Catalytic Asymmetric [3+1]-Cycloaddition Reaction of Ylides with Electrophilic Metallo-enolcarbene Intermediates

The first asymmetric [3+1]-cycloaddition was successfully achieved by copper(I) triflate/double-sidearmed bisoxazoline complex catalyzed reactions of β-triisopropylsilyl-substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio- and diastereoselectivities (up to 99 % ee, and >20:1 d.r.). Additionally, the [3+1]-cycloaddition of catalytically generated metallo-enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.     

Convenient Preparation of Trans-1,3-Dioxadecalin via the Prins Reaction

The acid catalyzed condensation of cyclohexene with aqueous formaldehyde can be controlled on a preparatively useful scale to give a 60–80% yield of trans-1,3-dioxadecalin.     

High resolution181Hf TDPAC spectroscopy using fast BaF2-detectors

A high resolution TDPAC setup with four BaF₂ detectors was introduced for measurements in chemical and biological systems. High electric field gradients and large asymmetry parameters could be determined very precisely. The data are compared to previous NaI(Tl) measurements on HfF₄·HF·2H₂O, HfO₂, and¹⁸¹Hf-labelled transferrin.     

Helix persistence and breakdown in oligoureas of metaphenylenediamine: apparent diastereotopicity as a spectroscopic marker of helix length in solution

Oligomeric ureas derived from m-phenylenediamine with chain lengths of up to seven urea linkages were made by iterative synthetic pathways. Three families were synthesized: 4 and 20, bearing a terminal chiral sulfinyl group; 24, bearing a terminal rotationally restricted amide group, and 30 bearing a terminal achiral bromophenyl group. The distal end of the oligomers was capped with an N-benzyl group to act as a diastereotopic probe. With a terminal sulfinyl group, the 1H NMR signals arising from the CH2 group of the diastereotopic probe remained anisochronous even when separated from the stereogenic center by up to 24 bonds (in 20c). With a rotationally restricted amide, anisochronicity was no longer apparent beyond 17 bond lengths (in 24c). No anisochronicity was observable with a terminal bromophenyl group. We interpret these results as indicating that the oligoureas of short lengths adopt a defined helical secondary structure in solution, but that in longer oligomers the helicity breaks down and transmission of chirality in these systems is limited to about 24 bond lengths. We propose that "apparent diastereotopicity" (anisochronicity) provides a general empirical method for identifying secondary structure in solution.     

Computational studies of Fe(III) binding to bryostatins, bryostatin analogs, siderophores and marine natural products: arguments for ferric complexes in medicinal applications

In this computational study, geometric factors are calculated by applying semi-empirical methods (PM3) that support experimental evidence from this lab where bryostatins can bind trivalent iron with six Fe-O bonds forming an octahedral geometry. The geometric factors are calculated for all 20 structures (Fe3+ bound to bryostatin 1-20) as a neutral, monovalent, and divalent species. The average Fe-O bond distances and bond angles are compared to those of known marine and terrestrial siderophores. From these two data sets, we then examined other known marine natural products (MNPs) that can form a hexavalent complex with six Fe-O bonds and draw conclusions about their potential biological role as marine siderophores. This computational data indicates that Fe(III) strongly bonds to a host of MNPs, increasing their water solubility, contracting their structure, hence allowing transport through cell membranes more readily, and in some cases, stabilizing ester bonds that are susceptible to hydrolysis. It is argued that administering medicinally bryostatin, its analogs or other MNPs as a ferric complex, holds some fundamental chemical advantages compared to its administration as a neutral uncomplexed species.     

Solutions to specification errors in stress testing models

The regulatory and business need to expand the use of macroeconomic-scenario-based forecasting and stress testing in retail lending has led to a rapid expansion in the types and complexity of models being applied. As these models become more sophisticated and include lifecycle, credit quality, and macroeconomic effects, model specification errors become a common, but rarely identified feature of many of these models. This problem was discovered decades ago in demography with Age-Period-Cohort (APC) models, and we bring those insights to the retail lending context with a detailed discussion of the implications here. Although the APC literature proves that no universal, data-driven solution is possible, we propose a domain-specific solution that is appropriate to lending. This solution is demonstrated with an auto loan portfolio.     

The duplicate method of uncertainty estimation: are eight targets enough?

This paper presents methods for calculating confidence intervals for estimates of sampling uncertainty (s(samp)) and analytical uncertainty (s(anal)) using the chi-squared distribution. These uncertainty estimates are derived from application of the duplicate method, which recommends a minimum of eight duplicate samples. The methods are applied to two case studies--moisture in butter and nitrate in lettuce. Use of the recommended minimum of eight duplicate samples is justified for both case studies as the confidence intervals calculated using greater than eight duplicates did not show any appreciable reduction in width. It is considered that eight duplicates provide estimates of uncertainty that are both acceptably accurate and cost effective.     

Determination of domoic acid toxins in shellfish by biosense ASP ELISA--a direct competitive enzyme-linked immunosorbent assay: collaborative study

A collaborative study was conducted on the Biosense amnesic shellfish poisoning (ASP) enzyme-linked immunosorbent assay (ELISA) for the determination of domoic acid (DA) toxins in shellfish in order to obtain interlaboratory validation data for the method. In addition, a method comparison study was performed to evaluate the ASP ELISA as an alternative to the current liquid chromatography (LC) reference method for DA determination. The study material comprised 16 shellfish samples, including blue mussels, Pacific oysters, and king scallops, spiked with contaminated mussel homogenates to contain 0.1-20 mg DA/kg shellfish flesh. The shellfish samples were extracted with 50% aqueous methanol, and the supernatants were directly analyzed. Sixteen participating laboratories in 10 countries reported data from the ASP ELISA, and 4 of these laboratories also reported data from instrumental LC analysis. The participating laboratories achieved interlaboratory precision estimates for the 8 Youden paired shellfish samples in the range of 10-20% for RSD(r) (mean 14.8 +/- 4%), and 13-29% for RSDR (mean 22.7 +/- 6%). The precision estimates for the ELISA data did not show a strong dependence on the DA concentration in the study samples, and the overall precision achieved was within the acceptable range of the Horwitz guideline with HorRat values ranging from 1.1 to 2.4 (mean HorRat 1.7 +/- 0.5). The analysis of shellfish samples spiked with certified reference material (CRM)-ASP-MUS-b gave recoveries in the range of 88-122%, with an average recovery of 104 +/- 10%. The estimate on method accuracy was supported by a correlation slope of 1.015 (R2 = 0.992) for the determined versus the expected DA values. Furthermore, the correlation of the ASP ELISA results with those for the instrumental LC analyses of the same sample extracts gave a correlation slope of 1.29 (R2 = 0.984). This indicates some overestimation of DA levels in shellfish by the ELISA, but it is also a result of apparent low recoveries for the LC methods. This interlaboratory study demonstrates that the ASP ELISA is suitable for the routine determination and monitoring of DA toxins in shellfish, and that it offers a rapid and cost-effective methodology with high sample throughput.