Direct conversion of α-oxocarboxylic acids to enantiomerically enriched α-hydroxy carboxylic acids via neighboring group control
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α-Oxocarboxylic acids can be reduced to the corresponding α-hydroxy carboxylic acids employing DIP-CI(TM) as a reducing agent. The α-carboxylic substituent exerts a remarkable neighboring group effect on the reduction. The reaction presumably proceeds in an intramolecular fashion through a 'rigid' bicyclic transition state assembly, which produces enantioselectivities approaching 99%.
- Wang, Zhe,La, Brittany,Fortunak, Joseph M.,Meng, Xian-Jun,Kabalka, George W.
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p. 5501 - 5504
(2007/10/03)
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- The development of hydrazide γ-Turn mimetics
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Monte Carlo calculations show a classical γ-turn in a family of metabolites known as the malformins. This led to the synthesis of epimeric seven-membered ring γ-turn mimetics starting from leucine. NMR temperature coefficient studies were also performed.
- Ferguson, Mark D.,Meara, Joseph P.,Nakanishi, Hiroshi,Lee, Min S.,Kahna, Michael
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p. 6961 - 6964
(2007/10/03)
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- Pheromone synthesis, CLXXVII: Synthesis of the enantiomers of 2-methyl-4-heptanol and 2-methyl-4-octanol, the pheromone components of the West Indian sugarcane borer
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Both the enantiomers of 2-methyl-4-heptanol (1) and 2-methyl-4-octanol (2), the components of the male-produced aggregation pheromone of the West Indian sugarcane borer (Metamasius hemipterus), were synthesized by starting from the enantiomers of leucine. VCH Verlagsgesellschaft mbH, 1996.
- Takenaka, Motonobu,Takikawa, Hirosato,Mori, Kenji
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p. 1963 - 1964
(2007/10/03)
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- Total synthesis of the cyclic depsipeptide leualacin
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The fungal metabolite leualacin (1), a potent calcium channel antagonist, was synthesized in 15 steps from commercially available amino acids in 25% overall yield using standard solution methods. The synthesis is general and thus would accommodate the incorporation of amino acid replacements as well as the inclusion of peptide mimics and isosteres.
- McLaren
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p. 6082 - 6084
(2007/10/03)
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- Building units for N-backbone cyclic peptides. 2. Synthesis of protected N-(ω-thioalkylene) amino acids and their incorporation into dipeptide units
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A new family of amino acids which contain an ω-thioalkylene group on the N(α)-amino nitrogen was synthesized by alkylation of ω-thioalkylamines with triflates of α-hydroxy acids. The reaction proceeded with inversion of configuration yielding optically pure products. The N(α)-(ω-thioalkylene)amino acids were orthogonally protected to allow their incorporation into peptides by solid-phase peptide synthesis (SPPS) methodology. In addition some of these new protected N(α)-(ω-thioalkylene)amino acids were incorporated into dipeptides by 'solution' techniques.
- Bilan, Gal,Gilon, Chaim
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p. 10513 - 10522
(2007/10/02)
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- Matrix metalloproteinase inhibitors containing a (carboxyalkyl)amino zinc ligand: Modification of the P1 and P2' residues
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Systematic modification of the presumed P1 side chain in a series of (carboxyalkyl)amino-based inhibitors of matrix metalloproteinases enabled identification of the 2-(1,3-dihydro-1,3-dioxo-2H-benz[f]isoindol-2-yl)ethyl group as a preferred substituent imparting potent inhibition of the enzymes collagenase and gelatinase. It was subsequently found that the P2'-P3' residues in this series could be replaced by small non-peptide residues, while maintaining inhibitory potency. The imide group in this series of compounds can undergo autocatalytic hydrolysis under neutral conditions.
- Brown,Brown,Bickett,Chambers,Davies,Deaton,Drewry,Foley,McElroy,Gregson,McGeehan,Myers,Norton,Salovich,Schoenen,Ward
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p. 674 - 688
(2007/10/02)
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- Synthesis of (15)N-Labelled Chiral Boc-Amino Acids from Triflates: Enantiomers of Leucine and Phenylalanine
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An efficient synthesis of (15)N-labelled chiral Boc-amino acids by triflate alkylation of di-tert-butyl iminodicarbonate is reported.Both enantiomers of Boc-Leucine and -phenylalanine were synthesized from commercial α-amino acids of opposite configuration via α-hydroxy carboxylic acids provided by diazotization, thus extending the scope of an earlier exploratory study.The high chiral purity of the final products was confirmed by HPLC.These labelled amino acid derivatives are suitable for direct application to the synthesis of labelled peptides.
