A borderline case between meso and stable C1: an axially chiral, yet configurationally semi-stable biphenyl with two oppositely configured [10]paracyclophane portions

The synthesis of the bi[10]paracyclophanes 2 and 4 from the meso-configured bioxepine 3 is described. These compounds are stereochemically remarkable: the biaryl axis that connects the constitutionally identical, but oppositely configured planar-chiral paracyclophane portions, is configurationally semi-stable. Thus, 2 is an unprecedented borderline case of a (planar-chiral)-(axially chiral)-(planar-chiral) molecule that is right in between a meso-compound (as a macroscopical result of the—albeit slow—rotation about the central C,C-bond) and C₁-symmetry (with respect to the existence of separable—even though configurationally unstable—discrete atropo-enantiomers). Despite their restricted configurational stability, these atropo-enantiomers were resolved on a chiral phase at 5 °C and were stereochemically assigned by LC-CD coupling, in combination with quantum chemical CD calculations.     

Optically active bisbibenzyls from Bazzania trilobata: isolation and stereochemical analysis by chromatographic, chiroptical, and computational methods

Bazzanin S, a new chlorinated bisbibenzyl of the isoplagiochin D type, as well as isoplagiochin D itself were isolated from the liverwort Bazzania trilobata. The structure of bazzanin S was elucidated based on extensive NMR spectral evidence and by mass spectrometry. Both macrocyclic compounds, bazzanin S and isoplagiochin D, as well as previously reported bazzanins exhibit optical activity, but are not enantiopure in nature. The enantiomeric ratios of a broad array of different cyclic bisbibenzyls, isoplagiochin D, bazzanins A-C and F-J, and bazzanin S, were determined by HPLC on a chiral phase. Exemplarily for the halogen-free parent compound isoplagiochin D, elucidation of the absolute configuration was achieved by quantum chemical CD calculations.     

The absolute configuration of streptonigrin

A theoretical study of the molecular circular dichroism (CD) of the antitumor antibiotic natural product streptonigrin is described, aiming at the secure assignment of its absolute configuration by comparison of the CD spectra predicted for M and P, with the experimental one. The stereostructure of streptonigrin was previously investigated by two other groups, yet leading to two different attributions. Although streptonigrin possesses two biaryl axes, only the ‘southern’ one is configurationally stable and thus responsible for the chiroptical properties, since the ‘northern’ AB-ring system of the molecule is kept in plane with ring C by hydrogen bonding. All computational methods applied within this work to simulate the CD spectrum—semiempirical approaches and time-dependent density functional theory (TDDFT)—consistently attribute the M-configuration to streptonigrin.     

Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

The absolute axial configurations of knipholone and knipholone anthrone by TDDFT and DFT/MRCI CD calculations: a revision

Triggered by a seemingly inconsistent twisting direction in the atroposelective ring cleavage reaction of biaryl lactones by using the ‘lactone concept’, the absolute axial configurations of the most important phenylanthraquinones, knipholone (1), and knipholone anthrone (2) were reassigned on the basis of renewed quantum chemical circular dichroism (CD) calculations using advanced, higher-level methods, viz. a time-dependent DFT (TDDFT) and a multireference configurational interaction approach (DFT/MRCI). Additional confirmation of the new configurational assignment of 1 and 2 was achieved by their stereochemically unambiguous interconversion, and further corroborated by the transformation of 1 into an ‘leuco’ phenylanthracene derivative 3, i.e., a compound with a substantially different chromophore, whose absolute configuration was independently assigned again by quantum chemical CD calculations. Accordingly, the dextrorotatory enantiomer of knipholone, (+)-1, and its anthrone, (+)-2, has the P-configuration, while the laevorotatory forms, (−)-1 and (−)-2 (which likewise exist in nature), are M-configured. From this new configurational assignment, the absolute axial stereostructures of a whole series of further naturally occurring phenylanthraquinones may now be deduced.     

Three dimeric anthracene derivatives from the fruits of Bulbine abyssinica

From the fruits of Bulbine abyssinica three new dimeric anthracene derivatives, (P)-8,9,1′,8′-tetrahydroxy-3,3′-dimethyl[10,7′-bianthracene]-1,4,9′,10′-tetraone (trivial name abyquinone A), (10R)-1,4,8,1′,8′-pentahydroxy-3,3′-dimethyl-[10,7′-bianthracene]-9,9′,10′(10H)-trione (trivial name abyquinone B), and (10R)-3′,4′-dihydro-1,4,8,3′,8′,9′-hexahydroxy-3,3′-dimethyl-[10,7′-bianthracene]-9,1′(10H,2′H)-dione (trivial name abyquinone C) were isolated. Despite their structural differences, these three compounds are connected to each other by the apparently biomimetic conversion of abyquinone C (a preanthraquinonylanthrone with two stereogenic centers) into B (an anthraquinonylanthrone with one stereogenic center) and finally into A (an axially chiral bianthraquinone) under mild conditions, involving a highly efficient center-to-axis chirality transfer. In addition, the known anthraquinones islandicin and chrysophanol were identified. The structures were determined on the basis of spectroscopical evidences, chemical transformations, and quantum chemical CD calculations.     

