Chiral building-blocks by chemoenzymatic desymmetrization of 2-ethyl-1,3-propanediol for the preparation of biologically active natural products

2-Ethyl-1,3-propanediol 1 and its related di-O-acetate 2 were desymmetrized by partial chemoenzymatic acetylation and deacetylation, by Pseudomonas fluorescens lipase (Amano P.; PFL), to (R)-1-O-acetyl-2-ethyl-1,3-propanediol 3. On treatment of 3 with I₂/Ph₃P/imidazole the related (S)-1-O-acetyl-2-ethyl-3-iodopropanol 4 was obtained and transformed into the corresponding triphenylphosphonium salt 5. Reaction of [(S)-3-acetoxy-2-ethylpropylidene]triphenylphosphorane 6, prepared from 5, with 2,3:4,5-di-O-isopropylidene-β-d-arabino-hexos-2-ulopyranose 7 gave (Z)-3-C-acetoxymethyl-1,2,3,4,5-pentadeoxy-6,7:8,9-di-O-isopropylidene-β-d-manno-dec-4-ene-6-ulo-6,10-pyranose 8 which was hydrogenated to 9 and subsequently deacylated to 10. Treatment of 10 with Me₂CO/H⁺ caused a rearrangement to (3R,4R,5S,6R,9R)-9-ethyl-5-hydroxy-3,4-isopropylidenedioxy-1,7-dioxaspiro[5.5]undecane 11, which closely matched the skeleton of the talaromycins.     

An efficient enantioselective synthesis of (R,R)-formoterol,a potent bronchodilator,using lipases

The potent β₂-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described.     

Synthesis,spectral characterization,theoretical, antimicrobial,DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand

Novel Cu(II) (1) and Zn(II) (2) complexes with 4-(1-(4-morpholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) (L) have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory) studies result confirms that, LMCT mechanism have been done between L and M(II) ions. The antimicrobial studies indicate that the ligand L and complexes 1 & 2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 & 2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 & 2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0). The K_b values of ligand L and complexes 1 & 2 are higher in acidic buffer at pH 4.0 (K_b = 2.42 × 10⁵, L; 2.8 × 10⁵, 1; 2.65 × 10⁵, 2) and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 & 2 have been studied. The in vitro anticancer activities results show that complexes 1 & 2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L.     

Tetracyclic triterpenoids from Melia azedarach, L.—III

From petroleum ether extracts of the bark of M. azedarach four novel tetracyclic triterpenoids have been isolated and characterized to be C₃₀ compounds of the euphane (20R) series. Previously known triterpenoids from Meliaceae have all been 20S compounds. Kulinone 1 is the first known euphane or tirucallane (20S) derivative oxygenated in the D ring; kulactone 2, kulolactone 3 and methyl kulonate 4 are additionally oxygenated in the side chain. Compounds 2 and 3 have a 2-oxa-trans-bicyclo[3,3,0]-octanone structure.     

N,N-Dimethylaniline and 1-(trifluoromethyl)benzene-functionalized tetrakis(ethynyl)pyrenes: synthesis,photophysical, electrochemical and computational studies

We have synthesized a series of tetrakis(ethynyl)pyrenes functionalized with N,N-dimethyaniline and 1-(trifluoromethyl)benzene as a peripheral electron-donor and electron-acceptor moiety, respectively. In solvatochromic studies, compounds with one peripheral donor and three peripheral acceptors (2), with two donors and two acceptors (3 and 4), with three donors and one acceptor (5) show enhanced charge transfer compared with tetra-donor (6) and tetra-acceptor (1) compounds. The redox peak reversibility depends on the number of peripheral donors and acceptors appended to tetrakis(ethynyl)pyrenes as well as on their substitution pattern as revealed by cyclic voltammetric studies. The photophysical and electrochemical properties of compounds 1–5 have been compared with compound (6) reported recently by J.-W. Oh et al. [Angew. Chem., Int. Ed. 2009, 48, 2522–2524]. The density functional theory (DFT) based calculations such as spin density distribution (SDD) of cation/anion radicals, electrostatic potential (ESP) density distribution, non-adiabatic reduction potentials (NRP) for cation radicals, and vertical detachment energy (VDE) for anion radicals supported the experimental observations. The differences in oxidation peak reversibility for different substitution pattern have been rationalized by calculated static first hyperpolarizability (β). Our observations would be helpful in designing new ECL-active materials, where ECL (electrogenerated chemiluminescence) efficiency can be improved through improving radical stability.     

Attenuol—structure,stereochemistry and synthesis

A new lignan, attenuol, isolated from Knema attenuata (Wall.) Warb., has been assigned structure (1) on the basis of spectral data. Lignan (1) and the stereoisomer (4) (2-epiattenuol) have been synthesized and the structure assigned to attenuol has been confirmed.     

