Poster Session Abstracts

Tuesday Afternoon - 3:30 p.m. - 5:00 p.m.

NSC Hallway

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Poster set-up will be on a first come first serve basis in the NSC hallway, there will be no assigned positions.

Oral presentation times are listed here. Abstracts will be on their respective sub-page.

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Evaluation of Fibrous Silica Particles for Liquid Chromatography

Nahyr A. López Dauphin, Luis A. Colón

The State University of New York at Buffalo, Department of Chemistry

Silica remains the most commonly used support material for the stationary phase in liquid chromatography (LC) due to its thermal stability, lack of shrinking or swelling when exposed to organic solvents, and separation reproducibility. The use of LC is limited to the advancements in the development of chromatographic column technology. Recently, the development of fibrous silica particles (FSPs) was achieved via sol-gel methods.1 FSPs possess an inherent fibrous morphology that provides very high surface area. Particles with high surface area are advantageous for LC because they can afford higher loading capacity than conventional regular particles. Herein, we present a preliminary evaluation of FSPs for use in high performance liquid chromatography (HPLC).

Effect of Manganese Exposure on the Accumulation and Spatial Distribution of Essential Trace Metals in Rat Brain by Laser Ablation - Inductively Coupled Plasma Mass Spectrometry (LA-ICP/MS)

Mary Grace Guardian, Elizabeth J. Mullin, Senthilvelan Manohar, Diana S. Aga, Richard Salvi

The State University of New York at Buffalo, Department of Chemistry

Manganese (Mn) is an essential nutrient required for a variety of metabolic functions such as enzyme activation, reproductive hormone function, human physiological development, and in the development and normal function of the brain. Trace levels of Mn, approximately 2 mg/day, is beneficial to humans; however, chronic exposure to high concentrations of Mn leads to a disorder called Manganism. Manganism is primarily considered an occupational disorder identified in professions associated with prolonged exposure to abnormally high atmospheric Mn levels such as in welding and mining. Symptoms include reduced response speed, irritability, intellectual deficits, into a more prominent and irreversible extrapyramidal dysfunction resembling Parkinson’s disease. In this study, female rats were provided with drinking water ad libitum that contained 10 mg/mL manganese chloride (MnCl2) for 10 and 60 days. Rat brain slices that include the striatum, globus pallidus and hippocampus were obtained by cutting the brain in 40-μm thick slices and fixing them to glass slides. Samples were then analyzed using optimized parameters for laser ablation - inductively coupled plasma mass spectrometry (LA-ICP/MS). Results showed that prolonged Mn-ingestion affects concentration and spatial distributions of iron (Fe), copper (Cu) and zinc (Zn) in the brain regions studied. In-house matrix match standards were successfully prepared to obtain a semi-quantitative result of the analysis.

Characterization of GlyGlu

Tahir Kuraan,1 Alexander E Callow,1 Amanda Hoff,1,2 Nicholas P Piccirillo,1 Kaile M Benner,1 John Lisko,1 Matthias Zeller,1 ,3 Russell J Moser,1

Ganesaratnam K. Balendiran1

1.) Youngstown State University, Department of Chemistry 2.) Northwestern Medicine Central DuPage Hospital,

3.) Purdue University, Department of Chemistry

Dipeptide, GlyGlu consists of amino, amide and carboxyl functional groups is an important molecule. Structural characterization of GlyGlu reveals the important role of intermolecular and intramolecular hydrogen bonding. Hydrogen bonds play multiple roles in a molecule and hence define some of its properties. While intermolecular hydrogen bonding may be responsible for molecular interactions/recognition, intramolecular hydrogen bonding may contribute to its stability. Herein we present the outcome of the application of spectroscopy techniques. These findings may be valuable in vivo and/or in vitro usages.


