Crystal structure, conformation, and absolute configuration of kanamycin A

Kanamycin, an antibiotic complex produced by Streptomyces kanamycetius isolated from Japanese soil, was described by Okami and Umezawa as early as 1957 and consists of three components: Kanamycin A (the major component), B, and C. The disulfate salt of kanamycin A [4-O-(6-amino-6-deoxy-alpha-d-glucopyranosyl)-6-O-(3-amino-3-deoxy-alpha-d-glucopyranosyl)-2-deoxystreptamine] is a broad-spectrum antibiotic that is used to treat gonorrhea, salmonella, tuberculosis, and many other diseases. Crystals of kanamycin A monosulfate monohydrate obtained from water are triclinic, space group P1, with a=7.2294(14), b=12.4922(15), c=7.1168(9), alpha=94.74(1), beta=89.16(1), gamma=91.59(1), V=640.2(2)A(3), micro(CuKalpha)=18.4cm(-1), FW 600.6, D(calc)=1.558g/cm(3), CAD-4 diffractometric data (2693 reflections, 25543sigma(I)), structure by shelx-86 and refined by full-matrix least squares to a final R value of 0.038. The wrong conformer had an R value of 0.043. Both of the d-glucose moieties are attached to the deoxystreptamine by alpha linkages. This absolute configuration agrees with the earlier determination by both chemical and X-ray methods with photographic data. The (phi,psi) values for the glycosidic linkages are 101.6 degrees , -121.1 degrees , 106.3 degrees , and -140.4 degrees , respectively. Kanamycin interacts with the ribosomal S12 protein to stabilize the codon-anticodon binding between mRNA and the aminoacyl tRNA and inhibits the elongation of peptide chains through a series of reactions resulting in the prevention of ribosomes from moving along mRNA.     

The absolute configuration of phaseic and dihydrophaseic acids

A sample of phaseic acid methyl ester (5 mg, isolated from tomato plants fed (±)-abscisic acid, was reduced to a mixture of the epimeric dihydrophaseates which were separated by TLC. The more polar epimer was identical with the dihydrophaseate isolated from beans by Walton et al. [14]. Comparison of the NMR and IR spectra (H-bonding) of the two epimers shows the secondary hydroxyl of the less polar epimer is cis to the oxymethylene group, which is cis to the tertiary hydroxyl group. The absolute configuration of this centre is known so the absolute configuration of phaseic acid can be deduced. Phaseic acid is (−)-3-methyl-5{8[1(R), 5(R)-dimethyl-8(S)-hydroxy-3-oxo-6-oxabicyclo-(3,2,1)-octane]} 2-cis-4-trans-pentadienoic acid and both it and the reduction products exist in chair conformations. The more polar epimer isolated by Walton et al. is (−)-3-methyl-5{8[3(S,8(S)-dihydroxy-1(R,5(R)-dimethyl-6-oxabicyclo-(3,2,1)-octane]}2-cis-4-trans-pentadienoic acid. It is suggested that the less polar epimer should be referred to as epi-dihydrophaseic acid.     

The absolute configuration of 1-carboxyethyl substituents on common hexoses by circular dichroism

Determination of the absolute configuration of the 1-carboxyethyl substituent on a monosaccharide by circular dichroism measurements was found to be a sensitive and simple method. It relies on comparison of the spectrum of a 1-carboxyethyl substituted sugar or sugar derivative with the spectra of (R)- and (S)-lactic acid in the region 200-260 nm in which the (R)- and (S)-configuration give negative and positive deltaepsilon, respectively. The oligo- or poly-saccharide containing a 1-carboxyethyl substituted sugar is hydrolyzed to monomers and the 1-carboxyethyl substituted sugar isolated by chromatography. The CD spectrum obtained for the 1-carboxyethyl substituted sugar in water solution at pH 2 is then compared with spectra of (R)- and (S)-lactic acid. The sign for the absorption and a maximum of comparable intensity and appearance around 210 nm, identify the stereochemistry.     

