Synthesis of the diazatricycloundecane scaffold via gold(I)-catalysed Conia-ene-type 5- exo-dig cyclization and stepwise substituent assembly for the construction of an sp 3 -rich compound library.
Tomoya DoiKohei UmederaKazuki MiuraTaiki MoritaHiroyuki NakamuraPublished in: Organic & biomolecular chemistry (2023)
The bridged diazatricycloundecane sp 3 -rich scaffold was synthesised via the gold(I)-catalysed Conia-ene reaction. The electron-donating property of the siloxymethyl group on alkyne 1 enabled 6- endo-dig cyclization, whereas the ethoxy carbonyl group on alkyne 4 led to 5- exo-dig cyclization with complete regioselectivity in the Conia-ene reaction. The resulting bridged diazatricycloundecane scaffold 5 allowed the construction of a library of sp 3 -rich compounds. Among the compounds synthesised, compounds 6e and 6f inhibited the hypoxia inducible factor 1 (HIF-1) downstream signaling pathway without affecting HIF-1α mRNA expression.