Computational investigation of proton-coupled electron transfer in quinone-based aqueous batteries

Maureen Kitheka, Morgan Myler, Ye Zhang, Michael de la Torre, Yan Yao, Puja Goyal

The State University of New York at Binghamton, Department of Chemistry

The growing interests in the integration of electricity generated from renewable sources into the grid and increased electrification in the transport section calls for batteries that are inexpensive, long-lasting, safe and most importantly environmentally friendly. Aqueous rechargeable batteries featuring low-cost and non-flammable water-based electrolytes are intrinsically safe. However, they exhibit short cycle life and are therefore unable to meet the growing large-scale applications. Quinones have seen an increased attention in energy storage and conversion applications including redox flow batteries, dye-sensitized solar cells and water splitting devices. Here, we investigate aqueous rechargeable batteries with crystalline quinones as anode material. The mechanism of charge storage, more specifically, electron and proton storage in crystalline quinones has remained elusive through solely experimental studies. We present results from computational investigations of the mechanism of proton-coupled electron transfer in crystalline quinones using the density functional tight-binding method and molecular dynamics simulations. The insights gained lead to new avenues to designing higher capacity batteries with longer lifetimes.

Direct Observation and Analysis of a New Functional Group: The HaloAminoNitroAlkane (HANA)

Hayden Foy, Michael S. Crocker, Kazuyuki Tokumaru, Travis Dudding, Maren Pink, Jeffrey N. Johnston

Brock University

Conventional amide synthesis is a mainstay of discipline-spanning applications, and it is a reaction type that historically developed as a singular paradigm when considering the carbon-nitrogen bond forming step. Umpolung Amide Synthesis (UmAS) exploits the unique properties of an α-halo nitroalkane in its reaction with an amine to produce an amide. When integrated with enantioselective methods for nitroalkane synthesis, UmAS enables convergent amide synthesis in four steps from aldehyde feedstocks. The ‘umpolung’ moniker reflects evidence that the nucleophilic nitronate carbon and N-haloamine electrophile engage in the key carbon-nitrogen bond-forming step to form a tetrahedral intermediate (TI). Consequently, this character renders UmAS as an epimerization-free α-amino amide synthesis. Direct evidence for the TI, however, has escaped capture. A longstanding approach to the study of reaction mechanisms is the preparation of a hypothesized (or analogous) intermediate. This report details a theoretical study of the mechanism of formation and degradation of a tetrahedral intermediate (TI’) bearing the essential features of the TI in Umpolung Amide Synthesis.

Identifying protein features important for drug repurposing using the CANDO platform

William Mangione, Zackary Falls, Ram Samudrala

The State University of New York at Buffalo, Department of Biomedical Informatics

Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. The accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000-fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria, tuberculosis, and large cell carcinoma results in more drugs that could be validated in the biomedical literature compared to using those suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.


Computational Studies of Formic Acid Oxidation on Platinum-Gold Surfaces

Christina Zeng, Julien Panetier

The State University of New York at Binghamton, Department of Chemistry

In the search for cleaner energy sources, formic acid fuel cells represent a viable candidate for several reasons (a) the convenience of storing and transporting liquid formic acid at room temperature, (b) the environmentally benign nature of formic acid, (c) the relative simplicity of the two-electron process of formic acid oxidation to carbon dioxide compared to other small molecule conversions to energetically favorable materials, such as carbon dioxide to methanol. Furthermore, platinum surfaces can activate cleavage of the formic acid C-H bond at particularly low overpotentials. However, platinum surfaces have a dual pathway mechanism: the dehydrogenation pathway directly oxidizes formic acid to carbon dioxide, whereas dehydration suffers from a strongly adsorbed carbon monoxide intermediate which poisons the catalyst. In order to selectively undergo the dehydrogenation pathway while maintaining low overpotentials, platinum has been alloyed with other metals to synthesize bi-metallic and tri-metallic catalysts. Our research focuses on using computational methods to design platinum-gold surfaces on copper that can selectively undergo the dehydrogenation pathway while suppressing the dehydration pathway. One way to approach this issue is by measuring the barriers associated with adsorption of formic acid versus carbon monoxide on the surface, as the composition and unit cell parameters of the alloy are changed.


Linker Assisted Assembly of CdS/MoS2 Quantum Dots on Nanosheets Heterostructures for Efficient Photoelectrochemical Hydrogen Generation

