Showing papers in "Helvetica Chimica Acta in 2008"

Isolation and X-Ray Structures of Reactive Intermediates of Organocatalysis with Diphenylprolinol Ethers and with Imidazolidinones

Abstract: Reaction of 2-phenylacetaldehyde with the Me3Si ether of diphenyl-prolinol, with removal of H2O, gives a crystalline enamine (1). The HBF4 salts of the MePh2Si ether of diphenyl-prolinol and of 2-(tert-butyl)-3-methyl- and 5-benzyl-2,2,3-trimethyl-1,3-imidazolidin-4-one react with cinnamaldehyde to give crystalline iminium salts 2, 3, and 4. Single crystals of the enamine and of two iminium salts, 2 and 3, were subjected to X-ray structure analysis (Figs. 1, 2, and 6), and a 2D-NMR spectrum of the third iminium salt was recorded (Fig. 7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five-membered heterocycles, i.e., D, E (Scheme 2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl-prolinol derivatives (from the Cambridge File CSD; Table 1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig. 4). The iminium ions 3 and 4 are compared with N-acylated imidazolidinones F and G (Figs. 9, 12, and 13, and Table 3), and common structural aspects such as minimalization of 1,5-repulsion (the ‘A1,3-effect’), are discussed. The crystal structures of the simple diphenyl-prolinol⋅HBF4 salt (Fig. 3) and of Boc- and benzoyl-(tert-butyl)methyl-imidazolidinone (Boc-BMI and Bz-BMI, resp.; Figs. 10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high-level-of-theory DFT calculations (Figs. 5 and 8, and Table 2). Delicate details including pyramidalization of trigonal N-atoms, distortions around iminium CN bonds, shielding of diastereotopic faces, and the π-interaction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations.

Electrophilic S‐Trifluoromethylation of Cysteine Side Chains in α‐ and β‐Peptides: Isolation of Trifluoro‐methylated Sandostatin® (Octreotide) Derivatives

Abstract: The new electrophilic trifluoromethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF3 groups to the S-atom of cysteine side chains of α- and β-peptides (up to 13-residues-long; products 7–14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2-position). The products are purified by chromatography, and identified by 1H-, 13C-, and 19F-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling, imaging, PET) are discussed.

Nanocrystalline ZnO for Knoevenagel Condensation and Reduction of the Carbon,Carbon Double Bond in Conjugated Alkenes

Abstract: A novel efficient and eco-friendly nanocrystalline ZnO catalyst was used for the Knoevenagel condensation and for the reduction of CC double bonds at room temperature in the absence of solvents.

Copper-Free Sonogashira Coupling of Acid Chlorides with Terminal Alkynes in the Presence of a Reusable Palladium Catalyst: An Improved Synthesis of 3-Iodochromenones (=3-Iodo-4H-1-benzopyran-4-ones)

Abstract: Pd/C is used as an efficient catalyst for the copper-free Sonogashira coupling of acid chlorides and terminal alkynes to afford ynones in high yields (Tables 1 and 3). Cyclization of (2-methoxyaryl)-substituted ynones induced by I2/ammonium cerium(IV) nitrate (CAN) at room temperature gave 3-iodochromenones (=3-iodo-4H-1-benzopyran-4-ones) in excellent yield (Table 4).

Dioxopiperazine Alkaloids Produced by the Marine Mangrove Derived Endophytic Fungus Eurotium rubrum

Abstract: Cultivation of the fungal strain Eurotium rubrum, an endophytic fungus that was isolated from the inner tissue of stems of the mangrove plant Hibiscus tiliaceus, resulted in the isolation of two new dioxopiperazine derivatives, namely, dehydrovariecolorin L (1) and dehydroechinulin (2), together with eight known dioxopiperazine compounds including variecolorin L (3), echinulin (4), isoechinulin A (5), dihydroxyisoechinulin A (6), preechinulin (7), neoechinulin A (8), neoechinulin E (9), and cryptoechinuline D (10). The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature. Compounds 1, 2, 9, and 10 were investigated for their a,a-diphenyl-beta-picrylhydrazyl (DPPH) radical-scavenging activity. In addition, the new compounds, 1 and 2, were evaluated for their cytotoxic activity against the P-388, HL-60, and A549 cell lines.

