Absolute Konfiguration der Equisetumalkaloide (+)-Palustrin,Palustridin ((+)-Monohydrochlorid) sowie der (−)-Dihydropalustraminsäure und weiterer Derivate. 16. Mitteilung über Schachtelhalmalkaloide

Determination of the absolute configuration of alkaloids from Equisetum sp.,e.g. (+)-palustrin, palustridin ((+)-hydrochloride), and (?)-dihydropalustramic acid and derivatives The absolute configuration of the title alkaloids has been determined using chiroptical methods (ORD., superposition of CD. values of appropriate models and a modified Horeau method). (+)-Palustrin is (13R, 17 S, 1′S)-17-(1-hydroxypropyl)-1,5,10-triazabicyclo [11.4.0]heptadec-15-en-11-on.     

Absolute configuration of C76 from optical rotatory dispersion.

The absolute configuration of C76 has been determined as (+)589-(fC)-C76 , for the first time, by comparing the experimental and predicted optical rotatory dispersion (ORD) patterns. The experimental ORD pattern was derived from the experimental electronic circular dichroism (ECD) spectrum using the Kramers-Kronig (KK) transform. The theoretical ORD spectra were calculated in the resonant region using linear response theory, and also using the KK transform of the theoretical ECD spectrum, at different theoretical levels, namely BHLYP/6-31G*, B3LYP/6-31G*, BLYP/6-31G*, and HF/6-31G*. Good agreement noted between experimental and predicted spectra allows for an unambiguous determination of the absolute configuration.     

Determination of the absolute configuration of [3(2)](1,4)barrelenophanedicarbonitrile using concerted time-dependent density functional theory calculations of optical rotation and electronic circular dichroism

The technique of time-dependent density functional theory (TDDFT) has very recently been applied to the calculation of both transparent spectral region optical rotations and electronic circular dichroism (CD). Here, we report the concerted application of the new methodologies to the determination of the absolute configuration (AC) of [3(2)](1,4)barrelenophanedicarbonitrile, 1, the first optically active barrelenophane. 1 is conformationally flexible: the two three-carbon bridges of 1 can each exhibit two conformations, leading to three inequivalent conformations of 1: a, b, and c. Conformational structures and energies are predicted using DFT at the B3LYP/6-31G level. Comparison of the calculated structures to structures obtained via X-ray crystallography of (+)-1 shows that (remarkably) all three conformations a-c are simultaneously present in crystalline (+)-1. The sodium D line specific rotations, [alpha](D), and CD spectra of a-c are calculated using TDDFT at the B3LYP/aug-cc-pVDZ level. Comparison of the conformationally averaged specific rotation and CD spectrum to the experimental data of Matsuda-Sentou and Shinmyozu leads to the AC 9S,12S(+)/9R,12R(-). The same AC is obtained both from [alpha](D) and from the CD, strongly supporting its reliability.     

Determination of the absolute configuration of flexible molecules by ab initio ORD calculations: a case study with cytoxazones and isocytoxazones

Ab initio calculations of the optical rotatory power of the natural cytokine modulator cytoxazone 1 and its trans-diastereomer 2, as well as the structural isomers cis-3 and trans-4 isocytoxazones, have been performed at four different wavelengths (589, 546, 435, and 405 nm) by Density Functional Theory. The calculation of ORD curves provides a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The absolute configurations of isocytoxazones has been established as (+)-(4R,5S)-cis-3 and (+)-(4S,5S)-trans-4.     

Determination of the absolute configurations of natural products via density functional theory calculations of vibrational circular dichroism, electronic circular dichroism, and optical rotation: the iridoids plumericin and isoplumericin

The absolute configurations (ACs) of the iridoid natural products, plumericin (1) and isoplumericin (2), have been re-investigated using vibrational circular dichroism (VCD) spectroscopy, electronic circular dichroism (ECD) spectroscopy, and optical rotatory dispersion (ORD). Comparison of DFT calculations of the VCD spectra of 1 and 2 to the experimental VCD spectra of the natural products, (+)-1 and (+)-2, leads unambiguously to the AC (1R,5S,8S,9S,10S)-(+) for both 1 and 2. In contrast, comparison of time-dependent DFT (TDDFT) calculations of the ECD spectra of 1 and 2 to the experimental spectra of (+)-1 and (+)-2 does not permit definitive assignment of their ACs. On the other hand, TDDFT calculations of the ORD of (1R,5S,8S,9S,10S)-1 and -2 over the range of 365-589 nm are in excellent agreement with the experimental data of (+)-1 and (+)-2, confirming the ACs derived from the VCD spectra. Thus, the ACs initially proposed by Albers-Sch?nberg and Schmid are shown to be correct, and the opposite ACs recently derived from the ECD spectra of 1 and 2 by Els?sser et al. are shown to be incorrect. As a result, the ACs of other iridoid natural products obtained by chemical correlation with 1 and 2 are not in need of revision.     

