The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

The catalytic enantioselective synthesis of densely functionalized organic molecules that contain all-carbon quaternary stereocentres is a challenge to modern chemical methodology. The catalytically controlled, asymmetric α-alkylation of ketones represents another difficult task and is of major interest to our and other research groups. We report here a palladium-catalysed enantioselective process that addresses both problems simultaneously and allows the installation of vicinal all-carbon quaternary and tertiary stereocentres at the α-carbon of a ketone in a single step. This multiple bond-forming process is carried out on readily available β-ketoester starting materials and proceeds by conjugate addition of a palladium enolate, generated in situ, to activated Michael acceptors. As a result, the CO2 moiety of the substrate is displaced by a C–C fragment in an asymmetric cut-and-paste reaction with high yield, diastereomeric ratio and enantiomeric excess. The selective construction of multiple adjacent stereocentres is an important challenge for synthetic organic methodology, and only a handful of catalytic methods exist that can forge adjacent quaternary and tertiary stereocentres. Here, a palladium-catalysed multiple-bond-forming cascade leads to the construction of such systems in high yield, diastereomeric ratio and enantiomeric excess.

Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.

The rheology of Marmite™, a popular yeast extract spread, was studied using a range of techniques. Steady-state data indicated a structured, thixotropic material at ambient temperature; the extent of breakdown and restructuring exhibited a dependence on both stress and strain. At higher temperatures the extent of thixotropy decreased and behaviour approached Newtonian. Non-steady-state data indicated a period of shear-thickening at shear rates below those at which shear-thinning occurs. Creep tests indicated a transition between solid and liquid regimes at a critical stress that is a strong function of the solids content of the sample. A 'true' yield stress was not found although this may be related to the limits of the region which could be accessed experimentally.

Described in this report is the first total synthesis of elatol, a halogenated sesquiterpene in the chamigrene natural product family. The key disconnections in our synthetic approach include an enantioselective decarboxylative allylation to form the all-carbon quaternary stereocenter and a ring-closing olefin metathesis to concomitantly form the spirocyclic core as well as the fully substituted chlorinated olefin. This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ADVERTISEMENT RETURN TO ISSUEPREVIntroducing Our Auth...Introducing Our AuthorsNEXTIntroducing Our AuthorsSeok Joon Kwon, Amanda J. Krzysiak, Ernest K. Boamah, David E. White, Haruhiko Fuwa, and Aaron N. SneadCite this: ACS Chem. Biol. 2007, 2, 6, 360–361Publication Date (Web):June 15, 2007Publication History Received31 May 2007Accepted31 May 2007Published online15 June 2007Published inissue 1 June 2007https://pubs.acs.org/doi/10.1021/cb700118phttps://doi.org/10.1021/cb700118potherACS PublicationsCopyright © 2007 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views188Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (735 KB) Get e-Alertsclose Get e-Alerts

10-Decarbamoyl-mitomycin C (DMC), a mitomycin C (MC) derivative, generates an array of DNA monoadducts and interstrand cross-links stereoisomeric to those that are generated by MC. DMC was previously shown in our laboratory to exceed the cytotoxicity of MC in a human leukemia cell line that lacks a functional p53 pathway (K562). However, the molecular signal transduction pathway activated by DMCDNA adducts has not been investigated. In this study, we have compared molecular targets associated with signaling pathways activated by DMC and MC in several human cancer cell lines. In cell lines lacking wild-type p53, DMC was reproducibly more cytotoxic than MC, but it generated barely detectable signal transduction markers associated with apoptotic death. Strikingly, DMCs increased cytotoxicity was not associated with an increase in DNA double-strand breaks but was associated with early poly(ADP-ribose) polymerase (PARP) activation and Chk1 kinase depletion. Alkylating agents can induce increased PARP activity associated with programmed necrosis, and the biological activity of DMC in p53-null cell lines fits this paradigm. In cell lines with a functional p53 pathway, both MC and DMC induced apoptosis. In the presence of p53, both MC and DMC activate procaspases; however, the spectrum of procaspases involved differs for the two drugs, as does induction of p73. These studies suggest that in the absence of p53, signaling to molecular targets in cell death can shift in response to different DNA adduct structures to induce non-apoptotic cell death.

