2(S),3(S)-3-hydroxy-4-methyleneglutamic Acid from Gleditsia caspica

A new natural product, 2(S),3(S)-3-hydroxy-4-methyleneglutamic acid (G3) has been isolated from seeds of Gleditsia caspica. The structure has been established by chemical and spectroscopic methods. Catalytic reduction of G3 yields 2(S),4(S)-4-methylglutamic acid and a new amino acid, 2(S),3(S),4(S)-3-hydroxy-4-methylglutamic acid. Ozonolysis of G3 followed by oxidation gives 2(S),3(R)-3-hydroxyaspartic acid. The S- (or l-) configurations at C₂ in G3 and in 2(S),3(S),4(S)-3-hydroxy-4-methyglutamic acid and the S-configurations at C₃ for G3 and 2(S),3(S),4(S)-3-hydroxy-4-methylglutamic acid and at C₄ for 2(S),3(S),4(S)-3-hydroxy-4-methylglutamic acid are inferred from the configurations at C₂ in 2(_S),4(_S)-4-methylglutamic acid and at C₂ and C₃ in 2(S),3(R)-3-hydroxyaspartic acid. The seeds also contain appreciable quantities of 2(S),3(S),4(R)-3-hydroxy-4-methylglutami c acid (G1) and 2(S),4(R)-4-methylglutamic acid.     

Hydrothermal synthesis and characterization of a zinc-substituted gallium phosphite, [H3N(CH2)2NH3]1/2 · [GaZn(HPO3)3(H2O)2]

An organically templated zinc-substituted gallium phosphite, [H₃N(CH₂)₂NH₃]_1/2 · [GaZn(HPO₃)₃(H₂O)₂] was synthesized under mild hydrothermal conditions in the presence of ethylenediamine (en) as structure-directing agent and characterized by single-crystal X-ray diffraction analysis. It crystallizes in the orthorhombic space group Pbcn with unit cell parameters: a = 18.6146(10) Å, b = 11.0454(6) Å, c = 10.9074(4) Å, V = 2242.62(19) Å³ and Z = 8. This compound has a three-dimensional framework built up from secondary building units (SBU) of Ga(III) (or Zn(II)) and HPO₃ pseudopyramid by sharing vertices. The structure displays a two-dimensional channel system running along the [0 0 1] and [0 1 0] direction with 5-, 8- and 10-membered rings. The diprotonated ethylenediamine template molecules are located in the channels. In this structure, some of the Ga(III) sites are occupied by Zn(II) atoms. The compound was also characterized by IR spectroscopy, inductively coupled plasma (ICP), X-ray photoelectron spectra (XPS), differential thermal and thermogravimetric analyses.     

Ureidosuccinic acid permeation in Saccharomyces cerevisiae

Some strains of Saccharomyces cerevisiae exhibit a specific transport system for ureidosuccinic acid, which is regulated by nitrogen metabolism. Ureidosuccinic acid uptake occurs with proline but with ammonium sulfate as nitrogen source it is inhibited. The V for transport is 20–25 μmol/ml cell water per min. The apparent K_m is 3 · 10^-5. For the urep1 mutant (ureidosuccinic acid permease less) the internal concentration never exceeds the external one.In the permease plus strain ureidosuccinic acid can be concentrated up to 10 000 fold and the accumulated compound remains unchanged in the cells. Energy poisons such as dinitrophenol, carbonyl cyanide-m-chlorophenyl-drazone (CCCP) or NaN₃ inhibit the uptake. No significant efflux of the accumulated compound occurs even in the presence of these drugs.The specificity of the permease is very strict, only amino acids carrying an α-N-carbamyl group are strongly competitive inhibitors.The high concentration capacity of the cells and the lack of active exit of the accumulated compound support the hypothesis of a carrier mediated active transport system.     

E-2(S)-amino-3-methyl-3-pentenoic acid from coniogramme intermedia

A new amino acid, E-2(S)-amino-3-methyl-3-pentenoic acid was isolated from Coniogramme intermedia. The structure was elucidated by elementary analysis, optical rotation, catalytic hydrogenation, ¹H and ¹³C NMR spectra.     