Enantioselective binding of an 11-cis-locked cyclopropyl retinal. The conformation of retinal in bovine rhodopsin

[formula: see text] The conformation of the retinal chromophore in rhodopsin is central for understanding the visual transduction process. The absolute twist around the 12-s bond of the chromophore in rhodopsin has been determined by studies with 11-cis-locked 11,12-cyclopropylretinal analogues (11S,12R)-2 and (11R,12S)-3, enantioselectively synthesized with the aid of an enzyme. The finding that enantiomer 2 binds to opsin while the other 3 does not defines the absolute sense of twist around the 12-s bond.     

Relative and absolute configurations of ganefromycin alpha

The full structure of ganefromycin alpha has been determined. The relative configurations were determined from 3JH,H coupling constants and NOE data, while the absolute configurations in moleties A and B were determined separately by difference CD of their acylate derivatives, which showed typical exciton couplets. The configurations of the stereogenic centers in ganefromycin alpha are 8S, 9S, 11R, 12S, 13S, 21S, 22R, 23R, 24R, and 26S.     

Vibrational-exciton couplings for the amide I, II, III, and A modes of peptides

The couplings between all amide fundamentals and their overtones and combination vibrational states are calculated. Combined with the level energies reported previously (Hayashi, T.; Zhuang, W.; Mukamel, S. J. Phys. Chem. A 2005, 109, 9747), we obtain a complete effective vibrational Hamiltonian for the entire amide system. Couplings between neighboring peptide units are obtained using the anharmonic vibrational Hamiltonian of glycine dipeptide (GLDP) at the BPW91/6-31G(d,p) level. Electrostatic couplings between non-neighboring units are calculated by the fourth rank transition multipole coupling (TMC) expansion, including 1/R3 (dipole-dipole), 1/R4 (quadrupole-dipole), and 1/R5 (quadrupole-quadrupole and octapole-dipole) interactions. Exciton delocalization length and its variation with frequency in the various amide bands are calculated. The simulated infrared amide I and II absorptions and CD spectra of 24 residue alpha-helical motifs (SPE3) are in good agreement with experiment.     

Determining absolute configuration in flexible molecules: a case study

Assigning absolute configuration of molecules continues to be a major problem. Determining absolute configuration in conformationally flexible systems is challenging, even for experts. Here, we present a case study in which we use a combination of molecular modeling, solution NMR, and X-ray crystallography to illustrate why it is difficult to use solution methods alone for configuration assignment. For the case examined, a comparison of calculated and experimental optical rotatory dispersion (ORD) data provides the most straightforward way to assign the absolute configuration.     

Comparison of time-dependent density-functional theory and coupled cluster theory for the calculation of the optical rotations of chiral molecules

A comparison of the abilities of time-dependent density-functional theory (TDDFT) and coupled cluster (CC) theory to reproduce experimental sodium D-line specific rotations for 13 conformationally rigid organic molecules is reported. The test set includes alkanes, alkenes, and ketones with known absolute configurations. TDDFT calculations make use of gauge-including atomic orbitals and give origin-independent specific rotations. CC rotations are computed using both the origin-independent dipole-velocity and origin-dependent dipole-length representations. The mean absolute deviations of calculated and experimental rotations are of comparable magnitudes for all three methods. The origin-independent DFT and CC methods give the same sign of [alpha]D for every molecule except norbornanone. For every large-rotation ketone and alkene for which DFT and CC yield the incorrect sign as compared to liquid-phase experimental data, the corresponding optical rotatory dispersion (ORD) curve is bisignate, suggesting that the two models cannot reliably reproduce the relative excitation energies and antagonistic rotational strengths of multiple competing electronic states that contribute to the total long-wavelength rotation. Several potential sources of error in the theoretical treatments are considered, including basis set incompleteness, vibrational and temperature effects, electron correlation, and solvent effects.     

