Traceless Cleavage of Protein-Biotin Conjugates under Biologically Compatible Conditions.

Biotinylation of amines is widely used to conjugate biomolecules, but either the resulting label is non-removable or its removal leaves a tag on the molecule of interest, thus affecting downstream processes. We present here a set of reagents (RevAmines) that allow traceless, reversible biotinylation under biologically compatible, mild conditions. Release following avidin-based capture is achieved through the cleavage of a (2-(alkylsulfonyl)ethyl) carbamate linker under mild conditions (200 mm ammonium bicarbonate, pH 8, 16-24 h, room temperature) that regenerates the unmodified amine. The capture and release of biotinylated proteins and peptides from neutravidin, fluorescent labelling through reversible biotinylation at the cell surface and the selective enrichment of proteins from bacterial periplasm are demonstrated. The tags are easily prepared, stable and offer the potential for future application in proteomics, activity-based protein profiling, affinity chromatography and bio-molecule tagging and purification.

Grignard-mediated reduction of 2,2,2-trichloro-1-arylethanones.

2,2,2-Trichloro-1-aryl-ethanones can be reduced by RMgX to the corresponding 2,2-dichloro-1-arylethen-1-olates and trapped with a range of electrophiles resulting in either reduction, reduction/aldol, reduction/Claisen condensation or reduction/aldol-Tishchenko products. In addition we demonstrate that 2,2-dichloro-1-arylethen-1-olates undergo counter-ion controlled Darzens condensations, which can be followed by a thermal rearrangement as a route to 1,3-diaryl-3-chloropropane-1,2-diones.

Reduction of 2,2,2-trichloro-1-arylethanones by RMgX: mechanistic investigation and the synthesis of substituted α,α-dichloroketones.

2,2,2-Trichloro-1-arylethanones undergo high yielding reductions to the corresponding 2,2-dichloro-1-arylethanones in the presence of RMgX. A single electron transfer mechanism for the reaction is proposed based on trapping experiments. Reaction of the intermediate enolates with a range of electrophiles is described, providing a convenient route to substituted α,α-dichloro-ß-hydroxyketones and related molecules.

Platinum and palladium-triazole complexes as highly potential antitumor agents.

The palladium complexes [(dppe)Pd(L)(2)PdCl(2)], [(dppe)Pd(L)(2)PtCl(2)], [(dppp)Pd(L)(2)PdCl(2)], [(dppm) Pd(L)(2)NiCl(2)], and [(dppm)Pd(L)(2)SnCl(4)] 15-19 were prepared. The antiproliferative activity of the newly synthesized complexes as well as their previously prepared analogues 3-14 and 20-26 were screened against a large panel of human cancer cell lines derived from haematological CD4(+) human T-cells containing an integrated HTLV-1 genome (MT-4). The complex 12a, b exhibited remarkable antiproliferative activity against MT-4, CD4(+) human acute T-lymphoblastic leukemia (CCRF-CEM), human splenic B-lymphoblastoid cells (WIL-2NS), human acute B-lymphoblastic leukemia (CCRF-SB), skin melanoma (SK-MEL-28), and prostate carcinoma (DU145) cell lines (CC(50 )= 0.5 microM, 0.4 +/- 0.05 microM, 0.6 +/- 0.05 microM, 0.4 +/- 0.1 microM, and 0.8 +/- 0.2 microM, respectively), meanwhile, 9a, b, 14a, b, and 23 showed significant activity against the CCRF-SB cell lines (CC(50) = 0.6 +/- 0.06 microM, 0.7 +/- 0.05 microM, 0.6 +/- 0.05 microM, and 0.8 +/- 0.15 microM, respectively). Further, 19 exhibited activity against the CCRF-CEM cell line (CC(50 )= 0.4 +/- 0.05 microM).

Microwave-assisted synthesis of acyclic C-nucleosides from 1,2- and 1,3-diketones.

A simple, rapid and regioselective approach for the synthesis of C-acyclic nucleosides 3, 4, 6, and 9 of dihydropyrimidine, imidazole and indeno[1,2-b]pyridine-9-one derived from 1,2- and 1,3-diketones was performed. By using DMF or pyridine as solvent or bentonite clay as a support, in the presence of TMSTf, ZnCl(2), NH(4)OAc, or NH(4)NO(3), all the desired products were obtained within 5-25 minutes under microwave irradiation (MWI). Acid hydrolysis of 6 and 9 afforded the free acyclic C-nucleosides 7 and 10, respectively. Upon treatment with NaOMe under MWI, 3 and 14 rearranged to the C-nucleoside 4 and 16.