Ascorbalamic acid: An ascorbigen-like plant constituent yielding in hot acid 3-(2-furoyl)alanine

Ascorbalamic acid (C₉H₁₃NO₈) was isolated from Brassica olerocea L. MS study of various methylated derivatives suggested a structure (Ia) derivable by CC coupling of C-3 of alanine with C-2 of ascorbic acid, followed by lactone → lactam rearrangement. Other derivatives provided supporting evidence, as did study of the reaction of L-3-chloroalanine with L-ascorbic acid in vitro. On treatment with hot 6 M HCl, ascorbalamic acid yielded L-aspartic acid and 3-(2-furoyl)alanine. For identification of the latter, DL-3-(2-furoyl)alanine and its N-2,4-dinitrophenyl and N-acetyl methyl ester derivatives were synthesized. Unlike ascorbigens, ascorbalamic acid is probably present in the living plant. It seemed to be present in all crucifers examined, but to have a capricious distribution in other orders. During permethylation, rearrangements of ester groups were observed, both with ascorbalamic acid and with pyrrolidonecarboxylic acid as a model.     

Discovery of (E)-1-amino-4-phenylbut-3-en-2-ol derivatives as novel neuraminidase inhibitors

Neuraminidase has been considered as an important target for designing agents against influenza viruses. In a discovery of anti-influenza agents with epigoitrin as the initial lead compound, a series of 1-amino-2-alkanols were synthesized and biologically evaluated. The in vitro evaluation indicated that (E)-1-amino-4-phenylbut-3-en-2-ol (C1) had better inhibitory activities than 2-amino-1-arylethan-1-ol derivatives. To our surprise, sulfonation of C1 with 4-methoxybenzenesulfonyl chloride afforded more active inhibitor II with up to 6.4?μM IC₅₀ value against neuraminidase. Furthermore, docking of inhibitor II into the active site of NA found that the H atoms in both NH₂ and OH groups of inhibitor II were the key factors for potency. Molecular docking research did not explained very well the observed structure-activity relationship (SAR) from amino acid residue level, but also aided the discovery of (E)-1-amino-4-phenylbut-3-en-2-ol derivatives as novel and potent NA inhibitors.     

The reaction of the cis-dioxorhenium(V) core with N,O-donor ligands: mono and bidentate coordination of 3-methyl-2-aminophenol

The reaction of cis-[ReO₂I(PPh₃)₂] with 3-methyl-2-aminophenol (H₂map) in ethanol led to the formation of trans-[Re(map)(Hmap)I(PPh₃)₂]I. The X-ray crystal structure shows that the ligand map is coordinated monodentately through the doubly deprotonated amino nitrogen and is therefore present as an imide. The chelate Hmap is coordinated via the neutral amino nitrogen and the singly deprotonated phenolate oxygen, which is coordinated trans to the imido nitrogen. In benzene equimolar quantities of cis-[ReO₂I(PPh₃)₂] and 4-methyl-2-aminophenol (H₂amp) produced the five-coordinate cis-[ReO₂(Hamp)(PPh₃)]. A twofold molar excess of 2-aminophenol (H₂ap) yielded the six-coordinate [ReO(Hap)(ap)(PPh₃)]. The chelate ap is coordinated through the deprotonated phenolate oxygen and the singly deprotonated amino nitrogen (amide).     

3-[2-Amino-2-imidazolin-4(5)-yl]alanine (enduracididine) and 2-[2-amino-2-imidazolin-4(5)-yl] acetic acid in seeds of Lonchocarpus sericeus

3-[2-Amino-2-imidazolin-4(5)-yl]alanine (enduracididine) and 2-[2-amino-2-imidazolin-4(5)-yl] acetic acid have been isolated from seeds of Lonchocarpus sericeus. The concentration of each compound was ca 0.5 % of the fresh seed weight.     

Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib’s core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC₅₀ 11, 2.4?×?10², 2.8?×?10³, and 1.1?×?10²?nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.     

Identification of (S)-11-cycloheptyl-4-methylundecanoic acid in acylphosphatidylglycerol from Alicyclobacillus acidoterrestris

A method is described for the identification of molecular species of acylphosphatidylglycerols containing a branched cyclo fatty acid ((S)-11-cycloheptyl-4-methylundecanoic acid; brc19:0) from Alicyclobacillus acidoterrestris and its identification as picolinyl ester by means of GC-MS. The combination of TLC, negative RP-HPLC-ESI-MS/MS, enzymatic hydrolysis, and GC-MS was used to identify unusual molecular species of acylphosphatidylglycerols with cyclic and branched FA. The acid, brc19:0, was also synthesized to unambiguously confirm its structure. According to feeding experiments with ¹³C-labeled propionate, the C₃ internal unit (branched methyl) of brc19:0 is assembled from propionate and not from methionine.     

