Showing papers in "Helvetica Chimica Acta in 2004"

Molecular Structure, Vibrational Spectra, and Hydrogen Bonding of the Ionic Liquid 1‐Ethyl‐3‐methyl‐1H‐imidazolium Tetrafluoroborate

Abstract: The IR and Raman spectra and conformations of the ionic liquid 1-ethyl-3-methyl-1H-imidazolium tetrafluoroborate, [EMIM][BF4] (6), were analyzed within the framework of scaled quantum mechanics (SQM). It was shown that SQM successfully reproduced the spectra of the ionic liquid. The computations revealed that normal modes of the EMIM+ (.) BF4- ion pair closely resemble those of the isolated ions EMIM+ and BF4-, except for the antisymmetric BF stretching vibrations of the anion, and the out-of-plane and stretching vibrations of the H-C(2) moiety of the cation. The most plausible explanation for the pronounced changes of the latter vibrations upon ion-pair formation is the H-bonding between H-C(2) and BF4-. However, these weak H-bonds are of minor importance compared with the Coulomb interactions between the ions that keep them closely associated even in dilute CD2Cl2 Solutions. According to the 'gas-phase' computations, in these associates, the BF4- anion is positioned over the imidazolium ring of the EMIM+ cation and has short contacts not only with the H-C(2) of the latter, but also with a proton of the Me-N(3) group.

Intramolecular Asymmetric Amidations of Sulfonamides and Sulfamates Catalyzed by Chiral Dirhodium(II) Complexes

Abstract: Enantioselective intramolecular amidation of aliphatic sulfonamides was achieved for the first time by means of chiral carboxylatodirhodium(II) catalysts in conjunction with PhI(OAc)2 and MgO in high yields and with enantioselectivities of up to 66% (Scheme 3, Table 1). The best results were obtained with (Rh2{(S)-nttl)4) and (Rh2{(R)-ntv)4) as catalysts ((S)-nttl (S)--(tert-butyl)-1,3-dioxo-2H-benz(de)isoquinoline-2-acetato, (R)-nto (R)--isopropyl-1,3-dioxo-2H-benz(de) isoquinoline-2-acetato). In addition, these carboxylatodi- rhodium(II) catalysts were also efficient in intramolecular amidations of aliphatic sulfamates esters, although the enantioselectivity of these latter reactions was significantly lower (Scheme 4, Table 3). Introduction. ± Amidation of saturated CH bonds and aziridination of olefins catalyzed by metal complexes based on Fe, Mn, Ru, Cu, or Rh are established methodologies for CN bond-formation (1) and, consequently, for the synthesis of amine derivatives. Some years ago, the Rh II -catalyzed aziridination (2) and sulfona- midation (3) with phenyliodinanes derived from aromatic sulfonamides has been investigated in our group. The reactions exhibited features analogous to the corresponding metal-catalyzed carbene-transfer reactions (4). The aziridination was found to be stereospecific, except in the case of stilbene, and the amidation proceeded with retention of configuration at the reacting C-atom, indicating intervention of a metal-complexed nitrene, in analogy to the corresponding intermediate metallocar- benes resulting from decomposition of diazo compounds with Rh II catalysts. Some preliminary experiments showed that the system was suitable for asymmetric nitrene transfer. However, it suffered several shortcomings. Owing to the requirement of aromatic sulfonamides as precursors for the phenyliodinanes (5), the possibilities of carrying out intramolecular aziridinations and/or amidations (6) appeared very limited. In addition, a large excess of substrate was necessary in the case of intermolecular reactions to achieve satisfactory yields, while reactions carried out with an excess of reagent over the substrate produced unsatisfactory results. Finally, some reactions, in particular intermolecular amidations, proceeded very sluggishly and resulted in decomposition of the phenyliodinanes to afford sulfonamides without generation of the expected products of nitrene insertion. The transition-metal-catalyzed nitrene transfer has been further developed by other groups. Dodd, Dauban, and co-workers reported that, contrary to the traditional opinion (7), phenyliodinanes derived from aliphatic sulfonamides are isolable and may be used for nitrene-transfer reactions (8). In addition, they found conditions allowing

Transition‐Metal‐Based Lewis Acid Catalysis of Aza‐Type Michael Additions of Amines to α,β‐Unsaturated Electrophiles in Water

Abstract: Several transition-metal-based Lewis acid catalysts, especially FeCl3⋅7 H2O, CrCl3⋅6 H2O, and SnCl4⋅4 H2O, were shown to be highly effective for aza-type Michael reactions between electrophilic α,β-unsaturated compounds and both aliphatic and aromatic amines in aqueous solution Advantages of the new protocol include 1) high-yielding reactions that can be conducted at ambient temperature; 2) the use of inexpensive, stable transition-metal salts as catalysts; and 3) plain H2O as an environmentally benign solvent

