We report a one-pot procedure for forming a dimeric pyrroloindoline framework with a thionium reagent. The cyclization of tryptamine with DMSO and Tf(2)O, followed by substitution with indole derivatives, produced racemic 3a-indolylpyrroloindolines. The method enables rapid access to heterodimeric pyrroloindolines as well as to homodimeric pyrroloindolines.
The cross-coupling of tryptamine with substituted aniline to access C3a-nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a-N1'-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.
The one-pot 2-and 3-functionalization of 2,3-disubstituted indoles using a hypervalent iodine reagent has been developed. The substitution at the 2-position of indoles took place using phenyliodinebis(trifluoroacetate) with oxygen and carbon nucleophiles in moderate yields. The combination of iodosobenzene and trimethylsilyl azide afforded 3-azide derivatives preferentially.The latter reaction was applied to other 2,3-disubstituted indoles.Recently, Ishibashi's group revealed the combination of phenyliodine diacetate (PIDA) and tetrabutylammonium iodide (TBAI) reacted with tetrahydrocarbazoles to give 2-acetoxy derivatives. 6 Alternatively, Du Bois and co-workers developed that the reaction of tetrahydrocarbazoles using imino 3 -iodanes with a rhodium catalyst affords 2-and 3-amino derivatives. 7Recently, we developed the concise 2-functionalization of indole derivatives using a thionium species generated from DMSO-TFAA (Scheme 1). 8
The hypervalent iodine-mediated one-pot C-H functionalization at the 2-or 3-position of indole derivatives is studied. Ph-I(N 3)2 needed for the introduction of the azido group can be prepared in situ from iodosobenzene and trimethylsilylazide. -(HIGUCHI, K.; KAWASAKI*, T.; INABA, M.; NAGANUMA, A.; ISHIZAKI, T.; TAYU, M.; Heterocycles 89 (2014) 9, 2105-2121, http://dx.doi.org/10.3987/COM-14-13065 ; Meiji Pharm. Univ., Kiyose, Tokyo 204, Japan; Eng.) -M. Bohle 09-152
Mucus hypersecretion is a hallmark of respiratory diseases, and excess airway mucus can worsen these conditions. Therefore, it is important to control the production of airway mucus in the treatment of respiratory diseases. The phosphodiesterase inhibitor ibudilast has been reported to be effective in treating sputum and postnasal drip in patients with chronic airway inflammation. On the basis of the hypothesis that ibudilast could inhibit mucus production in the airway, in the present study, we examined the effects of ibudilast on the production of MUC5AC, a major protein component of mucus. In in vitro studies using NCI-H292 cells, ibudilast suppressed MUC5AC production induced by various stimuli. In addition, ibudilast inhibited extracellular signal-regulated kinase (ERK)1/2 phosphorylation and MUC5AC gene transcription. Furthermore, it attenuated MUC5AC production and Muc5ac mRNA expression in lipopolysaccharide-treated mice in vivo. Collectively, these findings demonstrate that ibudilast has an inhibitory effect on mucus production, which could at least partly be attributed to the inhibition of ERK1/2 phosphorylation and the repression of MUC5AC gene transcription.
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