STUDIES ON CHIRAL THIOPHOSPHORIC ACIDS AND THEIR DERIVATIVES 11.——THE RESOLUTION OF O-METHYL O-PHENYL THIOPHOSPHORIC ACID AND ABSOLUTE CONFIGURATIONS OF ITS OPTICAL ISOMERS

Racemic O-methyl O-pheayl thiophosphoric acid 1 has been successfully resolved through its quinine and brucine salts in methanol solution by fractional crystallization. The absolute configurations of the optically active 1 have been established as (+)-R-1 and (-)-S-1 by chemical correlation.

8,4′-Oxyneolignane glucosides from an aqueous extract of“ban lan gen”(Isatis indigotica root)and their absolute configurations

Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A-F(1–6), were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis and enzyme hydrolysis. The validity of Δδ_(C8-C7) values to distinguish threo and erythro aryl glycerol units and Cotton effects at 235±5 nm to determine absolute configurations at C-8 in 1–6 and their aglycones(1a–6a) are discussed.

AN AB INITIO STU DY ON THE CORELATION BETWEEN THE ABSOLUTE CONFIGURATION AND THE CD SPECTRA OF ORGANIC PEROXIDES

Correlation between the absolute configuration and the CD spectra of organic peroxides was studied by ab initio method with a mo- d el moleeule CH_3-O-O-CH_3.For P form when 0°≤θ(twist angle of C-O-O-C) <90°, there is positive Cotton effect;when 90°<θ≤180°, there is nega- tive Cotton effect;the curve is bisignate at θ=90°.

Determination of the Absolute Configuration of Rohitukine

The absolute configuration of rohitukine, isolated from the stem-bark of Dysoxylum binectariferum, was determined to be 5,7-dihydroxy-2-methyl-8-[4-(3S, 4R-3-hydroxy-1-methyl) -piperidinyl]-4H-1-benzopyran-4-one by X-ray crystallographic analysis on the crystal of 4-bromobenzoyl derivatives of rohitukine. At the same time, the modified Mosher method was proved to be unsuitable for determining the absolute configuration of C-3 position in rohitukine.

Synthesis and Absolute Configuration of (2S,3S,3aS,6S,7aR)-2,3-Dihydroxy-2-((R)-1-hydroxy-3-methylbutyl)-3,6-dimethylhexahydrobenzofuran-4(2H)-one

To investigate the anti-ulcer effect of bisabolangelone reduction derivatives, the sesquiterpene was further proceeded with dihydroxylation reaction. The structure of the target compound was characterized by IR, ESI-MS, 2D NMR and elemental analysis, and its absolute configuration was confirmed with a Flack parameter of 0.08（16） by X-ray crystallography using a Cu radiation source. Compound（3）, C（15）H（26）O5, crystal data： monoclinic system, space group P21, a = 11.467（2）, b = 6.0303（12）, c = 11.711（2） A, β = 99.70（3）°, V = 798.3（3） A3, Z = 2, F（000） = 312, Dc = 1.191 g/cm3, μ = 0.723 mm-1） R = 0.0303 and wR = 0.0797 for 2590 independent reflections（Rint = 0.0164） and 2563 observed ones（I 〉 2σ（I））.

The Use of a Combination of RDC and Chiroptical Spectroscopy for Determination of the Absolute Configuration of Fusariumin A from the Fungus Fusarium sp.

A new alkylpyrrole derivative,fusariumin A(1),was isolated from the culture broth of the fungus Fusarium sp.The absolute configuration of fuasiumin A has been established as(2'R,3'R)using a combination of RDC(residual dipolar coupling)-based NMR and DFT-supported chiroptical spectroscopy.It is worth to note that in this study without the aid of the RDC analysis,an unambiguous determination of configuration and conformation was not feasible due to the excessive conformational possibilities of this open-chain compound.

Synthesis, Crystal Structure and Absolute Configuration of (+)-O-Phenyl Cyclophosphorodiamidate

The title compound, (+)-O-phenyl cyclophosphorodiamidate (C28H33N2O2P, Mr = 460.53), has been synthesized and characterized by 31P NMR, 1H NMR and elemental analysis. X-ray diffraction analysis at 273(2) K indicates that it belongs to orthorhombic system, space group P212121 with a = 11.518(4), b = 13.449(4), c = 16.539(5) ? V = 2562(1) 3, Z = 4, Dc = 1.194 g/cm3, F(000) = 984 and m(MoKa) = 0.134 mm-1. The structure parameters were refined by full-matrix least-squares on F2 to R = 0.0459 and wR = 0.0640. The flack x parameter is 0.03(10), and the absolute configuration of the phosphorus atom in the title compound is S.

