Correlated C-C and C-O bond conformations in saccharide hydroxymethyl groups: parametrization and application of redundant 1H-1H, 13C-1H, and 13C-13C NMR J-couplings

Methyl alpha- and beta-pyranosides of d-glucose and d-galactose 1-4 were prepared containing single sites of (13)C-enrichment at C4, C5, and C6 (12 compounds), and (1)H and (13)C[(1)H] NMR spectra were obtained to determine a complete set of J-couplings ((1)J, (2)J, and (3)J) involving the labeled carbon and nearby protons and carbons within the exocyclic hydroxymethyl group (CH(2)OH) of each compound. In parallel theoretical studies, the dependencies of (1)J, (2)J, and (3)J involving (1)H and (13)C on the C5-C6 (omega) and C6-O6 (theta;) torsion angles in aldohexopyranoside model compounds were computed using density functional theory (DFT) and a special basis set designed to reliably recover the Fermi contact contribution to the coupling. Complete hypersurfaces for (1)J(C5,C6), (2)J(C5,H6)(R), (2)J(C5,H6)(S), (2)J(C6,H5), (2)J(C4,C6), (3)J(C4,H6)(R), (3)J(C4,H6)(S), and (3)J(C6,H4), as well as (2)J(H6)(R)(,H6)(S), (3)J(H5,H6)(R), and (3)J(H5,H6)(S), were obtained and used to parametrize new equations correlating these couplings to omega and/or theta;. DFT-computed couplings were also tested for accuracy by measuring J-couplings in (13)C-labeled 4,6-O-ethylidene derivatives of d-glucose and d-galactose in which values of omega and theta; were constrained. Using a new computer program, Chymesa, designed to utilize multiple J-couplings sensitive to exocyclic CH(2)OH conformation, the ensemble of experimental couplings observed in 1-4 were analyzed to yield preferred rotamer populations about omega and theta;. Importantly, due to the sensitivity of some couplings, most notably (2)J(H6)(R)(,H6)(S), (2)J(C5,H6)(R), and (2)J(C5,H6)(S), to both omega and theta;, unique information on correlated conformation about both torsion angles was obtained. The latter treatment represents a means of evaluating correlated conformation in 1,6-linked oligosaccharides, since psi and theta; are redundant in these linkages. In the latter regard, multiple, redundant scalar couplings originating from both sides of the glycosidic linkage can be used collectively to evaluate conformational correlations between psi/theta; and C5-C6 bond rotamers.     

Improved preparation of (1S,3’R,4’S,5’S,6’R)-5-chloro-6-[(4-ethylphenyl)methyl]-3’,4’,5’,6’-tetrahydro-6’-(hydroxymethyl)-spiro[isobenzofuran-1(3H),2’-[2H]pyran]-3’,4’,5’-triol

A convenient approach for the preparation of(1S,3’R.4’S,5’S,6’R)-5-chloro-6-[(4-ethylphenyl)methyl]- 3’,4’,5’,6’-tetrahydro-6’-(hydroxymethyl)-spiro[isobenzofuran-1(3H),2’-[2H]pyran]-3’,4’,5’-triol is developed. The targeted compound was synthesized from 2-bromo-4-methylbenzoic acid in nine steps and the isomers of undesired ortho-products were avoided during the preparation.     

Geminal 2JCCH spin-spin coupling constants as probes of the phi glycosidic torsion angle in oligosaccharides

Two-bond (13)C-(1)H NMR spin-spin coupling constants ((2)J(CCH)) between C2 and H1 of aldopyranosyl rings depend not only on the relative orientation of electronegative substituents on the C1-C2 fragment but also on the C-O torsions involving the same carbons. The latter dependencies were elucidated theoretically using density functional theory and appropriate model pyranosyl rings representing the four relative configurations at C1 and C2, and a 2-deoxy derivative, to probe the relationship between (2)J(C2,H1) magnitude and sign and the C1-O1 (phi, phi) and C2-O2 (alpha) torsion angles. Related calculations were also conducted for the reverse coupling pathway, (2)J(C1,H2). Computed J-couplings were validated by comparison to experimentally measured couplings. (2)J(CCH) displays a primary dependence on the C-O torsion involving the carbon bearing the coupled proton and a secondary dependence on the C-O torsion involving the coupled carbon. These dependencies appear to be caused mainly by the effects of oxygen lone pairs on the C-H and C-C bond lengths along the C-C-H coupling pathway. New parameterized equations are proposed to interpret (2)J(C1,H2) and (2)J(C2,H1) in aldopyranosyl rings. The equation for (2)J(C2,H1) has particular value as a potential NMR structure constraint for the C1-O1 torsion angle (phi) comprising the glycosidic linkages of oligosaccharides.     

