Chemical Education: General, Organic, and Biochemistry

This poster details the discovery of several novel cascade reactions enabling the generation of arrays of pharmacologically relevant small molecules. As such, the synthetic routes are high in molecular complexity generating power and operationally friendly producing attractive compounds for inclusion in file enhancement strategies. Compound libraries and core chemotypes have been designed utilizing the ‘Chemtech’ portfolio of technologies and occupied scaffold space compared to existing nearest neighbors in the NIH molecular repository. Cascade sequences are launched from a common multi-component reaction precursor. Combined, this collaborative effort is navigating chemical space, delivering libraries and member molecules possessing ‘high iterative efficiency potential’ for expedited value chain progression. Bench to bedside case studies demonstrating the value of such approaches to file enhancement will be briefly discussed. Iterative Efficiency = f (Iterative Speed, accessible chemical diversity) 144. Determination of Phenolic Content, Antioxidant Activity and Mineral Content of Popolo (Solanum americanum) Leaves Leticia U. Colmenares, PhD and Jon Lai, Natural Science, UH-Windward Community College, Kaneohe, HI This research studies the phenolic content (determined by GAE, Gallic Acid Equivalent using FolinCiocalteu reagent and HPLC), antioxidant activity (determined by TEAC, Trolox Equivalent Antioxidant Capacity using the ABTS Assay) and the mineral (Cu, Fe and Zn) content using AAS of leaf extracts of Popolo (Solanum americanum), an indigenous Hawaiian plant. This plant has been known for its medicinal value by ancient Hawaiians and is used in other countries as medicine and vegetable. The measured antioxidant activity of 7.93 mg TEAC and 20.14 mg GAE per gram dry weight of popolo is higher than many medicinal herbs and common vegetables in the literature. Currently under-utilized, the plant’s potential use as an agricultural, nutritional and herbal product is enhanced by these data. 145. Synthesis of 1,3-Azaborines as Potential Inhibitors of HIV-1 Protease Jesse Lee Nye, Pei-Mien Chen, Elizabeth Nicolaeva, Tajinder Heer, Amanda Blackmore and Levente Fabry-Asztalos, PhD, Chemistry, Central Washington University, Ellensburg, WA HIV/AIDS has affected about 40 million people. One type of drug that is used to treat HIV/AIDS is a protease inhibitor. HIV-1 protease is one enzyme responsible for the propagation of mature viral particles. By inhibiting HIV-1 protease it is possible to slow the replication of the virus and delay the onset of AIDS. Often, HIV-1 protease becomes resistant to inhibitors; therefore, new drugs are needed. Here, we propose the synthesis of novel protease inhibitors using known and new synthetic methodologies. The proposed structures are borinic acids containing a heterocyclic ring with a nitrogen beta to the boron. Similar non-heterocyclic compounds have shown good inhibitory values and we hope that these inhibitors will possess better inhibitory properties, have increased bioavailability, have less toxicity, and potentially be more stable than their non-heterocyclic counterparts and the protease inhibitors currently in use. Important intermediates have been synthesized and are being used in the final reactions of the proposed synthetic scheme. We hope that these compounds will become lead compounds for further drug discovery for HIV/AIDS. 146. Taxanes: From Yew Tree Bark and Needles and Soil! Alex Samuels, Department of Chemistry, University of Portland, Portland, OR and Angela Hoffman, Chemistry, University of Portland, Portland, OR Paclitaxel (Taxol®) is a cytotoxic compound that was originally found in the bark of the Pacific yew tree, Taxus brevifolia. Today paclitaxel is an important chemotherapy agent used to treat lung, ovarian, breast, and other cancers. The most common technique for obtaining the drug is to extract the paclitaxel from Taxus species plant material or to extract taxanes such as baccatin III from the plant and produce paclitaxel by semisynthesis. We have already shown that paclitaxel can be extracted from soil in which yew trees have grown. Our goal was to increase the yield of paclitaxel per tree, rooting medium and water runoff from trees grown in a green house. These studies have shown promising results. By utilizing two simple extractions, it is possible to get more paclitaxel out of every yew tree. Support was provided by The University of Portland and NSF grant no. 0521648. 