Small molecule macroarray construction via palladium-mediated carbon-carbon bond-forming reactions: highly efficient synthesis and screening of stilbene arrays.
Small molecule macroarray construction via palladium-mediated carbon-carbon bond-forming reactions: highly efficient synthesis and screening of stilbene arrays.
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DOI：
10.1002/chem.200903445
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发表时间：
2010-03-01
影响因子：
4.3
通讯作者：
Blackwell, Helen E.
中科院分区：
文献类型：
--
作者：
Frei, Reto;Blackwell, Helen E.
The use of small molecule probes to interrogate biological phenomena has become a prominent research approach in chemical biology.[1, 2] As the demand for probe molecules continues to grow, the need to develop new methodology for the rapid generation and evaluation of small molecules has also become more urgent.[3, 4] Our laboratory is engaged in the development of the small molecule macroarray as tool for the rapid parallel synthesis and biological screening of drug-like molecules and peptidomimetics.[5–8] Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose supports (ie, laboratory filter paper)[9] yielding spatially addressed libraries of 10–1000 unique compounds (≈ 50–200 nmol of compound/spot; Figure 1A). The simplicity of macroarray construction, coupled to its compatibility with a range of biological assay formats performed either on or off of the planar support, renders this library synthesis technique attractive for a range of research applications. To find wider usage, however, the scope of chemical reactions that are compatible with the macroarray platform must be extended, and this has motivated considerable recent research in this area.[10]To date, the majority of reactions performed on planar cellulose supports have been simple, acylation-type reactions.[11–13] In view of the prevalence of metal-mediated, carbon–carbon bond forming reactions in both chemical probe and pharmaceutical discovery,[14] we sought to explore the feasibility of these reactions on the small molecule macroarray. Herein, we report the application of palladium-mediated Heck reactions for the efficient construction of stilbene macroarrays. Preliminary bacteriological screening of these arrays post-synthesis revealed several stilbenes with novel activities. This work represents both a chemical and biological advance for the small molecule macroarray technique, and further underscores the utility of this approach for chemical probe discovery.
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通讯作者：
Mata, Ernesto G.
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Geske, Grant D.;O'Neill, Jennifer C.;Blackwell, Helen E.
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Blackwell, Helen E.
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通讯作者：
RINK, H
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Bowman, Matthew D.;O'Neill, Jennifer C.;Blackwell, Helen E.
通讯作者：
Blackwell, Helen E.
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