Synthesis of novel chiral ionic liquids and their phase behavior in mixtures with smectic and nematic liquid crystals

Abstract: Alkylation of 1-alkyl-1H-imidazoles 2a–f with citronellyl bromide 1b opens access to chiral 1H-imidazolium bromides 3a–f (Scheme 1). A similar strategy yielded the chiral pyridinium ionic liquid 6 (Scheme 2). Dialkylation of 1H-imidazole (7) gave the C2-symmetric 1,3-dicitronellyl-1H-imidazolium bromide (8) (Scheme 3). Differential scanning calorimetry and optical polarizing microscopy revealed smectic mesophases for 1-citronellyl-3-tetradecy-1H-limidazolium bromide (3e) and 1-citronellylpyridinium bromide (6) (Table). In binary mixtures with smectic and nematic liquid crystals 9 and 10, 1-citronellyl-3-methyl-1H-imidazolium bromide (3a) behaved differently. Increasing quantities of 3a cause a decrease of the smectic-phase width for the mixture 3a/9 (Fig. 3), whereas the phase width of the nematic phase for 3a/10 remained nearly constant (Fig. 4).

Annosqualine: a Novel Alkaloid from the Stems of Annona squamosa

Abstract: Annosqualine (=(10′bR)-1′,5′,6′,10′b-tetrahydro-9′-hydroxy-7′,8′-dimethoxyspiro[cyclohexa-2,5-diene-1,2′-pyrrolo[2,1-a]isoquinoline]-3′,4-dione; 1), a novel alkaloid with an unprecedented skeleton, and a new amide, dihydrosinapoyltyramine (=3-(4-hydroxy-3,5-dimethoxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]propanamide; 2), were isolated from the stems of Annona squamosa L., together with six known alkaloids. The structures of all compounds were elucidated spectroscopically by means of optical rotation, 1H-, 13C-, and 2D-NMR, and by EI-MS, or by comparison with the spectral data of authentic samples. A possible biogenetical pathway towards annosqualine (1) is proposed.

Catalytic Asymmetric Chlorination of β-Keto Esters with Hypervalent Iodine Compounds

Abstract: (Dichloroiodo)toluene (=dichloro(4-methylphenyl)iodine; 2) was found to be a suitable chlorinating agent in the catalytic asymmetric chlorination of β-keto esters 3 catalyzed by the [Ti(TADDOLato)] complex 1 (=bis(acetonitrile)dichloro[(4R,5R)-2,2-dimethyl-α,α,α′,α′-tetra(naphthalen-1-yl)-1,3-dioxolane-4,5-dimethanolato(2−)-κO,κO′]titanium), whereby α-chlorinated products were obtained in moderate to good yields and enantioselectivities of up to 71% (Scheme 2, Table 2) The enantioselectivity of the reaction shows a remarkable temperature dependence, the maximum selectivity being obtained at ca 50°

NMR Investigations into the Vase-Kite Conformational Switching of Resorcin[4]arene Cavitands

Abstract: We report the detailed investigation of temperature- and pH-triggered conformational switching of resorcin[4]arene cavitands 1–10 (Figs. 1, 8, and 9). Depending on the experimental conditions, these macrocycles adopt a vase conformation, featuring a deep cavity for potential guest inclusion, or two kite conformations (kite 1 and kite 2) with flat, extended surfaces (Schemes 1 and 2). The thermodynamic and kinetic parameters for the interconversion between these structures were determined by variable-temperature NMR (VT-NMR) spectroscopy (Figs. 2–7 and 10, and Tables 1 and 2). It was discovered that vase→kite switching of cavitands is strongly solvent-dependent: it is controlled not only by solvent polarity but also by solvent size. Conformational interconversions similar to those of the parent structure 1 with four quinoxaline flaps are also observed when the octol base skeleton is differentially or incompletely bridged. Only octanitro derivative 2 was found to exist exclusively in the kite conformation under all experimental conditions. The detailed insight into the vase⇌kite conformational equilibrium gained in this investigation provides the basis for the design and construction of new, dynamic resorcin[4]arene cavitands that are switchable between bistable states featuring strongly different structures and functions.

