Total Synthesis of Ritterazine B.

The first total synthesis of the cytotoxic alkaloid ritterazine B is reported. The synthesis features a unified approach to both steroid subunits, employing a titanium-mediated propargylation reaction to achieve divergence from a common precursor. Other key steps include gold-catalyzed cycloisomerizations that install both spiroketals and late stage C-H oxidation to incorporate the C7' alcohol.

Nanocars with Permanent Dipoles: Preparing for the Second International Nanocar Race.

With the desire to synthesize surface-rolling molecular machines that can be translated and rotated with extreme precision and speed, we have synthesized a series of five nanocars. Each structure features a permanent dipole moment, generated by an N,N-dimethylamino- moiety on one end of the car coupled with a nitro group on the other end. These cars are designed to be stimulated with an electric field gradient from a scanning probe microscopy tip. The nanocars all possess unexplored combinations of structural features: tert-butyl wheels, short alkyne chassis, and combination sets of wheels including one set of tert-butyl wheels and another set of larger adamantane wheels on the same car. Each of these features needs to be assessed as preparation for the second International Nanocar Race that is taking place in 2022.

Chemical permeation of similar disposable nitrile gloves exposed to volatile organic compounds with different polarities: Part 1: Product variation.

Many glove manufacturers of chemical protective clothing produce chemical resistance guides to aid in selection of an appropriate product. Some manufacturers provide permeation data, but others provide a general rating system without reporting testing their own products. A critical issue is that considerable variation in chemical resistance, both with breakthrough times and steady-state permeation rates, have been observed with disposable nitrile gloves. The main purpose of this study was to determine whether significant variation in chemical resistance was present between products from a single brand that provided a generalized chemical resistant guide. The objective was to determine if the ratings noted on the chemical resistance guide were sufficient for protection against chemical permeation. The chemical permeation of ten disposable nitrile gloves against three organic solvents of varying polarity (cyclohexane, tert-butanol, and cyclohexanol) was performed in triplicate. Despite the similar chemical resistant ratings for the products, significant variation in both breakthrough times and steady-state permeation rates were observed among the ten nitrile gloves. The largest variation in breakthrough time was about 8-fold. The largest variation in steady-state permeation rate was about 177-fold. A proposed chemical resistance rating system was used to further evaluate the variation in performance, as it would relate to similar rating systems used by glove manufacturers or brands. Polarity played a role in the observed performance, with the nitrile gloves providing increased protection with an increase in solvent polarity, more notably with the dielectric constant. Using a proposed rating system, the percentages of products rating as excellent to good were 20% (cyclohexane), 60% (tert-butanol), and 90% (cyclohexanol). Ultimately, the ratings noted on the general chemical resistance guide were not sufficient for worker protection against chemical permeation. It is not valid to assume that little variation should exist among the different glove products under a same brand or based on the use of generic chemical resistant data. When critical, occupational health and safety professionals should base glove selection on product-specific chemical permeation data.

Chemical permeation of similar disposable nitrile gloves exposed to volatile organic compounds with different polarities Part 2. Predictive polymer properties.

A follow-up study evaluated the chemical and physical parameters of 10 disposable nitrile glove products in association with the observed variability in chemical permeation performance. The aim was to determine which polymer properties explained or were predictive of the observed wide variation in breakthrough time and steady state permeation rate. The physical and mechanical properties evaluated were thickness, area density, volume fraction and modulus 50-100%. The chemical composition properties evaluated were relative acrylonitrile content, relative carboxylation content, oily plasticizers, inorganic fillers and organic polymer content. A combination of correlation and multiple regression analyses were performed to evaluate the predictive nature of these parameters. For the regression analyses, stepwise, forward selection and backward elimination methods were used to determine an optimal regression fit. Both thickness and area density were strongly correlated with the breakthrough time. With the addition of volume fraction, these factors accounted for about 88-89% of the variation in breakthrough times. The correlation results for the steady-state permeation rate were largely inconclusive and only a moderate correlation with thickness was observed with one solvent. However, regression analyses revealed a moderate to strong association (R2 = 0.742; p < 0.001) between the permeation rate and thickness and volume fraction. With the inclusion of volume fraction in all regression models, the microstructure of the polymer played a critical role in chemical permeation, which requires further investigation. Based on these results, selection based on the availability of chemical permeation data for the product should always be preferred, especially when skin protection is critical. When chemical resistance ratings are based on general performance data, additional factors such as thickness and area density should be taken into consideration. In general, increases in thickness and area density are associated with increases in breakthrough time and decreases in the steady-state permeation rate. However, evidence in the literature and this study support the need for inclusion of additional factors associated with the microstructure of the polymer.

Solution-phase synthesis of a diverse library of benzisoxazoles utilizing the [3 + 2] cycloaddition of in situ-generated nitrile oxides and arynes.

A library of benzisoxazoles has been synthesized by the [3 + 2] cycloaddition of nitrile oxides with arynes and further diversified by acylation/sulfonylation and palladium-catalyzed coupling processes. The eight key intermediate benzisoxazoles have been prepared by the reaction of o-(trimethylsilyl)aryl triflates and chlorooximes in the presence of CsF in good to excellent yields under mild reaction conditions. These building blocks have been used as the key components of a diverse set of 3,5,6-trisubstituted benzisoxazoles.