Absolute Configuration of the Levocloperastine Fendizoate

Crystal structure of the levocloperastine fendizoate （C80H76Cl2N2O10, C20H25ClNO＋· C20H13O4-） has been determined by single-crystal X-ray diffraction. The crystal is of triclinic system, space group P1 with a = 10.1059（18）, b = 11.957（2）, c = 15.383（3） , α = 104.666（2）, β = 90.9700（10）, γ = 110.744（2）°, Z = 1, V = 1670.0（5） 3, Dc = 1.289 g/cm3, F（000） = 684, μ（MoKα） = 0.161 mm-1, Mr = 1296.33, the final R = 0.0343 and wR = 0.0676. The cations and anions are linked by the COO…NH hydrogen bonds of 2.709（3） and 2.690（3） and COO…OH hydrogen bonds of 2.632（3） and 2.631（3） . The configuration of the only one chiral carbon atom in this compound is R（rectus）.

Two New Compounds from Schisandra propinqua var.propinqua

Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.

Enantiomeric characterization and structure elucidation of Otamixaban

Otamixaban is a potent （Ki=0.5 nM） fXa inhibitor currently in late-stage clinical develop-ment at Sanofi for the management of acute coronary syndrome. Being unproductive in obtaining a suitable crystal of Otamixaban, the required enantiomeric characterization has been accomplished using vibrational circular dichroism （VCD） spectroscopy. Selected by a spectrum similarity index, the calculated spectra of several higher energy conformers were found to match well with the observed spectra. The characteristic IR bands of these conformers were also identified and attributed to the solvation effect. Combined with both the single crystal x-ray diffraction results for an intermediate and the proton NMR study, the absolute configuration of Otamixaban is unambiguously determined to be （R,R）.

Crystal and Molecular Structure of N-(1-Ethoxycarbonyl- ethyl)1-Ethoxycarbonylmethyl-3-ethyl-1,2,3,4- tetrahydro-4-oxo-1,3,2-benzodiazaphosphorin- 2-carboxamide 2-Oxide

The crystal structure of the title compound N-(1-ethoxycarbonyl-ethyl) 1-ethoxycarbonylmethy-3-ethyl-1,2,3,4-tetrahydro-4-oxo-1,3,2-benzodiazaphosphorin-2-carbox amide 2-oxide, (C19H_26N3O7P, Mr = 439.41), was determined by single crystal X-ray diffraction at 299(1) K. It crystallizes in the triclinic system, space group P (No.2) with a = 8.955(2), b = 11.863(2), c = 12.309(2) ?, ( = 62.67(3),β= 68.10(3), ( = 78.07(3)(, V = 1077(1) ?3, Z = 2, Dx =1.355 g·cm－3, ( = 0.71073 ?, ( = 0.1657 mm－1 and F(000) = 464. The structure was solved by direct methods. The final R factor is 0.071 and Rw is 0.076 for 2176 observed reflections with I ≥3((I). The results from X-ray crystallography analysis of the isomer with 31P NMR spectra exhibited as ( 4.09 show that the absolute configuration of the chiral phosphorus atom at P(1) was proved to be S-form, with reference to the known configuration of R-alanine moiety.

Setosphlides A-D, New Isocoumarin Derivatives from the Entomogenous Fungus Setosphaeria rostrate LGWB-10

Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives,setosphlides A-D(1-4),and four known analogues(5-8).Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods.The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra.The C-10 relative configurations for the pair of C-10 epimers(1 and 2)were established by comparing the magnitude of the computed 13C NMR chemical shifts(Δδcalcd.)with the experimental 13C NMR values(Δδexp.)for the epimers.All of the isolated compounds(1-8)were evaluated for their cytotoxicities against four human tumor cell lines MCF-7,MGC-803,HeLa,and Huh-7.

Chemical Constituents from the Stems of Ecdysanthera rosea

One new eudesmane sesquiterpenoid(1)named ecdysantherol A and two new benzene derivatives ecdysantherols B(2)and C(3),together with five known benzene derivatives(4–8)were isolated from the stems of Ecdysanthera rosea.The structures of the new compounds were elucidated by extensive spectroscopic methods and X-ray diffraction.The known compounds were identified by the comparison of their spectroscopic data with reported literature data.Compound 1 showed moderate antibacterial activity against the Providensia smartii with MIC value of 12.5 lg/mL.

New benzene derivatives from cultures of ascomycete Daldinia concentrica

Three new benzene derivatives,named daldins A-C(1-3),together with a known analogue,2-hydroxymethyl-3-(1-hydroxypropyl)phenol(4)have been isolated from cultures of ascomycete Daldinia concentrica.The structures of 1-4 with absolute configuration were established by means of spectroscopic methods and X-ray diffraction.All compounds showed no significant inhibition on five human cancer cell lines with IC50 values>40μmol.