Donor‐Substituted Perethynylated Dehydroannulenes and Radiaannulenes: Acetylenic Carbon Sheets Featuring Intense Intramolecular Charge Transfer

Abstract: In this article, we report the preparation of unprecedented π-conjugated macrocycles (Fig. 1) by acetylenic scaffolding using modular tetraethynylethene (TEE, 3,4-diethynylhex-3-ene-1,5-diyne) building blocks. A novel photochemical access to (Z)-bisdeprotected TEEs (Scheme 1) enabled the synthesis of the anilino-substituted perethynylated octadehydro[12]- (5) and dodecadehydro[18]annulenes (6) (Scheme 2). Following the serendipitous discovery of perethynylated radiaannulenes (Scheme 3) that can be viewed as hybrids between perethynylated dehydroannulenes and expanded radialenes, two series of monocyclic (7–9; Scheme 6) and bicyclic (10 and 11; Scheme 7) representatives were prepared. Substantial strain in the macrocyclic perimeter of radiaannulene 7 was revealed by X-ray crystal-structure analysis (Fig. 2). Nevertheless, mono- and bicyclic radiaannulenes are stable at room temperature in air for months. The opto-electronic properties of both dehydroannulenes and radiaannulenes are substantially enhanced by the introduction of the peripheral anilino donor groups that undergo strong intramolecular charge-transfer interactions with the electron-accepting all-C cores. As a result, the UV/VIS spectra feature intense, bathochromically shifted charge-transfer bands that disappear upon protonation of the anilino moieties and are fully recovered upon neutralization (Figs. 4–9). A comparison between anilino-substituted perethynylated dehydroannulenes, expanded radialenes, and radiaannulenes revealed that the efficiency of the intramolecular charge-transfer interaction strongly depends on the structure of the electron-accepting all-C perimeter. Electrochemical investigations (Table) demonstrated that the radiaannulenes are particularly powerful electron acceptors. Thus, bicyclic radiaannulene 11, which possesses eight peripheral 3,5-di(tert-butyl)phenyl substituents, is reversibly reduced at −0.83 V in THF (vs. Fc+/Fc), making it a better electron acceptor than buckminsterfullerene C60 under comparable conditions.

Fluorous-Silica-Supported Perfluoro-Tagged Palladium Complexes Catalyze Suzuki Couplings in Water

Abstract: Different Pd-complexes (see 2a–d and 3) with and without perfluoroalkyl tags were deposited on fluorous reversed-phase silica 1 and unmodified silica gel. These supported complexes were successfully used as precatalysts for the Suzuki reaction in H2O. H2O-Soluble aryl bromides were easily converted to the corresponding biphenyls. Although none of the complexes is H2O-soluble, the active catalyst is most likely homogeneously dissolved. Nevertheless, the Pd-leaching into the product was low.

Computational Interpretation of Vibrational Optical Activity: The ROA Spectra of (4S)‐4‐Methylisochromane and the (4S)‐Isomers of Galaxolide®

Abstract: The reliable computation of Raman-optical-activity (ROA) spectra of molecules of the size of the title compounds has, until now, not been possible. We show that our rarefied basis sets yield results in good agreement with the experimental data for (4S)-4-methylisochromane (=(4S)-3,4-dihydro-4-methyl-1H-2-benzopyran; 1), provided the equilibrium between the pseudo-equatorial and the pseudo-axial conformers is taken into account. Comparison between the measured and the computed ROA back-scattering spectra allows the unequivocal assignment of the absolute configuration of the molecule. Comparison with more-approximate calculations for the larger (4S)-isomers of Galaxolide® (2), which contain the (4S)-4-methylisochromane moiety, shows large-scale group frequencies on the same chiral fragments of the two molecules. The data confirm that ROA can be generated by interactions extending over several bonds, i.e., over larger distances than can be probed by NMR spectroscopy. Thus, the absolute configuration at C(7) of Galaxolide® is assignable independently of that at C(4). The computation of ROA for forward-scattering, which will soon be measurable for Galaxolide®, suggests that this scattering geometry provides additional stereochemical information that will be valuable in situations where absolute configurations at several stereogenic centers have to be assigned.

Triplet-Sensitized Photodeprotection of Oligonucleotides in Solution and on Microarray Chips

Abstract: Conditions and kinetics of triplet sensitization as a method for increasing the light sensitivity of photolabile protecting groups used for the photolithographic synthesis of oligonucleotide microarrays were quantitatively studied with the photolabile 2-(2-nitrophenyl)propyl protecting group in homogeneous solutions and on glass substrates by using laser flash photolysis, continuous illumination with HPLC analysis, fluorescence dye labelling, and hybridization. In terms of efficiency and avoidance of chemical side reactions, 9H-thioxanthen-9- one was the most-suitable sensitizer. Both in solution and on a glass substrate, the photostationary kinetics were quantitatively modelled and the relevant kinetic parameters determined. While the sensitization kinetics was diffusion-controlled both in solution and on the chip, the photostationary kinetics was essentially of zero order only on the chip because here the triplet-quenching effect of the released photoproduct 2-(2-nitrophenyl)pro- pene was suppressed as a consequence of the inhomogeneous reaction that took place in a narrow diffusion zone above the surface from where the photoproducts could quickly escape. The kinetic simulation allowed quantitative estimate of the density of reactive groups on the surface. It was further demonstrated that, with 9H- thioxanthen-9-one as a sensitizer, high-density oligonucleotide microarrays of high quality can be produced with one-third of the normal exposure time.

