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Tricyclic framework <jats:bold>7<\/jats:bold> was synthesized from 9\u2010azabicyclo[3,3,1]nonan\u20103\u2010one (<jats:bold>11)<\/jats:bold> via a gold(I)\u2010catalyzed Conia\u2010ene reaction. The electron\u2010donating group on the pendant alkyne of cyclization precursor <jats:bold>12\u2009b<\/jats:bold>\u2013<jats:bold>e<\/jats:bold> was the key to forming 6\u2010<jats:italic>endo<\/jats:italic>\u2010<jats:italic>dig<\/jats:italic> cyclized product <jats:bold>7<\/jats:bold> with complete regioselectivity. Using the synthetic strategy for regioselective construction of bridged tricyclic framework <jats:bold>7<\/jats:bold>, a diazatricyclododecene 3D\u2010scaffold <jats:bold>8\u2009a<\/jats:bold>, which enables the introduction of substituents into the scaffold to mimic amino acid side chains, was designed and synthesized. The peptide mimetics <jats:bold>21\u2009a<\/jats:bold>\u2013<jats:bold>u<\/jats:bold> were synthesized via step\u2010by\u2010step installation of three substituents on diazatricyclododecene scaffold <jats:bold>8\u2009a<\/jats:bold>. Compounds <jats:bold>21\u2009a<\/jats:bold>\u2013<jats:bold>h<\/jats:bold> were synthesized as \u03b1\u2010helix peptide mimics of hydrophobic ZZxxZ and ZxxZZ sequences (Z=Leu or Phe) and subjected to cell\u2010based assays: antiproliferative activity, HIF\u20101 transcriptional activity which is considered to affect cancer malignancy, and antiviral activity against rabies virus. Compound <jats:bold>21\u2009a<\/jats:bold> showed the strongest inhibitory activity of HIF\u20101 transcriptional activity (IC<jats:sub>50<\/jats:sub>=4.1\u00b10.8\u2005\u03bcM), whereas compounds <jats:bold>21\u2009a<\/jats:bold>\u2013<jats:bold>g<\/jats:bold> showed antiviral activity with IC<jats:sub>50<\/jats:sub> values of 4.2\u201312.4\u2005\u03bcM, suggesting that the 3D\u2010scaffold <jats:bold>8\u2009a<\/jats:bold> has potential as a versatile peptide mimic skeleton.<\/jats:p>","DOI":"10.1002\/chem.202101440","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T05:08:30Z","timestamp":1622524110000},"page":"11888-11894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Synthesis of Three\u2010Dimensional (Di)Azatricyclododecene Scaffold and Its Application to Peptidomimetics"],"prefix":"10.1002","volume":"27","author":[{"given":"Kohei","family":"Umedera","sequence":"first","affiliation":[{"name":"School of Life Science and Technology Tokyo Institute of Technology  Yokohama 226-8503 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Morita","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology Tokyo Institute of Technology  Yokohama 226-8503 Japan"},{"name":"Laboratory for Chemistry and Life Science Institute of Innovative Research Tokyo Institute of Technology  Yokohama 226-8503 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Yoshimori","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Medicine, Inc.  26-1, Muraoka-Higashi 2-chome Fujisawa 251-0012 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture Department of Veterinary Sciences University of Miyazaki  Miyazaki 889-2192 Japan"},{"name":"Faculty of Medicine Oita University  1-1, Idaigaoka, Hasama-machi Yufu-city, Oita 879-5593 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Katoh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Oita University  1-1, Idaigaoka, Hasama-machi Yufu-city, Oita 879-5593 Japan"},{"name":"Institute of Advanced Medcine Inc. 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