Cis-diastereoselectivity in pictet-spengler reactions of L-tryptophan and electronic circular dichroism studies.

The diastereoselective synthesis of optically active 1,3-disubstituted tetrahydro-ß-carbolines using polar protic Pictet-Spengler cyclization of (S)-tryptophan methyl ester with five aldehydes RCHO (R═CH(3), C(2)H(5), C(3)H(7), C(4)H(9), and C(6)H(5)) was studied. As an alternate route, the cyclization of (S)-tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro-ß-carboline carboxylic acids were also performed for comparison. (13)C NMR and electronic circular dichroism (ECD) studies and time-dependent density functional theory ECD calculations data established the relative 1,3 cis/trans and the absolute configuration (1S,3S/ 1R,3S) of the synthesized compounds. The solid-state and solution ECD study of the prepared compounds, supported by ECD calculation and X-ray data, afforded a reliable ECD method for the configurational assignment of 1,3-disubstituted tetrahydro-ß-carbolines and revealed the stereochemical factors that determine the characteristic ECD data.

Optimizing dirhodium(II) tetrakiscarboxylates as chiral NMR auxiliaries.

Thirteen enantiopure paddlewheel-shaped dirhodium(II) tetrakiscarboxylate complexes have been checked for their efficiency in the dirhodium method (differentiation of enantiomers by NMR spectroscopy); six of them are new. Their diastereomeric dispersion effects were studied and compared via so-called key numbers KN. Adducts of each complex were tested with five different test ligands representing all relevant donor properties from strong (phosphane) to very weak (ether). Only one of them, the dirhodium complex with four axial (S)-N-2,3-naphthalenedicarboxyl-tert-leucinate groups (N23tL), showed results significantly better for all ligands than the conventional complex Rh* [Rh(II)(2)[(R)-(+)-MTPA](4); MTPA = methoxytrifluoromethylphenylacetate]. On the basis of (1)H{(1)H} NOE spectroscopy and X-ray diffraction, a combination of favourable anisotropic group orientation and conformational flexibility is held responsible for the high efficiency of N23tL in enantiodifferentiation. Both complexes, Rh* and N23tL, are recommended as chiral auxiliaries for the dirhodium experiment.

Adamantanes as spherical nanosondes in adducts with a chiral dirhodium complex-discriminating enantiomers and probing spatial proximities.

Three different kinds of substituted chiral adamantane molecules-adamantanones, dioxolanoadamantanes and dithiolano-adamantanes-were studied in the dirhodium experiment (NMR measurement with 1:1 molar mixtures with Rh((II))(2)[(R)-(+)-MTPA](4) in CDCl(3)). Their different behavior in adduct formation is described, and the possibility of determining enantiomeric purities and absolute configurations is explored. Detailed inspection of one- and two-dimensional NMR experiments allowed for an interpretation of steric and electronic intra-adduct interaction showing that the phenyl groups of Rh* tend to enwrap the bound adamantane ligand so that through-space effects over a range of 6-7 Å away from the binding rhodium atom can be observed. Even slight differences in the relative orientation of phenyl groups can be monitored when comparing diastereomeric adducts via NMR signal dispersion.

Experimental verification of diverging mechanisms in the binding of ether, thioether, and sulfone ligands to a dirhodium tetracarboxylate.

Complexation of the oxygen atom in 2-butylphenylethers and sulfur in 2-butylphenylthioethers to a rhodium atom in dirhodium tetracarboxylate Rh((II)) (2)[(R)-(+)-MTPA](4) is compared. Oxygen atoms complex via electrostatic attraction exclusively leading to an increase in alpha effects on C-2 complexation shifts in the sequence OCH(3) > F > Br > NO(2). However, that trend is opposite in thioethers. This can be rationalized by an additional highest occupied molecular orbital (HOMO)-LUMO interaction and the response of this interaction upon complex formation shifts. Thereby, an experimental evidence was found for the existence of the HOMO-LUMO binding mechanism which has been proposed previously based on theoretical considerations and indirect spectroscopic evidence. Sulfones hardly bind to Rh((II)) (2)[(R)-(+)-MTPA](4). Diastereomeric dispersion effects at (13)C and (1)H signals can be observed for all compounds indicating that enantiodifferentiation is easy in all classes of functionalities.

Novel double functional protection of cephalostatin analogues using a gas-free chlorination method.

Herewith, we report on a method that allows to simultaneously protect both the ∆14,15 bond and the carbonyl group of the symmetrical bis-steroidal diketone 2. We found that environmentally friendly and gas-free chlorination is ideally suited to achieve this goal. This method was discovered during our efforts to methoxylate 2 in a solution of dichloromethane and basic methanol in the presence of diacetoxy iodobenzene. Unexpectedly, the ∆14,15 bonds were chlorinated once as well as twice in a statistical manner. Interestingly, the singly dichlorinated desymmetrized product is an ideal precursor for conduction a series of position selective transformations. Importantly, the carbonyl group present in the nonchlorinated hemisphere can be selectively reduced, olefinated or oximated, while the other carbonyl group stays unaltered. A structurally related "monomeric" steroid derivative undergoes ∆14,15 chlorination and 11-position methoxylation under same conditions. These findings represent a powerful entry for preparing new nonsymmetrical cephalostatin derivatives.