Five new quassinoids from the bark of Picrasma quassioides

Abstract: Five new quassinoids, named picraqualides A–E (1–5), together with eleven known ones, nigakilactone E (6), nigakilactone F (7), kusulactone (8), javanicin U (9), 12-norquassin (10), quassin (11), 2,3-didehydropicrasin B (12), nigakilactone B (13), nigakilactone C (14), picrasin B (15), and simalikalacton C (16), were isolated from the EtOH extract of the bark of Picrasma quassioides (D. Don) Benn. Their structures were determined mainly by spectroscopic methods, especially by 2D-NMR techniques and circular dichroism (CD). Some empirical rules were summarized on the basis of 13C-NMR spectral analysis to distinguish between OH (or Ac) groups attached at C(11) vs. C(13).

New Low‐Molecular‐Mass Gelators Based on L‐Lysine: Amphiphilic Gelators and Water‐Soluble Organogelators

Abstract: The new L-lysine alkali-metal salts 1–5 (M+=Na+ and K+) with different alkyl groups at the Nα-position were easily synthesized, and their hydro- and organogelation properties were investigated. All compounds were H2O-soluble, and some salts, especially the potassium salts, functioned as a hydrogenator that could gel water below 2 wt-%. These salts also had organogelation abilities for many organic solvents.

Furo[2,3-d]pyrimidines and oxazolo[5,4-d]pyrimidines as inhibitors of receptor tyrosine kinases (RTK)

Abstract: Receptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4-d]pyrimidines and furo[2,3-d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC50 values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p, and 20r, had an IC50 of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.

Insulin Secretagogues from Moringa oleifera with Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Activities

Abstract: Bioassay-directed isolation and purification of the methanol extract of Moringa oleifera fruits yielded bioactive N-benzyl thiocarbamates, N-benzyl carbamates, benzyl nitriles, and a benzyl ester. Among these, methyl 2-[4-(α-L-rhamnopyranosyl)phenyl]acetate (2), N-[4-(β-L-rhamnopyranosyl)benzyl]-1-O-α-D-glucopyranosylthiocarboxamide (3), 1-O-phenyl-α-L-rhamnopyranoside (5), and 4-[(β-D-glucopyranosyl)-(1→3)-(α-L-rhamnopyranosyl)]phenylacetonitrile (6) are novel, and their structures were determined by spectroscopic methods. The known compounds isolated and characterized from the MeOH extract were niazirin (=4-(α-L-rhamnopyranosyl)phenylacetonitrile; 1), niazicin A (=methyl N-{4-[(4′-O-acetyl-α-L-rhamnopyranosyl)benzyl]}thiocarbamate; 4), methyl N-{4-[(α-L-rhamnopyranosyl)benzyl]}carbamate (7), and methyl N-{4-[(4′-O-acetyl-α-L-rhamnopyranosyl)benzyl]}carbamate (8). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic β-cells (INS-1), compounds 4, 5, 6, 7, and 8 at 100 ppm significantly stimulated insulin release. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibition assays revealed that 5 and 6 were most active at 83 ppm. Compound 6, however, demonstrated greater specificity for inhibition of COX-2 enzyme (46%) than COX-1 enzyme. Lipid peroxidation assays revealed that 4 and 6 at 50 ppm inhibited peroxidation reactions by 80 and 95%, respectively, while 3 and 8 inhibited lipid peroxidation by 35%. These compounds did not inhibit the cell growth when tested with human breast (MCF-7), central nervous system (CNS, SF-268), lung (NCI-H460), or colon (HCT-116) cancer cell lines. Moreover, these compounds were not cytotoxic at the concentrations tested.

New antibacterial diterpenes from Pseudopterogorgia elisabethae

Abstract: From the MeOH extract of Pseudopterogorgia elisabethae, collected from the Bahamas, four new diterpenes, elisabethin E (1), elisabethin F (2), pseudopterosin P (3), and pseudopterosin Q (4), were isolated and their structures established with the aid of extensive spectroscopic studies. Compounds 3 and 4 showed antibacterial activity selectively against the Gram-positive bacteria Streptococcus pyogenes, Staphylococcus aureus, and Enterococcus faecalis.

