1. Copper-Catalyzed Asymmetric Conjugate Additions of Bis(pinacolato)diboron and Dimethylzinc to Acyl- N-methylimidazole Michael Acceptors: A Highly Stereoselective Unified Strategy for 1,3,5,... n (OH, Me) Motif Synthesis
Jimmy Lauberteaux, Christophe Crévisy, Olivier Baslé, Renata Marcia de Figueiredo, Marc Mauduit, Jean-Marc Campagne Org Lett. 2019 Mar 15;21(6):1872-1876.doi: 10.1021/acs.orglett.9b00479.Epub 2019 Feb 25.
A unified strategy for the construction of prevalent 1,3,5,... n (OH, Me) motifs based on consecutive copper-catalyzed asymmetric conjugate borylation (ACB) and methylation (ACA) reactions involving α,β-unsaturated 2-acyl- N-methylimidazoles is described. Good yields and high diastereoselectivities have been obtained in ACA and ACB reactions for both matched and mismatched pairs as illustrated in the synthesis of syn/ anti and anti/ anti (Me, OTBS, Me) and (OH, OTBS, Me) motifs.
2. Mutagenicity of N-OH-MOCA (4-amino-4'-hydroxylamino-bis-3,3'-dichlorodiphenylmethane) and PBQ (2-phenyl-1,4-benzoquinone) in human lymphoblastoid cells
T M Reid, D G DeBord, K L Cheever, R E Savage Jr Toxicol Lett. 1998 May;95(3):205-10.doi: 10.1016/s0378-4274(98)00039-3.
The genotoxic potential of two occupationally significant chemicals, 4,4'-methylene-bis-2-chloroaniline (MOCA) and 2-phenyl-1,4-benzoquinone (PBQ), was explored by monitoring the induction of mutations at the HPRT locus of AHH-1 human lymphoblastoid cells. Exposure of AHH-1 cells to the putative carcinogenic metabolite of MOCA, N-OH-MOCA, induced a 6-fold increase in mutant frequency and resulted in base pair substitutions primarily at A:T base pairs. In contrast, exposure to PBQ did not result in an increased mutant frequency although this compound was significantly more cytotoxic than N-OH-MOCA at equimolar doses. The induction of mutations at A:T sites by N-OH-MOCA is consistent with the type of DNA damage known to be produced by MOCA and provides a specific marker of genotoxic damage for exposed populations.
3. Synthesis, structures and cytotoxic effects in vitro of cis- and trans-[PtIVCl4(NHC)2] complexes and their PtII precursors
Tobias Rehm, Matthias Rothemund, Thomas Dietel, Rhett Kempe, Rainer Schobert Dalton Trans. 2019 Nov 21;48(43):16358-16365.doi: 10.1039/c9dt02438g.Epub 2019 Oct 18.
Four new bis(N,N-dialkylbenzimidazol-2-ylidene)dichlorido platinum(ii) complexes 2 featuring N-alkyl substituents of increasing size (a: Me, b: Et, c: n-butyl, d: n-octyl) were synthesised and oxidised with PhICl2 to give the corresponding [PtIVCl4(N,N-dialkylbenzimidazol-2-ylidene)2] complexes 4 as potential anticancer prodrugs. The known bis(N,N-dibenzylimidazol-2-ylidene)dichlorido platinum(ii) complex 1 was likewise oxidised to [PtIVCl4(N,N-dibenzylimidazol-2-ylidene)2] 3. In contrast, oxidation of complexes 1 and 2 with H2O2 or hypochlorites, or exchange of chlorido for hydroxo ligands in tetrachlorido complexes 4 failed to give isolable complexes of type [PtIVCl4-n(OH)n(NHC)2]. In MTT assays the [PtIICl2(NHC)2]/[PtIVCl4(NHC)2] complex couples 1/3, 2c/4c, and trans-2c/trans-4c, bearing either N-benzyl or N-butyl substituents, each showed similar single-digit micromolar IC50 values against at least three out of five human cancer cell lines, presumably due to an intracellular reduction of the PtIV complexes to their active PtII congeners. Unlike cisplatin, whose anticancer effect requires functional p53, each of them was active both in wildtype and in p53-negative HCT116 colon carcinoma cells. In ethidium bromide saturation assays with isolated DNA, cis-(bis-NHC)PtII complexes such as 1 caused morphological DNA changes more pronounced than those initiated by cisplatin, while the corresponding cis-(bis-NHC)PtIV complexes such as 3 interacted with DNA in a less structure-modifying way.
