1-Alkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones as glycine templates. Synthesis of Fiscalin B

An excess of base allows the regio- and diastereoselective alkylation at C(4) of the glycine templates 1-methyl(isopropyl)-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones 9a and 9b without the need for N(2)-protecting groups. While the alkylation of 9a gave exclusively the 1,4-anti-isomers, the isopropyl derivative 9b required much longer reaction times and occurred with lower diastereoselectivity. Fiscalin B 3 was obtained by alkylation of 9b with N-Boc-3-indolylmethyl bromide followed by indole deprotection.     

Diverse motifs of mannoside clustering on a beta-cyclodextrin core

[reaction: see text] A new method for the synthesis of beta-cyclodextrin-based cluster mannosides by application of the Sonogashira cross-coupling reaction is described. The method allows for the persubstitution of the beta-cyclodextrin at either 2- and 3-positions to give two types of heptavalent clusters, at both 2- and 6-positions to give clusters with 14 mannopyranoside units and at 2-, 3-, and 6-positions to obtain clusters with 21 mannopyranoside ligands.     

Synthesis of 6,19-sulfamidate bridged pregnanes

Conformationally restrained substituted pregnane-20-one derivatives were obtained by an intramolecular nitrene addition onto a C-5/C-6 double bond involving a tethered C-19 sulfamoyl moiety. The resulting aziridine underwent regioselective nucleophilic ring opening at C-5 at room temperature with cyanide, fluoride, and acetate. In the isolated case of acetate, a reversal of regioselectivity was observed at higher temperatures, a result attributed to a rearrangement process involving aziridine ring opening at the C-5 position and subsequent migration of the acetyl moiety to C-6.     

SFE of rosemary oil: Assessment of the influence of process variables and extract characterization

The effects of temperature and solvent density on the characteristics of the extracts obtained from supercritical fluid extraction (SFE) of the volatile compounds from Brazilian rosemary (Rosamarinus officianalis L., Labiatae) using carbon dioxide (CO₂) as solvent were investigated. The experiments were performed in a semi-batch laboratory scale home-made unit at two temperatures, viz. 310.15 and 320.15 K, over the pressure range of 100-160 bar. This study allowed to determine the crossover point and the maximum solubility of the oil. The products were analyzed by HRGC-MS, and compounds grouped in three different classes according to their molecular mass distribution in order to evaluate the influence of the variables studied on the characteristics of the extracts. The model proposed by Sovová was adopted in an attempt to interpret the mass transfer phenomena in the extraction process.     

High resolution on a quadrupole ion trap mass spectrometer

By using a modified ion trap mass spectrometer, resolution in excess of 30,000 (FWHM) at m I z 502 is demonstrated. The method of increasing resolution in the ion trap mass spectrometer operated in the mass-selective instability mode depends on decreasing the rate of scanning the primary radio frequency amplitude as well as using resonance ejection at the appropriate frequency and amplitude. A theoretical basis for the method is introduced.     

Human neural stem cell growth and differentiation in a gradient-generating microfluidic device

This paper describes a gradient-generating microfluidic platform for optimizing proliferation and differentiation of neural stem cells (NSCs) in culture. Microfluidic technology has great potential to improve stem cell (SC) cultures, whose promise in cell-based therapies is limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms should provide much greater control over cell microenvironment and rapid optimization of media composition using relatively small numbers of cells. Our platform exposes cells to a concentration gradient of growth factors under continuous flow, thus minimizing autocrine and paracrine signaling. Human NSCs (hNSCs) from the developing cerebral cortex were cultured for more than 1 week in the microfluidic device while constantly exposed to a continuous gradient of a growth factor (GF) mixture containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). Proliferation and differentiation of NSCs into astrocytes were monitored by time-lapse microscopy and immunocytochemistry. The NSCs remained healthy throughout the entire culture period, and importantly, proliferated and differentiated in a graded and proportional fashion that varied directly with GF concentration. These concentration-dependent cellular responses were quantitatively similar to those measured in control chambers built into the device and in parallel cultures using traditional 6-well plates. This gradient-generating microfluidic platform should be useful for a wide range of basic and applied studies on cultured cells, including SCs.     