Synthesis, Structure, and Spectroscopic and Electrochemical Properties of Heteroleptic Bis(phthalocyaninato) Rare Earth Complexes with a C4 Symmetry

Abstract: A series of eleven heteroleptic bis(phthalocyaninato) rare earth double-deckers [MIII(pc){pc(α-OC5H11)4}] 1–11 (M=Y, SmLu; pc=phthalocyaninato; pc(α-OC5H11)4=1,8,15,22-tetrakis(1-ethylpropoxy)phthalocyaninato) were prepared as racemic mixtures by [MIII(pc)(acac)]-induced (acac=acetylacetonato) cyclic tetramerization of 3-(1-ethylpropoxy)phthalonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing pentanol. These compounds could also be prepared by treating [MIII(pc)(acac)] with the metal-free phthalocyanine H2{pc(α-OC5H11)4} in refluxing octanol. The whole series of double-decker complexes 1–11 were characterized by elemental analysis and various spectroscopic methods. The molecular structures of the Sm, Eu, and Er complexes 1, 2, and 8, respectively, were also determined by single-crystal X-ray diffraction analysis. The effects of the rare earth ion size on the reaction yield, molecular structure, and spectroscopic and electrochemical properties of these complexes were systematically examined.

Kopsifolines A–F: a New Structural Class of Monoterpenoid Indole Alkaloids from Kopsia

Abstract: Six new indole alkaloids, named kopsifolines A–F (1–6), with an unprecedented hexacyclic carbon skeleton, constituting a new structural group of monoterpenoid indole alkaloids, were obtained from the leaf extract of a Malayan Kopsia species, and their structures were established by spectroscopic analysis.

Syntheses and Glycosidase Inhibitory Activities of 2‐(Aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol Derivatives

Abstract: New 2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol derivatives were synthesized from (5S)-5-[(trityloxy)methyl]pyrrolidin-2-one (6) (Schemes 1 and 2) and their inhibitory activities toward 25 glycosidases assayed (Table). The influence of the configuration of the pyrrolidine ring on glycosidase inhibition was evaluated. (2R,3R,4S,5R)-2-[(benzylamino)methyl]-5-(hydroxymethyl)pyrrolidine-3,4-d iol ((+)-21) was found to be a good and selective inhibitor of a-mannosidase from jack bean (K-i=1.2 muM) and from almond (K-i= 1.0 muM). Selectivity was lost for the non-benzylated derivative (2R,3R,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol ((+)-22) which inhibited alpha-galactosidases, beta-galactosidases, beta-glucosidases, and alpha-N-acetylgalactosaminidase as well.

An experimental and mechanistic investigation of the complexities arising during inhibition of the Briggs-Rauscher reaction by antioxidants

Abstract: A method to determine the relative antioxidant capacity of radical scavengers based on the inhibition of the oscillations of the BriggsRauscher (BR) oscillating reaction was previously reported. A semiquantitative mechanistic interpretation of the inhibitory effects required two steps to obtain simulated inhibition times in very good agreement with the experimental ones. The first step is inhibitory, involving H-atom transfer from antioxidant to the HOO. radical; the second step is a first-order degradation of the antioxidant to unspecified products. Since the degradation may be due to oxidation and/or iodination of the antioxidant, we studied the kinetics of the subsystems IO(H+)+antioxidant and I2(H+)+antioxidant. We used 2,5- and 2,6-dihydroxybenzoic acids, caffeic acid (=3-(3,4-dihydroxyphenyl)prop-2-enoic acid), ferulic acid (=3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid), pyrocatechol (=benzene-1,2-diol), and hydroquinone (=benzene-1,4-diol) as antioxidants. Spectra in the wavelength range 500–250 nm were repeated at given time intervals to follow the peaks of the iodine and oxidation products, which were mainly quinones. For the iodination of the above diphenols (=benzenediol derivatives) the substitution and/or addition reactions with I2 or HOI were found to be relatively slow compared to oxidation by IO. Approximate rate constants for oxidation were obtained on the basis of a reasonable kinetic model by using a suitable numerical integration program. Although these complexities can arise also in the completely inhibited BR oscillator, we believe that the inhibitory effects are due to the HOO. scavenging action by diphenols or by quinones since HOO. radicals are also potential reducing agents. We propose two steps that could maintain a small reservoir of diphenol, while both quinone and diphenol deplete HOO. radicals. In short, the complexities do not affect the method for monitoring the relative activity of antioxidants based on the BR oscillating reaction. The effects of temperature on the inverse of the oscillatory time in the BR-uninhibited system, on the inverse of inhibition times, and on the time length of the resumed oscillations for four antioxidants were also investigated. Apparent average activation energies were obtained.

