147-85-3Relevant articles and documents
Optical resolution, characterization, and X-ray crystal structures of diastereomeric salts of chiral amino acids with (S)-(-)-1-phenylethanesulfonic acid
Yoshioka,Ohtsuki,Da-Te,Okamura,Senuma
, p. 3012 - 3020 (1994)
Ten DL-Amino acids (AA), including neutral, and basic amino acids, and an imino acid, were optically resolved, without derivatization into their covalent compounds, by means of fractional crystallization of their diastereomeric salts with (-)-1-phenylethanesulfonic acid (PES) in various solvents. Several pairs of the diastereomeric crystalline salts formed during the resolutions were analyzed by DSC and spectroscopy, which showed that the successful resolutions were attributable to differences in various physicochemical properties between the more-soluble D-AA · (-)-PES and less-soluble L-AA · (-)-PES. Chiral recognition of the most successfully resolved species, DL-p-hydroxyphenylglycine (HPG) salt, was explored by comparing the X-ray crystal structures of D- and L-HPG · (-)-PES. The two crystal structures differed obviously in their hydrogen-bonding networks: the less-soluble L-HPG · (-)-PES only had strong hydrogen-bonded infinite chains of HPG in a 'head-to-tail' arrangement through the p-hydroxyl group, the structure of which was more geometrically stable than that of the more-soluble D-HPG · (-)-PES. The differences in the two crystal structures related to striking differences in their solubilities and thermal properties.
Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium
Al-Awadhi, Fatma H.,Ratnayake, Ranjala,Paul, Valerie J.,Luesch, Hendrik
, p. 3276 - 3282 (2016)
In search of novel protease inhibitors with therapeutic potential, our efforts exploring the marine cyanobacterium Lyngbya sp. have led to the discovery of tasiamide F (1), which is an analogue of tasiamide B (2). The structure was elucidated using a combination of NMR spectroscopy and mass spectrometry. The key structural feature in 1 is the presence of the Phe-derived statine core, which contributes to its aspartic protease inhibitory activity. The antiproteolytic activity of 1 and 2 was evaluated in vitro against cathepsins D and E, and BACE1. Tasiamide F (1) displayed IC50values of 57?nM, 23?nM, and 0.69?μM, respectively, indicating greater selectivity for cathepsins over BACE1 compared with tasiamide B (2). Molecular docking experiments were carried out for compounds 1 and 2 against cathepsins D and E to rationalize their activity towards these proteases. The dysregulated activities of cathepsins D and E have been implicated in cancer and modulation of immune responses, respectively, and these proteases represent potential therapeutic targets.
The relative catalytic efficiency of β-lactamase catalyzed acyl and phosphyl transfer
Slater, Martin J.,Laws, Andrew P.,Page, Michael I.
, p. 77 - 95 (2001)
Phosphonamidates which bear a simple resemblance to penicillin type structures have been synthesised as potential inhibitors of β-lactamases: -ethyl N-(benzyloxycarbonyl) amidomethyl phosphonyl amides, PhCH2OCONHCH2P(O)(OEt)NR2, the amines HNR2 being L-proline, D-proline, L-thiazolidine, and o-anthranilic acid. The proline derivatives completely and irreversibly inactivated the class C β-lactamase from Enterobacter cloacae P99, in a time-dependent manner, indicative of covalent inhibition. The inactivation was found to be exclusive to the class C enzyme and no significant inhibition was observed with any other class of β-lactamase. The anthranilic acid derivative exhibited no appreciable inactivation of the β-lactamases. The phosphonyl proline and phosphonyl thioproline derivatives were separated into their diastereoisomers and their individual second order rate constants for inhibition were found to be 7.72 ± 0.37 and 8.3 × 10-2 ± 0.004 M-1 s-1 for the L-proline derivatives, at pH 7.0. The products of the inhibition reaction of each individual diastereoisomer, analyzed by electrospray mass spectroscopy, indicate that the more reactive diastereoisomers phosphonylate the enzyme by P-N bond fission with the elimination of proline. Conversely, gas chromatographic detection of ethanol release by the less reactive proline diastereoisomer suggests phosphonylation occurs by P-O bond fission. The enzyme enhances the rate of phosphonylation with P-N fission by at least 106 compared with that effected by hydroxide-ion. The pH dependence of the rate of inhibition of the β-lactamase by the more reactive diasteroisomer is consistent with the reaction of the diprotonated form of the enzyme, EH2, with the inhibitor, I (or its kinetic equivalents EH with IH). This pH dependence and the rate enhancement indicate that the enzyme appears to use the same catalytic apparatus for phosphonylation as that used for hydrolysis of β-lactams. The stereochemical consequences of nucleophilic displacement at the phosphonyl centre are discussed.
Cyclopentapeptides from Dianthus chinensis
Han, Jing,Huang, Maobo,Wang, Zhe,Zheng, Yuqing,Zeng, Guangzhi,He, Wenjun,Tan, Ninghua
, p. 550 - 553 (2015)
A new cyclopentapeptide dianthin I (1), together with two known ones pseudostellarin A (2) and heterophyllin J (3), was isolated from the aerial parts of Dianthus chinensis. The structure of 1 was elucidated as cyclo-(Gly1- l-Phe2- l-Pro3- l-Ser4- l-Phe5) on the basis of extensive spectroscopic analyses and chemical methods.