羟甲芬太尼对映异构体的^1H NMR及立体化学

本文对强效镇痛剂羟甲芬太尼(OMF)八个对映异构体中的其中四个, 即(-)-cis-(3R,4S,2'R)-OMF (1), (+)-cis-(3-R,4S,2'S)-OMF (2),(+)-trans-(3S,4S,2'R)-OMF (3), 和(+)-trans-(3S,4S,2'S)-OMF (4)进行了^1HNMR研究, 归属了所有的共振谱线。对哌啶环质子间偶合常数的分析表明, 所有顺式和反式异构体中的哌啶环都呈现相同的椅式构象。在顺式异构体中3-甲基位于直立键, 而4-N-苯基丙酰胺基位于平伏键, 反式异构体中它们均位于平伏键。讨论了3-甲基和4-N-苯基丙酰胺基的立体取代对NMR的影响, 在顺式异构体中4-N-苯基丙酰胺基的构象相对固定, 而在反式异构体中则较为自由。     

Isolation and characterization of dinochrome A and B,anti-carcinogenic active carotenoids from the fresh Water red tide Peridinium bipes

Two epimeric carotenoids, named dinochromes A (2) and B (3), were isolated from the fresh water red tide Peridinium bipes, as anti-carcinogenic compounds. The stereostructure of dinochrome A and B were characterized to be (3S,5R,6R,3'S,5'R,8'R)- and (3S,5R,6R,3'S,5'R,8'S)-5',8'-epoxy-6,7-didehydro-5,6,5',8'-tetrahydro-beta,beta-carotene-3,5,3'-triol 3-O-acetate, respectively by (1)H- and (13)C-NMR, and circular dichroism (CD) data. Dinochromes A (2) and B (3) inhibit 12-O-tetradecanoyl phorbol 13-acetate (TPA)-stimulated (32)P-incorporation into the phosholipids of HeLa cells. Furthermore, dinochrome A was found to inhibit the proliferation of human malignant tumor cells, such as GOTO, OST and HeLa cells.     

Structural dependencies of interresidue scalar coupling (h3)J(NC') and donor (1)H chemical shifts in the hydrogen bonding regions of proteins

A study is presented of the structural dependencies for scalar J-coupling and the amide donor (1)H chemical shifts in the hydrogen bonding regions of proteins. An analysis of the interactions between the donor hydrogen and acceptor oxygen orbitals in an N-H...O=C moiety suggests that there are three major structural factors for (15)N-(13)C coupling across hydrogen bonds: (1) the H...O' internuclear separation r(HO)('), (2) the H...O'=C' angle theta(2), and (3) indirect contributions involving the oxygen loan pair electrons should lead to a dependence on the H...O'=C'-N' dihedral angle rho. Density functional theory (DFT) and finite perturbation theory (FPT) were used to obtain the Fermi contact (FC) contributions to interresidue coupling in formamide dimers with systematic variation of these structural parameters. The computed (h3)J(NC)(') exhibit good correlations with cos(2) theta;(2) combined with an exponential dependence on r(HO)('). The correlation is further improved by including a dependence on the dihedral angle rho. For each of the 34 H-bonds having observable interresidue coupling in the immunoglobulin binding domain of streptococcal protein G, a formamide dimer was generated from the crystallographic structure with energy-optimized donor H-atom positions. The computed coupling constants are in reasonable agreement with the experimental, and there are excellent correlations with the simple equations involving theta;(2) and r(HO) if alpha-helix and beta-sheet regions are treated separately. This dichotomy is removed by introducing the dependence on the dihedral angle rho. Justification for the use of formamide dimers is provided by almost identical interresidue coupling constants for larger sequences extracted from the X-ray structure. The amide donor (1)H chemical shifts, which were based on DFT and GIAO (gauge including atomic orbital) methods, are in poorer agreement with the experimental data but exhibit excellent correlation with r(HO)('), theta(2), and rho.     