The first sorbicillinoid alkaloids, the antileukemic sorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain

The saltwater culture of a Penicillium chrysogenum strain isolated from the Mediterranean sponge Ircinia fasciculata yielded three new sorbicillin-derived compounds (1-3), whose structures were elucidated mainly by 2D NMR and mass spectrometry. Among them, sorbicillactones A (1) and B (2) are the first sorbicillinoid natural products that contain nitrogen. Compound 1 is anti-HIV active and it exhibits a strong cytotoxic activity against L5178y leukemic cells, combined with a relatively low toxicity to cervical carcinoma HeLa S3 cells and pheochromocytoma PC 12 cells. The absolute configurations of 1 and 2 were elucidated by quantum chemical calculation of circular dichroism (CD) spectra. Another compound isolated, sorbivinetone (3), might be an artifact derived from sorbicillinol (4) by Diels-Alder reaction with ethyl vinyl ether. Furthermore, the known sorbicillinoid fungal metabolites oxosorbicillinol (5), sorbicillin (6), and bisvertinolone (7) were identified, as well as the alkaloids meleagrine and roquefortine C. The biosynthetic origin of sorbicillactone A (1) from acetate, alanine, and methionine was investigated by feeding experiments with ¹³C-labeled precursors.     

Shearinines D-K, new indole triterpenoids from an endophytic Penicillium sp. (strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels

A chemical examination of the endophytic fungus Penicillium sp. isolated from the mangrove plant Aegiceras corniculatum resulted in the isolation and characterization of eight new indole triterpenes named shearinines D-K (1-8), along with shearinine A (9), paspalitrem A (10), and paspaline (11). Their stereostructures were determined by extensive spectroscopic data analyses and quantum chemical circular dichroism calculations. The biosynthetic relationship of all 11 alkaloids is suggested. Shearinines D (1), E (2), and (with reduced potency) G (4) exhibit significant in vitro blocking activity on large-conductance calcium-activated potassium channels.     

Polyisoprenylated benzophenone derivatives from the fruits of Garcinia cambogia and their absolute configuration by quantum chemical circular dichroism calculations

Three new tetracyclic polyisoprenylated xanthones, named oxy-guttiferones M, K2, and I, along with oxy-guttiferone K and guttiferone M, have been isolated from the fruits of Garcinia cambogia. Their structures were elucidated by MS and NMR spectroscopic experiments. The absolute configurations of oxy-guttiferone K, taken as a model of tetracyclic xanthones, and guttiferone M, as a model of polyisoprenylated benzophenones, have been determined by comparison of their experimentally measured circular dichroism (CD) curves with the TDDFT-predicted curves.     

Synthesis and absolute configuration of (1S,8S)-as-hydrindacene-1,8-diol as determined by the circular dichroism exciton chirality method

2,3,6,7-Tetrahydro-as-indacene-1,8-dione 4 was prepared in 4 steps starting from 2-methyl-furan by modification of a literature procedure. Appliance of Noyori’s asymmetric transfer hydrogenation, resulted in (1S,8S)-1,2,3,6,7,8-hexahydro-as-indacene-1,8-diol 5 in high yield (81%) and excellent enantioselectivity (>99% ee) or (8S)-8-hydroxy-3,6,7,8-tetrahydro-2H-as-indacen-1-one 6 in moderate yield (58%) and equally high enantioselectivity (98.5% ee), depending on the conditions. The asymmetric reduction was expected to yield the (S)-alcohols using the (S,S)-Ts-DPEN ligand, which was confirmed by the appliance of the exciton chirality method on the corresponding bis(p-dimethylamino)benzoate 7.     

Bridged bioxepines and bi[10]paracyclophanes—synthesis and absolute configuration of a bi[10]paracyclophane with two chiral planes and one chiral axis

A preparative synthesis of novel bioxepines and bi[10]paracyclophanes with meso- and rac-configuration is described. The bi[10]paracyclophane (−)-6b with two elements of planar chirality and one chiral axis has been obtained in enantiomerically pure form. Its absolute configuration was determined by quantum chemical calculation of the circular dichroism and comparison with the experimental CD spectrum.     