Phenolic Derivatives from Fruits of Dipteryx lacunifera DUCKE and Evaluation of Their Antiradical Activities

Abstract: The fruits of Dipteryx lacunifera, known as ‘fava de morcego’ and ‘garampara’, comprise pleasant tasting kernels that contain high amounts of fatty acids (mainly oleic acid) and are commonly consumed by inhabitants of the northeast of Brazil. In the present study, the crude EtOH extract of the fruit kernels was separated into hexane-, Et2O-, AcOEt-, and H2O-soluble fractions. The Et2O fraction was found to exhibit the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity in vitro, and was subjected to further fractionation. Column chromatography over silica gel and Sephadex LH-20, followed by preparative HPLC-C18, afforded (−)-eriodictyol (1), (−)-butin (2), luteolin (3), 3′,4′,7-trihydroxyflavone (4), butein (5), and sulfuretin (6). The antiradical activities of compounds 1, 2, 4, and 6, together with the positive controls rutin, butylated hydroxy toluene (BHT), and tert-butylhydroquinone (TBHQ), were evaluated with the DPPH assay and were found to decrease in the order rutin>4>1>6>2>TBHQ>BHT.

Physicochemical Profiling of Sartans: A Detailed Study of Ionization Constants and Distribution Coefficients

Abstract: A detailed investigation of the ionization and lipophilicity profiles of selected sartans (valsartan, losartan, irbesartan, candesartan, candesartan cilexetil), a class of antihypertensives commonly used in therapy, is presented. The pKa macroconstants were determined by integrated potentiometry, capillary electrophoresis, and UV spectrophotometry. The measured pKa macroconstants were connected with the ionizable centers present in each molecule with the aid of model compounds. Potentiometric titrations with the GLpKa apparatus were performed to determine the distribution profile (logD vs. pH) of valsartan, while the shake-flask procedure was used to characterize the distribution profile of the other compounds. Valsartan showed a lipophilicity profile consistent with the presence of two acidic centers. Losartan and irbesartan, which contain one acidic and one basic center, displayed the classical bellshaped profile of ordinary ampholytes. By contrast, a more complex situation emerged in the case of candesartan, due to the large number of ionization equilibria involved. The low solubility of candesartan cilexetil, together with the ease of hydrolysis of the ester moiety, prevented a successful investigation of its ionization and lipophilicity profiles.

Two Novel Triterpenoids from Portulaca oleracea L.

Abstract: Two novel triterpenoids, (2α,3α)-3-{[4-O-(β-D-glucopyranosyl)-β-D-xylopyranosyl]oxy}-2,23-dihydroxy-30-methoxy-30-oxoolean-12-en-28-oic acid (1) and (2α,3α)-2,23,30-trihydroxy-3-[(β-D-xylopyranosyl)oxy]olean-12-en-28-oic acid (2) were isolated from Portulaca oleracea L., and they both showed weak cytotoxic activity assayed with the MTT method.

New Open‐Chain and Cyclic Tetrapeptides, Consisting of α‐, β2‐, and β3‐Amino‐Acid Residues, as Somatostatin Mimics – A Survey