Synthesis of 1,4‐Diethynyl‐ and 1,1,4,4‐Tetraethynylbutatrienes

Abstract: In this paper, we report the synthesis and opto-electronic properties of differentially substituted 1,4-diethynyl- and 1,1,4,4-tetraethynylbuta-1,2,3-trienes. These novel chromophores greatly extend the series of building modules for oxidative coupling, which includes 1,2-diethynyl- and 1,1,2,2-tetraethynylethenes and 1,3-diethynylallenes (Fig. 1). A general synthesis of 1,1,4,4-tetraethynylbutatrienes, which tolerates a significant number of peripheral substituents, starts from pentadiynols that are oxidized to the corresponding dialkynyl ketones, followed by Corey–Fuchs dibromo-olefination, and transition metal mediated dimerization (Schemes 2 and 3). A similar protocol, including oxidation of propargyl aldehydes, dibromo-olefination, and dimerization yields the less stable 1,4-diethynylbutatrienes (Scheme 4). Attempts to prepare 1,1,4,4-tetraethynylbutatrienes with four terminal electron-donor-substituted aryl groups failed so far, mainly due to difficulties in the dibromoolefination step (Scheme 6). cis-trans-Isomerization of differentially substituted 1,1,4,4-tetraethynylbutatrienes is remarkably facile, with barriers to rotation in the range of those for peptide bond isomerization (ΔG≠≈20 kcal mol−1). Barriers to rotation of 1,4-diethynylbutatrienes are higher (ΔG≠≈25 kcal mol−1), allowing in some cases the isolation of pure isomers. Both UV/VIS spectroscopy (Figs. 2 and 3) and electrochemical studies (Table) demonstrate that the all-C-cores in diethynyl- and tetraethynylbutatrienes have strong electron-acceptor properties that are greatly enhanced with respect to those of diethynyl- and tetraethynylethenes with two C(sp)-atoms less. Substitution with peripheral electron donor groups leads to efficient intramolecular charge-transfer interactions, as evidenced by intense, bathochromically shifted longest-wavelength bands in the UV/VIS spectra.

Synthesis, Spectroscopic Studies, and Crystal Structures of Phenylorganotin Derivatives with [Bis(2,6‐dimethylphenyl)amino]benzoic Acid: Novel Antituberculosis Agents

Abstract: The novel triphenyl adduct of 2-[(2,6-dimethylphenyl)amino]benzoic acid (HDMPA; 1), i.e., [SnPh3(DMPA)] (2), the dimeric tetraorganostannoxane [Ph2(DMPA)SnOSn(DMPA)Ph2]2 (3), and the monomeric adduct [SnPh2(DMPA)2] (4), where DMPA is monodeprotonated HDMPA, have been prepared and structurally characterized by means of IR, 1H-NMR, and 13C-NMR spectroscopy. The structures of 1 and 2 have been determined by X-ray crystallography. Single-crystal X-ray-diffraction analysis of 1 revealed that there are two molecules in the asymmetric unit, HD1 and HD2, differing in conformation, both forming centrosymmetric dimers linked by H-bonds between the carboxylic O-atoms. X-Ray analysis of 2 revealed a pentacoordinate structure containing Ph3Sn coordinated to the carboxylato group. Significant CH/π interactions and intramolecular H-bonds stabilize the structures of 1 and 2, which self-assembled via CH/π and π/π-stacking interactions. The Ph3Sn adduct 2 was found to be a promising antimycobacterial lead compound, displaying activity against Mycobacterium tuberculosis H37Rv. The cytotoxiciy in the Vero cell line is also reported.

Atom Economy and Yield of Synthesis Sequences

Abstract: Atom economy (AE) or atom utilization was one of the first defining terms in the sustainable chemistry movement. In contrast to the often-cited twelve (qualitative) principles of green chemistry, AE represents a metric for quantification purposes. The theoretical efficiency of a reaction expressed by its stoichiometric equation can be determined by AE=Product [g/mol]/(Substrate 1+Substrate 2+…) [g/mol] and compared with synthetic alternatives. Of course, the atom economy will be of limited use, if starting materials differ much in complexity, i.e., in the degree of refinement. In these cases, their syntheses have to be taken in consideration, too. But, the further the retrospect goes and the more preceding synthesis steps ramify, the more complex the calculation gets. To overcome this limitation, we introduce a stepwise approach that is enabled by a simple modification of the above formula (P=product; S=substrate; Syn.=synthesis): AE=P [g/mol]/((S1/AE(Syn. of S1))+(S2/AE(Syn. of S2))+…) [g/mol]. To illustrate this equation, which is derived mathematically, the convergent multistep synthesis of the natural product trans-chrysanthemic acid is subjected to a stepwise method of calculation. The equation can be understood as a general expression for related ratios, i.e., there are corresponding modified equations for yield, selectivity, etc. In terms of the yield, it is no longer necessary to decide between the chains of the convergent synthesis, when possibly forced to ignore significant parts of the sequence. For demonstration purposes, the yield of the convergent synthesis of the natural product peridinin has been determined with a correspondingly modified equation.

