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.     

Auditory localization in the vertical plane: accuracy and constraint on bodily movement

In two preliminary experiments, listeners were instructed to limit increasingly the movement of their heads and/or bodies while attempting to localize narrow bands of noise centered on 2.3 or 8.3 kHz. With increasing constraint on movement, the high-frequency band was incorrectly perceived as elevated above the horizon. The low-frequency band, when actually elevated above the horizon, was not so regularly perceived incorrectly as being below the horizon, a finding inconsistent with a previous report. A third experiment, which more closely replicated the task conditions and strategies of the previous study, did tend to reveal the anomalous low-frequency error. The error is explicable as a default response to which listeners whose sensitivity to the vertical dimension, in general, appears imperfect are prone. From various reports, it emerges that about 25% of presumed normally hearing people exhibit this insensitivity.     

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.     

Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10-Deoxymethynolide

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2-migration and give a much broader range of α-functionalized enones. Finally, the methodology was applied to a 14-step synthesis of the enone-containing polyketide 10-deoxymethynolide.     

Photodetachment of Deprotonated R-Mandelic Acid: The Role of Proton Delocalization on the Radical Stability

The photodetachment and stability of R-Mandelate, the deprotonated form of the R-Mandelic acid, was investigated by observing the neutral species issued from either simple photodetachment or dissociative photodetachment in a cold anions set-up. R-Mandalate has the possibility to form an intramolecular ionic hydrogen-bond between adjacent hydroxyl and carboxylate groups. The potential energy surface along the proton transfer (PT) coordinate between both groups (O⁻…H⁺…⁻OCO) features a single local minima, with the proton localized on the O⁻ group (OH…⁻OCO). However, the structure with the proton localized on the ⁻OCO group (O⁻…HOCO) is also observed because it falls within the extremity of the vibrational wavefunction of the OH…⁻OCO isomer along the PT coordinate. The stability of the corresponding radicals, produced upon photodetachment, is strongly dependent on the position of the proton in the anion: the radicals produced from the OH…⁻OCO isomer decarboxylate without barrier, while the radicals produced from the O⁻…HOCO isomer are stable.     

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.     

Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps.     

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.