Abstract: Cyclo-β-tetrapeptides are known to adopt a conformation with an intramolecular transannular hydrogen bond in solution. Analysis of this structure reveals that incorporation of a β2-amino-acid residue should lead to mimics of ‘α-peptidic β-turns’ (cf.A, B, C). It is also known that short-chain mixed β/α-peptides with appropriate side chains can be used to mimic interactions between α-peptidic hairpin turns and G protein-coupled receptors. Based on these facts, we have now prepared a number of cyclic and open-chain tetrapeptides, 7–20, consisting of α-, β2-, and β3-amino-acid residues, which bear the side chains of Trp and Lys, and possess backbone configurations such that they should be capable of mimicking somatostatin in its affinity for the human SRIF receptors (hsst1–5). All peptides were prepared by solid-phase coupling by the Fmoc strategy. For the cyclic peptides, the three-dimensional orthogonal methodology (Scheme 3) was employed with best success. The new compounds were characterized by high-resolution mass spectrometry, NMR and CD spectroscopy, and, in five cases, by a full NMR-solution-structure determination (in MeOH or H2O; Fig. 4). The affinities of the new compounds for the receptors hsst1–5 were determined by competition with [125I]LTT-SRIF28 or [125I] [Tyr10]-CST14. In Table 1, the data are listed, together with corresponding values of all β- and γ-peptidic somatostatin/Sandostatin® mimics measured previously by our groups. Submicromolar affinities have been achieved for most of the human SRIF receptors hsst1–5. Especially high, specific binding affinities for receptor hsst4 (which is highly expressed in lung and brain tissue, although still of unknown function!) was observed with some of the β-peptidic mimics. In view of the fact that numerous peptide-activated G protein-coupled receptors (GPCRs) recognize ligands with turn structure (Table 2), the results reported herein are relevant far beyond the realm of somatostatin: many other peptide GPCRs should be ‘reached’ with β- and γ-peptidic mimics as well, and these compounds are proteolytically and metabolically stable, and do not need to be cell-penetrating for this purpose (Fig. 5).

Total Synthesis of the Alkaloid (±)‐Aspidophytine Based on Carbonyl Ylide Cycloaddition Chemistry

Abstract: The RhII-catalyzed cycloaddition cascade of an indolyl-substituted α-diazo imide was used for the total synthesis of the complex pentacyclic alkaloid (±)-aspidophytine. Treatment of the resulting dipolar cycloadduct with BF3⋅OEt2 induces a domino fragmentation cascade. The reaction proceeds by an initial cleavage of the oxabicyclic ring and formation of a transient N-acyl iminium ion which reacts further with the adjacent tert-butyl ester and sets the required lactone ring present in aspidophytine. A three-step sequence was then used to remove both the ester and OH groups. Subsequent functional group manipulations allowed for the high-yielding conversion to (±)-aspidophytine.

Novel Bibenzyl Derivatives from the Tubers of Bletilla striata

Abstract: Three novel bibenzyl derivatives, blestritins A - C (1 - 3), along with 18 known constituents, were isolated from the tubers of Bletilla striata (Orchidaceae), a traditional Chinese medicine used for the treatment of tuberculosis and haemorrhage of the stomach and lungs. Their structures were identified on the basis of spectroscopic analyses. Introduction. - Bletilla striata (Thunb.) Reichb. f. (Orchidaceae) is mainly distributed in East Asia, and its tubers are used as a Chinese traditional medicine for the treatment of tuberculosis and haemorrhage of the stomach or lung (1). Previous phytochemical studies on Bletilla species have led to the isolation of phenanthrene derivatives (2 - 11), bibenzyls (2) (4), flavonoids and phenolic compounds (5), and cyanidin glycosides (12). As part of our ongoing chemical study on Bletilla striata, three novel bibenzyl derivatives, blestritins A - C (1 - 3), were isolated from the tubers of B. striata, together with 18 known constituents. We report herein the isolation and structural elucidation of these compounds.

Three new sesquiterpenoids from Xylaria sp NCY2

Abstract: Three new sesquiterpenoids, xylarenones A (1) and B (2), and xylarenic acid (3), were obtained from the endophytic fungal strain Xylaria sp. NCY2, which was isolated from Torreya jackiiChun. Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR experiments, and by HR-Q-TOF mass spectrometry. The antitumor and antibacterial properties of the new compounds were evaluated.

