Saturday May 5th – Presentations

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New Strategies for the C–H Functionalization of Amines

Daniel Seidel

University of Florida

01:30 PM
Organic Chemistry

This lecture will cover our recent efforts in the development of reaction cascades for the rapid buildup of molecular complexity via the mild α- and β-C–H bond functionalization of amines. Mechanistically distinct approaches will be discussed.

Hierarchical Self-assembly of Supramolecular Norias

Bo Song, Xiaopeng Li

Department of Chemistry, University of South Florida

02:00 PM
Organic Chemistry

In biological systems, the shapes, complexity and functions of DNA- and protein-based assemblies are encoded by the defined sequence of nucleotides and amino acids. Inspired by nature, we herein introduced the concept of “programming of sequence-specific ligands” and designed a series of linear building blocks with specific sequence through bridging terpyridine ligands with Ru(II) coordination. Being different from traditional methods such as controlling the size, angle, dimensionality of the ligand, this strategy allows us to predict and design structures based on the linkage of the building blocks in ligand. Different generations of “Supramolecular Norias” (N1 to N5) with increasing complexity were thus obtained after the self-assembly with different transition metals. The resulting structures were characterized via multi-dimensional mass spectrometry analysis (ESI-MS, TWIM-MS) as well as a series of NMR (1H, COSY, NOESY) analysis. Moreover, the larger size supramolecules N4 and N5 were hierarchically self-assemble into uniform 2D nanostructures on HOPG surface as recorded by STM, or uniform nanotubes, which were observed under TEM.

The dimerization of benzo[1,2-b:4,5-b']dithiophen-4-ol

Ania Sotuyo and Ronald K. Castellano

Department of Chemistry University of Florida

02:20 PM
Organic Chemistry

BDT (benzo[1,2-b:4,5-b']dithiophen-4-ol) has been a popular building block for optoelectronic materials. Recently, we decided to remake BDT by adding a hydroxyl group for the purpose of accessing a tautomerically capable BDT. As we delved into benzo[1,2-b:4,5-b']dithiophen-4-ol (BDTOH) as a novel π building block, we found some interesting behavior not mentioned in the original literature. Although tautomerization for BDTOH (pKT = 2.75, 99.8% enol) was comparable theoretically with that of anthrone (pKT = -3.10, 99.9% keto), the tautomeric phenomenon was not observed. Instead, the compound undergoes an irreversible chemical oxidation in 10 mM CDCl3, ushering in a new set biaryl dimers. While the dimerization pathway is unknown, NMR studies done in oxygen-free and radical-free environments did not inhibit the process. Further attempts to derivatize BDTOH through synthesis garnered another new set of π-extended dimers.

 

Synthetic Explorations with Unsymmetrical Oxyallyl and 2-Amidoallyl Cations

Rendy Kartika

Louisiana State University

03:00 PM
Organic Chemistry

We have developed a new strategy that enables carbon-carbon bond formation at the α-position of ketone-derived compounds with an exquisite control of regioselectivity via an intermediacy of unsymmetrical silyloxyallyl and 2-amidoallyl cations that are generated under mild catalytic conditions.  This robust chemistry has been applied toward the synthesis of various complex structural motifs, such as all-carbon quaternary centers, 1,4-dicarbonyls, silyldienol ethers, functionalized enamides, heterocyclic compounds, and others.  Our results will be discussed in this presentation.

Catalytic enantio- and regioselective alkynylation of pyridines

Kathryn L. Olsen, Mukesh Pappoppula, Aaron Aponick

University of Florida

03:30 PM
Organic Chemistry

The α-chiral tetrahydroquinoline (THQ) motif is found in a myriad of natural products and biologically active molecules. Alkynylation of pyridines at the α-position would afford chiral 1,2-dihydropyridines containing multiple synthetic handles allowing for functionalization to more complex systems. We have previously reported a highly enantioselective copper catalyzed alkynylation of quinolinium salts using the atropisomeric imidazole-based biaryl P,N-ligand, StackPhos. Encouraged by these results, we envisioned a catalytic enantioselective alkynylation of pyridines using StackPhos. The development of this methodology and its application will be presented.

New Methods for the Synthesis of Molecules Containing All-Carbon Quaternary Centers

Katelyn M. Chandoa, Ryan E. Michaelb and Tarek Sammakiac

a) Avista Pharma Solutions; b) C4 Therapeutics; c) University of Colorado Boulder

03:50 PM
Organic Chemistry

The stereoselectve synthesis of all-carbon quaternary centers has been a long-standing problem in organic synthesis. In this talk, we will describe a new approach to this problem that takes advantage of the reactivity of N-vinyl nitrones and ketenes. When combined, these substrates undergo a cascade reaction that begins with a (3+2) cycloaddition and is followed by a [3,3] sigmatropic rearrangement and a 1,3-shift to produce a 1,4-carbonyl equivalent bearing vicinal stereo centers. Using di-substituted ketenes, products bearing all-carbon quaternary centers are produced with high levels of stereoselectivity. The scope and mechanism of this process will be described in this talk.

Photosensitizers Derived from Chlorophyll

Kevin M. Smith

Louisiana State University

06:15 PM
Organic Chemistry

Chlorin-e6 (1) is a degradation product1-3 from chlorophyll-a that possesses three chemically distinct carboxylate sites (at positions 131-, 152-, and 173-) suitable for conjugation with biomolecules.  An aspartic acid conjugate (Talaporfin, NPe6 or LS-11) originally identified as the 173-conjugate (2),4 but subsequently revised to be the 152-conjugate (3),3,5 is actively undergoing clinical trials as a photodynamic therapy (PDT) sensitizer.

The presentation will summarize the evidence leading to the reassignment of the structure for Talaporfin,3,5 and report syntheses of numerous amino-acid and non-amino acid mono- and bis-conjugates of chlorin e6.3,6-9 The cellular uptake, dark- and photo-toxicity, and in vitro intracellular localization of the new conjugates will also be discussed.

 

Figure 1 – Structures of chlorin-e6 (1) and its 173- (2) and 152- (3) aspartic acid conjugates

 

References

 

K. M. Smith, D. A. Goff and D. J. Simpson, J. Am. Chem. Soc., 107 (1985) 4946. G. W. Kenner, S. W. McCombie and K. M. Smith, J. Chem. Soc., Perkin Trans 1, (1973) 2517. J. A. Hargus, F. R. Fronczek, M. G. H. Vicente and K. M. Smith, Photochem. Photobiol., 83 (2007) 1006. J. C. Bommer and B. F. Ogden, U.S. Patent 4,693,885 (1987). S. Gomi, T. Nishizuka, O. Ushiroda, N. Uchida, H. Takahashi and S. Sumi, Heterocycles, 48 (1998) 2231. R. G. W. Jinadasa, X. Hu, M. G. H. Vicente and K. M. Smith, J. Med. Chem., 54 (2011) 7464. H. Chen, R. G. W. Jinadasa, L. Jiao, F. R. Fronczek, A. L. Nguyen and K. M. Smith, Eur. J. Org. Chem., (2015) 3661. R. G. W. Jinadasa, Z. Zhou, M. G. H. Vicente and K. M. Smith, Org. Biomol. Chem., 14 (2016) 1049. H. Chen, S. W. Humble, Z. Zhou, A. L Nguyen, M. G. H. Vicente and K. M. Smith. J. Porphyrins Phthalocyanines, submitted (2017).

 

Acknowledgements: The author thanks the US National Institutes of Health (grants R01 CA132861 and R01 CA179902) for support of this research.