Publication Date:
2015-03-15
Description:
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 C(sp3)-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687482/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Junqi -- Ballmer, Steven G -- Gillis, Eric P -- Fujii, Seiko -- Schmidt, Michael J -- Palazzolo, Andrea M E -- Lehmann, Jonathan W -- Morehouse, Greg F -- Burke, Martin D -- GM080436/GM/NIGMS NIH HHS/ -- GM090153/GM/NIGMS NIH HHS/ -- R01 GM080436/GM/NIGMS NIH HHS/ -- R01 GM090153/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1221-6. doi: 10.1126/science.aaa5414.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. ; Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. mdburke@illinois.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766227" target="_blank"〉PubMed〈/a〉
Keywords:
Automation
;
Boronic Acids/chemistry
;
Chemistry Techniques, Synthetic/instrumentation/*methods
;
Cyclization
;
Molecular Structure
;
Organic Chemicals/*chemical synthesis/chemistry/isolation & purification
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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