Iridoids from the Bark of Alstonia scholaris

Abstract: Four new 11-noriridoids named scholareins A-D (1-4), along with three known derivatives, isoboonein (5). alyxialactone (6). and loganin (7), were isolated from EtOH extracts of the bark of Alstonia scholaris bv chromatographic methods. Their structures were identified by extensive mass-spectrometric and spectroscopic (especially 2D-NMR) experiments.

One-Pot Diastereoselective Synthesis of Densely Functionalized 2H-Indeno[2,1-b]furans. Single-Crystal X-Ray Structure of Dimethyl 8,8a-Dihydro-8-oxo-8a-(2,2,2-trichloroethoxy)-2H-indeno[2,1-b]furan-2,3-di­carboxylate

Abstract: Highly reactive 1 : 1 intermediates were produced in the reaction of Ph3P and dialkyl acetylenedicarboxylates (=dialkyl but-2-ynedioates). Protonation of these intermediates by alcohols (2,2,2-trichloroethanol, propargyl alcohol (=prop-2-yn-1-ol), MeOH, benzyl alcohol, and allyl alcohol (=prop-2-en-1-ol) led to vinyltriphenylphosphonium salts 4, which underwent a Michael addition reaction with the conjugate base to produce the corresponding stabilized phosphonium ylides 5 (Scheme). Wittig reaction of the stabilized phosphonium ylides with ninhydrin (6) led to the corresponding densely functionalized 2H-indeno[2,1-b]furans 10 in fairly good yields (Table 1). The structures of the final products were confirmed by IR, 1H- and 13C-NMR spectroscopy, and mass spectrometry. The configuration of dimethyl 8,8a-dihydro-8-oxo-8a-(2,2,2-trichloroethoxy)-2H-indeno[2,1-b]furan-2,3-dicarboxylate (10a) was established by a single-crystal X-ray structure determination, establishing that the one-pot multicomponent condensation reaction was completely diastereoselective.

Liquid-Crystalline Thiol- and Disulfide-Based Dendrimers for the Functionalization of Gold Nanoparticles

Abstract: Liquid-crystalline dendrons carrying either a thiol or disulfide function which display nematic, smectic A, columnar, or chiral nematic phases have been synthesized. Their mesomorphic properties are in agreement with the nature of the mesogenic units and structure of the dendrons. The first-generation poly(aryl ester) dendron containing two cyanobiphenyl mesogenic units was used to functionalize gold nanoparticles. For full coverage, a smectic-like supramolecular organization on the nanometer scale is observed, when the gold nanoparticles are spread onto carbon-coated copper grids. This result indicates that the dendritic ligands reported here act as self-organization promoters.

A Concise Total Synthesis of Diospongins A and B

Abstract: The total synthesis of the diarylheptanoids (−)-diospongin A (1) and B (2) was achieved stereoselectively via the δ-lactone intermediate 6. The key reactions involved are a stereoselective reduction of β-keto ester and the Horner–Wadsworth–Emmons and intramolecular oxy-Michael reactions.

Surprising Formation of Chlorinated Butenolides from Dialkyl Acetylenedicarboxylates and Hexachloro­acetone in the Presence of Triphenyl Phosphite

Abstract: Triphenyl phosphite reacts smoothly with dialkyl acetylenedicarboxylates and hexachloroacetone to produce alkyl 2-(dichloromethylene)-2,5-dihydro-5-oxo-4-(trichloromethyl)furan-3-carboxylates in good yields.