Studies on fungal metabolites—XXXI: Anthraquinonoid colouring matters of Penicillium islandicum sopp and some other fungi (−)luteoskyrin, (−)rubroskyrin, (+)rugulosin and their related compounds

The structures of (+)rugulosin, (?)luteoskyrin and (?)rubroskyrin have been reexamined by NMR and new structures 18, 19 and 20 proposed respectively. Their absolute structures were established on the basis of the X-ray analysis of (+)dibromodehydrotetrahydrorugulosin (27). The minor analogous metabolites, (?)4a-oxyluteoskyrin (31) of P. islandicum and (+)4a-oxyrugulosin (32) of P. brunneum, have been formulated. On oxidation of (?)luteoskyrin and (+)rugulosin with pertrifluoroacetic acid (?)4a,4a′-dioxyluteoskyrin (33) and (+>4a,4a′-dioxyrugulosin (34) were formed, while with MnO₂ (+)4a,4a′-dehydrorugulosin (35) was obtained. The structures of lumiluteoskyrin (37), and deoxylumiluteoskyrin (38), photooxidation products of luteoskyrin and deoxyluteoskyrin, respectively, have been elucidated.     

A simplest isolable monocyclic thiepin. Synthesis,structure, and thermal stability of 2,7-di-tert-butylthiepin

As an example of a simplest isolable monocyclic thiepin, 2,7-di-tert-butylthiepin (2) has been synthesized from 2,6-di-tert-butylthiopyrylium salt, and the thermal properties together with the X-ray crystal structure of (2) have been examined.     

Genus Chloranthus: A comprehensive review of its phytochemistry,pharmacology, and uses

This paper is intended to review advances in the botanical, traditional uses, phytochemical, pharmacological and development and utilization studies of the genus Chloranthus. Chloranthus, a genus of the family Chloranthaceae, which is mainly distributed in the temperate and tropical regions of Asia, has been used as a folk remedy for swollen boils, snake bites and bruises. Up to now, 418 compounds have been reported from the genus Chloranthus, including 383 terpenoids, 4 coumarins, 6 lignans, 2 simple phenylpropanoids, 4 flavonoids, 6 amides, 5 organic acids and some other types of compounds. Among them, the main chemical constituents are sesquiterpenes and their diterpenoids. Modern pharmacological studies have shown that most of the Chloranthus plants possessed anti-cancer, anti-inflammatory, antibacterial, antiviral, and antimalarial activities. As one of the most important genera in China, Chloranthus should be paid further attention to gathering information about the pharmacological mechanism and value active compounds. This paper summarized the phytochemistry, pharmacology, and uses of genus Chloranthus in order to lay a foundation and provide reference for the follow-up research and wide application of the genus.     

Spectalinine and iso-6-carnavaline,two unprecedented piperidine alkaloids from the seeds of cassia spectabilis

Along with the alkaloïds (+)spectaline (1) and (?)iso-6-cassine (2), two new piperidinol alkaloïds have been isolated from the seeds of Cassia spectabilis DC. They have been shown to possess structures 3 and 4 through chemical and spectral studies.     

A new family of supramolecular multiferrocenyl rhomboids:Synthesis,characterization,and their electrochemical behavior

Two novel,supramolecular,multiferrocenyl rhomboids 5 and 6 have been successfully constructed from newly designed 60 ferrocenyl donor precursor 1 via coordination-driven self-assembly.The structures of all multiferrocenyl rhomboids were characterized by multinuclear NMR(¹H and ³¹P),CSI-TOF-MS, and PM6 semi-empirical molecular simulation,and their electrochemical behaviors have been investigated.     

Alkaloids from rhamnaceae—XXVI : Nummularine -D, -E and -F,new cyclopeptide alkaloids from Zizyphus nummularia

From the benzene extract of the root bark of Zizyphus nummularia three new peptide alkaloids have been isolated: nummularine-D 1, -E 3 and -F 5. All three contain the 14-membered ring system. Nummularine-D is N-desmethyl-integerrenine. Nummularine-E has N,N-dimethylthreonine and nummularine-F has N,N-dimethylglycine as terminal amino-acid, neither of which has been found in such alkaloids before.     

Synthesis,structure, and conformation of terphenylene-derived azacalix[4]aromatics

Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)– 4,4″-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, respectively. The bridging –NH– functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1 and 2 have been transformed to the corresponding –N(CH₃)– bridged azacalix[2]arene[2]terphenylenes 3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,3″-diamine derived azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the terphenyl-4,4″-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate conformation.     

Synthesis,characterization and biological activities of some azo derivatives of aminothiadiazole derived from nicotinic and isonicotinic acids

In this study we synthesized the new compounds containing bis-1,3,4-thiadiazole 3(A–D)_n from many reaction steps (cyclization, diazotization and etherification respectively). The compounds have been characterized by melting point, FT-IR and ¹H NMR data. All the synthesized compounds have been evaluated in vitro for their antimicrobial activities against several microbes like: Escherichia coli, Klebsiellia pneumonia, Pseudomonas aeruginosa, Serratia marscens and Staphylococcus aureus and show that some of these compounds have very good antibacterial activity.     