Acide 2(R)-amino-3-butenoique (vinylglycine) dans les carpophores de Rhodophyllus nidorosus

2(R)-amino-3-butenoic acid (vinylglycine), the simplest β,γ-unsaturated α-amino acid, has been isolated from the mushroom Rhodophyllus nidorosus (Fr.) Quél. The amino acid occurs as partly racemized d-form. The structure has been confirmed by comparison with synthetic material.     

4-Carboxy-4-hydroxy-2-aminoadipic acid and other acidic amino acids in Caylusea abyssinica

Two diastereoisomers of 4-carboxy-4-hydroxy-2-aminoadipic acid have been isolated from leaves and inflorescences of Caylusea abyssinica. Green parts of the plant also contain appreciable amounts of the two diastereoisomers of 4-hydroxy-4-methylglutamic acid, 3-(3-carboxyphenyl)alanine, (3-carboxyphenyl)glycine, 3-(3-carboxy-4-hydroxyphenyl)alanine, (3-carboxy-4-hydroxyphenyl)glycine and in low concentration 2-aminoadipic acid, saccharopine [(2S, 2′S)-N⁶-(2-glutaryl)lysine] and some γ-glutamyl peptides. The acidic amino acids were separated from other amino acids on an Ecteola ion exchange column with M pyridine as eluant.     

Synthesis and characterization of complexes of the type [Pt(amine)4]I2 and trans-[Pt(CH3NH2)2(H3CNC(CH3)2)2]I2 by crystallography and multinuclear magnetic resonance spectroscopy

Complexes of the type [Pt(amine)₄]I₂ were synthesized and characterized mainly by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. The compounds were prepared with different primary amines, but not with bulky amines, due to steric hindrance. In ¹⁹⁵Pt NMR, the signals were observed between −2715 and −2769 ppm in D₂O. The coupling constant ³J(¹⁹⁵Pt-¹H) for the MeNH₂ complex is 42 Hz. In ¹³C NMR, the average values of the coupling constants ²J(¹⁹⁵Pt-¹³C) and ³J(¹⁹⁵Pt-¹³C) are 18 and 30 Hz, respectively. The crystal structure of [Pt(EtNH₂)₄]I₂ was determined by X-ray diffraction methods. The Pt atom is located on an inversion center. The structure is stabilized by H-bonding between the amines and the iodide ions. The compound with n-BuNH₂ was found by crystallographic methods to be [Pt(n-BuNH₂)₄]₂I₃(n-BuNHCOO). The crystal contains two independent [Pt(CH₃NH₂)₄]²⁺ cations, three iodide ions and a carbamate ion formed from the reaction of butylamine with CO₂ from the air. When the compound [Pt(CH₃NH₂)₄]I₂ was dissolved in acetone, crystals identified as trans-[Pt(CH₃NH₂)₂(H₃CNC(CH₃)₂)₂]I₂ were isolated and characterized by crystallographic methods. Two trans bonded MeNH₂ ligands had reacted with acetone to produce the two N-bonded Schiff base Pt(II) compound.     

Conversion of (2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid to xanthoxin acid by Cercospora cruenta, a fungus producing (+)-abscisic acid

(±)-(2Z,4E)-5-(1′,2′-epoxy-2′,6′,6′-trimethylcyclohexyl)-3-methyl-2,4-pentadienoic acid was metabolized by Cercospora cruenta, which has the ability to produce (+)-abscisic acid (ABA), to give (±)-(2Z,4E)-xanthoxin acid, (±)-(2Z,4E)-5′-hydroxy-1′,2′-epoxy-1′,2′-dihydro-β-ionylideneacetic acid, (±)-1′,2′-epoxy-1′,2′-dihydro-β-ionone and trace amounts of ABA.     

(25S)-Cholesten-26-oic acid derivatives from an Indonesian soft coral Minabea sp.

(25S)-3-Oxocholesta-1,4-dien-26-oic acid (1) and a new (25S)-18-acetoxy-3-oxocholesta-1,4-dien-26-oic acid (2) were isolated from a soft coral Minabea sp. (cf. aldersladei) collected in North Sulawesi, Indonesia, together with two known cholic-acid-type compounds, 3-oxochol-1,4-dien-24-oic acid (3) and 3-oxochol-4-en-24-oic acid (4). The structures of these compounds were determined on the basis of their spectroscopic data. The absolute stereochemistry at C-25 of 2 was determined by comparative ¹H NMR study using chiral anisotropic reagents [(S)- and (R)-phenylglycine methyl esters]. This is the first to report compound 1 as a natural product.     