2‐Azido‐2‐deoxycellulose: Synthesis and 1,3‐Dipolar Cycloaddition

Abstract: Chitosan (1) was prepared by basic hydrolysis of chitin of an average molecular weight of 70000 Da, 1H-NMR spectra indicating almost complete deacetylation. N-Phthaloylation of 1 yielded the known N-phthaloylchitosan (2), which was tritylated to provide 3a and methoxytritylated to 3b. Dephthaloylation of 3a with NH2NH2⋅H2O gave the 6-O-tritylated chitosan 4a. Similarly, 3b gave the 6-O-methoxytritylated 4b. CuSO4-Catalyzed diazo transfer to 4a yielded 95% of the azide 5a, and uncatalyzed diazo transfer to 4b gave 82% of azide 5b. Further treatment of 5a with CuSO4 produced 2-azido-2-deoxycellulose (7). Demethoxytritylation of 5b in HCOOH gave 2-azido-2-deoxy-3,6-di-O-formylcellulose (6), which was deformylated to 7. The 1,3-dipolar cycloaddition of 7 to a range of phenyl-, (phenyl)alkyl-, and alkyl-monosubstituted alkynes in DMSO in the presence of CuI gave the 1,2,3-triazoles 8–15 in high yields.

Highly Oxygenated Triterpenoids from the Marine Red Alga Laurencia mariannensis (Rhodomelaceae)

Abstract: Two new and one known squalenoid-derived triterpenoids. namely, laurenmariannol (1) and (21 alpha)-21-hydroxythyrsiferol (2). and the known thyrsiferol (3) were isolated and identified from the marine red alga Laurencia mariannensis, which was collected off the coast of Hainan and Weizhou Islands of China. The structures of these compounds were established by means of spectroscopic analyses, as well as by comparison with literature data. Compounds I and 2 displayed significant cytotoxic activity against P-388 tumor cells with IC(50) values of 0.6 and 6.6 mu g/ml, respectively.

Synthesis and selected transformations of 1H-imidazole 3-oxides derived from amino acid esters

Abstract: A series of new optically active 1H-imidazole 3-oxides 5 with a substituted acetate group at N(1) as the chiral unit were prepared by the reaction of a-(hydroxyimino) ketones, a-amino acid methyl esters, and formaldehyde. In an analogous reaction, ethyl 2-(hydroxyimino)-3-oxobutyrate and 1,3,5- trialkylhexahydro-1,3,5-triazines gave 3-oxido-1H-imidazole-4-carboxylates 14, which easily rearranged into the 2-oxo derivatives 15. Selected examples of N-oxides 5 could be transformed into the corresponding 2,3-dihydro-1H-imidazole-2-thione derivatives 10 via a 'sulfur-transfer reaction', and the reduction of the histidine derivative 5i with Raney-Ni yielded the optically active 2,3-bis(imidazolyl)propanoate 12. Furthermore, reaction of the (1H-imidazol-1-yl)acetates with primary amines yielded the corresponding acetamides.

Eight New Diterpenoids from the Roots of Euphorbia nematocypha

Abstract: From the dried roots of Euphorbia nematocypha, eight new diterpenoids, with ent-atisane (i.e., 1–5) and isopimarane (i.e., 6–8) type skeletons, together with five known compounds, were isolated. The structures of these new compounds were elucidated by spectroscopic data. Compounds 1–8 were evaluated for their cytotoxicity against a small panel of human cancer cell lines.

Lignanamides and Sesquiterpenoids from Stems of Mitrephora thorelii

Abstract: The first phytochemical investigation on stems of Mitrephora thorelii led to the isolation of three new lignanamides, thoreliamides A–C (1–3), and a new sesquiterpenoid, thorelinin (4), together with ten known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic analyses. Thoreliamide C is the first trimer derived from cinnamic acid amide units.

Secondary Metabolites from the Fungus Chaetomium brasiliense

Abstract: Two new depsidones, mollicellins I and J (1 and 2, resp.), and a new chromone, 2-(hydroxymethyl)-6-methylmethyleugenin (3), along with six known compounds, 4-9, were isolated from the ethyl acetate extract of a solid-state fermented culture of Chaetomium brasiliense. Their structures were elucidated based on spectroscopic analysis. Mollicellins I and H (5) exhibited significant growth inhibitory activity against human breast cancer (Bre04), human lung (Lu04), and human neuroma (N04) cell lines with GI(50) values between 2.5-8.6 mu g/ml.

