Co-reporter:Edwin Alfonzo, Felix Steven Alfonso, and Aaron B. Beeler
Organic Letters June 2, 2017 Volume 19(Issue 11) pp:
Publication Date(Web):May 22, 2017
DOI:10.1021/acs.orglett.7b01222
We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-p-tolylpyrylium tetrafluoroborate (MD(p-tolyl)PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts.
Co-reporter:Han Yueh, Qiwen Gao, John A. Porco Jr., Aaron B. Beeler
Bioorganic & Medicinal Chemistry 2017 Volume 25, Issue 23(Issue 23) pp:
Publication Date(Web):1 December 2017
DOI:10.1016/j.bmc.2017.06.010
Herein, we report the development of continuous flow photoreactors for large scale ESIPT-mediated [3+2]-photocycloaddition of 2-(p-methoxyphenyl)-3-hydroxyflavone and cinnamate-derived dipolarophiles. These reactors can be efficiently numbered up to increase throughput two orders of magnitude greater than the corresponding batch reactions.Download high-res image (49KB)Download full-size image
Co-reporter:Oscar J. Ingham, Ronald M. Paranal, William B. Smith, Randolph A. Escobar, Han Yueh, Tracy Snyder, John A. Porco Jr., James E. Bradner, and Aaron B. Beeler
ACS Medicinal Chemistry Letters 2016 Volume 7(Issue 10) pp:929
Publication Date(Web):September 1, 2016
DOI:10.1021/acsmedchemlett.6b00239
A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8.Keywords: epigenetic; HDAC; HDAC8; Histone deacetylase; histone deacetylase 8; triazole;
Co-reporter:Reem Telmesani;Sung H. Park;Tessa Lynch-Colameta ; Aaron B. Beeler
Angewandte Chemie International Edition 2015 Volume 54( Issue 39) pp:11521-11525
Publication Date(Web):
DOI:10.1002/anie.201504454
Abstract
Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.
Co-reporter:Reem Telmesani;Sung H. Park;Tessa Lynch-Colameta ; Aaron B. Beeler
Angewandte Chemie 2015 Volume 127( Issue 39) pp:11683-11687
Publication Date(Web):
DOI:10.1002/ange.201504454
Abstract
Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.
Co-reporter:Véronique I. Martin, John R. Goodell, Oscar J. Ingham, John A. Porco Jr., and Aaron B. Beeler
The Journal of Organic Chemistry 2014 Volume 79(Issue 9) pp:3838-3846
Publication Date(Web):April 3, 2014
DOI:10.1021/jo500190b
We have developed an automated photochemical microfluidics platform that integrates a 1 kW high-pressure Hg vapor lamp and allows for analytical pulse flow or preparative continuous flow reactions. Herein, we will discuss the use of this platform toward the discovery of new chemotypes through multidimensional reaction screening. We will highlight the ability to discretely control wavelengths with optical filters, allowing for control of reaction outcomes.
