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(±)-7,7′-Dihydroxy-8,8′-biquinolyl (6) was resolved into its enantiomorphic atropisomers via reverse phase (C18) chromatographic separation of epimeric bismenthyl carbonates, (-)-lk-9 and (+)-ul-9, derived from 6 and (+)-menthyl chloroformate. The faster eluting diastereoisomer, (-)-lk-9, was revealed to possess an (aS)-configurated biaryl axis by X-ray crystallographic analysis. Saponification of the separated bismenthyl carbonates gave enantioenriched samples of biquinolyl 6, and absolute stereochemical configurations were assigned to the two optical isomers as (-)-(aS)-6 and (+)-(aR)-6 by correlation with their respective progenitors, (-)-lk-9 and (+)-u/-9. First-order rate constants for the enantiomerization of 6 in water were obtained over the temperature range 316–366 K, and activation parameters were determined as ΔH† = 34.0 kcal mol-1 and ΔS† = 18.7 cal mol-1 K-1 by Eyring plot analysis. A low level (AM1) computational study of the rotational dynamics of 6 showed excellent agreement with kinetic experimental data and suggested that enantiomerization occurs preferentially via a syn pathway. In common with (-)-(aS)-1, 1′-bi-2-naphthol (BINOL), (-)-(aS)-6 showed positive exciton chirality in its electronic circular dichroism (CD) spectrum and gave a characteristic couplet composed of a positive maximum Cotton effect at 250 nm and a negative minimum at 234 nm (ΔΔ∊ = +40 M-1 cm-1 at 64% ee). [ABSTRACT FROM AUTHOR]

7,7′-Bis(((dimethylamino)carbonyl)oxy)-8,8′-biquinolyl (5) was prepared in 71% yield by regioselective directed ortho metalation (DoM) of N,N-dimethyl O-quinol-7-yl carbamate (2) with LDA followed by oxidation with anhydrous ferric chloride. DoM of 5 with excess LDA induced double anionic ortho-Fries rearrangement and gave 6,6′-bis((dimethylamino)carbonyl)-7,7′-dihydroxy-8,8′-biquinolyl (8). Treatment of N,N-diethyl O-(8-iodoquinol-7-yl) carbamate (16) with LDA in THF solvent at -78 °C, followed by addition of anhydrous ferric chloride, resulted in an efficient tandem halogen-dance dimerization process which afforded 7,7′-bis(((diethylamino)-carbonyl)oxy)-6,6′-diiodo-8,8′-biquinolyl (17) directly in 54% yield. [ABSTRACT FROM AUTHOR]

The complex [ZnBr2L ¹] (L ¹ = ferrocenylmethyl-bis[2-{pyrid-2-yl }-ethyl]amine) contains bidentate L¹ by crystallography and NMR spectroscopy and decomposes during recrystallization from CH2-Cl2/pentane via both C-N bond cleavage and formation steps, Other [MBr2L¹] (M = Co, Ni, Cu) compounds do not undergo this reaction and contain L¹ bound in the more usual tridentate coordination mode. [ABSTRACT FROM AUTHOR]

The conformation of a bisindolylmaleimide may be controlled by the size of a macrocyclic ring in which ills constrained. A range of techniques were used to demonstrate that the tether controls both the ratio of the two limiting conformers (syn and anti) in solution and the extent of conjugation between the maleimide and indole rings. Screening the conformationally diverse bisindolylmaleimides against a panel of protein kinases allowed their ATP binding sites to be compared using a chemical approach which, like sequence alignment, does not require detailed structural information. This approach lead to the conclusion that several AGC group protein kinases (including PKCα, PKCβ, MSK1, p70 S6K, PDK-1, and MAPKAP-K1α) may be best inhibited by bisindolylmaleimides which adopt a compressed approximately C2-symmetric anti conformation; in constrast, GSK3β may be best inhibited by bisindolylmaleimides whose ground state is a distorted syn conformation. It is concluded that PDK-1, whose structure has been determined by X-ray crystallography, and its mutants, may serve as particularly useful surrogates for the study of PKC inhibitors. [ABSTRACT FROM AUTHOR]