The Synthesis of Chromane Meroterpenoids via Biomimetic Cascade Reactions

In the current climate of synthetic organic chemistry the development of efficient, practical organic synthetic methodologies is of the utmost importance. Of particular interest is the rapid generation of molecular complexity. The field of biomimetic synthesis uses natural product biosynthesis as a guide, or source of inspiration for laboratory total synthesis. Nature often employs cascade or domino reactions which are chemically predisposed to occur. In this thesis the biomimetic synthesis of several chromane (benzopyran) natural products is reported. Chapter 1 is an introductory essay on the development of biomimetic cascade reactions with several examples from the past 40 years. This chapter also introduces ortho-quinone methides, a reactive intermediate which visited frequently throughout this thesis. Chapter 2 describes the three-step divergent synthesis of rhodonoid C and D, and synthesis of the related alkaloid murrayakonine D. Herein a new bioinspired acid-catalysed (3+2) epoxyolefin cycloaddition produced two rings, three stereocentres, one C-C bond, and one C-O bond in a single step. In Chapter 3 the first asymmetric synthesis of (−)-bruceol – a caged pyranocoumarin meroterpenoid – is detailed. The concise three-step synthesis utilised a biomimetic cascade initiated by a chemoselective Jacobsen-Katsuki epoxidation (and kinetic resolution) as the key step. This reaction could also be catalysed by a bacterial cytochrome P450 monooxygenase enzyme. NMR analysis of synthetic bruceol lead to the discovery of isobruceol, an isomeric meroterpenoid which had been misidentified as bruceol. This was confirmed by re-isolation, total synthesis, and X-ray analysis of isobruceol. Chapter 4 covers the synthesis of several bruceol related natural products via photochemical reactions. Chromenes are intrinsically good chromophores, and as such mild solar irradiation of the chromene precursors to bruceol and isobruceol completed the synthesis of the “cyclol” natural products eriobrucinol, isoeriobrucinol A, and isoeriobrucinol B by intramolecular [2+2] cycloaddition reactions. These chromenes also underwent singlet oxygen ene reactions to complete the synthesis of protobruceols II – IV. Chapter 5 looks at the biosynthesis of seven unnamed prenylated bruceol derivatives. Speculating on the observed isolated compounds, it likely all seven natural products had the common precursor we coined “prenylbruceol A”. It had previously been suggested the biosynthesis of these compounds involves what we consider to be an unlikely C alkylation. We put forth an alternative proposal involving O alkylation, followed by Claisen and Cope rearrangements to reach the correct connectivity for an intramolecular hetero-Diels-Alder reaction. This hypothesis was the basis for an attempted biomimetic synthesis of prenylbruceol A. After this approach was unsuccessful two alternative approaches were taken which were also ultimately unsuccessful. In lieu of a total synthesis, the isolation of the prenylbruceols was revisited through a mild extraction of Philotheca myoporoides using the pressurised hot water extraction technique. Gratifyingly, the extraction yielded prenylbruceol A proving that it is indeed a natural product. The natural prenylbruceol A was then used in a semisynthesis of three other members of the family (prenylbruceols B – D) using singlet oxygen chemistry.Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 202

Measurement of loss in superconducting microstrip at millimeter-wave frequencies

We have developed a new technique for accurate measurement of the loss of superconducting microstrips at mm-wave frequencies. In this technique, we optically couple power to slot antenna, which is connected to one port of a hybrid coupler. One of the output ports of the hybrid delivers power to a series of mm-wave microstrip resonators which are capacitively coupled to a feedline followed by an MKID (microwave kinetic inductance detector) that measures the transmitted power. Two other MKIDs are connected to the remaining ports of the hybrid to measure the total incident optical power and the power reflected from the mm-wave resonators, allowing |S_(21)|^2 and |S_(11)|^2 to be accurately determined and resonance frequency fr and quality factor Q to be retrieved. We have fabricated such a Nb/SiO_2/Nb microstrip loss test device which contains several mm- wave resonators with f_r~100 GHz and measured it at 30 mK. All the resonators have shown internal quality factor Qi~500–2000, suggesting a loss tangent of ~5×10^(−4)−2×10^(−3) for the SiO_2 in use. For comparison, we have also fabricated a 5 GHz microstrip resonator on the same chip and measured it with a network analyzer. The loss tangent at 5 GHz derived from fitting the f_0 and Q data to the two-level system (TLS) model is 6×10^(−4), about the same as from the mm-wave measurement. This suggests that the loss at both microwave and mm-wave frequencies is probably dominated by the TLS in SiO_2. Our results are of direct interest to mm/submm direct detection applications which use microstrip transmission lines (such as antenna-coupled MKIDs and transition-edge sensors), and other applications (such as on-chip filters). Our measurement technique is applicable up to approximately 1 THz and can be used to investigate a range of dielectrics