Hydroxymethyl group conformation in saccharides: structural dependencies of (2)J(HH), (3)J(HH), and (1)J(CH) spin-spin coupling constants

Experimental and theoretical methods have been used to correlate (2)J(HH) and (3)J(HH) values within the exocyclic hydroxymethyl groups (CH(2)OH) of saccharides with specific molecular parameters, and new equations are proposed to assist in the structural interpretation of these couplings. (3)J(HH) depends mainly on the C-C torsion angle (omega) as expected, and new Karplus equations derived from J-couplings computed from density functional theory (DFT) in a model aldopyranosyl ring are in excellent agreement with experimental values and with couplings predicted from a previously reported general Karplus equation. These results confirm the reliability of DFT-calculated (1)H-(1)H couplings in saccharides. (2)J(HH) values depend on both the C-C (omega) and C-O (theta) torsions. Knowledge of the former, which may be derived from other parameters (e.g., (3)J(HH)), allows theta to be evaluated indirectly from (2)J(HH). This latter approach complements more direct determinations of theta from (3)J(HCOH) and potentially extends these more conventional analyses to O-substituted systems lacking the hydroxyl proton. (1)J(CH) values within hydroxymethyl fragments were also examined and found to depend on r(CH), which is modulated by specific bond orientation and stereoelectronic factors. These latter factors could be largely, but not completely, accounted for by C-C and C-O torsional variables, leading to only semiquantitative treatments of these couplings (details discussed in the Supporting Information). New equations pertaining to (2)J(HH) and (3)J(HH) have been applied to the analysis of hydroxymethyl group J-couplings in several mono- and oligosaccharides, yielding information on C5-C6 and/or C6-O6 rotamer populations.     

Structure elucidation and NMR spectral assignments of three new lignan glycosides from Akebia trifoliata

Three new lignan glycosides (1-3) were isolated from the stems of Akebia trifoliata. Their structures were elucidated as (7R,8R,7'R,8'R)3,3',5,5'tetramethoxy-4,4'dihydroxy-7,9':7',9-diepoxylignan-4-O-beta-D-glucopyranoside (1), (7S,8S,8'R)-4,4',9-trihydroxy-3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (2), (7R,8R,8'S)-4,4',9-trihydroxy3,3',5,5'-tetramethoxy-7,9'-epoxylignan-7'-one 9-O-beta-D-glucopyranoside (3) by spectral analyses, primarily NMR, MS and CD. The NMR assignments for the compounds were carried out using 1H, 13C, DEPT, COSY, HSQC, HMBC and ROESY NMR experiments.     

Indirect nuclear 57Fe-13C and 57Fe-1H spin-spin coupling in ferrocenes and cyclopentadienyliron complexes: measurements and DFT calculations

Several 57Fe-labeled ferrocene derivatives and other cyclopentadienyliron complexes were studied by 57Fe and 13C NMR with respect to isotope-induced chemical shifts 1Delta12/13C(57Fe) and the magnitude and sign of coupling constants 1J(57Fe,13C) and 2J(57Fe,1H). The geometries of the complexes were optimized by DFT methods [B3LYP/6-311+G(d,p)] and chemical shifts (GIAO) and coupling constants were calculated at the same level of theory. The trends in calculated 57Fe nuclear shielding agree well with the experimental data and, in the case of coupling constants 1J(57Fe,13C) and 2J(57Fe,1H), both sign and magnitude are correctly reproduced.     

Isolation and structural elucidation of the geometrical isomers of lutein and zeaxanthin in extracts from human plasma.

