Cobalt Mediated Oxidative Cyclizations: The Diastereoselective Synthesis of trans-Tetrahydrofuran Rings

The Mukaiyama oxidative cyclization has been a major area of study within the Pagenkopf group and within the field of THF containing natural products. This document contains a brief discussion of the major divisions of THF synthesis; SN2, cycloadditions, and transition mediated strategies. The development of the Mukaiyama cyclization is described from the earliest applications of cobalt acac type ligand in Mukaiyama’s work to the initial discovery of the cyclization reactivity. Initial finding from the Mukaiyama group is shown, accompanied by its applications to the synthesis of mucosin, aplysiallene, and bullatacin. Previous attempts at improved catalyst design are presented with characterization via x-ray crystallography. The development of a novel (Z)-2-hydroxy-5,5-dimethyl-1-(4-methyl-1-piperazinyl)-2-Hexene-1,4-dione, water-soluble, ligand system for the Mukaiyama oxidative cyclization has been accomplished in an efficient and reproducible fashion. The ligand was utilized in cobalt catalyzed oxidative cyclizations of trans-tetrahydrofuran rings. Improved catalyst performance was discovered including; greater catalyst stability, higher product yield and simplified purification. Increased catalyst performance also allowed for an increased substrate scope as compared to earlier generations of the catalyst. Substrate scope exploration demonstrated that oxidizable positions were tolerated by the new catalyst. Discussion of subsequent applications of the Co(nmp)2 in total synthesis is also included. Previous catalyst systems for the Mukaiyama cyclization proved unable to cyclize more highly substituted THF precursors. Under the cyclize conditions with Co(nmp) 2,various substrates were able to be cyclized to achieve new THF and oxime products. 2,2,5 tetrahydrofuran substitution patterns were explored and were accessible in moderate yields. Finally, the synthesis of cyclocapitelline is discussed to demonstrate the utility of cyclization conditions in synthesis

Pulping characteristics of reafforestation species grown in Solomon Islands (ODNRI Bulletin No. 32)

Samples of Pinus caribaea, Pinus oocarpa, Campnosperma brevipetiolata, Eucalyptus deglupta, Terminalia brassii and Terminalia calamansanai, all of which have shown potential for growing in plantations in Solomon Islands, were examined to determine their potential value for the production of pulpwood chips for export. Details are given of growing conditions, size of trees, wood characteristics, fibre dimensions and pulping by sulphate, soda and soda/anthraquinone processes. P. caribaea, P. oocarpa, C. brevipetiolata and F. deglupta were all considered promising for the production of pulpwood. T. brassii and T. calamansanai, both of which required very severe chemical conditions to pulp, were not considered promising

Expanding Clinical Presentations Due to Variations in THOC2 mRNA Nuclear Export Factor

Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in neurodevelopmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in

Expanding clinical presentations due to variations in THOC2 mRNA nuclear export factor

Multiple TREX mRNA export complex subunits (e.g., THOC1, THOC2, THOC5, THOC6, THOC7) have now been implicated in euro developmental disorders (NDDs), neurodegeneration and cancer. We previously implicated missense and splicing-defective THOC2 variants in NDDs and a broad range of other clinical features. Here we report 10 individuals from nine families with rare missense THOC2 variants including the first case of a recurrent variant (p.Arg77Cys), and an additional individual with an intragenic THOC2 microdeletion (Del-Ex37-38). Ex vivo missense variant testing and patient-derived cell line data from current and published studies show 9 of the 14 missense THOC2 variants result in reduced protein stability. The splicing-defective and deletion variants result in a loss of small regions of the C-terminal THOC2 RNA binding domain (RBD). Interestingly, reduced stability of THOC2 variant proteins has a flow-on effect on the stability of the multi-protein TREX complex; specifically on the other NDD-associated THOC subunits. Our current, expanded cohort refines the core phenotype of THOC2 NDDs to language disorder and/or ID, with a variable severity, and disorders of growth. A subset of affected individuals' has severe-profound ID, persistent hypotonia and respiratory abnormalities. Further investigations to elucidate the pathophysiological basis for this severe phenotype are warranted.Raman Kumar, Elizabeth Palmer, Alison E. Gardner, Renee Carroll, Siddharth Banka ... Jozef Gecz ... et al

Swift Detects a Remarkable Gamma-Ray Burst, GRB 060614, That Introduces a New Classification Scheme

Gamma ray bursts (GRBs) are known to come in two duration classes, separated at {approx}2 s. Long bursts originate from star forming regions in galaxies, have accompanying supernovae (SNe) when near enough to observe and are likely caused by massive-star collapsars. Recent observations show that short bursts originate in regions within their host galaxies with lower star formation rates, consistent with binary neutron star (NS) or NS - black hole (BH) mergers. Moreover, although their hosts are predominantly nearby galaxies, no SNe have been so far associated with short GRBs. We report here on the bright, nearby GRB 060614 that does not fit in either class. Its {approx}102 s duration groups it with long GRBs, while its temporal lag and peak luminosity fall entirely within the short GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short GRBs. This combination of a long duration event without accompanying SN poses a challenge to both a collapsar and merging NS interpretation and opens the door on a new GRB classification scheme that straddles both long and short bursts

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd