Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly.

Interactions between U2AF homology motifs (UHMs) and U2AF ligand motifs (ULMs) play a crucial role in early spliceosome assembly in eukaryotic gene regulation. UHM-ULM interactions mediate heterodimerization of the constitutive splicing factors U2AF65 and U2AF35 and between other splicing factors that regulate spliceosome assembly at the 3' splice site, where UHM domains of alternative splicing factors, such as SPF45 and PUF60, contribute to alternative splicing regulation. Here, we performed high-throughput screening using fluorescence polarization assays with hit validation by NMR and identified phenothiazines as general inhibitors of UHM-ULM interactions.

Selective C-2 alkylation of tryptophan by a Pd(II)/norbornene-promoted C-H activation reaction.

A palladium(II)-catalyzed norbornene-mediated regioselective alkylation at the C-2 indole position of N-tert-butyloxycarbonyl (Boc)-protected (S)-tryptophan ethyl ester is reported. The protocol employs mild reaction conditions and is tolerant of a range of functional groups. The reaction proceeds without racemization at the stereogenic center of the amino acid.

Copper-catalyzed CuAAC/intramolecular C-H arylation sequence: Synthesis of annulated 1,2,3-triazoles.

Step-economical syntheses of annulated 1,2,3-triazoles were accomplished through copper-catalyzed intramolecular direct arylations in sustainable one-pot reactions. Thus, catalyzed cascade reactions involving [3 + 2]-azide-alkyne cycloadditions (CuAAC) and C-H bond functionalizations provided direct access to fully substituted 1,2,3-triazoles with excellent chemo- and regioselectivities. Likewise, the optimized catalytic system proved applicable to the direct preparation of 1,2-diarylated azoles through a one-pot C-H/N-H arylation reaction.

Well-defined ruthenium(II) carboxylate as catalyst for direct C-H/C-O bond arylations with phenols in water.

The ruthenium(II) carboxylate complex [Ru(O(2)CMes)(2)(p-cymene)] enabled efficient direct arylations of unactivated C-H bonds with easily available, inexpensive phenols. Extraordinary chemoselectivity of the well-defined ruthenium catalyst set the stage for challenging C-H/C-O bond functionalizations to occur under solvent-free conditions as well as in water, and allowed first direct C-H bond arylations with user-friendly diaryl sulfates as electrophiles.

Regioselective syntheses of fully-substituted 1,2,3-triazoles: the CuAAC/C-H bond functionalization nexus.

Regioselective syntheses of 1,4,5-trisubstituted 1,2,3-triazoles were accomplished by three different strategies, relying on (i) the interception of stoichiometrically formed 5-cuprated-1,2,3-triazoles, (ii) the use of stoichiometrically functionalized alkynes or (iii) catalytic C-H bond functionalizations. This perspective article summarizes progress in this research area until June 2010.