The potential to use ice cores from alpine glaciers in the midlatitudes to reconstruct paleoclimatic records has not been widely recognized. Although excellent paleoclimatic records exist for the polar regions, paleoclimatic ice core records are not common from midlatitude locations. An ice core removed from the Upper Fremont Glacier in Wyoming provides evidence for abrupt climate change during the mid‐1800s. Volcanic events (Krakatau and Tambora) identified from electrical conductivity measurements (ECM) and isotopic and chemical data from the Upper Fremont Glacier were reexamined to confirm and refine previous chronological estimates of the ice core. At a depth of 152 m the refined age‐depth profile shows good agreement (1736±10 A.D.) with the 14C age date (1729±95 A.D.). The δ18O profile of the Upper Fremont Glacier (UFG) ice core indicates a change in climate known as the Little Ice Age (LIA). However, the sampling interval for δ18O is sufficiently large (20 cm) such that it is difficult to pinpoint the LIA termination on the basis of δ18O data alone. Other research has shown that changes in the δ18O variance are generally coincident with changes in ECM variance. The ECM data set contains over 125,000 data points at a resolution of 1 data point per millimeter of ice core. A 999‐point running average of the ECM data set and results from ƒ tests indicates that the variance of the ECM data decreases significantly at about 108 m. At this depth, the age‐depth profile predicts an age of 1845 A.D. Results indicate the termination of the LIA was abrupt with a major climatic shift to warmer temperatures around 1845 A.D. and continuing to present day. Prediction limits (error bars) calculated for the profile ages are ±10 years (90% confidence level). Thus a conservative estimate for the time taken to complete the LIA climatic shift to present‐day climate is about 10 years, suggesting the LIA termination in alpine regions of central North America may have occurred on a relatively short (decadal) timescale.

MetaphilosophyVolume 16, Issue 2-3 p. 206-213 SLIPPERY SLOPE ARGUMENTS DAVID E. WHITE, DAVID E. WHITE St. John Fisher College, Rochester, NY 14618 USASearch for more papers by this author DAVID E. WHITE, DAVID E. WHITE St. John Fisher College, Rochester, NY 14618 USASearch for more papers by this author First published: April 1985 https://doi.org/10.1111/j.1467-9973.1985.tb00165.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume16, Issue2-3April 1985Pages 206-213 RelatedInformation

Journal of the American Ceramic SocietyVolume 51, Issue 11 p. 666-667 Dry-Pressing of a Urania Pycnometer DAVID E. WHITE, DAVID E. WHITESearch for more papers by this authorROBERT J. BEALS, ROBERT J. BEALSSearch for more papers by this author DAVID E. WHITE, DAVID E. WHITESearch for more papers by this authorROBERT J. BEALS, ROBERT J. BEALSSearch for more papers by this author First published: November 1968 https://doi.org/10.1111/j.1151-2916.1968.tb12644.x Supported by the United States Atomic Energy Commission. The writers are, respectively, engineering assistant and associate ceramic engineer, Argonne National Laboratory, Argonne, Illinois 60439. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume51, Issue11November 1968Pages 666-667 RelatedInformation

We modeled a 1,000 MW (1 GW) (nameplate) windplant in the large wind resource of the North America Great Plains, delivering exclusively hydrogen fuel, via a new gaseous hydrogen (GH2) pipeline, to an urban market at least 200 miles distant. All windplant electric energy output would be converted, at the windplant, to hydrogen, via 1,500 psi output electrolyzers, directly feeding the GH2 transmission pipeline without costly compressor stations at inlet or at midline. The new GH2 pipeline is an alternative to new electric transmission lines. We investigate whether the pipeline would provide valuable energy storage. Large-scale electricity and hydrogen pipeline systems are comparable in capital and O&M costs. 1 We present a simple model by which we estimate the cost of wind-source hydrogen fuel delivered to the distant city gate in year 2010, at GW scale. Cavern GH2 storage may allow "firming" the Great Plains wind resource at modest cost.