Publication Date:
2015-01-03
Description:
At the forefront of new synthetic endeavors, such as drug discovery or natural product synthesis, large quantities of material are rarely available and timelines are tight. A miniaturized automation platform enabling high-throughput experimentation for synthetic route scouting to identify conditions for preparative reaction scale-up would be a transformative advance. Because automated, miniaturized chemistry is difficult to carry out in the presence of solids or volatile organic solvents, most of the synthetic "toolkit" cannot be readily miniaturized. Using palladium-catalyzed cross-coupling reactions as a test case, we developed automation-friendly reactions to run in dimethyl sulfoxide at room temperature. This advance enabled us to couple the robotics used in biotechnology with emerging mass spectrometry-based high-throughput analysis techniques. More than 1500 chemistry experiments were carried out in less than a day, using as little as 0.02 milligrams of material per reaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buitrago Santanilla, Alexander -- Regalado, Erik L -- Pereira, Tony -- Shevlin, Michael -- Bateman, Kevin -- Campeau, Louis-Charles -- Schneeweis, Jonathan -- Berritt, Simon -- Shi, Zhi-Cai -- Nantermet, Philippe -- Liu, Yong -- Helmy, Roy -- Welch, Christopher J -- Vachal, Petr -- Davies, Ian W -- Cernak, Tim -- Dreher, Spencer D -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):49-53. doi: 10.1126/science.1259203. Epub 2014 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Process and Analytical Chemistry, Merck Research Laboratories, Merck and Co. Inc., Rahway, NJ 07065, USA. ; Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Research Laboratories, Merck and Co. Inc., West Point, PA 19486, USA. ; Department of Pharmacology, Merck Research Laboratories, Merck and Co. Inc., Kenilworth, NJ 07033, USA. ; Department of Discovery Chemistry, Merck Research Laboratories, Merck and Co. Inc., Kenilworth, NJ 07033, USA. ; Department of Discovery Chemistry, Merck Research Laboratories, Merck and Co. Inc., West Point, PA 19486, USA. ; Department of Discovery Chemistry, Merck Research Laboratories, Merck and Co. Inc., Rahway, NJ 07065, USA. ; Department of Discovery Chemistry, Merck Research Laboratories, Merck and Co. Inc., Boston, MA 02115, USA. timothy_cernak@merck.com spencer_dreher@merck.com. ; Department of Process and Analytical Chemistry, Merck Research Laboratories, Merck and Co. Inc., Rahway, NJ 07065, USA. timothy_cernak@merck.com spencer_dreher@merck.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554781" target="_blank"〉PubMed〈/a〉
Keywords:
Biotechnology
;
Catalysis
;
High-Throughput Screening Assays/*methods
;
Mass Spectrometry
;
*Nanoparticles
;
Nanotechnology/*methods
;
Palladium/chemistry
;
Pharmaceutical Preparations/*chemical synthesis
;
Robotics/methods
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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