Two New Dammarane-Type Bisdesmosides from the Fruit Pedicels of Panax notoginseng

Abstract: Two new dammarane-type triterpenoidal saponins, notoginsenosides FP1 (1) and FP2 (2), were isolated from the fruit pedicels of Panax notoginseng, along with 22 known compounds. Their structures were elucidated on the basis of spectroscopic evidences and chemical methods. The known compounds were identified as ginsenosides Rg(1) (3), Re (4), Rb-3 (5), Re (6), Rd (7), Rb-2 (8), Rb-1 (9), F-2 (10), and F-1 (11); as notoginsenosides R-1 (12), Fa (13), and Fc (14); as vina-ginsenoside R-7 (15); as gypenosides IX (16), XVII (17), and XIII (18), and as chikusetsusaponin-L-5 (19), quercetin 3-O-beta-D-glucopyranosyl-(1 -> 2)-beta-D-galactopyranoside (20), kaempferol 3-O-beta-D-glucopyranosyl-(1 -> 2)-beta-D-galactopyranoside (21), benzyl-beta-primeveroside (22), (S)-tryptophan (23), and icariside B-6 (24). Compounds 15, 19 and 22-24 are reported for the first time from the title plant.

Ligand Effects on the Mechanisms of Thermal Bond Activation in the Gas-Phase Reactions NiX+/CH4→Ni(CH3)+/HX (X=H, CH3, OH, F). Short Communication

Abstract: The thermal ion-molecule reactions NiX++CH4Ni(CH3)++HX (X=H, CH3, OH, F) have been studied by mass spectrometric methods, and the experimental data are complemented by density functional theory (DFT)-based computations. With regard to mechanistic aspects, a rather coherent picture emerges such that, for none of the systems studied, oxidative addition/reductive elimination pathways are involved. Rather, the energetically most favored variant corresponds to a σ-complex-assisted metathesis (σ-CAM). For X=H and CH3, the ligand exchange follows a ‘two-state reactivity (TSR)’ scenario such that, in the course of the thermal reaction, a twofold spin inversion, i.e., tripletsinglettriplet, is involved. This TSR feature bypasses the energetically high-lying transition state of the adiabatic ground-state triplet surface. In contrast, for X=F, the exothermic ligand exchange proceeds adiabatically on the triplet ground state, and some arguments are proposed to account for the different behavior of NiX+/Ni(CH3)+ (X=H, CH3) vs. NiF+. While the couple Ni(OH)+/CH4 does not undergo a thermal ligand switch, the DFT computations suggest a potential-energy surface that is mechanistically comparable to the NiF+/CH4 system. Obviously, the ligands X act as a mechanistic distributor to switch between single vs. two-state reactivity patterns.

Phochinenins A-F, Dimeric 9,10-Dihydrophenanthrene Derivatives, from Pholidota chinensis

Abstract: Six new compounds, phochinenins A–F (1–6), dimerized from 9,10-dihydrophenanthrene and dihydrostilbene through direct coupling or an oxygen bridge, along with eight known compounds, were isolated from the whole plants of Pholidota chinensis. Their structures were elucidated on the basis of extensive spectroscopic investigations (1D-, 2D-NMR, and HR-EI-MS).

Stability of 7,8‐Dihydropterins in Air‐Equilibrated Aqueous Solutions

Abstract: 6-Substituted 7,8-dihydropterins (=2-amino-7,8-dihydropteridin-4(1H)-ones) are heterocyclic compounds that occur in a wide range of living systems and participate in relevant biological functions. In air-equilibrated aqueous solutions, these compounds react with dissolved O2 (autooxidation). The rates of these reactions as well as the products formed strongly depend on the chemical structure of the substituents. 7,8-Dihydro-6-methylpterin and 7,8-dihydro-6,7-dimethylpterin that bear electron-donor groups as substituents are the most reactive derivatives and undergo oxidation of the pterin moiety to yield the corresponding oxidized derivatives (6-methylpterin and 6,7-dimethylpterin, resp.). The oxidations of 7,8-dihydrobiopterin, 7,8-dihydroneopterin, and 7,8-dihydrofolic acid are slower, and they yield 7,8-dihydroxanthopterin as the main product. 7,8-Dihydroxanthopterin, 6-formyl-7,8-dihydropterin, and sepiapterin are rather stable, and their consumption in air-equilibrated solutions is negligible for several days. The pseudo-first-order rate constants of the reactions between these compounds and O2 at 25° and 40° are reported. The biological implications of the results obtained are also discussed.