Chiral recognition of ethers by NMR spectroscopy.

Enantiomers of chiral ethers and acetals are notoriously difficult to differentiate because their reactivity is low and they are poor donors to any Lewis acid or metal ion. As an exception, epoxides are somewhat better donors. This review describes the properties of ethers, explains NMR methods for their chiral recognition and describes successful examples of ether differentiation. The majority of literature reports deals with chiral lanthanide shift reagents and dirhodium tetracarboxylate complexes, which were used as enantiopure auxiliaries to create diastereomeric adducts with dispersed (1)H and (13)C NMR signals. The various methods are compared as to which is best suited for which purpose.

Comparing various chiral dirhodium tetracarboxylates in the dirhodium method.

Three enantiopure dirhodium tetracarboxylates are compared in their NMR properties to differentiate chiral ligands of various kinds (dirhodium method). The complex with four (S)-2-methoxy-2-(1-naphthyl) propionate (MalphaNP) residues (Rh2) is slightly better for strong donors than the complex with four Mosher acid anions (Rh1), but it is inferior for weak donors. On the other hand, the dirhodium tetracarboxylate complex with four (S)-N-phthaloyl-(S)-tert.-leucinate residues (Rh3) is generally more effective than Rh1. These results are explained by the estimated conformational behavior of the substituents within the equatorial acid residues and the anisotropy (ring-current) effect of aryl groups.

A new method proposed for the determination of absolute configurations of alpha-amino acids.

Enantiopure alpha-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl(3), an equimolar amount of the chiral dirhodium complex Rh(II)(2)[(R)-(+)-MTPA](4) (MTPA-H = Mosher's acid) was added, and the (1)H NMR spectra of the resulting samples were recorded (dirhodium method). The relative intensities of (1)H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting alpha-amino acids. Binding atoms in the adducts were identified by comparing the (1)H and (13)C chemical shifts of the oxazolones in the absence and presence of Rh(II)(2)[(R)-(+)-MTPA](4). Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented.

Origin of 13C complexation shifts in the adduct formation of 2-butyl phenyl ethers with a dirhodium tetracarboxylate complex.

Complexation of the oxygen atom in 2-butyl phenyl ethers to a rhodium atom of the dirhodium tetracarboxylate Rh(II) 2[(R)-(+)-MTPA]4(Rh*, MTPA-H = methoxytrifluoromethylphenylacetic acid identical with Mosher's acid) deshields an sp3-hybridized 13C nucleus directly bonded to the ether oxygen; apparently, the inductive effect of the oxygen is enhanced when it is complexed to the rhodium atom. On the other hand, deshielding complexation shifts of aromatic ipso-carbons (alpha-positioned) are minute but ortho- and para-carbon signals are influenced by the resonance effect of oxygen. This effect can be modulated by further substituents at the benzene ring. In turn, this modulation of the resonance correlates linearly ith the magnitude of the inductive effect exerted on the aliphatic alpha-carbon atoms. Diastereomeric dispersion effects at 13C signals can be observed for most compounds, indicating that enantiodifferentiation is possible in this class of ethers.

Chemotypes in Achillea collina based on sesquiterpene lactone profile.

The lactone profile of six origins of Achillea collina growing in Bulgaria was studied and significant variability was observed. The reasons for the differences in the lactone composition are discussed. Twenty-five components in total were isolated and identified, while the presence of ten lactones was proved by intensive TLC analysis in comparison with reference compounds. The structures of the components 17, 20, 25-30 were established by spectroscopic methods. The structure of 7, a cyclization product of 6, was also discussed. The anti-inflammatory activity of some extracts, fractions and individual compounds was tested in vitro by determining the inhibitory effects on induced human neutrophils.

Sesquiterpene lactones from Achillea collina J. Becker ex Reichenb.

The flower heads of Achillea collina afforded 31 individual sesquiterpene lactones, among which nine guaianolides (1, 16, 20, 21, 23, 27-30), a germacranolide (18) and a dimeric guaianolide (31) were found to be new natural products. The lactones 2-4, 12, 14, 15, 17, 19 and 25 were isolated for the first time from the investigated species. Their structures were established by spectral methods.

Iridoid and lignan glycosides from Citharexylum spinosum L.

