New air-stable planar chiral ferrocenyl monophosphine ligands: Suzuki cross-coupling of aryl chlorides and bromides

[reaction: see text] A novel class of planar chiral electron-rich monophosphine ligands has been developed. The modular design allows a short and efficient synthesis of an array of aryl-ferrocenyl derivatives carrying the donating bis(dicyclohexyl)phosphino moiety. These new ligands have successfully been applied in the palladium-catalyzed Suzuki cross-coupling of activated as well as nonactivated aryl chlorides at room temperature. The asymmetric coupling of an aryl bromide and an aryl boronic acid was also tested, giving ees up to 54%.     

Organotin–Oxido Cluster‐Based Multiferrocenyl Complexes Obtained by Hydrolysis of Ferrocenyl‐Functionalized Organotin Chlorides

Three organotin–oxido clusters were formed by hydrolysis of ferrocenyl‐functionalized organotin chloride precursors in the presence of NaEPh (E=S, Se). [R^FcSnCl₃?HCl] ( C ; R^Fc = CMe₂CH₂C(Me)?N?N?C(Me)Fc) and [SnCl₆]^2? formed {(R^FcSnCl₂)₃[Sn(OH)₆]}[SnCl₃] ( 3 a ) and {(R^FcSnCl₂)₃[Sn(OH)₆]}[PhSeO₃] ( 3 b ), bearing an unprecedented [Sn₄O₆] unit, in a one‐pot synthesis or stepwise through [(R^FcSnCl₂)₂Se] ( 1 ) plus [(R^FcSnCl₂)SePh] ( 2 ). A one‐pot reaction starting out from FcSnCl₃ gave [(FcSn)₉(OH)₆O₈Cl₅] ( 4 ), which represents the largest Fc‐decorated Sn/O cluster reported to date.     

Enzymatic Conversion of Flavonoids using Bacterial Chalcone Isomerase and Enoate Reductase

Flavonoids are a large group of plant secondary metabolites with a variety of biological properties and are therefore of interest to many scientists, as they can lead to industrially interesting intermediates. The anaerobic gut bacterium Eubacterium ramulus can catabolize flavonoids, but until now, the pathway has not been experimentally confirmed. In the present work, a chalcone isomerase (CHI) and an enoate reductase (ERED) could be identified through whole genome sequencing and gene motif search. These two enzymes were successfully cloned and expressed in Escherichia coli in their active form, even under aerobic conditions. The catabolic pathway of E. ramulus was confirmed by biotransformations of flavanones into dihydrochalcones. The engineered E. coli strain that expresses both enzymes was used for the conversion of several flavanones, underlining the applicability of this biocatalytic cascade reaction.     

CH Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform Activation

Ingenol derivatives with varying degrees of oxidation were prepared by two‐phase terpene synthesis. This strategy has allowed access to analogues that cannot be prepared by semisynthesis from natural ingenol. Complex ingenanes resulting from divergent C? H oxidation of a common intermediate were found to interact with protein kinase C in a manner that correlates well with the oxidation state of the ingenane core. Even though previous work on ingenanes has suggested a strong correlation between potential to activate PKCδ and induction of neutrophil oxidative burst, the current study shows that the potential to activate PKCβII is of key importance while interaction with PKCδ is dispensable. Thus, key modifications of the ingenane core allowed PKC isoform selectivity wherein PKCδ‐driven activation of keratinocytes is strongly reduced or even absent while PKCβII‐driven activation of neutrophils is retained.     

2,2′-Bipyrimidine transition metal complexes: Synthesis, reaction chemistry and solid state structures