CCRaVAT and QuTie - enabling analysis of rare variants in large-scale case control and quantitative trait association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies have been successful in finding common variants influencing common traits. However, these associations only account for a fraction of trait heritability. There has been a shift in the field towards studying low frequency and rare variants, which are now widely recognised as putative complex trait determinants. Despite this increasing focus on examining the role of low frequency and rare variants in complex disease susceptibility, there is a lack of user-friendly analytical packages implementing powerful association tests for the analysis of rare variants.</p> <p>Results</p> <p>We have developed two software tools, CCRaVAT (Case-Control Rare Variant Analysis Tool) and QuTie (Quantitative Trait), which enable efficient large-scale analysis of low frequency and rare variants. Both programs implement a collapsing method examining the accumulation of low frequency and rare variants across a locus of interest that has more power than single variant analysis. CCRaVAT carries out case-control analyses whereas QuTie has been developed for continuous trait analysis.</p> <p>Conclusions</p> <p>CCRaVAT and QuTie are easy to use software tools that allow users to perform genome-wide association analysis on low frequency and rare variants for both binary and quantitative traits. The software is freely available and provides the genetics community with a resource to perform association analysis on rarer genetic variants.</p

Quasiparticle Trapping in Microwave Kinetic Inductance Strip Detectors

Microwave Kinetic Inductance Detectors (MKIDs) are thin-film, superconducting resonators, which are attractive for making large detector arrays due to their natural frequency domain multiplexing at GHz frequencies. For X-ray to IR wavelengths, MKIDs can provide high-resolution energy and timing information for each incoming photon. By fabricating strip detectors consisting of a rectangular absorber coupled to MKIDs at each end, high quantum efficiency and spatial resolution can be obtained. A similar geometry is being pursued for phonon sensing in a WIMP dark matter detector. Various materials have been tested including tantalum, tin, and aluminum for the absorbing strip, and aluminum, titanium, and aluminum manganese for the MKID. Initial Ta/Al X-ray devices have shown energy resolutions as good as 62 eV at 6 keV. A Ta/Al UV strip detector with an energy resolution of 0.8 eV at 4.9 eV has been demonstrated, but we find the coupling of the MKIDs to the absorbers is unreliable for these thinner devices. We report on progress probing the thicknesses at which the absorber/MKID coupling begins to degrade by using a resonator to inject quasiparticles directly into the absorber. In order to eliminate the absorber/MKID interface, a modified design for implanted AlMn/Al UV strip detectors was developed, and results showing good transmission of quasiparticles from the absorber to MKID in these devices are presented

GLIDERS - A web-based search engine for genome-wide linkage disequilibrium between HapMap SNPs

<p>Abstract</p> <p>Background</p> <p>A number of tools for the examination of linkage disequilibrium (LD) patterns between nearby alleles exist, but none are available for quickly and easily investigating LD at longer ranges (>500 kb). We have developed a web-based query tool (GLIDERS: Genome-wide LInkage DisEquilibrium Repository and Search engine) that enables the retrieval of pairwise associations with r²≥ 0.3 across the human genome for any SNP genotyped within HapMap phase 2 and 3, regardless of distance between the markers.</p> <p>Description</p> <p>GLIDERS is an easy to use web tool that only requires the user to enter rs numbers of SNPs they want to retrieve genome-wide LD for (both nearby and long-range). The intuitive web interface handles both manual entry of SNP IDs as well as allowing users to upload files of SNP IDs. The user can limit the resulting inter SNP associations with easy to use menu options. These include MAF limit (5-45%), distance limits between SNPs (minimum and maximum), r²(0.3 to 1), HapMap population sample (CEU, YRI and JPT+CHB combined) and HapMap build/release. All resulting genome-wide inter-SNP associations are displayed on a single output page, which has a link to a downloadable tab delimited text file.</p> <p>Conclusion</p> <p>GLIDERS is a quick and easy way to retrieve genome-wide inter-SNP associations and to explore LD patterns for any number of SNPs of interest. GLIDERS can be useful in identifying SNPs with long-range LD. This can highlight mis-mapping or other potential association signal localisation problems.</p