147. Natural Products From Forest Resources for Use as Arthropod and Fungal Biocides Joe Karchesy, Marc C. Dolan, Daniel K. Manter, Nicholas A. Panella, Yvette Karchesy, Gabrielle Dietrich, Rick G. Kelsey, Javier Peralta-Cruz and Joseph Piesman, (1)College of Forestry, Oregon State University, Corvallis, OR, (2)Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, (3)USDA Agricultural Research Service, Ft. Collins, CO, (4)Arboviral Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, CO, (5)PNW Research Station, USDA Forest Service, Corvallis, OR, (6)Organic Chemistry, Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Nacional, Mexico City, Mexico Natural products from Pacific Northwest forest resources can offer alternatives to the use of synthetic pesticides for control of arthropods of public health concern and forest microbial pathogens. Tree heartwoods whose extracts showed high toxicity (LC50 <100 ppm) in preliminary brine shrimp bioassays, also were found to be good sources for biocide and repellent compounds. Comparisons were made for the activities of the isolated compounds, derivatives, and extracts from yellow, incense, Port-Orford, and western red cedars, and western juniper against mosquitoes (Aedes aegypti), ticks (Ixodes scapularis), fleas (Xenopsylla cheopis) and the microbe responsible for Sudden Oak Death (Phytophthora ramorum). For example, laboratory bioassays show that hinokitiol from western redcedar, thymoquinone from incense-cedar, and nootkatin from yellow-cedar all exhibit strong antimicrobial activity toward P. ramorum (EC50 = 2.0 to 10.0 ppm). The mode of action for nootkatin is disruption of the membranes surrounding zoospores and sporangia. Biocidal assays against arthropods showed that carvacrol, nootkatone, and valencene 13-ol were the most effective. Repellency against ticks showed that nootkatone and valencene-13-ol had repellent concentration (RC50) values of 0.0458 and 0.0712% (wt:vol) respectively compared to DEET (RC50 = 0.0728%). 148. REVERSED CHLOROQUINE COMPOUNDS THAT OVERCOME P. Falciparum RESISTANCE to QUINOLINE-BASED DRUGS Bornface Gunsaru, David. H. Peyton, Cheryl Hodson, Katherine Liebman, Steven Burgess, Westin Morrill, Shawheen Shomloo and Jane Xu Kelly, (1)Department of Chemistry, Portland State University, Portland, OR, (2)DesignMedix, Inc, Portland Malaria infects about 350 million people each year, of which nearly one million people die, many of them in Africa south of the Sahara. Chloroquine (CQ) was the drug of choice to treat malaria for nearly half a century, but widespread resistance has severely reduced its effectiveness. Reversal agents (chemosensitizers) can reinstate the activity of chloroquine, but high dosages of the reversal agent (RA) in a cocktail raise questions about the clinical viability of this approach. We hypothesized that covalently attaching a RA moiety to a chloroquine-like moiety would give a "reversed chloroquine" (RCQ) able to overcome the effects of resistance with a much reduced RA dose, as the RA is now part of the drug. A library of compounds was thus generated based on this design. From this library, RCQs were identified that exhibit lower IC50 values than CQ against even D6, a “chloroquine-sensitive” strain of P. falciparum malaria, and reduced the IC50 against various “chloroquine-resistant” strains typically by 2to 3orders-of-magnitude relative to CQ. Thus, the RCQ-approach may be viable in the struggle against malaria, as well as open a route toward new therapies for other diseases that have drug resistance mechanisms similar to malaria. 149. Antibacterial Potential and GC-MS Studies of Select Medicinal Plants of Mojave Desert Kaveh Zarrabi, Noppawen Nitrosesatien, Jung Jae Koh, Suheir Naserddin, Eva Abanyan, Maxym Myroshnychenko, James Estevez, Deborah Harber and Heidi Porter, (1)Physical Sciences, College of Southern Nevada, Las Vegas, NV, (2)Biological Sciences, College of Southern Nevada, Las Vegas, NV Six medicinal plants collected from Mojave Desert, Krameria erecta (Little leaf Rhatany), Eriodictyon clifornicum (Yerba Santa), Gutierrezia sarothrae (Snakeweed), Oenotheria biennis (Evening Primrose), Encelia farinosa (Brittle Bush), and Eriodictyon glutinosum (Yerba Santa). The plants were processed and extracted with water-methanol, methylene chloride, and hexane. 