Synthesis and characterization of homochiral polymeric S-malato molybdate(VI): toward the potentially stereospecific formation and absolute configuration of iron-molybdenum cofactor in nitrogenase

Reaction of sodium or potassium molybdate and excess malic acid in a wide range of pH values (pH 4.0–7.0) resulted in the isolation of two cis-dioxo-bis(malato)-Mo(VI) complexes, viz. Na₃[MoO₂H(S-mal)₂] and K₃[MoO₂H(S-mal)₂]·H₂O (H₃mal=malic acid). The sodium complex is also characterized by an X-ray structure analysis, showing that the mononuclear Mo units are linked together via very strong symmetric CO₂···H··· O₂C-hydrogen bond [2.432(5) Å], forming a polymeric chain. The molybdenum atoms are quasi-octahedrally coordinated by two cis-oxo groups and two bidentate malate ligands via its alkoxy and -carboxyl groups, while the β-carboxylic and carboxylate groups remain uncomplexed, as the coordination of vicinal carboxylate and alkoxide of homocitrate in FeMo cofactor of nitrogenase. The absolute configuration of the metal center in this S-malato complex is assigned as Λ and the homochirality within the chain is established as a homochiral form ···Λ_S–Λ_S–Λ_S–Λ_S···. It is proposed that the chiral configuration of the metal center in wild-type FeMo-co biosynthesis might be induced by the early coordination of the chiral R-homocitric acid, while a mixture of raceme might be obtained in the biosynthesis of NifV⁻ FeMo-cofactor. The absolute configuration of wild-type FeMo-cofactor is assigned as Δ_R.     

Synthesis and characterization of homochiral polymeric S-malato molybdate(VI): toward the potentially stereospecific formation and absolute configuration of iron-molybdenum cofactor in nitrogenase

Reaction of sodium or potassium molybdate and excess malic acid in a wide range of pH values (pH 4.0–7.0) resulted in the isolation of two cis-dioxo-bis(malato)-Mo(VI) complexes, viz. Na₃[MoO₂H(S-mal)₂] and K₃[MoO₂H(S-mal)₂]·H₂O (H₃mal=malic acid). The sodium complex is also characterized by an X-ray structure analysis, showing that the mononuclear Mo units are linked together via very strong symmetric CO₂···H··· O₂C-hydrogen bond [2.432(5) Å], forming a polymeric chain. The molybdenum atoms are quasi-octahedrally coordinated by two cis-oxo groups and two bidentate malate ligands via its alkoxy and α-carboxyl groups, while the β-carboxylic and carboxylate groups remain uncomplexed, as the coordination of vicinal carboxylate and alkoxide of homocitrate in FeMo cofactor of nitrogenase. The absolute configuration of the metal center in this S-malato complex is assigned as Λ and the homochirality within the chain is established as a homochiral form ···Λ_S–Λ_S–Λ_S–Λ_S···. It is proposed that the chiral configuration of the metal center in wild-type FeMo-co biosynthesis might be induced by the early coordination of the chiral R-homocitric acid, while a mixture of raceme might be obtained in the biosynthesis of NifV⁻ FeMo-cofactor. The absolute configuration of wild-type FeMo-cofactor is assigned as Δ_R.     

Crystal and molecular structure of sym-homospermidine monohydrate.

Sym-homospermidine, [formula; see text] is a naturally occurring rare-polyamine found in relatively large concentration in sandal leaves. As part of our studies on structure and interactions of polyamines, sym-homospermidine was purified from sandal leaves and its structure was determined by single crystal X-ray diffraction technique. The phosphate salt of the molecule crystallized in the triclinic space group P1- with a = 8.246(1)A, b = 8.775(1)A, c = 15.531(2)A, alpha = 74.20(1) degrees, beta = 88.36(1) degrees and gamma = 65.41(1) degrees. The structure was determined by direct methods and refined to a final R factor of 5.4% for 2087 reflections with magnitude of F(obs) greater than 5 sigma [F(obs)]. The amine exists in its most favourable all trans conformation. For each amine molecule three phosphate groups exist in the crystal structure, suggesting that two of the oxygens of each phosphate group are protonated. There is also a single water molecule in the asymmetric unit in contrast to that of spermidine phosphate which has 3 water molecules. These differences probably reflect the hydrogen bonding properties of mono-ionic and di-ionic phosphate groups. The structure is predominantly stabilized by a network of hydrogen bonds.     

