ABSTRACT
Gold(I)-catalyzed cascade cyclization of 1,4-diyn-3-ones with a pyridine N-oxide enabled direct construction of a benzo[6,7]cyclohepta[1,2- b]furan scaffold with the formation of four bonds. This reaction would proceed through oxidative cyclization, alkynyl migration, and 5- endo-dig type cyclization. Synthesis of benzotropone-fused naphtho[1,2- b]furans through a two-step sequence, including epoxidation and In(OTf)3-catalyzed intramolecular carbon-carbon bond formation, is also presented.
ABSTRACT
A gold-catalyzed cascade reaction of skipped diynes (1,4-diynes) and pyrroles has been developed. This reaction proceeds by the consecutive regioselective hydroarylation of two alkynes with a pyrrole, followed by a 7-endo-dig cyclization to give 1,6-dihydrocyclohepta[b]pyrroles in good yields. The direct synthesis of cyclohepta[b]indoles using indole nucleophiles has also been reported.
ABSTRACT
We recently reported that 4-epi-jaspine B exhibits potent inhibitory activity towards sphingosine kinases (SphKs). In this study, we investigated the effects of modifying the 2-alkyl group, as well as the functional groups on the THF ring of 4-epi-jaspine B using a diversity-oriented synthesis approach based on a late-stage cross metathesis reaction. The introduction of a p-phenylene tether to the alkyl group was favored in most cases, whereas the replacement of a carbon atom with an oxygen atom led to a decrease in the inhibitory activity. Furthermore, the introduction of a bulky alkyl group at the terminus led to a slight increase in the inhibitory activity of this series towards SphKs compared with 4-epi-jaspine B (the Q values of compound 13 for SphK1 and SphK2 were 0.2 and 0.4, respectively). Based on this study, we identified two isoform selective inhibitors, including the m-phenylene derivative 4 [IC50 (SphK1) ≥30µM; IC50 (SphK2)=2.2µM] and the methyl ether derivative 22 [IC50 (SphK1)=4.0µM; IC50 (SphK2) ≥30µM].