Assignment of absolute configuration of a chiral phenyl-substituted dihydrofuroangelicin

A phenyl-substituted chiral dihydrofuroangelicin, 4-methyl-8-(2-E-phenylethenyl)-8,9-dihydro-2H-furo[2,3-h]- 1-benzopyran-2-one, synthesized in racemic form, has been resolved by HPLC chiral separation, and its absolute configuration determined by the non-empirical exciton chirality method. The solution conformation has been investigated through NMR and molecular modeling methods: two minima found by molecular mechanics and DFT methods are in keeping with observed 1H-1H 3J coupling constants and NOE effects. The experimental CD spectrum for the second eluted enantiomer shows a positive couplet between 230 and 350 nm (amplitude A = + 15.7); by application of the exciton chirality method, the absolute configuration of this enantiomer at C8 is determined as (S). The experimental spectrum is in very good agreement with the one evaluated by means of DeVoe coupled-oscillator calculations, using the DFT calculated geometries.     

Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR: basis and applications

[structures: see text] The absolute configuration of 1,2-, 1,3-, 1,4-, and 1,5-diols formed by two secondary (chiral) hydroxy groups can be deduced by comparison of the NMR spectra of the corresponding bis-(R)- and bis-(S)-MPA esters. The correlation between the NMR spectra of the bis-ester derivatives and the absolute stereochemistry of the diol involves the comparison of the chemical shifts of the signals for substituents R1/R2 and for the hydrogens attached to the two chiral centers [H(alpha)(R1) and H(alpha)(R2)] in the bis-(R)- and the bis-(S)-ester and is expressed as delta deltaRS. Theoretical calculations [energy minimization by semiempirical (AM1), ab initio (HF), DFT (B3LYP), and Onsager methods, and aromatic shielding effect calculations] and experimental data (NMR and CD spectroscopy) indicate that in these bis-MPA esters, the experimental delta deltaRS values are the result of the contribution of the shielding/deshielding effects produced by the two MPA units that combine according to the actual stereochemistry of the diol. The reliability of these correlations is demonstrated with a wide range of diols of known absolute configuration derivatized with MPA and 9-AMA as auxiliary reagents. A simple graphical model that allows the simultaneous assignment of the two asymmetric carbons of a 1,n-diol by comparison of the NMR spectra (delta deltaRS signs) of its bis-(R)- and bis-(S)-AMAA ester derivatives is presented.     

Basicity of nucleophilic carbenes in aqueous and nonaqueous solvents-theoretical predictions

The complete basis set method CBS-QB3 was used in conjunction with the CPCM solvation model to predict both the absolute and relative pKa's of 12 nucleophilic carbenes in dimethyl sulfoxide (DMSO), acetonitrile (MeCN), and water. Average absolute pKa values in DMSO ranged from 14.4 +/- 0.16 for 3-methylthiazol-2-ylidene (12) to 27.9 +/- 0.23 in the case of bis(dimethylamino)carbene (11), while values in MeCN were determined to be between 25.7 +/- 0.16 (12) and 39.1 +/- 0.25 (11). Relative pKa calculations yielded similar results. Calculations in aqueous solution gave pKa's between 21.2 +/- 0.2 (12) and 34.0 +/- 0.3 (11). Excellent agreement between calculated and experimental pKa's was obtained for the few cases where experimental numbers are available, confirming that this theoretical approach may be used to calculate highly accurate pKa values.     

Chiroptical spectroscopic determination of molecular structures of chiral sulfinamides: t-butanesulfinamide

The absolute configuration of t-butanesulfinamide has been determined as (-)-(S) using three different chiroptical spectroscopic methods, namely, vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotatory dispersion (ORD). Furthermore, the predominant conformation of this molecule is determined to have S=O and NH2 groups staggered with respect to the three methyl groups and to have amine hydrogens in gauche orientation with respect to S=O. The quality of predictions obtained for vibrational properties, namely, vibrational absorption and VCD, is found to be satisfactory with the B3LYP functional and 6-31G* basis set. However, this basis set is found to be inadequate for obtaining reliable predictions of electronic properties, namely, electronic absorption and ECD, but a larger aug-cc-pVDZ basis set is found to provide satisfactory prediction of electronic properties. t-Butanesulfinamide serves as an example which invalidates the recommendation of using the 6-31G* basis set for molecules that exhibit the same sign for the long-wavelength ECD band and ORD. This molecule also emphasizes the importance of simultaneous investigation of ECD and ORD, and the use of multiple chiroptical spectroscopic methods, for reliable determination of molecular stereochemistry.     

