Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus.

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza.

Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay.

Design, validation, and implementation of a rapid-injection NMR system.

A Rapid Injection NMR (RINMR) apparatus has been designed and constructed to allow the observation of fast chemical reactions in real time by NMR spectroscopy. The instrument was designed to allow the rapid (<2 s) injection and mixing of a metered volume of a reagent into a spinning NMR tube followed by rapid acquisition of the data resulting from the evolution of the chemical process. The various design criteria for this universal system included the ability to deliver any chemical reagent at any temperature and allow for the observation of any nucleus.

On the mechanism of Lewis base catalyzed aldol addition reactions: kinetic and spectroscopic investigations using rapid-injection NMR.

The mechanistic foundations of the Lewis base catalyzed aldol addition reactions have been investigated. From a combination of low-temperature spectroscopic studies ((29)Si and (31)P NMR) and kinetic analyses using a rapid-injection NMR apparatus (RINMR), a correlation of the ground states and transition structures for the aldolization reactions has been formulated. The aldol addition of the tert-butylsilyl ketene acetal of tert-butyl propanoate with 1-naphthaldehyde is efficiently catalyzed by a combination of silicon tetrachloride and chiral phosphoramide Lewis bases.

Neutral and cationic phosphoramide adducts of silicon tetrachloride: synthesis and characterization of their solution and solid-state structures.

The solution and solid-state structures of hexamethylphosphoramide (HMPA) adducts of tetrachlorosilane (SiCl4) are discussed. In solution, the meridional and facial isomers of the hexa-coordinate cationic complex 3 HMPASiCl3 + Cl(-) (2) predominate at all HMPA concentrations, and are in equilibrium with the hexa-coordinate neutral trans- and cis-2 HMPASiCl4 complexes (1), as well as the penta-coordinate cationic cis-2 HMPASiCl3 + Cl(-) (3). Single crystal X-ray analyses are reported for the ionized mer-3 HMPASiCl3 + HCl2 (-) and the neutral trans-2 HMPASiCl4 complexes.

Sequencing of three-component olefin metatheses: total synthesis of either (+)-gigantecin or (+)-14-deoxy-9-oxygigantecin.

[Structure: see text] An efficient, flexible, and highly convergent strategy for accessing skipped bis-THF containing Annonaceous acetogenins is demonstrated by the synthesis of each of (+)-gigantecin (1) and its constitutional isomer (+)-14-deoxy-9-oxygigantecin (11). The skeleton of each compound is produced, at will, from the same precursors via a three-component ring-closing/cross-metathesis sequence that differs only in the ordering of the RCM vs CM events. Another notable aspect is the use of in situ epoxide-closing and -opening of iodohydrins with dimethylsulfonium methylide to provide inverted allylic alcohols.

Reaction titration: a convenient method for titering reactive hydride agents (Red-Al, LiAlH4, DIBALH, L-Selectride, NaH, and KH) by No-D NMR spectroscopy.

The concentration of reactive metal hydride (Met-H) reducing agents can be determined (in < or = 20 min) using No-D NMR spectroscopy. The method involves (i) reacting Met-H with an excess of p-methoxybenzaldehyde, (ii) quenching with excess acetic acid, (iii) recording the No-D NMR spectrum of this homogeneous mixture, and (iv) deducing the concentration of Met-H from the % conversion (as measured by integration). By a conceptually related method, the titer of the basic alkali metal hydrides KH and NaH can also be determined.

No-D NMR spectroscopy as a convenient method for titering organolithium (RLi), RMgX, and LDA solutions.

[reaction: see text] The concentration of organolithium, organomagnesium halide, and lithium diisopropylamide solutions can be reliably determined using No-D NMR spectroscopy by integration against the added internal standard 1,5-cyclooctadiene (COD) (or cyclooctene). In addition, common impurities and degradation products can be assessed.

No-D NMR (no-deuterium proton NMR) spectroscopy: a simple yet powerful method for analyzing reaction and reagent solutions.

[reaction: see text] The title technique is a convenient and powerful method for directly monitoring or assaying any reaction mixture or reagent solution. Examples of some common processes (Fischer esterification, lithiation, butyllithium/THF compatibility, olefin metathesis, and a quantification assay), each interrogated in its native solvent, are presented. The spectral data are easy to acquire, and the information content makes a compelling case for routine use of No-D NMR spectroscopy.

Toward computing relative configurations: 16-epi-latrunculin B, a new stereoisomer of the actin polymerization inhibitor latrunculin B.

The title compound, 16-epi-latrunculin B (3), has been isolated from the sponge Negombata magnifica collected from the Red Sea near Hurghada, Egypt. This new natural product was determined to be an epimer of latrunculin B (1), which was found in the same sponge collection. The structure of 3 was initially deduced from proton and carbon NMR chemical shift trends and proton-proton nuclear Overhauser effect experiments.