Metal complexes of porphycene,corrphycene, and hemiporphycene: stability and coordination chemistry

Porphyrin (P), porphycene (Pc), corrphycene (Cn), and hemiporphycene (Hpc) represent a series of well defined "4-N in" constitutional porphyrin isomers. These isomers, in the form of their octaethyl derivatives, represent a congruent set of porphyrinoids whose properties can be compared. In this study we report how variations in electronic structure and nitrogen-core size in the free-base forms of these four systems are reflected in the properties of their corresponding metal complexes. Specifically, the effects that these differences have on the axial ligation properties of the Zn(II), Mg(II), Ni(II), and Co(II) complexes of P, Pc, Cn, and Hpc in toluene using pyridine as the axial ligand are detailed. Also reported are the relative stabilities of these complexes under acidic conditions. It is shown that for the zinc, magnesium, and cobalt complexes, there are distinct differences in the ability to maintain four-, five-, or six-coordinate geometries in the presence of similar concentrations of pyridine. By contrast, no apparent differences in axial ligand binding affinity are seen for the four nickel complexes. Little difference in stability was likewise seen when these same complexes were subject to acid-mediated demetallation, with all four falling into stability class II, according to the accepted porphyrin stability ranking system. High stabilities were also seen in the case of the cobalt complexes, with the Pc and Cn complexes being of stability class III and the P and Hpc derivatives falling into stability class II. The Zn(II) and Mg(II) complexes were all far less stable than the corresponding Ni(II) and Co(II) complexes. In this case, semiquantitative analyses of the rate of acid-induced decomposition revealed the following stability sequence P>Cn>Hpc>Pc for both the Zn(II) and Mg(II) complexes. Single-crystal X-ray diffraction structures were solved for the Zn(II), Mg(II), and Ni(II) complexes of the octaethyl derivatives of Hpc, Cn, and Pc as well as a Co(II) octamethylcorrphycene and are reported as part of this study. These solid-state structures confirm four-coordinate species for the Ni(II) complexes, four- and five-coordinate species for the Mg(II) and Zn(II) complexes, and a six-coordinate species for the lone Co(II) complex.     

Photooxygenation of 9-methyl-1,2,3,4-tetrahydrocarbazole: A kinetic study

The reaction of the singlet oxygen with 9-methyl-1,2,3,4-tetrahydrocarbazole has been undertaken to give a benzazonine derivative in good yield. Rose-bengal supported on an anionic resin was used as heterogeneous photosensitizing agent. Kinetic evaluation has been made for the additon of singlet oxygen to the indole ring at room temperature.

---

9--1,2,3,4- . , , . .

     

Role of secondary structure in the asymmetric acylation reaction catalyzed by peptides based on chiral C alpha-tetrasubstituted alpha-amino acids

In a recent series of papers, Miller and co-workers were able to show that His(pi-Me)-based, terminally protected peptides are potent catalysts of the asymmetric acyl transfer reaction, useful for the kinetic resolution of alcohols. In a structure-supporting solvent, one of the most active compounds, an Aib-containing tetrapeptide, is folded in a doubly intramolecularly H-bonded beta-hairpin motif incorporating a type-II' beta-turn conformation. In this work, we have expanded the study of the Miller tetrapeptide by examining a set of analogues and shorter sequences (dipeptide amides), characterized by chiral C(alpha)-tetrasubstituted alpha-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and (1)H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the beta-hairpin 3D-structure and the catalytic activity of the peptides. A tetrapeptide analogue slightly more selective than the Miller compound has been found. However, the terminally protected, industrially more appealing, dipeptide amides are poorly effective.     

Elucidating the initial dynamics of electron photodetachment from atoms in liquids using variably-time-delayed resonant multiphoton ionization

We study the photodetachment of electrons from sodium anions in room temperature liquid tetrahydrofuran (THF) using a new type of three-pulse pump-probe spectroscopy. Our experiments use two variably-time-delayed pulses for excitation in what is essentially a resonant 1+1 two-photon ionization: By varying the arrival time of the second excitation pulse, we can directly observe how solvent motions stabilize and trap the excited electron prior to electron detachment. Moreover, by varying the arrival times of the ionization (excitation) and probe pulses, we also can determine the fate of the photoionized electrons and the distance they are ejected from their parent Na atoms. We find that as solvent reorganization proceeds, the second excitation pulse becomes less effective at achieving photoionization, and that the solvent motions that stabilize the excited electron following the first excitation pulse occur over a time of approximately 450 fs. We also find that there is no spectroscopic evidence for significant solvent relaxation after detachment of the electron is complete. In combination with the results of previous experiments and molecular dynamics simulations, the data provide new insight into the role of the solvent in solution-phase electron detachment and charge-transfer-to-solvent reactions.