Arianna Rothfuss, Nuwanthi Suwandaratne, Aaron Sheng, David F. Watson

The State University of New York at Buffalo, Department of Chemistry

Efficient photoelectrochemical (PEC) water splitting is crucial for improving the efficiency of solar energy conversion, a route towards replacing the use of fossil fuels. In an effort to improve upon PEC water splitting, we attached cysteine-capped CdS quantum dots (QDs) to MoS2 nanosheets to form cysteine-CdS/MoS2 heterostructures via linker assisted assembly (LAA). LAA provides maximal control over (1) size, (2) size distribution, and (3) surface functionalization of adsorbed QDs. The resulting type-II interface of these heterostructures is useful for efficient charge separation, which is expected to reduce the rate of charge recombination and to promote the reduction of protons to H2. Upon successful preparation of the heterostructures, we characterized them with (1) ultraviolet-visible (UV-Vis) spectroscopy, (2) infrared (IR) absorbance spectroscopy, (3) transmission electron microscopy (TEM), (4) scanning electron microscopy (SEM), and (5) energy dispersive x-ray spectroscopy (EDS). Finally, the PEC study revealed that heterostructures produced an enhanced photocurrent of 0.3mA under white LED light illumination (100mW/cm2) at 0.2V vs the saturated calomel electrode relative to bare MoS2, which showed no photocurrent. Moreover, CdS/MoS2 quantum dots-on-nanosheets heterostructures generated H2 with a Faradaic efficiency approaching 100%. These results suggest that the LAA CdS/MoS2 heterostructures are promising architectures for light harvesting and PEC water splitting.

Tuning the Surface Ordering of Self-Assembled Ionic Surfactants on Semiconducting Single-Walled Carbon Nanotubes: Concentration, Tube Diameter, and Counterions

Soha Algoul, Sanghamitra Sengupta, Thomas Bui, and Luis Velarde

The State University of New York at Buffalo, Department of Chemistry

We have analyzed the extent of ordering of different concentrations of Sodium dodecyl sulphate (SDS) encapsulated with different diameter Single Wall Carbon nanotubes (SWCNT) with and without external alkaline chloride salts on thin glass film surfaces by using Sum Frequency Generation Spectroscopy (SFG). We have observed a distinct ordering pattern of surfactant while encapsulated with (7, 6) and (6, 5) SWCNTs - both are semiconducting. With great amount of reproducibility in our experimental data we have found that surfactant ordering goes down with decreasing surfactant concentration on both SWCNT surfaces. However the extent of ordering is higher for smaller diameter SWCNT at higher surfactant concentration and the trend changes at concentration below critical micellar concentration of surfactant. Assuming a weak van der Waal type force is working between SDS–SWCNT macromolecular assemblies and changing the nature of this interaction to strong electrostatic type when excess salts are added to the system explains our experimental observations. Our SFG spectra have also successfully determined and reproduced the ordering trend at presence of external ions. The observed order is K+ > Na+ > Ca2+ in case of (7, 6) type SWCNT, whereas the observed trend is Na+ > K+ > Ca2+ for (6, 5) SWCNT at 14mM SDS concentration.


Improved anti-cancer effects of docetaxel toward prostate cancer cell lines via encapsulation in PLGA-chitosan nanocarriers loaded with anti-IL-8 siRNA and up-conversion nanoparticles for theranostic applications

Julia Bulmahn, Hilliard L. Kutscher, Katherine Cwiklinski, Ravikumar Aalinkeel, Paras N. Prasad

The State University of New York at Buffalo, Department of Chemistry

The aim of this study is to develop a novel multimodal theranostic nanoformulation to improve the efficacy of docetaxel toward prostate cancer cell lines. To accomplish this, we developed chitosan (CS) coated poly (lactic co-glycolic) acid (PLGA) nanocarriers loaded with docetaxel, to improve cellular uptake and decrease the concentration necessary to achieve desired anti-cancer effects. Anti-IL-8 siRNA electrostatically bound to the surface of up-conversion nanoparticles (UCNPs) is also incorporated to suppress IL-8 expression, synergistically enhancing the cytotoxicity of docetaxel. IL-8 was chosen as a gene target due to its role in promoting angiogenesis, tumorigenicity and metastasis. NaYF4;Yb20%;Er2%@NaYF4;Gd50% core-shell UCNPs facilitate optical and MR imaging capabilities allowing for real time visualization of therapeutic effects. PLGA-CS nanocarriers were synthesized via a nano-emulsion method. Drug loading and release profiles were determined using HPLC. Cytotoxicity was evaluated via an MTT assay against human prostate adenocarcinoma (PC-3) cells. This nanoformulation exhibits a >10,000 fold reduction in the IC50 when compared with free drug, while unloaded PLGA-CS nanocarriers exhibit limited cytotoxicity. UCNPs are effective vectors for delivery of IL-8 siRNA as demonstrated by a gene silencing assay and have enabled imaging of cellular uptake in PC-3 cells. Future work will include evaluation of T1 MRI contrast and expansion into DU-145 and LNCaP cell lines.