18 plant extracts were tested for their antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes. Water-methanol extracts of Oenotheria Biennis and Krameia ececta have shown significant antibacterial activities. The minimum inhibitory concentration (MIC) of these two plants was 31.25 and 62.5 μg/ml respectively. GC-MS analyses of the plant extracts exhibiting antibacterial activities are presented. 150. The Snthessis of CDCA (Chenodeoxycholic acid) Derivates and Their Transation Complexes Murat Turkyilmaz and Fatma Genc, Department of Chemistry, Trakya University, Edirne, Turkey Bile acids have played important role in several area of chemistry in recent years. There is a vast amount of potential pharmacological applications of bile acids and their derivatives which includes analgesics, radiopharmaceuticals and antibiotics. These compounds are useful for development of supramolecular and nanomolecular systems. Between the two hydroxyl groups, the most reactive one is the hydroxyl at the C-3 position. We prepared the beta mesylate from methyl cholate using triphenylphosphine and diisopropyl azodicarboxylate (DIAD). Sodium azide attacks the mesylate by an SN2 reaction to afford azide ester, which is reduced by triphenylphosphine in aqueous THF to give our ligand. Therefore we converted C-3 hydroxyl group of CDCA (chenodeoxycholic acid) to amino group and then we binded some transitation metals to amino and hydroxyl groups. All compounds was confirmed. 151. Esterification of Lithocholic Acid with Some Analgesics H.R. Ferhat Karabulut, Murat Donmez and Hasan Ozyildirim, (1)Department of Chemistry, Trakya University, Edirne, Turkey, (2)Trakya University, Edirne, Turkey Bile acids and their derivatives have been used in the treatment of bile acid deficiency which is one of the major predisposing factors of dissolution of cholesterol gallstones. Also they can be used as carriers for liver-specific drugs. In literature the medicinal applications of bile acids, their conjugates and non-opiate analgesic complexes have been discussed. In our study, we planned to get some analgesic derivatives with bile acid. We used lithocholic acid as a bile acid and first of all we converted lithocholic acid to methyl ester and then it was reacted with naproxen, diclofenac and flurobiprofen using DCC (dicyclohexylcarbodiimide) or Yamaguchi methods. We had better results by Yamaguchi method than DCC method. These compounds were confirmed by IR spectrum, H NMR, C NMR spectrum. 152. Recent Work Toward a Total Synthesis of the GABA Antagonist, (–)-Anisatin Jeffrey A. Charonnat, Nobuko Nishimura, Yvonne Nguyen and Donna Manglona, Department of Chemistry and Biochemistry, CSU Northridge, Northridge, CA (–)-Anisatin is an extremely potent, non-competitive GABA antagonist that acts irreversibly at the presynapse but reversibly at the postsynapse. This poster presents recent work toward a total synthesis of (–)-anisatin. 153. Recent Progress Toward the Synthesis of Cananodine Toby J. Ligon and James R. Vyvyan, Department of Chemistry, Western Washington University, Bellingham, WA A synthetic approach to the synthesis of cananodine (1), a guaipyridine alkaloid isolated from the fruits of Cananga odorata, is described. Cananodine (1) is a valuable synthetic target because it exhibits significant activity against two human hepatocellular carcinoma cell lines. Key steps in the synthetic route to 1 include a Suzuki-Miyaura-type cross coupling of pyridine triflate (3) with alkenylboronate (4), and an intramolecular epoxide alkylation of 2 to form the 7-membered ring of the natural product. Model studies and current progress toward the synthesis of 1 will be presented. 154. Progress Toward the Synthesis of Heliannuol A Using 8-Endo Epoxide Cyclizations Katie R. Tallman, Erik W. Werner and James R. Vyvyan, Department of Chemistry, Western Washington University, Bellingham, WA Heliannuol A is part of family of allelochemicals that have been isolated in small quantities from the sunflower, Helianthus annuus, and has been shown to selectively inhibit the germination and growth of other plants. A heliannuol A analogue was synthesized via an 8-endo phenol epoxide strategy utilizing a conformational constraint and Lewis acid catalysis. The synthesis of the epoxide and cyclization results will be presented. 