- Degerbeck, Fredrik,Fransson, Bengt,Grehn, Leif,Ragnarsson, Ulf
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- A Novel Highly Diastereoselective Synthesis of Cyano Esters by Regioselective Ring Opening of Chiral Oxazolidinium Methiodides with Sodium Cyanide
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Sodium cyanide reacts with chiral oxazolidinium methiodides, prepared by quaternization of oxazolidines with methyl iodide, leading regio- and stereoselectively (d.e. 82-94percent) to cyano esters in moderate to good chemical yields (51-95percent).The open compounds are isolated as a pure diastereomer by a single recrystallization of their ammonium methiodides, and converted into enantiomerically pure α-hydroxy acids by heating with a concentrated solution of hydrochloric acid. - Key words: Chiral Oxazolidinium Iodides; alpha-Cyano ethers, Diastereoselective Ring Opening; alpha-Hydroxy Acids; Asymmetric Synthesis.
- Andres, Celia,Delgado, Manuel,Pedrosa, Rafael,Rodriquez, Raquel
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p. 8325 - 8328
(2007/10/02)
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- Catalytic asymmetric glyoxylate-ene reaction: A practical access to α-hydroxy esters in high enantiomeric purities
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An efficient asymmetric catalysis is developed for the glyoxylate-ene reaction to afford the α-hydroxy esters of biological and synthetic importance. The key to the success is the use of the chiral titanium complex prepared in situ from (i-PrO)2TiX2 (X = Cl or Br) and the (R)- or (S)-binaphthol in the presence of molecular sieves (MS 4A). The presence of the molecular sieves (zeolite) is clarified to facilitate the alkoxy-ligand exchange reaction. Thus, the use of MS is shown to be essential for the in situ preparation step of the chiral catalyst and not for the ene reaction step. The present catalytic process is applicable to various 1,1-disubstituted olefins by the judicious choice of the dichloro or dibromo catalyst.
- Mikami, Koichi,Terada, Masahiro,Nakai, Takeshi
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p. 3949 - 3954
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF D-α-HYDROXY CARBOXYLIC ACIDS FROM L-AMINO ACIDS
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Optically active D-α-hydroxy carboxylic acids are obtained from L-amino acids via L-α-halocarboxylic acids and their stereoselective reaction with cesium p-nitrobenzoate.
- Kunz, Horst,Lerchen, Hans-Georg
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p. 1873 - 1876
(2007/10/02)
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- Enzymatic Synthesis of Optically Pure (R)-(-)-Mandelic Acid and Other 2-Hydroxycarboxylic Acids: Screening for the Enzyme, and Its Purification, Characterization and Use
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An enzyme that reduces benzoylformate with NADH to form (R)-mandelate was extracted from cells of Streptococcus faecalis IFO 12964 and purified to more than 95percent purity as evidenced by gel electrophoresis.Physicochemical and enzymic properties were studied.From the substrate specificity, we concluded that the enzyme was a kind of (R)-2-hydroxyisocaproate dehydrogenase.Optically pure (R)-(-)-mandelic acid was prepared with the enzyme, NADH, and alcohol, formate or glucose dehydrogenase in 84 ca. 93percent yield.Five (R)-2-hydroxyalkanoic acids (C4 - C6) or their Ba salts, (R)-(+)-3-phenyllactic acid and (S)-(-)-3-chlorolactic acid were also prepared with the enzyme.
- Yamazaki, Yoshimitsu,Maeda, Hidekatsu
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p. 2621 - 2632
(2007/10/02)
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- A SYNTHON FOR CHIRAL GLYCOLATE ENOLATE (ROC-HCOOR'): A CAMPHOR-BASED OXAZOLINE
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Alkylations of the anion (7a) derived from a camphor-based oxazoline proceed in good yield.Hydrolysis affords the corresponding α-hydroxy acids in high ee.
- Kelly, T. Ross,Arvanitis, Argyrios
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- N-(α-Hydroxyalkanoyl) Derivatives of Leu-Val-Phe-OCH3 as Inhibitors of Renin
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The following N-(α-hydroxyalkanoyl) derivatives of Leu-Val-Phe-OCH3 were synthesized and tested for their ability to inhibit human amniotic renin: D- and L-α-hydroxyisocaproyl-Leu-Val-Phe-OCH3, D- and L-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3, L-2-hydroxy-3-phenylpropanoyl-Leu-Val-Phe-OCH3, and D- and L-α-hydroxyphenylacetyl-Leu-Val-Phe-OCH3.Analysis of the compounds through the use of Dixon plots showed all of the compounds to be competitive inhibitors of renin.All but D-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3 were found to be more active than the known tetrapeptideinhibitor Leu-Leu-Val-Phe-OCH3 (1).The two most active compounds of the series were L-α-hydroxyisocaproyl-Leu-Val-Phe-OCH3 (Ki = 0.23 mM) and L-α-hydroxyisovaleryl-Leu-Val-Phe-OCH3 (Ki = 0.3 mM).
- Johnson, Rodney L.
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p. 666 - 669
(2007/10/02)
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