Edward Njoo

All Publications

• Benchtop F-19 nuclear magnetic resonance spectroscopy enabled kinetic studies and optimization of the synthesis of carmofur CANADIAN JOURNAL OF CHEMISTRY Wang, X., Vu, J., Luk, C., Njoo, E. 2023

  View details for DOI 10.1139/cjc-2022-0266

  View details for Web of Science ID 001034069300001

• Benchtop 19F Nuclear Magnetic Resonance (NMR) Spectroscopy Provides Mechanistic Insight into the Biginelli Condensation toward the Chemical Synthesis of Novel Trifluorinated Dihydro- and Tetrahydropyrimidinones as Antiproliferative Agents ACS OMEGA Chen, R., Singh, P., Su, S., Kocalar, S., Wang, X., Mandava, N., Venkatesan, S., Ferguson, A., Rao, A., Le, E., Rojas, C., Njoo, E. 2023; 8 (11): 10545-10554

  Abstract

  Benchtop nuclear magnetic resonance (NMR) spectroscopy has enabled the monitoring and optimization of chemical transformations while simultaneously providing kinetic, mechanistic, and structural insight into reaction pathways with quantitative precision. Moreover, benchtop NMR proton lock capabilities further allow for rapid and convenient monitoring of various organic reactions in real time, as the use of deuterated solvents is not required. The complementary role of 19F NMR-based kinetic monitoring in the fluorination of bioactive compounds has many benefits in the drug discovery process since fluorinated motifs additionally improve drug pharmacology. In this study, 19F NMR spectroscopy was utilized to monitor the synthesis of novel trifluorinated analogs of monastrol, a small molecule dihydropyrimidinone kinesin-Eg5 inhibitor, and to probe the mechanism of the Biginelli cyclocondensation, a multicomponent reaction used to synthesize dihydropyrimidinone and tetrahydropyrimidinones through a Bronsted- or Lewis-acid catalyzed cyclocondensation between ethyl acetoacetate, thiourea, and an aryl aldehyde. In the present study, a trifluorinated ketoester serves a dual purpose as being the source of the trifluoromethyl group in our fluorinated dihydropyrimidinones and as a spectroscopic handle for real-time reaction monitoring and tracking of reactive intermediates by 19F NMR. Further, upon extending this workflow to a diverse array of 3- and 4-substituted aryl aldehydes, we were able to derive Hammett linear free energy relationships (LFER) to determine stereoelectronic effects of para- and meta-substituted aryl aldehydes to corresponding reaction rates and mechanistic routes. In addition, we used density functional theory (DFT) calculations to corroborate our experimental results through the thermodynamic values of key intermediates in each mechanism. Finally, these studies culminate in the synthesis of a novel trifluorinated analog of monastrol and its subsequent biological evaluation in vitro. More broadly, we show an application of benchtop 19F NMR spectroscopy as an analytical tool in the real-time investigation of a mechanistically and chemically complex multicomponent reaction mixture.

  View details for DOI 10.1021/acsomega.3c00290

  View details for Web of Science ID 000952535600001

  View details for PubMedID 36969393

  View details for PubMedCentralID PMC10034998

• Practical synthesis of the therapeutic leads tigilanol tiglate and its analogues. Nature chemistry Wender, P. A., Gentry, Z. O., Fanelli, D. J., Luu-Nguyen, Q. H., McAteer, O. D., Njoo, E. 2022

  Abstract

  Tigilanol tiglate is a natural product diterpenoid in clinical trials for the treatment of a broad range of cancers. Its unprecedented protein kinase C isoform selectivity make it and its analogues exceptional leads for PKC-related clinical indications, which include human immunodeficiency virus and AIDS eradication, antigen-enhanced cancer immunotherapy, Alzheimer's disease and multiple sclerosis. Currently, the only source of tigilanol tiglate is a rain forest tree, Fontainea picrosperma, whose limited number and restricted distribution (northeastern Australia) has prompted consideration of designed tree plantations to address supply needs. Here we report a practical laboratory synthesis of tigilanol tiglate that proceeds in 12 steps (12% overall yield, >80% average yield per step) and can be used to sustainably supply tigilanol tiglate and its analogues, the latter otherwise inaccessible from the natural source. The success of this synthesis is based on a unique strategy for the installation of an oxidation pattern common to many biologically active tiglianes, daphnanes and their analogues.

  View details for DOI 10.1038/s41557-022-01048-2

  View details for PubMedID 36192432

• Resourceful and Effective Ways of Bridging Afterschool STEM Programs and Local Community Connected Science Learning Njoo, E., Narain, S., Pabbisetty, L., Agrawal, M. 2018; 1 (8)
• Determining amyloidogenicity of Islet Amyloid Polypeptide (IAPP) across mammalian species Moffet, D., Njoo, E., Rinauro, D., Pilcher, S., Palato, L., Johnstone, B., Menefee, K., Tun, A. AMER CHEMICAL SOC. 2017

  View details for Web of Science ID 000430568504220

• Acclimation to elevated emersion temperature has no effect on susceptibility to acute, heat-induced lipid peroxidation in an intertidal mussel (Mytilus californianus) MARINE BIOLOGY Jimenez, A., Alves, S., Dallmer, J., Njoo, E., Roa, S., Dowd, W. 2016; 163 (3)

  View details for DOI 10.1007/s00227-016-2828-8

  View details for Web of Science ID 000372302600011