All-E-(3R,3'R,6'R)-lutein, all-E-(3R,3'R)-zeaxanthin, all-E-(3R,3'S,6'R)-3'-epilutein and some geometrical isomers of the former two dihydroxycarotenoids have been separated from an extract of human plasma by semipreparative high-performance liquid chromatography on a silica-based nitrile-bonded column. In the order of chromatographic elution, the isolated fractions were identified as all-E-lutein, all-E-zeaxanthin, all-E-3'-epilutein, 9Z-lutein, 9'Z-lutein, a mixture of 13Z-lutein and 13'Z-lutein, 9Z-zeaxanthin, 13Z-zeaxanthin and 15Z-zeaxanthin. The structures of all compounds, including the relative configuration at C(3') and C(6') of the luteins and the position of the stereomutated double bonds in the geometrical isomers, were unambiguously established by 1H nuclear magnetic resonance spectroscopy. The absolute configuration of the three all-E compounds was derived by circular dichroism and is also assumed to be valid for the geometrical isomers. The ultraviolet-visible absorption and mass spectra of each of the individually isolated compounds were also in agreement with the proposed structures.     

New ent-kaurane diterpenes with chiral epoxyangelate moieties from Wedelia prostrata

Four new ent-kaurane diterpenes with chiral epoxyangelate moieties, (2′R,3′R)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (1), (2′S,3′S)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (2), (2′S,3′R)-3 a- (2',3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (3) and (2′R,3′S)-3α- (2′,3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (4), along with eight known diterpenes (5-12), were isolated from Wedelia prostrata. The absolute configurations of the new structures were determined by X-ray crystallography,ECD calculations and chemical methods. All compounds were evaluated for their cytotoxicity activities on human HepG-2 cells,with IC_(50) values of 11.72 ±0.22 μmol/L to 54.75±1.12 μmol/L.     

Synthesis and assignment of the absolute configuration of the anti-Helicobacter pylori agents CJ-12,954 and CJ-13,014

The synthesis of the spiroacetal-containing anti-Helicobacter pylori agents (3S,2'S,5'S,7'S)- (ent-CJ-12,954) and (3S,2'S,5'R,7'S)- (ent-CJ-13,014) has been carried out based on the convergent union of a 1:1 mixture of heterocycle-activated spiroacetal sulfones and with (3S)-phthalide aldehyde . The synthesis of the (3R)-diastereomers (3R,2'S,5'S,7'S)- and (3R,2'S,5'R,7'S)- was also undertaken in a similar manner by union of (3R)-phthalide aldehyde with a 1:1 mixture of spiroacetal sulfones and . Comparison of the (1)H and (13)C NMR data, optical rotations and HPLC retention times of the synthetic compounds (3S,2'S,5'S,7'S)- and (3S,2'S,5'R,7'S)- and the (3R)-diastereomers (3R,2'S,5'S,7'S)- and (3R,2'S,5'R,7'S)-, with the naturally occurring compounds, established that the synthetic isomers and were in fact enantiomeric to the natural products CJ-12,954 and CJ-13,014. The (2S,8S)-stereochemistry in protected dihydroxyketone , the precursor to the mixture of spiroacetal sulfones and was established via union of readily available (S)-acetylene with aldehyde in which the (4S)-stereochemistry was established via asymmetric allylation. Deprotection and cyclization of protected dihydroxyketone afforded an inseparable 1:1 mixture of spiroacetal alcohols and that were converted into a 1:1 inseparable mixture of spiroacetal sulfones and . Phthalide-aldehyde was prepared via intramolecular acylation of bromocarbamate in which the (3S)-stereochemistry was established via asymmetric CBS reduction of ketone .     

NMR confirmation that tryptophan dehydrogenation occurs with syn stereochemistry during the biosynthesis of CDA in Streptomyces coelicolor

Doubly labeled (2'S,3'R)-[3'-2H1,13C1]-tryptophan was fed to the Trp-His auxotrophic Streptomyces coelicolor strain WH101. Mass spectrometry showed single and double incorporation of the labeled Trp into the calcium-dependent lipopeptide antibiotic (CDA4a). From 13C NMR spectroscopy, it was apparent that the C3'-signal of the (Z)-2',3'-dehydrotryptophan (position 11 in CDA4) was a 1:1:1 triplet indicating that the deuterium atom in the pro-R position of the methylene group is retained during Trp-oxidation. This provides definitive proof that Trp dehydrogenation occurs through the loss of the 2' and pro-3'S hydrogen atoms with overall syn stereochemistry.     