Synthesis, spectroscopy and magnetism of novel metal complexes of 3-aminoflavone (3-af). X-ray crystal structure of 3-af and [Cu(3-af)2(NO3)2]

The synthesis and characterization of four new complexes with the bioactive ligand 3-aminoflavone (3-af) are reported. The complexes of general formula [M(3-af)₂(H₂O)₂](NO₃)₂ · nH₂O], where M = Co(II), Ni(II), and Zn(II), and n = 0, 2, 0, respectively, and [Cu(3-af)₂(NO₃)₂] compound were prepared and studied. In particular, to investigate the binding in detail, the crystal structures of the free ligand (3-af) and [Cu(3-af)₂(NO₃)₂] (1) were determined. The new coordination compounds were identified and characterized by elemental analysis, magnetic measurements, and infrared and ligand-field spectra. The crystal structure of the Cu(II) complex reveals that the ligand acts as a N,O-bidentate chelate ligand forming a five-membered ring with the copper(II) ion. The copper(II) ion is octahedrally surrounded by the two amino nitrogens and two carbonyl oxygens from two chelating organic ligands in trans arrangement. Two molecules of coordinated nitrate anions occupy axial positions. The spectral and magnetic properties are in accordance with the structural data of the copper(II) compound. From X-ray powder-diffraction patterns and IR spectra, the complexes of nickel(II) (2) and cobalt(II) (3) were found to be mutually isomorphous. The results of the spectroscopic studies suggest a mononuclear structure of 2 and 3 complexes. The variable-temperature (1.8-300 K) magnetic susceptibility data of 2 indicate a weak ferromagnetic interaction. The magnetic behavior of complex 3 is characteristic of cobalt(II) systems with an important orbital contribution via spin-orbit-coupling and also suggests a weak ferromagnetic interaction.     

X-ray structure of a mono(1-methylthyminato) complex of cisplatin,chloro-(1-methylthyminato-N3)-cis-diammineplatinum(II) monohydrate

The crystal structure of chloro-(1-methyltyminato- N3)-cis-diammineplatinum(II) monohydrate, cis- (NH₃)₂Pt(C₆H₇N₂O₂)Cl·H₂O, is reported. The compound crystallizes in space group P$\text{1}$ with a = 6.911(2) Å, b = 8.598(3) Å, c = 11.464(4) Å, α = 100.13(3)°, β = 120.03(3)°, γ = 93.16(3)°, Z = 2. The structure was refined to R = 0.048 and R_w = 0.057. The compound contains the deprotonated 1-methylthymine ligand coordinated to Pt through N3 (1.973(10) Å). This distance represents the shortest Pt-N3(pyrimidine-2.4-dione) bond reported so far. The two PtNH₃ bond lengths differ significantly: PtNH₃ (trans to Cl) is longer (2.052(10) Å) than PtNH₃ (trans to N3 of 1-MeT) (2.002(11) Å). The PtCl distance (2.326(3) Å) is normal, as is the large dihedral angle between the Pt coordination plane and the nucleobase (76.5°).     

First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus

The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC₅₀ = 19.8 μg/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50 μM.     

Syntheses, characterizations and crystal structures of two lead(II) diphosphonates: Pb2[NH(CH2PO3)2] · 2H2O and Pb3[HO2C(CH2)3NH(CH2PO3)2]2 · 2H2O

Hydrothermal reactions of lead(II) acetate and HO₂C(CH₂)₃N(CH₂PO₃H₂)₂ at 170 and 140 °C, respectively, resulted in two different lead diphosphonates, namely, Pb₂[NH(CH₂PO₃)₂] · 2H₂O (1), in which the butyric acid moiety of the HO₂C(CH₂)₃N(CH₂PO₃H₂)₂ has been cleaved and a novel layered compound, Pb₃[HO₂C(CH₂)₃NH(CH₂PO₃)₂]₂ · 2H₂O (2). Their crystal structures have been determined by single crystal X-ray diffraction. In compound 1, the interconnection of the lead(II) ions by bridging amino-diphosphonate ligands leads to the formation of a 3D network. Compound 2 features an unusual triple-layer structure with the non-coordinated butyric acid moieties as pendant groups between the layers.     

The co-occurrence of two diastereoisomers of 2,3-diaminobutanoic acid in root nodule hydrolysates of Lotus tenuis

The non-protein amino acid 2, 3-diaminobutanoic acid has been identified in the root nodules of Lotus tenuis inoculated with Rhizobium strain NZP2213. The co-occurrence of this compound in two diastereoisomeric forms was established by comparative GC retention time measurements on a Chirasil—Val capillary column.