Total Synthesis of Olivacine and Ellipticine via a Lactone Ring-Opening and Aromatization Cascade.

Effective preparation of olivacine and ellipticine via late-stage D-ring cyclization is described. Key features of the synthetic routes include trifluoroacetic acid-mediated formation of a lactone that is fused to a tetrahydrocarbazole derivative and its one-pot two-step ring opening and aromatization mediated by para-toluenesulfonic acid and palladium on carbon, respectively.

Concise total syntheses of (±)-noruleine and (±)-uleine.

The first total synthesis of (±)-noruleine and a concise synthesis of (±)-uleine have been accomplished via the DDQ mediated dehydrogenative cyclization of a tetrahydrocarbazole derivative bearing a non-substituted amide functionality to prepare the key azocino[4,3-b]indole precursor.

An entry to the azocino[4,3-b]indole framework through a dehydrogenative activation of 1,2,3,4-tetrahydrocarbazoles mediated by DDQ: formal synthesis of (±)-uleine.

It is presented that hexahydro-1,5-methano[4,3-b]indoles were efficiently synthesized in high yields (up to 89% yield) through the cyclization reaction of starting tetrahydrocarbazoles bearing a monoalkylaminocarbonylmethyl moiety at the C-2 position mediated by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). A mechanistic proposal is also given that mainly includes two cascade reactions: (i) formation of a vinylogous iminium cation via DDQ-mediated dehydrogenation of tetrahydrocarbazole functionality and (ii) intra-molecular and syn-selective addition of the amide functionality as the nucleophile to the vinylogous iminium cation. Furthermore, this cyclization reaction was successfully utilized in the formal total synthesis of (±)-uleine, an Aspidospermatan skeletal type alkaloid.

6,6-[Ethyl-enebis(sulfanediyl)]-2-(2-methoxy-ethyl)-1,2,3,4,5,6-hexa-hydro-1,5-methano-1H-azocino[4,3-b]indol-3-one.

The title compound, C(19)H(22)N(2)O(2)S(2), consists of a tetra-cyclic ring system containing an azocine skeleton with methoxy-ethyl and dithiol-ane groups as substituents. The benzene and five-membered N-heterocyclic rings are nearly coplanar, making a dihedral angle of 0.81 (12)°. The dithiol-ane ring adopts an envelope conformation. Inter-molecular N-H⋯O hydrogen-bonding and weak C-H⋯π inter-actions are present in the crystal structure.

2-Ethyl-6,6-ethyl-enedisulfanediyl-7-methoxy-methyl-1,2,3,4,5,6-hexa-hydro-1,5-methano-azocino[4,3-b]indol-3-one.

The title compound, C(20)H(24)N(2)O(2)S(2), consists of a tetra-cyclic ring system containing an azocino skeleton with ethyl, dithiol-ane and methoxy-methyl groups as substituents. The benzene and five-membered rings are nearly coplanar, with a dihedral angle of 2.78 (11)°. The dithiol-ane ring adopts an envelope conformation. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into chains nearly parallel to the c axis. Two C-H⋯π inter-actions are also present.

Ion-exchanger synthesis using reversible addition-fragmentation chain transfer polymerization.

An ion-exchanger with polyanionic molecular brushes was synthesized by a "grafting from" route based on "surface-controlled reversible addition-fragmentation chain transfer polymerization" (RAFT). The RAFT agent, PhC(S)SMgBr was covalently attached to monodisperse-porous poly(dihydroxypropyl methacrylate-co-ethylene dimethacrylate), poly(DHPM-co-EDM) particles 5.8 microm in size. The monomer, 3-sulfopropyl methacrylate (SPM), was grafted from the surface of poly(DHPM-co-EDM) particles with an immobilized chain transfer agent by the proposed RAFT protocol. The degree of polymerization of SPM (i. e. the molecular length of the polyanionic ligand) on the particles was controlled by varying the molar ratio of monomer/RAFT agent. The particles carrying polyanionic molecular brushes with different lengths were tested as packing material in the separation of proteins by ion exchange chromatography. The columns packed with the particles carrying relatively longer polyanionic ligands exhibited higher separation efficiency in the separation of four proteins. Plate heights between 130-200 microm were obtained. The ion-exchanger having poly-(SPM) ligand with lower degree of polymerization provided better peak-resolutions on applying a salt gradient with higher slope. The molecular length and the ion-exchanger group content of polyionic ligand were adjusted by controlling the degree of polymerization and the grafting density, respectively. This property allowed control of the separation performance of the ion-exchanger packing.

Poly(N-isopropylacrylamide) layers on silicon wafers as smart DNA-sensor platforms.