Intermolecular C-O Addition of Carboxylic Acids to Arynes: Synthesis of o-Hydroxyaryl Ketones, Xanthones, 4-Chromanones, and Flavones.

An efficient and simple route to biologically and pharmaceutically important o-hydroxyaryl ketones, xanthones, 4-chromanones, and flavones has been developed utilizing readily available carboxylic acids and commercially available o-(trimethylsilyl)aryl triflates.

Use of benzynes for the synthesis of heterocycles.

About two decades after Kobayashi's discovery in 1983 of a very mild way of generating highly reactive aryne intermediates, the synthetic community embraced o-(trimethylsilyl)aryl triflates as convenient and versatile aryne precursors for the synthesis of carbocycles and heterocycles, as well as natural products and pharmaceutically promising drug candidates. This review provides a comprehensive overview of the construction of heterocycles using Kobayashi's silylaryl triflate aryne precursors. It is organized according to the type of heterocycle generated.

Synthesis of o-(dimethylamino)aryl ketones, acridones, acridinium salts, and 1H-indazoles by the reaction of hydrazones and arynes.

A novel, efficient route to biologically and pharmaceutically important o-(dimethylamino)aryl ketones, acridones, acridinium salts, and 1H-indazoles has been developed starting from readily available hydrazones of aldehydes and o-(trimethylsilyl)aryl triflates. The reaction proceeds through arynes under mild conditions, tolerates a wide range of functional groups, and provides the final products in good to excellent yields.

Palladium-catalyzed annulation of arynes by o-halobenzamides: synthesis of phenanthridinones.

The palladium-catalyzed annulation of arynes by substituted o-halobenzamides produces N-substituted phenanthridinones in good yields. This methodology provides this important heterocyclic ring system in a single step by simultaneous C-C and C-N bond formation, under relatively mild reaction conditions, and tolerates a variety of functional groups.

Synthesis of 3,7-diiodo-2,6-di(thiophen-2-yl)benzo[1,2-b:4,5-b']difurans: functional building blocks for the design of new conjugated polymers.

3,7-Diiodo-2,6-di(thiophen-2-yl)benzo[1,2-b:4,5-b']difurans are efficiently prepared by an iodine-promoted double cyclization. This new heterocyclic core is readily modified by the attachment of alkyl chains for improved solubility. The use of these compounds for the synthesis of new conjugated polymers is also reported.

Synthesis of 9-Substituted Xanthenes by the Condensation of Arynes with ortho-Hydroxychalcones.

The reaction of o-(trimethylsilyl)aryl triflates, CsF, and o-hydroxychalcones affords a general and efficient way to prepare biologically interesting 9-substituted xanthenes. This chemistry presumably proceeds by tandem intermolecular nucleophilic attack of the phenoxide of the chalcone on the aryne and subsequent intramolecular Michael addition. The introduction of an external base, Cs(2)CO(3), has proven beneficial in this reaction.

One-pot synthesis of 1-alkyl-1H-indazoles from 1,1-dialkylhydrazones via aryne annulation.

The reaction of readily accessible 1,1-dialkylhydrazones with commercially available o-(trimethylsilyl)aryl triflates provides a direct one-step route to pharmaceutically important 1-alkylindazoles. The products are obtained in high yields by one-pot NCS-chlorination/aryne annulation or Ac(2)O-acylation/deprotection/aromatization protocols.

Synthesis of benzisoxazolines by the coupling of arynes with nitrones.

A variety of substituted benzisoxazolines have been synthesized by the [3 + 2] cycloaddition of nitrones and arynes. The reaction scope is broad, the reaction conditions are mild, and the process tolerates a variety of functional groups.

Iodocyclization, followed by palladium-catalyzed coupling: a versatile strategy for heterocyclic library construction.

The iodocyclization of functionally-substituted alkynes provides an excellent way to prepare a wide range of iodoheterocycles, which can then be readily elaborated through palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, Hartwig-Buchwald, and carbonylation processes into libraries of medicinally relevant heterocycles. The synthesis of libraries of indoles, benzofurans, benzothiophenes, isocoumarins and pyrones, cyclic imidates, isoxazoles, furans using this approach is reviewed. This technology is very versatile, proceeds under mild reaction conditions in high yields, and tolerates considerable functionality.

Synthesis of o-(dimethylamino)aryl ketones and acridones by the reaction of 1,1-dialkylhydrazones and arynes.

A novel, efficient route to biologically and pharmaceutically important o-(dimethylamino)aryl ketones and acridones has been developed starting from readily available 1,1-dimethylhydrazones of aldehydes and o-(trimethylsilyl)aryl triflates. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and provides the final products in good to excellent yields.

Intermolecular C-O addition of carboxylic acids to arynes.

A novel, efficient, and expedient route to biologically and pharmaceutically important o-hydroxyaryl ketones, xanthones, 4-chromanones, and flavones has been developed starting from readily available carboxylic acids and commercially available o-(trimethylsilyl)aryl triflates.

Synthesis of benzisoxazoles by the [3 + 2] cycloaddition of in situ generated nitrile oxides and arynes.

A variety of substituted benzisoxazoles has been prepared by the [3 + 2] cycloaddition of nitrile oxides and arynes. Both components, being highly reactive intermediates, have been generated in situ by fluoride anion from readily prepared aryne precursors and chlorooximes. The reaction scope is quite general, affording a novel, direct route to functionalized benzisoxazoles under mild reaction conditions.