Chelating properties of permethylated 6A,6D-dideoxy-6A,6D-bis(1-imidazolyl)cyclodextrins towards Pt(II) and Ru(III)

Two imidazole-coordinating groups have been successfully grafted onto the C-6^A and C-6^D positions of permethylated α- and β-cyclodextrin scaffolds. Both water-soluble ligands L1 and L2 turned out to behave as good chelators when reacted with K₂PtCl₄. In the resulting diamagnetic cis-chelate complexes, the metal cation is pending above the cavity entrance. Paramagnetic ruthenium(III) chelate complexes have also been successfully synthesised from L1 and L2. In these more sterically demanding octahedral complexes, the imidazole groups coordinate the metal centre in a trans-fashion.     

Isolation of a new indoxyl alkaloid,Amoenamide B,from Aspergillus amoenus NRRL 35600: Biosynthetic implications and correction of the structure of Speramide B

A new prenylated indoxyl alkaloid, Amoenamide B (1), was isolated from Aspergillus amoenus NRRL 35600 along with Asperochramide A (2). Although many prenylated oxindole alkaloids, containing bicyclo[2.2.2]diazaoctane cores, have been isolated from the fungus of the genera Aspergillus and Penicillium to date, 1 is the fourth compound with the indoxyl unit containing the cores. During the structure elucidation of 1, we found that the planar structure matched to that of Speramide A (3), isolated from A. ochraceus KM007, but the reported structure of 3 was incorrect and turned out to be that of Taichunamide H (4), recently isolated from A. versicolor HDN11-84.     

Asymmetric synthesis of pentenomycin I, epipentenomycin I, and their analogs

The synthetic utility of the intramolecular acylation of α-sulfinyl carbanions as an efficient and general synthetic approach for the preparation of (−)-pentenomycin I (1) and (−)-epipentenomycin I (5) and their enantiomers (ent-1 and ent-5), starting from chiral (2S,5S,6S)-ester 6 and ent-6, respectively, has been demonstrated. Easy accesses to pentenomycin analogs have also been demonstrated through the Pummerer, Suzuki-Miyaura, and Sonogashira reactions.     

Cyclopropanation reactions with α, β-epoxy diazomethyl ketones and rearrangement of α, β-epoxy cyclopropyl ketones

The cyclopropanation reactions of α, β-epoxy diazomethyl ketones 1 with olefins using Pd(OAc)₂ as catalyst is described. Differently substituted epoxy diazo ketones 1a-1f give with cyclohexene exo-norcarane derivatives. 3, 3-Diphenyloxiranyl-2 diazomethyl ketone 1a reacts with olefins like isobutene, E- and Z- butene-2 to give epoxy cyclopropyl ketones. 3, 3-Diphenyloxiranyl-2 cyclopropyl ketones 2a and 9 undergo two consecutive rearrangement reactions with BF₃ as catalyst. In the first step an epoxide rearrangement of 9 takes place to give β-ketoaldehyde 10, which in a second step rearranges to enolester 12. The latter reaction is most likely restricted to β-ketoaldehydes which have a quaternary α-C atom. A rationale for this unusual reaction has been proposed.     

The first synthesised examples of di-siloxy-substituted cyclopentadienyl zirconocenes,their synthesis,structure and activity in ethylene polymerisation

Bis-(1,2-(RMe₂SiO)₂)ZrCl₂ complexes with R = Me-(5a), iPr-(5b) and tBu-(5c) have been synthesised in good yields and characterised. Compounds 5a–c are the first synthesised examples of multi-siloxy-substituted cyclopentadienyl metallocenes. The siloxy-substituents have a for siloxy substituted metallocenes unique steric arrangement, with one almost in the same plane, and the other nearly perpendicular to the plane of the cyclopentadienyl ligand of the zirconocene. The ethylene/1-hexene co-polymerisation activity using methylalumoxane as co-activator gives low activities, with compound 5c (262.92 kg(PE)/g(Zr)/h) being the most active.     

New N-pyrazole, P-phosphinite hybrid ligands and corresponding Rh(I) complexes: X-ray crystal structures of complexes with [Rh, N, P-phosphinite, Cl, (CO)] core

Two new N-pyrazole, P-phosphinite hybrid ligands 3-(3,5-dimethyl-1H-pyrazol-1-yl)propyldiphenylphosphinite (L³) and 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyldiphenylphosphinite (L⁴) are presented. The reactivity of these ligands and two other ligands reported in the literature (3,5-dimethyl-1H-pyrazol-1-yl)methyldiphenylphosphinite (L¹) and 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyldiphenylphosphinite (L²) towards [RhCl(CO)₂]₂ (1) have been studied and complexes [RhCl(CO)L] (L = L² (2), L³ (3) and L⁴ (4)) have been obtained. For L¹ only decomposition products have been achieved. All complexes were fully characterised by analytical and spectroscopic methods and the resolution of the crystalline structure of complexes 2 and 3 by single-crystal X-ray diffraction are also presented. In these complexes, the ligands are coordinated via κ²(N,P) to Rh(I), forming metallocycles of seven (2 and 4) or eight (3) members and finish its coordination with a carbonyl monoxide and a trans-chlorine to phosphorus atom. In both complexes, weak intermolecular interactions are present. NMR studies of complexes 2-4 show the chain N-(CH₂)_x-O becomes rigid and the protons diastereotopic.