Studies on the constituents of Gentiana species. II. A new triterpenoid,and (S)-(+)- and (R)-(-)-gentiolactones from Gentiana lutea

A new triterpenoid, 12-ursene-3beta, 11alpha-diol 3-O-palmitate (1), has been isolated from the rhizomes and roots of Gentiana lutea, together with the artificial diene derivative, 9 (11), 12-ursadien-3beta-ol 3-O-palmitate (1a) and five known compounds (3-7). Their structures were established on the basis of spectral analysis. In addition, (+/-)-gentiolactone [(+/-)-2], isolated from this plant, was successfully separated into its enantiomers [(+)-2, (-)-2] for the first time, and the absolute configurations at C-9 of (+)-2, (-)-2 were assigned as S and R, respectively, from the optical rotations and the circular dichroism (CD) spectral data.     

Modeling the solvation of peptides. The case of (s)-N-acetylproline amide in liquid water

The structure and properties of (s)-N-acetylproline amide (NAP) in aqueous solution are studied by exploiting a continuum solvation model. The conformational preference of NAP as a function of the environment is discussed as well as data for a number of chiral and non-chiral spectroscopic and response properties (IR/VCD, Raman/VROA, UV/CD, ORD, NMR), whose calculation with the accounting of solvent effects is now possible due to recent developments introduced in the PCM approach. When available, calculated results are compared with experimental data, so as to evaluate the quality of the continuum approach to the solvation of this system.     

Synthesis and determination of the absolute configuration of fugomycin and desoxyfugomycin: CD spectroscopy and fungicidal activity of butenolides

The dibromoalkenes (S)-3 and (R)- and (S)-4 are intermediates in the syntheses of the naturally occurring fungicidal butenolides fugomycin (1) and desoxyfugomycin (2), respectively. The stereoselective bromine-lithium exchange that leads to the carbenoid 12 and the vinyllithium reagent 17 a on the one hand, and palladium-catalyzed coupling reactions of the dibromoalkene 3 and the bromolactone 22 on the other are key steps en route to the butenolides 1 and 2. The chiral building blocks (S)-3, (R)-4, and (S)-4 are readily available from (R)-isopropylideneglyceraldehyde 5, isobutyl (R)-lactate 6 a, and ethyl (S)-lactate 6 b, respectively. The synthetic procedure adopted here permits the absolute configuration of the natural products fugomycin (1) and desoxyfugomycin (2) to be assigned by comparison of their chiroptical properties with those of the synthetic products. The CD spectra of the bromolactone 22, calculated by two different density functional methods (TDDFT, DFT/MRCI), are found to be in good agreement with the measured spectra. On the basis of these calculations, the two CD bands observed could be assigned to n-pi* and pi-pi* transitions, respectively. Fugomycin (1) and the synthetic butenolide 20 displayed high fungicidal activity against botrytis in greenhouse experiments, whereas the saturated lactone 21 was practically inactive.     

Separation of Leucas aspera,a medicinal plant of Bangladesh,guided by prostaglandin inhibitory and antioxidant activities

According to the traditional usage of the plant for antiinflammation and analgesia, Leucas aspera was tested for its prostaglandin (PG) inhibitory and antioxidant activities. The extract showed both activities, i.e., inhibition at 3 x 10(-4) g/ml against PGE(1)- and PGE(2)-induced contractions in guinea pig ileum and a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities in these dual assay methods provided eight lignans and four flavonoids, LA-1- -12, among which LA-1- -7 and LA-10- -12 were identified as nectandrin B, meso-dihydroguaiaretic acid, macelignan, acacetin, apigenin 7-O-[6"-O-(p-coumaroyl)-beta-D-glucoside], chrysoeriol, apigenin, erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol, myristargenol B, and machilin C, respectively. LA-8 was determined to be (-)-chicanine, the new antipode of the (+) compound, by spectroscopic methods including CD and ORD. Chiral-HPLC analysis of LA-9 showed that it was a mixture of two enantiomers, (7R, 8R)- and (7S, 8S)-licarin A. All of these components were first isolated from L. aspera. PG inhibition was observed in LA-1, LA-2, and LA-5, and antioxidant activity in LA-1- -3 and LA-8- -12.     

土槿皮乙酸的绝对构型

报导了用圆二色散激子手性法测下土槿皮乙酸的绝对构型, 结果表明具有3s, 4s,10R及11R的绝对构型.