roject 3. Development of Microfluidic Technologies for Reaction Discovery, Methodology Development, and Library Synthesis. 3.
1 Specific Aims. This project represents a collaborative effort between the CMLD-BU and the laboratory of Professor Klavs Jensen of the Department of Chemical Engineering at MIT. The goal of this collaborative project is the development of microfluidic technologies to enable multidimensional reaction screening, photochemical and microwave-mediated reactions, automated reaction optimization, and chemical synthesis of libraries. Each section will address the development of the appropriate modules to be incorporated into an automated microfluidics platform. 1. Microfluidics-Enabled Photochemistry. This project will focus on the development of microfluidic devices with photochemistry capability for use in an automated platform. The photochemical module will be utilized in two chemical methodology projects 1) a multidimensional reaction screen exploring the chemistry of azirines; and 2) evaluation of the photochemical reactivity of complex scaffolds synthesized in the CMLD-BU. 2. Microwave Synthesis using Automated Microfluidics. This project will focus on the development of a microwave module for our automated microfluidics platform. Microwave-induced heating has been shown to be a powerful tool in organic synthesis and thus an important aspect in expansion of the capabilities of this platform. Microfluidics will also address a number of issues related to microwave synthesis such as scale and uniform heating. The project will also include evaluation of chemical methodologies specifically designed to take advantage of the microwave capability on our platform including tandem condensation/inverse demand Diels-Alder reactions of 1,2-dicarbonyls and amidrazones to afford complex alkaloidal scaffolds. 3. Microfluidics-Enabled Automated Optimization and Library Synthesis. This project focuses on two major items in library synthesis, reaction optimization, and parallel synthesis. We will adapt a reaction optimization algorithm, developed in the Jensen lab, to our automated platform. This system will allow us to automate optimization of reactions under development. Using our automated microfluidics platform we will be uniquely positioned to investigate reaction time, temperature, stoichiometry, and reagent variation. This project will also focus on several aspects of library synthesis which may be enabled by microfluidics including: a) heterogeneous catalysis b) multiple step synthesis c) and "inline" workup.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM067041-10
Application #
8380898
Study Section
Special Emphasis Panel (ZGM1-PPBC-3)
Project Start
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
10
Fiscal Year
2012
Total Cost
$364,600
Indirect Cost
$63,908
Name
Boston University
Department
Type
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Chu, Jennifer; Cencic, Regina; Wang, Wenyu et al. (2016) Translation Inhibition by Rocaglates Is Independent of eIF4E Phosphorylation Status. Mol Cancer Ther 15:136-41
Gandin, Valentina; Masvidal, Laia; Hulea, Laura et al. (2016) nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs. Genome Res 26:636-48
Yeo, Alan T; Chennamadhavuni, Spandan; Whitty, Adrian et al. (2015) Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines. Molecules 20:7474-94
Qin, Tian; Iwata, Takayuki; Ransom, Tanya T et al. (2015) Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of "Shapeshifting" Properties. J Am Chem Soc 137:15225-33
Luan, Yi; Barbato, Keith S; Moquist, Philip N et al. (2015) Enantioselective synthesis of 1,2-dihydronaphthalene-1-carbaldehydes by addition of boronates to isochromene acetals catalyzed by tartaric acid. J Am Chem Soc 137:3233-6
Stone, Steven D; Lajkiewicz, Neil J; Whitesell, Luke et al. (2015) Biomimetic kinetic resolution: highly enantio- and diastereoselective transfer hydrogenation of aglain ketones to access flavagline natural products. J Am Chem Soc 137:525-30
Rajasekaran, Devaraja; Siddiq, Ayesha; Willoughby, Jennifer L S et al. (2015) Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model. Oncotarget 6:26266-77
Qin, Tian; Skraba-Joiner, Sarah L; Khalil, Zeinab G et al. (2015) Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer. Nat Chem 7:234-40
Barbato, Keith S; Luan, Yi; Ramella, Daniele et al. (2015) Enantioselective Multicomponent Condensation Reactions of Phenols, Aldehydes, and Boronates Catalyzed by Chiral Biphenols. Org Lett 17:5812-5
Grenning, Alexander J; Snyder, John K; Porco Jr, John A (2014) Remodeling of fumagillol: discovery of an oxygen-directed oxidative Mannich reaction. Org Lett 16:792-5

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