Mechanistic Investigation of the Reaction Catalyzed by 5-methylthioribose 1-phosphate Isomerase in the Methionine Salvage Pathway

Subashi Ubayawardhana, Vamsee M. Veeramachineni, Andrew S. Murkin

The State University of New York at Buffalo, Department of Chemistry

Methionine, an essential amino acid in bacteria and eukarya, is recycled in the methionine salvage pathway. The conversion of 5-methylthioribose 1-phosphate (MTR-1-P) to 5-methylthioribulose 1-phosphate (MTRu-1-P) is a reaction included in this pathway and is catalyzed by the enzyme MTR1P isomerase. The reaction involves a ring opening and hydrogen transfer from C-2 to C-1, though the mechanism has not yet been deduced. Three mechanisms have been proposed for this reaction, characterized by (1) an oxocarbenium ion intermediate, (2) a phosphorylated enzyme intermediate, and (3) intramolecular phosphoryl group transfer. To further investigate the isomerase’s mechanism, deuterium kinetic isotope effects for the hydrogen transfer were determined using [2-2H]MTR1P. D(V/K) and DV were found to be 3.5 and 1.5, respectively, for Bacillus subtilis MTR1P isomerase, which indicates that hydrogen transfer is fully and partially rate limiting, respectively, on kcat/Km and kcat. In addition, 13C kinetic isotope effects were measured at C-2 and C-1 positions and their mechanistic implications are discussed.

Exploring the Feasibility of Inhibiting the Protein-Protein Interaction between Fatty Acid Binding Protein 4 and Peroxisome Proliferator Activated Receptor gamma

Ndidiamaka Obi, Adrian Whitty

Boston University

Aberrant protein-protein interactions (PPIs) are the underlying cause of many diseases, and their inhibition could potentially lead to new therapeutics. For example, over-expression of FABP4 mediates the down-regulation of PPARgamma, a phenomenon that has been implicated in the development of obesity-linked diabetes. Inhibiting this protein-protein interaction could potentially prevent development of the disease, while sparing other essential functions of these two proteins and thereby reducing the likelihood of on-target toxicity. Such an approach could be advantageous compared to current treatments, which can have serious side-effects. We are characterizing the FABP4/PPARgamma PPI, to establish the feasibility of inhibiting it with a small molecule. Specifically, we are using alanine scanning mutagenesis to identify which regions on each protein form the interaction interface, measuring binding using IP-Western blot and SPR. We are also computationally assessing the presence of druggable sites, using FTMap to identify the locations and strengths of binding energy hot spots. These studies will reveal whether the interaction is likely to be druggable, and will additionally provide guidance as to which approaches are most appropriate (e.g. conventional inhibitor versus a beyond Rule-of-Five compound versus a covalent inhibitor). The binding assays we develop for the alanine scanning study will then be used to pursue inhibitor discovery against this important target.


Anion Dependent Hydrogen Bonding States: Resulting Fluorescence Implications in a

Proton Sponge Model System

Matt Guest, Richard Le Sueur, Lee Belding, Melanie Pilkington, Travis Dudding

Brock University

Through-space, non-covalent interactions, particularly the hydrogen bond, play an indispensable role in chemical and biochemical processes, such as those regulating the vast network of reactions controlling life. Several model systems have aided in our understanding of the H-bond, among which peri-disubstituted naphthalene-based compounds classified as “proton sponges” hold particular historical significance. Our recent development of a cyclopropenium-based proton sponge has expanded the scope of interactions in these systems to include the generation of aromaticity, internal charge-transfer states, and ion-pair interactions.

Herein, in building upon the cyclopropenium based proton sponge platform, the counterion dependent nature of hydrogen bonding in this system has been studied by varying the anion component. X-ray crystallography indicated that by changing the anion, we were able to switch between inter-molecular hydrogen bonding and intra-molecular hydrogen bonding. This switching between hydrogen bond states influenced the structural, electronic, and photophysical properties of this system leading to significant differences in quantum yield, while leaving the absorption and emission unaffected. Furthermore, the relatively large changes in electronic and geometric properties arising from these varying hydrogen bond states has obvious potential in terms of developing new molecular switches.