Vincamajorines A and B,monoterpenoid indole alkaloids with new carbon skeletons from Vinca major

Two new monoterpenoid indole alkaloids, vincamajorines A (1) and B (2), were isolated from Vinca major. Their structures were elucidated by means of 1D and 2D NMR, and HREIMS spectroscopic data. The relative and absolute configurations were deduced by comparing the experimental ¹³C NMR, ECD spectra, and OR data with those theoretically calculated. Vincamajorine A (1) represents a new C₂₀ carbon skeleton arranged compactly in seven rings, and vincamajorine B (2) is an alkaloid with an unprecedented 6/5/7/5/6 pentacyclic ring system. A possible biosynthetic pathway was also proposed for the formation of 1 and 2.     

Synthesis of a new chiral cyclic aminal derived from rac-1,2-propanediamine

The cyclic aminal 4,9-dimethyl-1,3,6,8-tetraazatricyclo[4.4.1.1^3,8]dodecane 4c was synthesized by the reaction of commercial rac-1,2-propanediamine with paraformaldehyde in an aqueous solution. ¹H NMR analysis clearly revealed that the compound is chiral and racemic with an axis of chirality. To our knowledge, this is the first example of an azaadamantane derivative having axial chirality. This aminal was used in a Mannich type reaction with p-chlorophenol yielding 2,2′-[(4-methylimidazolidine-1,3-diyl)dimethanediyl]bis(4-chlorophenol) 7 as a racemic mixture. The crystal structure of 7 was determined by single X-ray diffraction analysis.     

Halichonadins A-D, new sesquiterpenoids from a sponge Halichondria sp.

A new dimeric sesquiterpenoid with two eudesmane skeletons through a urea linkage, halichonadin A (1), as well as three new eudesmane sesquiterpenoids having a carbamate, an isonitrile, or an amino functionality, halichonadins B (2), C (3), and D (4), respectively, have been isolated from a marine sponge Halichondria sp., and the gross structures and relative stereochemistry of 1-4 were elucidated on the basis of spectral data and chemical means.     

(N,N) vs. (N,S) chelation of palladium in asymmetric allylic substitution using bis(thiazoline) ligands: A theoretical and experimental study

New thiazoline-containing ligands including non-symmetric bis(thiazolines) and oxazoline-thiazolines were synthesized and then compared to C₂-symmetric bis(thiazolines) in the palladium-catalyzed allylic substitution. The experimental results obtained in this study support the hypothesis of a competition between the (N,N) and the (N,S) palladium chelation, when sterically hindered bis(thiazolines) are used as ligands. A quantum chemical study performed on the Pd-complexes derived from three selected ligands, two C₂-symmetric bis(thiazolines) and one oxazoline-thiazoline, also supports this hypothesis.     

Sphenalactones A-D, a new class of highly oxygenated trinortriterpenoids from Schisandra sphenanthera

Four novel highly oxygenated trinortriterpenoids, sphenalactones A-D (1-4), were isolated from the leaves and stems of Schisandra sphenanthera and their structures were elucidated by extensive analysis of 1D and 2D NMR data. Compounds 1-4 featured a C₂₇ backbone and showed anti-HIV-1 activity with EC₅₀ values in the range of 35.5-89.1 μg/mL with low cytotoxicity against C8166 cells (CC₅₀ > 200 μg/mL).     

Sarusubine A, a new dimeric Lythraceae alkaloid from Lagerstroemia subcostata

A new dimeric Lythraceae alkaloid with a cyclobutane ring, sarusubine A (1), has been isolated from the leaves of Lagerstroemia subcostata, and the structure and stereochemistry were elucidated by spectroscopic data.     

Resolution and chiroptical properties of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) and related compounds: quantum chemical CD calculations and X-ray diffraction analysis

Separation and stereochemical attribution of the two enantiomers of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been achieved by applying chromatography on a chiral phase HPLC column in hyphenation with circular dichroism (CD) spectroscopy (LC-CD coupling). Assignment of the absolute configuration of TaClo and its N-methyl analog has been achieved by quantum chemical CD calculations and has finally been confirmed by single-crystal X-ray diffraction analyses of the two enantiomers of N-formyl-TaClo as obtained in enantiomerically pure form by crystallization.     

Cytotoxic dimeric sesquiterpenoids from Curcuma parviflora: isolation of three new parviflorenes and absolute stereochemistry of parviflorenes A, B, D, F, and G

Three novel dimeric sesquiterpenoids, named parviflorenes G-I (1-3), have been isolated from Curcuma parviflora (Zingiberaceae), and their structures were elucidated by means of spectroscopic studies. Absolute stereochemistry of parviflorene G (1) as well as previously isolated related compounds, parviflorenes A (4), B (5), D (6), and F (7), was revealed by CD spectral data and chemical means. Parviflorenes G (1) and I (3) were cytotoxic against HeLa cells, while parviflorenes A (4) and F (7) were cytotoxic against all tested tumor cell lines in the human cancer cell line panel assay.