{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:33:56Z","timestamp":1789364036333,"version":"build-2803163510"},"reference-count":55,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1032518"],"award-info":[{"award-number":["OPP1032518"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite\u2019s life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp3)\u2013H arylation of azetidines at the C3 position. This newly developed protocol exhibits a broad substrate scope and provides access to valuable, stereochemically defined building blocks. BRD3914 was evaluated in P.\u00a0falciparum-infected mice, providing a cure after four oral doses.<\/jats:p>","DOI":"10.1021\/jacs.7b06994","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T23:14:30Z","timestamp":1500678870000},"page":"11300-11306","source":"Crossref","is-referenced-by-count":137,"title":["Synthesis\nof a Bicyclic Azetidine with In Vivo Antimalarial Activity Enabled\nby Stereospecific, Directed C(sp3)\u2013H Arylation"],"prefix":"10.1021","volume":"139","author":[{"given":"Micah","family":"Maetani","sequence":"first","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Zoller","sequence":"additional","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Melillo","sequence":"additional","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Verho","sequence":"additional","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Kato","sequence":"additional","affiliation":[{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Pu","sequence":"additional","affiliation":[{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eamon","family":"Comer","sequence":"additional","affiliation":[{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-7558","authenticated-orcid":true,"given":"Stuart L.","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Harvard University , , , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Broad Institute , , ,","place":["Cambridge, Massachusetts, United States, 02142"]},{"name":"Howard Hughes Medical Institute , , ,","place":["Cambridge, Massachussetts, United States, 02138"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,7,21]]},"reference":[{"key":"2026090123242273600_cit1","unstructured":"WHO.\n          \n          2016. http:\/\/www.who.int\/malaria\/publications\/world_malaria_report_2016\/en\/, accessed\nApril 1, 2017."},{"key":"2026090123242273600_cit2","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/nrd4573","volume":"14","author":"Wells","year":"2015","journal-title":"Nat. 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