From the aerial parts of Citharexylum spinosum L., one new iridoid glucoside, the 7-ss-O-acetate (1) of lamiide, along with four known iridoid glucosides, lamiide (2), lamiidoside (3), duranterectoside C (4), 8-epiloganin (5) and one known lignan glucoside (+)-lyonirenisol-3a-O-ss-D-glucopyranoside (6) were isolated. The compound structures were established by one- and two-dimensional 1H- and 13C-NMR as well as by ESI-MS spectra.

Glycosides from Bougainvillea glabra.

Three glycosides were isolated from Bougainvillea glabra and their structures were determined by extensive use of 1D and 2D NMR spectroscopy ((1)H and (13)C). First compound was identical to momordin IIc (quinoside D) [beta-D-glucopyranosyl 3-O-[beta-D-xylopyranosyl-(1 --> 3)-O-(beta-D-glucopyranosyluronic acid)] oleanolate], second compound was quercetin 3-O-alpha-L-(rhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopy-ranosyl(1 --> 2)]-beta-D-galactopyranoside and third compound was its derivative quercetin 3-O-alpha-L-(4-caffeoylrhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-galactopyranoside, a new natural product.

Isolation and structural elucidation of 3,4',5,7-tetraacetyl quercetin from Adina cordifolia (Karam ki Gaach).

3,4',5,7-tetraacetyl quercetin (1) was isolated from the heartwood of Adina cordifolia. The structure was elucidated on the basis of spectral evidence.

Antimicrobial activity and cytotoxicity of Carthamus lanatus.

Total dichloromethane, methanol and water extracts, their fractions as well as volatiles of Carthamus lanatus aerial parts were phytochemically screened and evaluated for antibacterial, antifungal and cytotoxic activity. The H(2)O/MeOH fraction of the CH(2)Cl(2) extract exhibited noticeable antibacterial activity. The same fraction and the volatiles showed significant cytotoxic activity.

Bioactive phenolics from Carthamus lanatus L.

Two flavonoid aglycons, eight flavonoid glycosides, chlorogenic acid and syringin were isolated from aerial parts of Carthamus lanatus. Isorhamnetin 3-O-beta-D-glucoside and chlorogenic acid were found for the first time in the genus Carthamus and respectively, quercimeritrin, astragalin, kaempferol 3-O-beta-D-sophoroside and syringin in the species. The ethyl acetate fraction of the methanol extract exhibited a higher antioxidant activity than the butanol fraction measured by the alpha,alpha-diphenyl-beta-picrazylhydrazyl (DPPH) free radical scavenging assay. Cytotoxicity and antioxidant activities of the main constituent, luteolin 7-O-beta-D-glucoside, were evaluated.

Oxygenated bisabolane fucosides from Carthamus lanatus L.

The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10-hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and stigmasterol 3-O-beta-D-glucoside. Asperuloside appears to be the second representative of the iridoid monoterpene group found in the plant family Asteraceae, which until recently was considered to lack iridoids. The main constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic activities.

Clastogenic effect of Carthamus lanatus L. (Asteraceae).

The clastogenic effect of total dichloromethane, methanol and water extracts, four bioactive fractions and three individual constituents from Carthamus lanatus aerial parts were evaluated in mice by bone marrow chromosome aberration assay with mitomycin C as positive control. Significant differences in the percentage of aberrant mitosis of the extracts were observed. The dichloromethane extract exhibited a considerable clastogenic effect and the water extract a negligible one. Different types of chromosome aberrations and time-dependant effects for the active fractions and individual compounds were found.

In vitro anti-inflammatory effect of Carthamus lanatus L.

The anti-inflammatory activity of four total extracts, their fractions and two main constituents (alpha-bisabolol beta-D-fucopyranoside and luteolin 7-O-glucoside) of Carthamus lanatus L. aerial parts, were assessed in vitro by determining the inhibitory effects on induced human neutrophils. The dichloromethane extract and its water-alcoholic part exhibited the most significant inhibitory effects.

Competition of ester, amide, ether, carbonate, alcohol and epoxide ligands in the dirhodium experiment (chiral discrimination by NMR spectroscopy).

Thirty-eight derivatives of 3-hydroxy-2-methylpropanoic acid, each with two different oxygen functionalities, were synthesized and subjected to the standard dirhodium experiment (1H NMR in the presence of an equimolar amount of the chiral dirhodium tetracarboxylate complex Rh*). Their structures represent ester, amide, carbonate, ether, alcohol and/or epoxy groups. Significant selectivity in the binding of those oxygen groups to the complex were determined. From these results, a priority list in binding to a rhodium atom of Rh* was established: epoxides > primary alcohols > ethers > or = esters > or = amides > carbonates > tertiary alcohols. This sequence allows the prediction of the preferred binding site of oxygen-containing groups in polyfunctional compounds, which frequently occur among natural products, and, particularly, in asymmetric synthesis of such compounds. Differentiation of the enantiomers by the dirhodium experiment is easily accomplished due to numerous signal dispersions in nearly all cases.