Fluorescence of Cyclopropenium Ion Derivatives

Richard Le Sueur, Matt Guest, Lee Belding, Travis Dudding

Brock University

Small organic fluorescent molecules find applications as light-emitting diodes, chemical sensors, and biological probes, cellular imaging agents, and light harvesting agents. Their utility is broadened by their many mechanisms of action, such as Förster resonance energy transfer, aggregation and disaggregation-induced emission, internal charge transfer, and recently, motion-induced changes in emission. Several classes of small organic fluorophores are commercially available. New classes of small organic fluorophores are highly desirable, especially, if they expand the range of properties sought by consumers.

In adding to this area of research, we recently developed a cyclopropenium substituted aminonaphthalene derivative coined the “Janus sponge” that fluoresced in both the solid and solution states. In view of these fascinating properties we recently synthesized a series of novel cyclopropenium-substituted amino compounds and investigated their photophysical properties. By systematic structural modifications of these compounds we were able to make measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory (TD-DFT) calculations, the origin of these trends was traced to internal charge transfer (ICT) coupled with ensuing structural reorganization. The findings provide valuable insight into the photophysical properties of these compounds which will be presented.

Oxidative Cyclization of Tryptamines with an Oxoammonium Salt Provides Rapid Access to

C3a-Oxygenated Pyrroloindolines

Katelyn Leets, Nivedita Mahajani, Alexandra Millimaci, John D. Chisholm

Syracuse University

The oxoammonium salt 4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate (Bobbitt’s salt) rapidly reacts with N-protected tryptamine and tryptophan derivatives to provide the C3a oxygenated pyrroloindolines, which are found in several complex natural products. Reactions conditions were optimized, and the substrate scope evaluated. Tryptamines decorated with electron donating or electron withdrawing groups give moderate to good yields. Substitution on the indole nitrogen provided little to no product. N-Protected tryptophan esters give moderate yields of cyclized product as a mixture of diastereomers. This method provides rapid access to cyclized pyrroloindolines, and may be utilized in the synthesis of natural products like the okaramines and kapakahine.

Synthesis of α-CF3 Diazo Compounds via the Interrupted Bamford-Stevens Reaction

Kevin Ma, Graham Murphy

University of Waterloo

Trifluoromethyl groups are important functionalities in medicinal chemistry, as they are present in many biologically active molecules. A popular tool used to introduce trifluoromethyl groups into compounds is the Togni reagent,1 an electrophilic-type hypervalent iodine (HVI) reagent. HVI reagents are advantageous to conventional transitional metal-based reagents, having similarly broad applications, but under milder conditions and with decreased negative environmental impact.2 The Murphy Group has recently developed an interrupted Wolff-Kishner reduction method, where adding the Togni reagent enables a trifluoromethylative reduction.3 Similarly, the Bamford-Stevens reaction can also be interrupted by the Togni reagent, converting tosylhydrazones into α-trifluoromethyl diazo compounds.4 This presentation will present the initial research involving the synthesis of α-trifluoromethyl diazo compounds using an interrupted Bamford-Stevens reaction.

1. Eisenberger, P.; Gischig, S.; Togni, A., Chem. Eur. J. 2006, 12 (9), 2579-2586.

2. Zhdankin, V. V., Hypervalent Iodine Chemistry: Preparation, Structure, and Synthetic Applications of Polyvalent Iodine Compounds. John Wiley & Sons Ltd.: New York, 2014.

3. Zhao, Z.; Ma, K. C. Y.; Murphy, G. K., submitted, 2019.

4. For the decomposition of tosylhydrazones to diazo compounds: Davies, H. W.; Schwarz, M., J. Org. Chem. 1965, 30 (4), 1242-1244.

Studies Towards the Synthesis of Phomactin A

Fortune Ononiwu, Nancy I. Totah

Syracuse University

Phomactin A is a specific PAF (platelet activating factor) antagonist, inhibiting both, PAF-induced platelet aggregation and binding of PAF to its receptors. Recent progress toward the synthesis of this unusual marine metabolite is presented. A key feature of this work is the face selective dihydropyrone Diels-Alder reaction to control the relative stereochemistry between C2 and the ring junction. Further elaboration of the oxadeclin core toward the target compound is described.