Crystal structure and absolute configuration of (+)546-[copy4Cl2]HDBT: An example of torsional isomerism

The crystal structure and absolute configuration of the (?)₅₈₉-dibenzoylmonohydrogentartrate salt of the cation [Co(pyridine)₄Cl₂]⁺ have been determined from a three-dimensional X-ray analysis. Single crystals were grown from dimethylsulfoxide: space group P2₁2₁2₁, Z = 4, and cell dimensions a = 21.463(4), b = 23.112(3), and c = 7.490(1) Å. Full-matrix least-squares refinement on F converged at R = 0.075, 196 variables and 2029 observations. The cation has pseudotetragonal coordinate geometry, with axial Cl and equatorial N atoms. The dihedral angles between the pyridine ligands and the equatorial plane are 47(1), 39(1), 50(1), and 45(1)° and torsional isomerism is responsible for the solid-state chiroptical properties of the cation. The preferential crystallization of the P atropisomer of the cation is attributed to a general electrostatic attraction between cation and anion.     

Assessing the absolute configuration of (7S,8R)-(−)-epoxyjasmone

The absolute configuration of cis-epoxyjasmone (−)-2, isolated from Trichosporum cutaneum CCT 1903 whole cells, has been unambiguously established as (7S,8R), [α]_D²⁰ −29.0° (c 1.3, CHCl₃), by a new two step method, using a regioselective epoxide opening as the key step followed by Mosher acid derivatization.     

Crystal and molecular structure of methyl 4-O-methyl-beta-D-ribo-hex-3-ulopyranoside

Methyl 4-O-methyl-beta-D-ribo-hex-3-ulopyranoside (2), a model compound for partially oxidized anhydroglucose units in cellulose, was crystallized from CHCl(3)/n-hexane by vapor diffusion to give colorless plates. Crystal structure determination revealed the monoclinic space group P2(1) with Z = 2C(8)H(14)O(6) and unit cell parameters of a = 8.404(2), b = 4.5716(10), c = 13.916(3)A, and beta = 107.467(4) degrees. The structure was solved by direct methods and refined to R = 0.0476 for 1655 reflections and 135 parameters. The hexulopyranoside occurs in a distorted chair conformation. Both hydroxyls are involved in hydrogen bonding and form zigzag bond chains along the b-axis. One of the two hydrogen bonds is bifurcated. The solid-state (13)C NMR spectrum of exhibits eight carbon resonances, with well-separated signals for the two methoxyls (1-OMe: 55.72 ppm, 4-OMe: 61.25 ppm) and a keto resonance with relatively large downfield shift (206.90 ppm). Differences in the C-4 and the methoxyls' chemical shifts in the solid and liquid states were found.     

Crystal and molecular structure of L-valyl-L-lysine hydrochloride.

L-Valyl-L-lysine hydrochloride, C11N3O3H23 HCl, crystallizes in the monoclinic space group P2(1) with a = 5.438(5), b = 14.188(5), c = 9.521(5) A, beta = 95.38(2) degrees and Z = 2. The crystal structure, solved by direct methods, refined to R = 0.036, using full matrix least-squares method. The peptide exists in a zwitterionic form, with the N atom of the lysine side-chain protonated. The two gamma-carbons of the valine side-chain have positional disorder, giving rise to two conformations, chi 1(11) = -67.3 and 65.9 degrees, one of which (65.9 degrees) is sterically less favourable and has been found to be less popular amongst residues branching at beta-C. The lysine side-chain has the geometry of g- tgt, not seen in crystal structures of the dipeptides reported so far. Interestingly, chi 2(3) (63.6 degrees) of lysine side-chain has a gauche+ conformation unlike in most of the other structures, where it is trans. The neighbouring peptide molecules are hydrogen bonded in a head-to-tail fashion, a rather uncommon interaction in lysine peptide structures. The structure shows considerable similarity with that of L-Lys-L-Val HCl in conformational angles and H-bond interactions [4].     

Structure and absolute configuration of a secolignan from Peperomia blanda

A secolignan, (−)-2-methyl-3-[bis(3′,4′-methylenedioxy-5′-methoxyphenyl) methyl]butyrolactone (1), with a rare cis configuration was isolated from the aerial parts of Peperomia blanda (Piperaceae). The structure of this compound was elucidated by a combination of spectroscopic methods, including ultraviolet, infrared, 1D- and 2D- nuclear magnetic resonance as well as high resolution mass spectrometry data. The absolute configuration of (−)-1 was determined as (2R,3S) by the comparison of experimental electronic circular dichroism (ECD) spectroscopy and time-dependent density functional theory (TDDFT) calculations.     