The aim of this study is to create thermo-responsive ('smart') biosensor (array) platforms. Poly(N-isopropylacrylamide) (poly(NIPA)) carrying two different functional groups (-SH and -COOH) at two ends was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Self-assembled monolayers (SAMs) with amino-terminated groups on the Si(001) surfaces were prepared using 3-aminopropyltrimethoxysilane (APTS). Ellipsometric measurements showed that monolayers with a thickness of about 1.10 nm were formed when the dipping time is about 1 h, while more profound agglomerations were observed for longer time periods and APTS solutions with higher concentrations. Poly(NIPA) molecules were then covalently attached to the silicon surfaces via APTS molecules. Afterwards, 5'-thiolated oligodeoxynucleotide-probes were immobilized onto these thiol-terminated poly(NIPA) layers on the surface by disulfide bond formation. An ellipsometer was used for detection (by hybridization) of the target oligos (the complementary of the probe oligos) within the aqueous media at two different temperatures, 25 degrees C and 45 degrees C, which are below and above the "Lower Critical Solution Temperature" (LCST) of poly(NIPA), respectively. Hybridization at low temperatures was significantly higher than those observed at higher temperatures. No respond (no hybridization) was monitored when the target is a non-complementary oligo sequence. These preliminary studies demonstrated that this approach can be used switch off and on the surface reactions on smart surface by using an external stimulus (temperature in this case).

Preparation of an ion-exchange chromatographic support by a "grafting from" strategy based on atom transfer radical polymerization.

A new "grafting from" strategy based on surface-initiated atom transfer radical polymerization (ATRP) was first used for the preparation of a polymer-based ion-exchange support for HPLC. The most important property of the proposed method is to be applicable for the synthesis of any type of ion exchanger in both the strong and the weak forms. Monodisperse, porous poly(glycidyl methacrylate-co-ethylene dimethacrylate), poly(GMA-co-EDM) particles 5.8 mum in size were synthesized by "modified seeded polymerization". Poly(dihydroxypropyl methacrylate-co-ethylene dimethacrylate), poly(DHPM-co-EDM) particles were then obtained by the acidic hydrolysis of poly(GMA-co-EDM) particles. The ATRP initiator, 3-(2-bromoisobutyramido)propyl(triethoxy)silane was covalently attached onto poly(DHPM-co-EDM) particles via the reaction between triethoxysilane and diol groups. In the next stage, the selected monomer carrying strong cation exchanger groups, 3-sulfopropyl methacrylate (SPM), was polymerized on the initiator-immobilized particles via surface-initiated ATRP. The degree of polymerization of SPM (i.e., length of polyionic ligand) on the particles was precisely controlled by adjusting ATRP conditions. Poly(SPM)-grafted poly(DHPM-co-EDM) particles obtained with different ATRP formulations were tried as chromatographic packing in the separation of proteins by ion-exchange chromatography. The proteins were successfully separated with higher column yields with respect to the previously proposed materials. The plate heights between 100 and 150 mum were achieved with the column packed with the particles carrying the shortest poly(SPM) chains. The plate height showed no significant increase with increasing flow rate in the range of 0.5-16 cm/min.

Poly(hydroxyethyl methacrylate-co-methacrylamidoalanine) membranes and their utilization as metal-chelate affinity adsorbents for lysozyme adsorption.

Different adsorbents have been reported in the literature for protein purification. The authors have developed a novel and new approach to obtain high protein adsorption capacity utilizing a 2-methacrylamidoalanine-containing membrane. Amino acid ligand 2-methacrylamidoalanine (MAAL) monomer was synthesized using methacryloyl chloride and alanine. Poly(2-hydroxyethylmethacrylate-co-2-methacrylamidoalanine) [p(HEMA-co-MAAL)] membranes were then prepared by UV-initiated photopolymerization of HEMA and MAAL in the presence of an initiator (azobisisobutyronitrile, AIBN). The synthesized MAAL monomer was characterized by NMR. p(HEMA-co-MAAL) membranes were characterized by swelling studies, porosimeter, SEM, FTIR, and elemental analysis. These membranes have macropores in the size range of 5-10 microm. Cu(II) ions (25.9 mmol/m2) were chelated on these membranes. p(HEMA-co-MAAL) membranes were used to study the adsorption of lysozyme from aqueous media containing different amounts of lysozyme (0.1-3.0 mg/l) and at different pH values (4.0-8.0). The non-specific adsorption of lysozyme on the pHEMA membranes was negligible (0.9 microg/cm2). Incorporation of MAAL increased the lysozyme adsorption significantly up to 2.96 mg/cm2. The lysozyme adsorption capacity of the Cu(II) incorporated membranes (9.98 mg/cm2) was greater than that of the p(HEMA-co-MAAL) membranes. More than 90% of the adsorbed lysozyme was desorbed in 1 h in the desorption medium containing 1.0 M NaCl and 0.025 M EDTA. The metal-chelate affinity membranes are suitable for repeated use for more than ten cycles without a noticeable loss of capacity.