Bauhinoxepins A and B: New Antimycobacterial Dibenzo[b,f]oxepins from Bauhinia saccocalyx

Abstract: Two new antimycobacterial dibenzo[b,f]oxepins, bauhinoxepins A (=3,3,5-trimethylbenzo[b]pyrano[g][1]benzoxepin-6,11-diol; 1) and B (=6-methoxy-7-methyl-2-(3-methylbut-2-enyl)dibenzo[b,f]oxepine-1,8-diol; 2), were isolated from the roots of Bauhinia saccocalyx, and their structures were elucidated by analysis of spectroscopic data. Bauhinoxepins A and B exhibited antimycobacterial activities with respective minimum-inhibitory concentrations (MIC) of 6.25 and 12.5 μg/ml. They were inactive (at 20 μg/ml) against the malarial parasite, and also inactive (at 20 μg/ml) towards the Vero, KB, and BC cell lines.

Do valine side chains have an influence on the folding behavior of β-substituted β-peptides?

Abstract: The influence of valine side chains on the folding/unfolding equilibrium and, in particular, on the 314-helical propensity of β3-peptides were investigated by means of molecular-dynamics (MD) simulation. To that end, the valine side chains in two different β3-peptides were substituted by leucine side chains. The resulting four peptides, of which three have never been synthesized, were simulated for 150 to 200 ns at 298 and 340 K, starting from a fully extended conformation. The simulation trajectories obtained were compared with respect to structural preferences and folding behavior. All four peptides showed a similar folding behavior and were found to predominantly adopt 314-helical conformations, irrespective of the presence of valine side chains. No other well-defined conformation was observed at significant population in any of the simulations. Our results imply that β3-peptides show a structural preference for 314-helices independent of the branching nature of the side chains, in contrast to what has been previously proposed on the basis of circular-dichroism (CD) measurements.

New Cholinesterase-Inhibiting Steroidal Alkaloids from Sarcococca saligna

Abstract: Seven new steroidal alkaloids, 2-hydroxysalignarine-E (=(2′E,20S)-20-(dimethylamino)-2β-hydroxy-3β-(tigloylamino)pregn-4-ene; 1), 5,6-dihydrosarconidine (=(20S)-20-(dimethylamino)-3β-(methylamino)-5α-pregn-16-ene; 2), salignamine (=(20S)-20-(methylamino)-3β-methoxypregna-5,16-diene; 3), 2-hydroxysalignamine (=(20S)-20-(dimethylamino)-2β-hydroxy-3β-methoxypregna-5,16-diene; 4), salignarine-F (=(2′E, 20S)-20-(dimethylamino)-4β-hydroxy-3β-(tigloylamino)pregn-5-ene; 5), salonine-C (=(2′E,20S)-20-(dimethylamino)-3β-(tigloylamino)pregna-4,14-diene; 6), and N-[formyl(methyl)amino]salonine-B (=(20S)-20-[formyl(methyl)amino]-3β-methoxypregna-5,16-diene; 7) have been isolated from the MeOH extract of Sarcococca saligna, along with the six known alkaloids dictyophlebine (8), epipachysamine-D (9), saracosine (10), iso-N-formylchonemorphine (11), sarcodinine (12), and alkaloid-C (13). The structures of 1–7 were deduced from spectral data. Compounds 1–13 demonstrated significant activity against acetyl- and butyrylcholinesterase.