Synthesis of Spiroketals by a Tandem Carbonyl Ene Spirocyclization Sequence

Muhammad Miharja, Troy Lam, Nancy I. Totah

Syracuse University

Spiroketal scaffolds are commonly found in complex natural products. Such compounds often exhibit biological activity, including antibiotic, anticancer, anti-inflammatory, and antiviral functions. Traditionally, spiroketals are prepared by the intramolecular cyclization of a dihydroxyketone. Our approach utilizes a tandem carbonyl ene-spirocyclization sequence that takes advantage of the inherent reactivity of exocyclic enol ethers for the formation of a carbon-carbon bond. This reaction is catalytic, high yielding, the reaction conditions are mild, and reactants are utilized in nearly equimolar quantities. Cyclization of the resulting β-hydroxydihydropyrans then provides the spiroketal. The development and application of this strategy for the synthesis of spiroketal units, both step-wise and in one pot, is described.

Syntheses and analysis of silica-supported isocyanide-base metal scavengers

Ruoshui Xu, Zackary R. Gregg, Elise Glickert, Steven T. Diver

The State University of New York at Buffalo, Department of Chemistry

Modern industrial practices utilize transition metal catalysts for drug synthesis. For toxicity concerns, the pharmaceutical products must have low levels of residual metals before going to the market. We successfully synthesized silica-supported isocyanides as effective metal scavengers. A titration method utilizing tetrazine-isocyanide click reaction was developed that enabled us to determine accurate isocyanide functional loadings by UV-visible spectroscopy or pronton NMR spectroscopy. With the help of this titration method, we were able to examine and compare the metal-scavenging ability of our silica-supported isocyanide materials.

Targeting Astrocytes using a Tetracycline-Inducible Expression System

Danielle Cervasio, Alyssa Preston, Kevin Tan, Scott Laughlin

Stony Brook University, Department of Chemistry

Astrocytes play a large role in the brain by responding to insult, creating protective barriers, and modulating neural activity. Although astrocytes are well established as an important cell type when it comes to understanding brain function and disease, there are few methods to visualize and target these cells, greatly hindering our capability to fully characterize and study them. Current methods utilizing genetic markers or fluorescent small molecules suffer from a need for fixation, specificity concerns, gap junction diffusion, and incapability for chemical modification. We have combated a few of these caveats by adding a new small molecule probe array to the toolkit, recently demonstrating that we can target of a variety of fluorophores to astrocytes. By leveraging organic chemistry to attach permanently positive, pyridinium-like substituents to a variety of fluorescent small molecules, we have been able to specifically label astrocytes and not surrounding neurons or glia. Using this newly developed method to probe astrocytes, we believe we can deliver diverse cargo like transcriptional activators, calcium sensors, or drugs to these cells to gain a better understanding of their basic function and biology. Currently, we are synthesizing a doxycycline-modified probe which will serve to activate transcription through the tetracycline-inducible gene expression system in a subset of astrocytes, further diversifying the cargo that we can deliver to these cells.

Carbonyl Pinch Approach: Rapid Assembly of Complex Polycyclic Scaffolds via a Tandem Alkynyl halo-Prins/Friedel-Crafts Alkylation Sequence

Shukree Abdul-Rashed, Alison J. Frontier

University of Rochester

Access to complex small-molecule libraries via robust and rather facile chemical methods is of paramount interest to the medical and pharmaceutical industries. However, accessing molecular scaffolds which possess the desired physicochemical properties remains adverse as these molecules typically possess a substantial degree of chemical complexity, and are not suitable for the operationally simple methods currently employed at the industrial level.1 As such, modern research developments in organic synthesis are devoted primarily toward facile methods of carbon-carbon bond formation and novel approaches to introducing stereochemical complexity. Herein, we propose the “carbonyl pinch” approach which involves an elaboration of cascades involving the alkynyl halo-Prins reaction to address these demands. This method is expected to be operationally simple, as well as utilize linear and relatively simple precursors from commercial sources to access these biologically relevant scaffolds with high efficiency and accuracy. Furthermore, the development of this methodology will increase the availability of small-molecule scaffolds for drug discovery programs and improve the efficiency of the search for new medicines.

Ref: (1): J. Med. Chem. 2011, 54, 6405-6416.