Journal
SCIENCE
Volume 347, Issue 6227, Pages 1221-1226Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaa5414
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Funding
- NIH [GM080436, GM090153]
- NSF [0747778]
- Bristol-Myers Squibb
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0747778] Funding Source: National Science Foundation
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Small-molecule synthesis usually relies on procedures that are highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even Csp3-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis.
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