Hydrolytic reaction of plant extracts to generate molecular diversity: New dammarane glycosides from the mild acid hydrolysate of root saponins of Panax notoginseng

Abstract: Molecular diversity was generated by hydrolyzing the crude root saponins of Panax notoginseng (BURK.) F. H. CHFN under mild acidic condition (AcOH/EtOH 1 : 1). From the acid hydrolysate, five new dammarane glycosides, named notoginsenoside T-1 (=(3beta,6alpha,12beta,20E,23RS)-24,25-epoxy-6-[(beta-D-glueopyranosyl)oxy]dam mar-20(22) -ene-3,12,23-triol; 1), notoginsenoside T-2 (=(3beta,6alpha,12beta,20E,23RS)-24,25-epoxy-6-[(beta0-D-glucopyranosyl)oxy]-23-methoxydammar-20(22)-ene-3,12-diol 2), notoginsenoside T-3 (=(3beta, 6alpha,12beta 20S)-6-[(beta-D-glucopyranosyl)oxy]-20-etlioxydammar-24-ene-3,12-diol; 3), notoginsenoside T-4 (= (3beta,6alpha,12beta,20S,22E,24RS)-6-[(beta-D-glucopyranosyl)oxy]dammar-22-ene-3,12.20,24,25-pentol; 4), and notoginsenoside T-5 (=(3beta,6alpha,12beta, 24E)-6-[beta-D-xylopyranosyl-(1-->2)-beta-D-glueopyranosyl)oxy]dammara-20(21),24-diene-3,12-diol;5), were isolated, together with 15 known dammarane glycosides, and their structures were elucidated on the basis of spectroscopic evidence. Among the known compounds, ginsenosides Rg(3) and Rh-1 were isolated as major constituents, in addition to ginsenosides Rg(5) Rh-4, and a mixture of (20R)- and (20S)-25-hydroxyginsenoside Rh-1. all of which were obtained from P. notoginseng for the first time.

Flavonoids from the Resin of Dracaena cochinchinensis

Abstract: Chemical investigation of the red herbal resin of Dracaena cochinchinensis resulted in the isolation of three new configurationally isomeric flavonoids: 6,4'-dihydroxy-7-methoxy-8-methylflavane (= 3,4-dihydro-2-(4-hydroxyphenyl)-7-methoxy-8-methyl-2H-[1]benzopyran-6-ol; 1), 5,4'-dihydroxy-7-methoxy-6-methylflavane (=3,4-dihydro-2-(4-hydroxyphenyl)-7-methoxy-6-methyl-2H-[1]benzopyran-5-ol; 2), and 7,4'-dihydroxy-5methoxyhomoisoflavane (-3,4-dihydro-3-[(4-hydroxyphenyl)methyl]-5-methoxy-2H-[1]benzopyran-7-ol; 3). Their structures Were identified by means of detailed spectral analysis. In addition, thirteen known compounds were isolated from D. cochinchinensis: 7-hydroxy-4'-methoxyflavane (4), 2,4,6-trimethoxy-4'-hydroxydihydrochalcone (5), 2,4-dimethoxy-4'-hydroxydihydrochalcone (6), 7,8(methylenedioxy)-4'-hydroxyhomoisoflavane (7), 4',7-dihydroxy-8-methylflavane (8), 2,6-dimethoxy-4,4'-dihydroxydihydrochalcone (9), 2-methoxy-4,4'- dihydroxydihydrochalcone (10), 7-methoxy-6,4'-dihydroxyhomoisoflavane (11), 2-methoxy-4,4'-dihydroxychalcone (112), 4',7-dihydroxyflavane (13), 7,4'-dihydroxyhomoisoflavane (14), 7,4'-dihydroxyhomoisoflavone (15), and 7,4'-dihydroxyflavone (16). Compounds 7, 8, 9, 14, and 15 have been isolated for the first time from this type of herbal source.

Microbial Transformation of Sesquiterpenes, (−)‐Ambrox® and (+)‐Sclareolide

Abstract: The microbial transformation of (−)-Ambrox® (1), a perfumery sesquiterpene, by a number of fungi, by means of standard two-stage-fermentation technique, afforded ambrox-1α-ol (2), ambrox-1α,11α-diol (3), ambrox-1α,6α-diol (4), ambrox-1α,6α,11α-triol (5), ambrox-3-one (6), ambrox-3β-ol (7), ambrox-3β,6β-diol (8), 13,14,15,16-tetranorlabdane-3,8,12-triol (9), and sclareolide (10) (Schemes 1 and 2). Further incubation of compound 10 with Cunninghamella elegans afforded 3-oxosclareolide (11), 3β-hydroxysclareolide (12), 2α-hydroxysclareolide (13), 2α,3β-dihydroxysclareolide (14), 1α,3β-dihydroxysclareolide (15), and 3β-hydroxy-8-episclareolide (16) (Scheme 3). Metabolites 2–5, 12, 13, and 16 were found to be new compounds. The major transformations include a reaction path involving hydroxylation, ether-bond cleavage and inversion of configuration. Metabolites 11–16 of sclareolide showed significant phytotoxicity (Table 1). The structures of the metabolites were characterized on the basis of spectroscopic techniques.