2,2′-Bipyrimidine metal complexes with Ti, Mo, Fe, Ru, Pt, Ag, and Cu transition metal atoms have been synthesized and structurally characterized. These molecules were prepared by following synthesis methodologies. The reaction of 2,2′-bipyrimidine (1; bipym) with {[Ti](μ-σ,π-CCSiMe₃)₂}AgOTf ([Ti] = (η⁵-C₅H₄SiMe₃)₂Ti, OTf = OSO₂CF₃) (2) in a 1:1 molar ratio gave [{[Ti](μ-σ,π-CCSiMe₃)₂}Ag(bipym)]OTf (3) which on further treatment with another equivalent of 2 produced [({[Ti](μ-σ,π-CCSiMe₃)₂}Ag)₂(μ-1,2,3,4-bipym)](OTf)₂ (4). As consequence thereof, the coordination number of Ag(I) was changed from 3 to 4. A platinum-bipym complex with two acetylide substituents was accessible by the gradual reaction of 1 with K₂[PtCl₄] (5) and two equivalents of HCCR (7a, R = SiMe₃; 7b, R = Fc; 7c, R = Rc; Fc = (η⁵-C₅H₄)(η⁵-C₅H₅)Fe; Rc = (η⁵-C₅H₄)(η⁵-C₅H₅)Ru) in di-iso-propylamine and in presence of [CuI]. Originating from cis-[(bipym)Pt(CCR)₂] (8a, R = SiMe₃; 8b, R = Fc; 8c, R = Rc) diverse multinuclear complexes with two, three or four different transition metals could be obtained. These are: [((CO)₄Mo)(μ-1,2,3,4-bipym)Pt(CCFc)₂] (10), [(AgClO₄)(μ-1,2,3,4-bipym){[Pt(μ-σ,π-CCFc)₂]AgOClO₃}] (12), [(McCC)₂Pt(μ-1,2,3,4-bipym)({[Ti](μ-σ,π-CCSiMe₃)₂}M)]X (15a, Mc = Fc, M = Cu, X = PF₆; 15b, Mc = Rc, M = Cu, X = PF₆; 15c, Mc = Fc, M = Ag, X = ClO₄), and [(McCC)₂Pt(μ-1,2,3,4-bipym)PtCl₂] (17). Like other organometallic Pt-Ag tweezer complexes, compound 12 decomposed to give FcCC-CCFc (13). During prolonged stirring of 15a and 15b, respectively, [(McCC)₂Pt(μ-1,2,3,4-bipym)({[Ti](μ-σ,π-CCSiMe₃)(μ-σ,π-CCH)}M)]X (15′a, M = Cu, X = PF₆; 15′b, M = Cu, X = PF₆) was formed.The structures of 8b, 8c, 15a′, and 15b′ in the solid state are reported. All complexes exhibit the anticipated planar dinuclear Pt-M structure (M = Pt, Cu, Ag) with the 2,2′-bipyrimidine unit in a μ-1,2,3,4-bridging mode.Electrochemical investigations were carried out with 8a, 8b, and 8c and show that no significant influence of R on the bipym redox potentials exists. The typical redox behavior for the bipym, ferrocene, ruthenocene units and platinum were observed.     

Synthesis of β-Ketoiminato Copper(II) Complexes and Their Use in Copper Deposition

The template synthesis of ethylenediamine ( 1 ) with 2-acetylcyclopentanone ( 2 ) and [Cu(OAc)₂ · H₂O] ( 5 ) produced [Cu(1-(2-cC₅H₆(O))C(Me)NCH₂)₂)] ( 6 ) in 82 % yield. Reaction of 5 with bis(benzoylacetone)diethylenetriamine ( 7 , = L H)^[1] gave [Cu(μ-OAc)( L )(H₂O)]₂ ( 8 ). The solid-state structures of 6 and 8 were determined confirming that 8 possesses intra- and intermolecular hydrogen bonds resulting in a dimer formation. The thermal behavior of 6 – 8 was studied by TG and TG-MS. Under oxygen CuO was formed, whereas under Ar Cu/Cu₂O ( 6 ) or Cu ( 8 ) was obtained. Complex 6 was used as CVD precursor for Cu and Cu-oxide deposition (substrate temp., 400–500 °C, N₂, 60 mL · min^–1; O₂, 60 mL · min^–1; pressure, 0.87–1.5 mbar). The as-obtained deposits show separated particles of different appearance at the substrate surface as evidenced by SEM. Non-volatile 8 was applied as spin-coating precursor for Cu and CuO formation [conc. 0.25 mol · L^–1; volume 0.2 mL; 3000 rpm; depos. time 2 min; heating rate 50 K · min^–1; holding time 60 min (Ar), 120 min (air) at 800 °C]. The samples on silicon consist of granulated particles (Ar) or are non-dense with a grainy topography (air). EDX and XPS measurements confirmed the formation of Cu (Ar) or CuO (O₂) with up to 13 mol-% C impurity.     