Efecto de tres especies de lombrices en la fertilidad del suelo y el crecimiento inicial del maíz (Zea mays).

In the present experiment, we evaluated the effect of three earthworm species on soil fertility and seedling growth of maize (Zea mays), a food plant of great importance in Mexico. One individual of each species (Balanteodrilus pearsei and Lavellodrilus bonampakensis, two native species and Pontoscolex corethrurus, an exotic), were used in the germination and initial maize growth experiment (vegetative phase v6), with four replicates per treatment and 9 seeds per pot, with 4 kg of soil each. Organic matter contents, total nitrogen and available phosphorus in the soil and in the maize leaves were determined at the end of the experiment. L. bonampakensis significantly increased foliar and root biomass, B. pearsei increased only shoot biomass and P. corethrurus decreased root biomass in relation to the control. Soil organic matter content increased significantly with earthworms, but for the remaining parameters, no significant differences were found between treatments with and without earthworms. Earthworm presence can affect soil fertility and initial maize growth positively, negatively or not at all, depending on the species involved. However, further research is necessary to better understand the relationships between native and exotic tropical earthworm species, plants and the soil.En el presente experimento se evaluó el efecto de tres especies de lombrices de tierra en la fertilidad del suelo y el crecimiento del maíz (Zea mays), planta de gran importancia alimenticia en la republica Mexicana. Un individuo de cada especie (Balanteodrilus pearsei, Lavellodrilus bonampakensis, especies nativas y Pontoscolex corethrurus, especie exótica) fue utilizado en el experimento de germinación y crecimiento inicial del maíz (fase vegetativa v6), con cuatro repeticiones por tratamiento y 9 semillas por recipiente, con 4 kg de suelo cada uno. Se determinaron los contenidos de materia orgá- nica, nitrógeno total y fósforo disponible en el suelo y en las hojas de maíz al final del experimento. L. bonampakensis aumentó significativamente la biomasa foliar y radicular, B. pearsei aumentó solamente la biomasa aérea y P. corethrurus disminuyó la biomasa de raíces en relación al testigo. El contenido de materia orgánica en el suelo fue significativamente mayor con lombrices que sin lombrices. Para los demás parámetros no se observaron diferencias significativas entre los tratamientos con y sin lombrices. La presencia de lombrices puede afectar la fertilidad del suelo y el crecimiento inicial del maíz de forma positiva, negativa o neutra, dependiendo de la especie. Sin embargo, más estudios son necesarios para comprender mejor la relación de las especies nativas y exóticas de lombrices tropicales con las plantas y el suelo

Electrical Manipulation of Telecom Color Centers in Silicon

Silicon color centers have recently emerged as promising candidates for commercial quantum technology, yet their interaction with electric fields has yet to be investigated. In this paper, we demonstrate electrical manipulation of telecom silicon color centers by fabricating lateral electrical diodes with an integrated G center ensemble in a commercial silicon on insulator wafer. The ensemble optical response is characterized under application of a reverse-biased DC electric field, observing both 100% modulation of fluorescence signal, and wavelength redshift of approximately 1.4 GHz/V above a threshold voltage. Finally, we use G center fluorescence to directly image the electric field distribution within the devices, obtaining insight into the spatial and voltage-dependent variation of the junction depletion region and the associated mediating effects on the ensemble. Strong correlation between emitter-field coupling and generated photocurrent is observed. Our demonstration enables electrical control and stabilization of semiconductor quantum emitters