Enantioselective Synthesis of β-Blockers via Hydrolytic Kinetic Resolution of Terminal Oxiranes by Using Bimetallic Chiral {{2,2′-[Cyclohexane-1,2-diylbis(nitrilomethylidyne)]bis[phenolato]}(2−)}cobalt ([Co(salen)])-Type Complexes

Abstract: The synthesis of chirally pure β-blockers was successfully achieved via hydrolytic kinetic resolution of butyl (±)-4-(oxiran-2-ylmethoxy)benzeneacetate ((±)-1) and (±)-4-(oxiran-2-ylmethoxy)benzeneacetonitrile ((±)-2) in the presence of bimetallic chiral [Co(salen)]-type complexes. The newly synthesized bimetallic chiral [Co(salen)]-type complexes exhibited excellent enantioselectivities of up to >98% ee in good yields (Tables 1–3).

Two New Cytotoxic Nonsulfated Pentasaccharide Holostane (=20‐Hydroxylanostan‐18‐oic Acid γ‐Lactone) Glycosides from the Sea Cucumber Holothuria grisea

Abstract: Two new lanostane-type nonsulfated pentasaccharide triterpene glycosides, 17-dehydroxyholothurinoside A (1) and griseaside A (2), were isolated from the sea cucumber Holothuria grisea. Their structures were elucidated by spectroscopic methods, including 2D-NMR and MS experiments, as well as chemical evidence. Compounds 1 and 2 possess the same pentasaccharide moieties but differ slightly in their side chains of the holostane-type triterpene aglycone. The structures of the two new glycosides were established as (3β,12α)-22,25-epoxy-3-{(O-β-D-glucopyranosyl-(14)-O-[O-3-O-methyl-β-D-glucopyranosyl-(13)-O-β-D-glucopyranosyl-(14)-6-deoxy-β-D-glucopyranosyl-(12)]-β-D-xylopyranosyl)oxy}-12,20-dihydroxylanost-9(11)-en-18-oic acid γ-lactone (1) and (3β,12α)-3-{(O-β-D-glucopyranosyl-(14)-O-[O-3-O-methyl-β-D-glucopyranosyl-(13)-O-β-D-glucopyranosyl-(14)-6-deoxy-β-D-glucopyranosyl-(12)]-β-D-xylopyranosyl)oxy}-12,20,22-trihydroxylanost-9(11)-en-18-oic acid γ-lactone (2). The 17-dehydroxyholothurinoside A (1) and griseaside A (2) exhibited significant cytotoxicity against HL-60, BEL-7402, Molt-4, and A-549 cancer cell lines.

Baimantuoluolines D-F, Three New Withanolides from the Flower of Datura metel L

Abstract: Three new withanolide compounds, named baimantuoluolines D–F, along with three known withanolides and a lignan were isolated from the flower of Datura metel L., the parts effective against psoriasis. The structures of the new compounds were elucidated as (5α,6β,12β,20R,22R,24R,25S)-21,24-epoxy-5,6,12-trihydroxy-27-methoxy-1-oxowith-2-enolide (1), (5α,6β,12β,20R,22R,24R,25S)-21,24-epoxy-5,6,12,27-tetrahydroxy-1-oxowith-2-enolide (2), and (5α,6β,12β,22R)-5,6,12,21-tetrahydroxy-1-oxowith-24-enolide(3) on the basis of physicochemical evidence.