Absolute Structure Determination of Chiral Organic Nanocrystals Using Zone-Axis Electron Diffraction

Enantiomorphic identification of chiral molecules is essential in organic chemistry and the pharmaceutical industry,as two enantiomorphic structures can show distinctively different properties.Here,we illustrate the absolute structural determination of organic nanocrystals using zone-axis electron diffraction by taking advantage of electron multiple scattering.Two enantiomorphs are distinguished by comparing the reflection intensities of Friedel pairs in the zone-axis electron diffraction pattern,after confirming the absolute indices of reflections by locating relative positions of diffraction spots from two patterns that deviate from a certain angle.We demonstrate the protocol with successful applications in two chiral drug nanocrystals.

Sarcocinerenoids A—J,Eight Rare Capnosane-Type and Two New Cage-Type Cembranoids with Promoting Angiogenesis Activity from the South China Sea Soft Coral Sarcophyton cinereum

Backgroundand Originality Content,Cembranoids are a structurally diverse class of diterpenoids commonly occurring in marine and terrestrial organisms.(+)-Cembrene was the first reported cembranoid diterpenoid discovered in 1962,l and more than 1400 cembranoid diterpenoids have been identified in the last six decades,[2]Cembranoids are characterized by a 14-membered carbocyclic ring,an isopropyl group and three methyl groups,which form their core carbon skeleton.Enzymatic processes such as oxidation,oxidative rearrangements and transannular cyclizations occur in organisms,leading to the formation of distinctive specialized metabolites such as epoxide,lactone,ester,furan,pyrane and other ringbased cembranoids.[2-3]

Absolute configuration of Buagafuran:An experimental and theoretical electronic circular dichroism study

Buagafuran is a novel drug candidate derived from natural product.Its absolute configuration has been confirmed by electronic circular dichroism combined with modern quantum-chemical calculation using time-dependent density functional theory.The predicted UV absorbance peak is underestimated by several nanometers compared with the experimental data.The applicability of empirical rule for the C=C-C-O system in Buagafuran has also been discussed.Our results show that electronic circular dichroism could be a useful tool for the absolute configuration assignment of chiral drugs,especially for the oily or semisolid substances,whose crystal structures are impossible to obtain.

Synthesis and Absolute Configuration of(2R,3S,4Z,6Z)-1,3-bis(benzyloxy)-8-chloro-7-((E)-(2-(2,4-dinitrophenyl)hydrazono)methyl)octa-4,6-dien-2-ol

Lewis acid-catalyzed[1,3]-sigmatropic O→C rearrangement was used to synthesize C-glycosides derivatives.The structure of the target compound was characterized by NMR and HR-ESI-MS,and its absolute configuration was confirmed.Compound 8(C(29)H(29)ClN4O7):monoclinic system,space group P212121,a=6.1484(2),b=12.3625(3),c=37.0127(8)A,V=2813.32(13)A3,Z=4,F(000)=1216.0,Dc=1.372 g/cm^3,μ=1.662 mm^1,R=0.0522 and wR=0.1358 for 5611 independent reflections(R(int)=0.0778)and 5169 observed ones(I>2σ(I)).

Synthesis and Absolute Configuration of((2R,3R,6S)-3-Hydroxy-6-(naphthalen-2-ylthio)-3,6-dihydro-2H-pyran-2-yl)methyl Pivalate

A stereo-selective palladium-catalyzed one-pot Tsuji-Trost reaction was used to prepare fourβ-thiogalactosides from unsaturated D-galactal and thiol.Their structures were characterized by nuclear magnetic resonance spectra and high-resolution electrospray ionization mass spectra.The absolute configuration was confirmed with a Flack parameter of 0.019(15)by X-ray crystallography using a Cu radiation source.Compound 6 a(C_(21)H_(24)O_(4)S):orthorhombic system,space group P2_(1)2_(1)2_(1),a=9.0919(4),b=9.6313(4),c=22.5936(11)A,V=1978.45(15)A^(3),Z=4,F(000)=792,D_(c)=1.250 g/cm^(3),μ=1.636 mm^(-1),R=0.0478 and wR=0.1384 for 3621 independent reflections(Rint=0.0390)and 3326 observed ones(I>2σ(I)).3-(4,5)-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide(MTT)cell viability assays indicated that these thiogalactosides showed anti-proliferative activities against human gastric cancer HGC-27 cells with IC_(50)values of 69~88μM.

Methods for determination of absolute configuration of monosaccharides

Monosaccharides are one of the most important structural components of biomolecules, such as polysac- charides, nucleic acids, glycolipids and glycoproteins. In structural analysis of polysaccharides and gly- coconjugates, the absolute configurations （D or L） of the constituent monosaccharides are usually deter- mined by measurement of the optical rotation, CD spectra or characteristic chromatographic retention behavior. However, each method has its unique advantages and limitations which should be considered while using them. In this review, an overview of the different methods for the determination of absolute configuration of monosaccharides and their underlying principles are summarized to serve as a reference for researchers.