155. Microwave-Assisted Organic Synthesis of 2,5-Disubstitutedbenzofuran-3Carboxlic Acids Jared Rigoli, Joe Rigoli and Aaron Mills, Assistant Professor, Department of Chemistry, University of Idaho, Moscow, ID Microwave-assisted organic synthesis (MAOS) has proven its utility in the synthesis of heterocycles. Previously, 2,5-disubstitutedbenzofuran-3-carboxlic acids have shown to have aniinflamitory, antiviral, and muscle relaxant properties. We report a new method for the rapid and efficient synthesis of 2,5-disubstitutedbenzofurans by the reaction of b-ketoesters, p-quinone, and a metal halide catalyst under microwave irradiation. Previously the synthesis of 2,5-disubstitutedbenzofuran3-carboxlic acids was plagued by low yields (~20-30%) and long reaction times (1-2 days). Using microwave irradiation, we studied the effect of varying solvent, metal catalyst, reaction times, and reaction temperature on benzofuran yields. Through the methodical optimization of the benzofuran cyclization reaction we obtained the products in > 70% yield and reduced the reaction time to 45 minutes. All the products were characterized by HNMR, CNMR and GC/MS. 156. Synthesis of 2,3-Dibenzyl-1,1-Difluoroglycerol Elizabeth A. Goossen, Daniel Tt. Yee, Timothy Rhoads, Kylie Vadnais, Austin Wisecup and Stephen D. Warren, Department of Chemistry, Gonzaga University, Spokane, WA Metabolic pathways frequently include 3-carbon unit intermediates. Fluorinated 3-carbon unit molecules can function as mimetics of metabolic intermediates and as biological probes of those pathways. D-mannitol is an inexpensive starting material that can serve as a common synthetic precursor for a variety of 3-carbon molecules. We optimized methods for the complete protection of D-mannitol’s hydroxy groups followed by selective deprotection of the terminal protecting groups. The 3,4-monoisopropylidene-D-mannitol product was selectively reprotected and cleaved to produce a variety of 3-carbon unit precursors. The 3-carbon units were fluorinated using the nucleophilic fluorination agent deoxofluor. These fluorinated mimetics could potentially be used as probes in biological systems. 157. Boron-Substituted Analogs of the Shvo Hydrogenation Catalyst: Applications in Directed C-H Borylation Liza Koren-Selfridge, Joel A. Hanson and Timothy B. Clark, Department of Chemistry, Western Washington University, Bellingham, WA Directed C-H functionalization reactions have received considerable attention recently due to the desire to incorporate functional groups into inexpensive unfunctionalized organic substrates. One such example of a C-H functionalization reaction uses metal boryl complexes to convert C-H bonds into CB bonds. The incorporation of a boron functional group into organic substrates through C-H functionalization reactions is ideal due to the ability to convert C-B bonds into C-C, C-O, or C-N bonds. Our work has focused on the use of boron-substituted analogues of the Shvo hydrogenation catalyst. The desired ruthenium boryl complex 1 was expected to result in directed C-H functionalization through hydrogen bonding of the hydroxy group with the substrate. Synthesis of complex 1 involved the activation of bis(catecholato)diboron reagent in the presence of 4methoxyphenol to generate the desired complex. This complex was then combined with butyl methyl ether under photolysis conditions, resulting in C-H functionalization product 2. Known complexes without the directing hydroxy group are also being synthesized in order to compare the selectivity of these complexes with complex 1. These results will verify that our product results from directed C-H functionalization (via the transition state TS-A) rather than resulting from the preferred reactivity of the methoxy methyl group. 158. Copper-Catalyzed Diboration of Ketones: Facile Synthesis of Tertiary AlphaHydroxy Boronate Esters Melissa L. McIntosh, Cameron M. Moore and Timothy B. Clark, Department of Chemistry, Western Washington University, Bellingham, WA The synthetic versatility of carbon-boron bonds makes organoboronate esters and acids valuable intermediates in organic synthesis. Alpha-heteroatom-substituted boronate esters have emerged over the past two decades as synthetically valuable intermediates in asymmetric homologation reactions. The synthesis of complex and highly functionalized versions of these boronate esters has been limited due to the required reaction conditions. Several recent reports have begun to highlight the ability to generate alpha-heteroatom-subsituted boronate esters by the diboration of polarized