Synthetic strategies to prepare 2-alkyl, 2-aryl and 2-acetylenyl substituted 4,6-diamino-1,3,5-triazines

We have developed synthetic protocols to generate 2-alkyl, 2-aryl and 2-acetylenyl substituted 4,6-diamino-1,3,5-triazines from the corresponding 2-chloro compound.     

Photochemistry of 2-alkoxymethyl-5-methylphenacyl chloride and benzoate

Irradiation of 2-(alkoxymethyl)-5-methyl-alpha-chloroacetophenones (1a-c) and 2-(methoxymethyl)-5-methylphenacyl benzoate (1d) in dry, nonnucleophilic solvents afforded 3-alkoxy-6-methylindan-1-ones (3a-c) in very high chemical yields. 3-Methylisobenzofuran-1(3H)-one (2) was, however, isolated as a major photoproduct in the presence of trace amounts of water. Quenching experiments and laser flash spectroscopy revealed that the indanone derivatives 3 are formed by 1,5-hydrogen migration from the lowest triplet excited state of the acetophenones 1 and cyclization of the resulting photoenols. In contrast, production of the lactone 2 in wet solvents was found to result from two consecutive photochemical transformations. The photoenols produced by photolysis of 1a-c add water as a nucleophile to form 2-acetyl-4-methylbenzaldehyde (4), which is further converted to 2 via a second, singlet state photoenolization process. Exhaustive photolysis of 1a in methanol produced the acetal 2-(dimethoxymethyl)-5-methylacetophenone (7a) as the exclusive product. The remarkable selectivity of these photoreactions may well be useful in synthetic organic chemistry.     

Monte Carlo vs molecular dynamics for all-atom polypeptide folding simulations

An efficient Monte Carlo (MC) algorithm including concerted rotations is directly compared to molecular dynamics (MD) in all-atom statistical mechanics folding simulations of small polypeptides. The previously reported algorithm "concerted rotations with flexible bond angles" (CRA) has been shown to successfully locate the native state of small polypeptides. In this study, the folding of three small polypeptides (trpzip2/H1/Trp-cage) is investigated using MC and MD, for a combined sampling time of approximately 10(11) MC configurations and 8 micros, respectively. Both methods successfully locate the experimentally determined native states of the three systems, but they do so at different speed, with 2-2.5 times faster folding of the MC runs. The comparison reveals that thermodynamic and dynamic properties can reliably be obtained by both and that results from folding simulations do not depend on the algorithm used. Similar to previous comparisons of MC and MD, it is found that one MD integration step of 2 fs corresponds to one MC scan, revealing the good sampling of MC. The simplicity and efficiency of the MC method will enable its future use in folding studies involving larger systems and the combination with replica exchange algorithms.     

Dynamic nuclear polarization-enhanced solid-state NMR of a 13C-labeled signal peptide bound to lipid-reconstituted Sec translocon

Dynamic nuclear polarization (DNP) has made it possible to record 2D double-quantum-filtered (DQF) solid-state NMR (ssNMR) spectra of a signal peptide bound to a lipid-reconstituted SecYEG translocon complex. The small quantity of peptide in the sample (~40 nmol) normally prohibits multidimensional ssNMR experiments. Such small amounts are not the exception, because for samples involving membrane proteins, most of the limited sample space is occupied by lipids. As a consequence, a conventional 2D DQF ssNMR spectrum with the sample used here would require many weeks if not months of measurement time. With the help of DNP, however, we were able to acquire such a 2D spectrum within 20 h. This development opens up new possibilities for membrane protein studies, particularly in the exploitation of high-resolution spectroscopy and the assignment of individual amino acid signals, in this case for a signal peptide bound to the translocon complex.