Dicondensed indolinobenzospiropyrans as precursors of thermo- and photochromic spiropyrans. Part II: Assignment of (1)H and (13)C NMR spectra

The (1)H and (13)C NMR spectra of dicondensed indolinobenzospiropyrans as precursors of thermo- and photochromic spiropyrans, DC1-DC5, were completely assigned. Especially, the (1)H assignment and coupling characteristics of the diastereotopic protons at the carbon-3 position of the benzopyran rings were achieved by conducting (1)H-(1)H COSY and nOe experiments. The dihedral angles (theta(1), theta(2) and theta(3)) calculated from the experimental values of the vicinal coupling constants ((3)J) of DC5 are in good agreement with the observed values in the solid state. All of the carbons in the DC dye molecules were investigated through a combination of heteronuclear 2D-shift correlation spectroscopy (HETCOR) and DEPT135.     

An "S"-shaped pentanuclear CuII cluster derived from the metal-assisted hydrolysis of pyCOpyCOpy: structural, magnetic and spectroscopic studies

Reaction of [Cu2(O2CMe)4(H2O)2] with 2,6-di-(2-pyridylcarbonyl)-pyridine (pyCOpyCOpy or dpcp) in MeCN-H2O 10:1, led to the pentanuclear copper(II) complex [Cu5(O2CMe)6{pyC(O)(OH)pyC(O)(OH)py}2] () which crystallizes in the triclinic P1 space group. The copper(II) atoms are arranged in an "S"-shaped configuration, and are bridged by the doubly deprotonated bis(gem-diol) form of the ligand, pyC(O)(OH)pyC(O)(OH)py2-. Magnetic susceptibility data indicate the interplay of both ferro- and antiferromagnetic intramolecular interactions stabilizing an S=3/2 ground state. Fitting of the data according to a next-nearest-neighbour model {H=-[J1(S1S2+S1'S2')+J2(S2S3+S3'S2')+J3(S1S3+S3'S1')+J4(S2S2')]} yields exchange coupling constants J1=+39.7 cm(-1), J2=-15.9 cm(-1), J3=-8.3 cm(-1) and J4=+4.3 cm(-1), leading to an S=3/2 ground state. X-Band EPR spectroscopy indicates a zero-field splitting of the ground state with |D3/2|=0.38 cm(-1).     

Conformational analysis of beta-glycosidic linkages in 13C-labeled glucobiosides using inter-residue scalar coupling constants

Four beta-linked glucobioses selectively (13)C labeled at C1' or C2' have been prepared. The inter-residue coupling constants, J(CH), and J(CC), have been determined and related to the solution conformations of the disaccharides using Karplus-type relationships. Relying only on the experimental coupling constants, glycosidic linkage conformation in methyl alpha-sophoroside (methyl 2-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside), methyl alpha-laminarabioside (methyl 3-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside), and methyl alpha-cellobioside (methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside) were found to be close to those observed in the solid state (39 degrees < phi(H) < 41 degrees , -24 degrees < psi(H) < -36 degrees ). The laminarabioside and cellobioside were found to have conformations that accommodate an intramolecular hydrogen bond to O5' that is observed in the solid state. In all compounds, the exocyclic hydroxymethyl groups retain a conformation close to that observed in unsubstituted glucose (gt/gg 1:1). Methyl alpha-gentiobioside (methyl 6-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside) shows greater flexibility at the psi-torsion than the other disaccharides, but the population distribution around the C5-C6 bond is essentially unaffected by substitution. None of the O2' hydroxyl groups of the beta-D-glucopyranosyl residues in any of the disaccharides appear to be involved in inter-residue hydrogen bonding since (1)JCH, (1)JCC, and (2)JCH values sensitive to C2'-O2' rotamer distribution remain close to those observed in methyl beta-D-glucopyranoside.     