Stereospecific synthesis and absolute configuration of mexiletine

Data on the absolute configuration of mexiletine (MEX) do not appear to have been published, although in several published reports the configuration is referred to as (?)-(R) and (+)-(S), based on information from manufactures providing the drug stereoisomers. We demonstrate that (?)-MEX has the (R)-configuration by mean of a new stereospecific synthesis. X-Ray analysis of an optical active sample of (+)-MEX as its hydrobromide salt, obtained from chemical resolution of the racemic mixture, was carried out in order to obtain precise information on bond lengths and angles, useful for studies on structure–activity relationships. We also report the NMR analysis in presence of Eu(hfc)₃ as shift reagent, which represents a simple method for the determination of enantiomeric excess (ee) in addition to the well-known chiral HPLC methods. © 1994 Wiley-Liss, Inc.     

Significance of chirality in pheromone science

Pheromones play important roles in chemical communication among organisms. Various chiral and non-racemic pheromones have been identified since the late 1960s. Their enantioselective syntheses could establish the absolute configuration of the naturally occurring pheromones and clarified the relationships between absolute configuration and bioactivity. For example, neither the (R)- nor (S)-enantiomer of sulcatol, the aggregation pheromone of an ambrosia beetle Gnathotrichus sulcatus, is behaviorally active, while their mixture is bioactive. In the case of olean, the olive fruit fly pheromone, its (R)-isomer is active for the males, and the (S)-isomer is active for the females. About 140 chiral pheromones are reviewed with regard to their stereochemistry–bioactivity relationships. Problems encountered in studying chirality of pheromones were examined and analyzed to think about possible future directions in pheromone science.     

Primary structure and configuration of tea polysaccharide

The monosaccharide composition of a tea polysaccharide (TGC) was determined by GC-MS method. Furthermore, the primary structure of tea polysaccharide and its configuration in the aqueous solution were investigated utilizing a combination of classical chemical methods and modern instrumental techniques including GC-MS, Proton NMR, UV and CD. The results indicate that TGC consists of 6 monosaccharides: Rha, Ara, Xyl, Glu, Man and Gal. The configuration of TGC in water solution is proposed to be an ordered helix. The possible primary structure of TGC was outlined as below: the basic structure of the main chain consists of Rha, Glu and Gal units. All three monosaccharides can potentially be connected to branch chains consisting of mainly Ara, and the linkages could be in β1 → 2, β 1 → 3, β 2 → 3 forms. When branch chain is absent in the basic structure of the main chain the linkage consists of only β 1 → 3; Xyl exists at the terminal end of either the main chain or the branch chain with β 1 → linkage.     

Primary structure and configuration of tea polysaccharide

Polysaccharide is a class of natural macromole-cules of which many species have been found to carry significant biological activities. Although the research on activities of saccharide has been at a lower level in the past comparing to those of proteins and nucleic acids, much progress has been made in recent years because of accelerated activities worldwide[1]. Such progress has been made mostly in areas of structural analysis, and researches on structure-activity relation-ships. The biologic…     

Crystal and molecular structure of methyl 4-O-methyl-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside

The cellulose model compound methyl 4-O-methyl-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside (6) was synthesised in high overall yield from methyl beta-D-cellobioside. The compound was crystallised from methanol to give colourless prisms, and the crystal structure was determined. The monoclinic space group is P2(1) with Z=2 and unit cell parameters a=6.6060 (13), b=14.074 (3), c=9.3180 (19) A, beta=108.95(3) degrees. The structure was solved by direct methods and refined to R=0.0286 for 2528 reflections. Both glucopyranoses occur in the 4C(1) chair conformation with endocyclic bond angles in the range of standard values. The relative orientation of both units described by the interglycosidic torsional angles [phi (O-5' [bond] C-1' [bond] O-4 [bond] C-4) -89.1 degrees, Phi (C-1' [bond] O-4 [bond] C-4 [bond] C-5) -152.0 degrees] is responsible for the very flat shape of the molecule and is similar to those found in other cellodextrins. Different rotamers at the exocyclic hydroxymethyl group for both units are present. The hydroxymethyl group of the terminal glucose moiety displays a gauche-trans orientation, whereas the side chain of the reducing unit occurs in a gauche-gauche conformation. The solid state (13)C NMR spectrum of compound 6 exhibits all 14 carbon resonances. By using different cross polarisation times, the resonances of the two methyl groups and C-6 carbons can easily be distinguished. Distinct differences of the C-1 and C-4 chemical shifts in the solid and liquid states are found.     