Viridamides A and B, lipodepsipeptides with antiprotozoal activity from the marine cyanobacterium Oscillatoria nigro-viridis
Simmons, T. Luke,Engene, Niclas,Urena, Luis David,Romero, Luz I.,Ortega-Barria, Eduardo,Gerwick, Lena,Gerwick, William H.
, p. 1544 - 1550 (2008)
Parallel chemical and phylogenetic investigation of a marine cyanobacterium from Panama led to the isolation of two new PKS-NRPS-derived compounds, viridamides A and B. Their structures were determined by NMR and mass spectroscopic methods, and the absolute configurations assigned by Marfey's method and chiral HPLC analysis. In addition to six standard, N-methylated amino and hydroxy acids, these metabolites contained the structurally novel 5-methoxydec-9-ynoic acid moiety and an unusual proline methyl ester terminus. Morphologically, this cyanobacterium was identified as Oscillatoria nigro-viridis, and its 16S rDNA sequence is reported here for the first time. Phylogenetic analysis of these sequence data has identified O. nigro-viridis strain OSC3L to be closely related to two other marine cyanobacterial genera, Trichodesmium and Blennothrix. Viridamide A showed antitrypanosomal activity with an IC50 of 1.1 μM and antileishmanial activity with an IC50 of 1.5 μM.
Structure of the Antifungal Nucleotide Antibiotic Phosmidosine
Phillips, Dennis R.,Uramoto, Masakazu,Isono, Kiyoshi,McCloskey, James A.
, p. 854 - 859 (1993)
The structure of phosmidosine (1), a novel proline-containing nucleotide antibiotic from Streptomyces durhameusis, active against the pathogenic fungus Botrytis cinerea, was determined by mass spectrometry and NMR spectroscopy.Homologs 2, 3, and the isomer 4 were detected and characterized using approaches based principally on tandem mass spectrometry and combined liquid chromatography-mass spectrometry which permitted assignment of most structural features directly in the crude isolate without prior isolation of individual components.Conversion of 1-4 to the O-isopropylidene derivatives 1a-4a by a microscale procedure resulted in enhanced fast atom bombardment ionization (FAB) signal to background sensitivity.Collision-induced dissociation mass spectra were aquired from molecular ions and ion source-generated fragment ions and used in conjunction with FAB-deuterium exchange methods for the assignment of structural differences between 1a-4a.
Structures and solution conformational dynamics of stylissamides G and H from the Bahamian Sponge Stylissa caribica
Wang, Xiao,Morinaka, Brandon I.,Molinski, Tadeusz F.
, p. 625 - 630 (2014)
Two new peptides, stylissamides G and H, were isolated from extracts of a sample of Stylissa caribica collected in deep waters of the Caribbean Sea. A single sample of S. caribica among a collection of 10 samples that were examined by LC-MS appeared to be a different chemotype from the others in that it lacked the familiar pyrrole-2-aminoimidazole alkaloids, stevensine and oroidin, and contained peptides of the stylissamide class. The structures of the title compounds were solved by integrated analysis of the MS and NMR spectra and chemical degradation. The solution conformation of stylissamide G was briefly examined by electronic circular dichroism and temperature-dependent 1H NMR chemical shifts of amide NH signals, which supported a conformationally rigid macrocycle.
Kinetics and mechanism of oxidation of captopril by diperiodatocuprate(III) in aqueous alkaline medium
Angadi, Mahantesh A.,Tuwar, Suresh M.
, p. 219 - 229 (2015)
Captopril is a sulfur containing drug which inhibits angiotensin-converting enzyme. Its kinetics of oxidation were studied spectrophotometrically using diperiodatocuprate(III) in aqueous alkali. Major oxidative product of captopril was identified as captopril disulfide along with trace amount of the hydrolyzed product, l-proline. Kinetics of oxidation was found to be first order each in [oxidant] and [reductant]. Rate of reaction was decreased by increasing [OH-], whereas added periodate retarded the rate. Other kinetic parameters viz., ionic strength, dielectric constant, temperature effect, and intervention of free radical were also studied. Activation parameters like EA, ΔH#, ΔS#, ΔG #, and log A were calculated. A suitable mechanism was proposed. Rate law for proposed mechanism was derived and verified. Reaction constants involved in various steps of mechanism were evaluated and used to regenerate first-order experimental rate constants at various experimental conditions.
Heterogeneous Asymmetric Hydrogenation of a Chiral Tripeptide containing Dehydroalanine and α,β-Dehydrobutyrine Residues
Takasaki, Michiaki,Harada, Kaoru
, p. 571 - 573 (1987)
The heterogeneous asymmetric hydrogenation of a linear tripeptide containing dehydroalanine and α,β-dehydrobutyrine has been carried out, giving asymmetric yields of alanine and butyrine of 94 and 54percent, respectively.
Enantioselective Enzymatic Cleavage of N-Benzyloxycarbonyl Groups
Patel, Ramesh N.,Nanduri, Venkata,Brzozowski, David,McNamee, Clyde,Banerjee, Amit
, p. 830 - 834 (2003)
A new enzymatic process for the enantioselective cleavage of N-benzyloxycarbonyl (Cbz) groups from protected amino acids and related compounds has been developed. The Cbz-deprotecting enzyme was isolated from cell extracts of Sphingomonas paucimobilis SC 16113 and purified to homogeneity. The purified protein has a molecular weight of 155,000 daltons and a subunit size of 44,000 daltons.