Three-bond sugar-base couplings in purine versus pyrimidine nucleosides: a DFT study of Karplus relationships for (3)J(C2/4-H1') and (3)J(C6/8-H1') in DNA

(3)J(C2/4-H1') and (3)J(C6/8-H1') scalar spin-spin coupling constants have been calculated for deoxyadenosine, deoxyguanosine, deoxycytidine, and deoxythymidine as functions of the glycosidic torsion angle chi by means of density functional theory. Except for deoxythymidine, (3)J(C2/4-H1') depends little on the base type. On the contrary, (3)J(C6/8-H1') follows the usual trans to cis ratio ((3)J(C-H(cis)) < (3)J(C-H(trans))) for purine nucleosides, but reveals the opposite relation ((3)J(C-H(cis)) > (3)J(C-H(trans))) for pyrimidine nucleosides. Our results compare well with the experiment for deoxyguanosine and predict a novel trend in the case of pyrimidine bases for which no NMR results are available in the syn region. A breakdown of the key Fermi contact part of (3)J(C6/8-H1') into MO contributions rationalizes this trend in terms of an unusual coupling mechanism in the syn orientation that is very effective for pyrimidine nucleosides and considerably weaker for purine nucleosides.     

NEOLIGNANS FROM PIPER KADSURA(Ⅱ)

Two new bicyclo[3,2,1]octanoid neolignans,named as kadsurenin I andkadsurenin J were isolated from Piper kadsura(Choiey)Ohwi.Based on the spectros-copic analysis(UV,IR,MS and NMR)and chemical derivatization,their structures wereestablished as 7R,8R,1'R,2'S,3'R-Δ~s'-3,4,5'-trimethoxy-2'-hydroxy-1',2',3',4'-tetrahydro-4'-oxo-7.3',8.1'-neolignan and 7R,8R,1'R,2'S,3'R-Δ~s'-3,4,5'-trimethoxy-2'-acetoxy-1',2',3',4'-tetrabydro-4'-oxo-7.3',8.1'-neolignan respectively.     

Antimicrobial C-glucoside from aerial parts of Diospyros nigra

A new C-alkylglucoside, diospyrodin [beta-1C-(1'S*,2'R*,3'R*,4'S*-1',2',3',4',5'-pentahydroxypentyl)-glucopyranoside] (1) has been isolated as its nonaacetate from the leaves and stems of Diospyros nigra. Its structure was elucidated on the basis of chemical and spectral properties and a single crystal X-ray analysis. It showed antimicrobial activity against Gram-positive and Gram-negative bacteria.     

4J(COCCH) and 4J(CCCCH) as probes of exocyclic hydroxymethyl group conformation in saccharides

[structure: see text] 1H NMR spectra of aldohexopyranosyl rings containing 13C-enrichment at either C1 or C3 reveal the presence of long-range 4J(C1,H6R/S) and 4J(C3,H6R/S) whose magnitudes depend mainly on the O5-C5-C6-O6 torsion angle. Using theoretical calculations (density functional theory, DFT; B3LYP/6-31G*) and conformationally constrained experimental model compounds, the magnitudes and signs of 4J(C1,H6R/S) and 4J(C3,H6R/S) have been established, and their dependencies on the geometry of the C1-O5-C5-C6-H6R/S and C3-C4-C5-C6-H6R/S coupling pathways, respectively, were determined. The latter dependencies mimic that observed previously for 4J(HH) in aliphatic compounds such as propane. DFT calculations also showed that inclusion of non-Fermi contact terms is important for accurate predictions of 4J(CH) values. Application to methyl alpha- and beta-D-glucopyranosides reveals different rotameric distributions about their hydroxymethyl groups, with the beta-anomer enriched in the gt rotamer, in agreement with recent multi-J redundant coupling analyses. 4J(C1,H6R/S) and 4J(C3,H6R/S) are expected to complement other recently developed J-couplings for the assignment of hydroxymethyl group conformation in oligosaccharides containing 1,6-glycosidic linkages.