Time-dependent density functional theory-assisted absolute configuration determination of cis-dihydrodiol metabolite produced from isoflavone by biphenyl dioxygenase

Escherichia coli cells containing the biphenyl dioxygenase genes bphA1A2A3A4 from Pseudomonas pseudoalcaligenes KF707 were found to biotransform isoflavone and produced a metabolite that was not found in a control experiment. Liquid chromatography/mass spectrometry (LC/MS) and ¹H and ¹³C nuclear magnetic resonance (NMR) analyses indicated that biphenyl dioxygenase induced 2′,3′-cis-dihydroxylation of the B-ring of isoflavone. In a previous report, the same enzyme showed dioxygenase activity toward flavone, producing flavone 2′,3′-cis-dihydrodiol. Due to growing interest in flavone chemistry and the absolute configuration of natural products, time-dependent density functional theory (TD-DFT) calculations were combined with circular dichroism (CD) spectroscopy to determine the absolute configuration of the isoflavone dihydrodiol. By computational methods, the structure of the isoflavone metabolite was determined to be 3-[(5S,6R)-5,6-dihydroxycyclohexa-1,3-dienyl]-4H-chromen-4-one. This structure was confirmed further by the modified Mosher’s method. The same protocol was applied to the flavone metabolite, and the absolute configuration was determined to be 2-[(5S,6R)-5,6-dihydroxycyclohexa-1,3-dienyl]-4H-chromen-4-one. After determination of the absolute configurations of the biotransformation products, we suggest the binding mode of these substrate analogs to the enzyme active site.     

Chiral resolution,determination of absolute configuration,and biological evaluation of (1,2-benzothiazin-4-yl)acetic acid enantiomers as aldose reductase inhibitors

Abstract

A novel series of (1,2-benzothiazin-4-yl)acetic acid enantiomers was prepared by chiral resolution, and their absolute configurations were determined using the PGME method. The biological evaluation of the racemate and single enantiomers has shown a remarkable difference for the aldose reductase inhibitory activity and selectivity. The (R)-(?)-enantiomer exhibited the strongest aldose reductase activity with an IC₅₀ value of 0.120?μM, which was 35 times more active than the S-(+)-enantiomer. Thus, the stereocenter at the C4 position of this scaffold was shown to have a major impact on the activity and selectivity.     

Crystal structure and microstructure of cholesteryl oleyl carbonate

The crystal structure as well as the microstructure, i.e., size and strain, of crystallites of cholesteryl oleyl carbonate was determined from X-ray powder diffraction data. The X-ray line broadening was analyzed through the refinement of TCH-pseudo-Voigt function parameters (isotropic effects) and the refinement of multipolar functions, i.e., symmetrized cubic harmonics (anisotropic effects). The crystal structure turns out to be primitive monoclinic, space group Pc, type I monolayer having two molecules per unit cell with parameters: a = 18.921 ± 0.006 Å, b = 12.952 ± 0.003 Å, c = 9.276 ± 0.002 Å and β = 91.32 ± 0.03°. The average size of a well ground specimen of crystallites was 60 nm. The average micro-strain, e.g., 45 × 10⁻⁴ has been tentatively attributed to fatty chain conformational disorder. The unit cell parameters, including the lamellar thickness, of COC crystal is very closely similar to those of another, structurally similar cholesterol ester, e.g., cholesteryl oleate (CO) crystal, space group P2₁, type II monolayer. Type I monolayer structure has been established for COC on the basis of the intensity calculations of the XRD profiles of both CO and COC. The dipolar and structural disorder in a 4:1 molar, binary mixture of CO and COC can be accommodated in an induced smectic phase with a lamellar thickness, which is nearly equal to that of pure CO or pure COC.