C-H···π interactions in the CHBrF2···HCCH weakly bound dimer

The microwave spectra of four isotopologues of the CHBrF(2)···HCCH weakly bound dimer have been measured in the 6-18 GHz region using chirped-pulse and Balle-Flygare Fourier-transform microwave spectroscopy. Spectra of (13)CH(79)BrF(2) and (13)CH(81)BrF(2) monomers have also been measured, and spectroscopic constants are reported. Measurement of spectra for the (79)Br and (81)Br isotopologues of CHBrF(2) complexed with both (12)C(2)H(2) and (13)C(2)H(2) have allowed the determination of a structure with C(s) symmetry for this complex. CHBrF(2) interacts with the triple bond of acetylene via a C-H···π contact (R(H···π) = 2.670(8) ?) with the Br atom lying in the ab plane, located 3.293(40) ? from a hydrogen atom of the HCCH molecule. The structure of CHBrF(2)···HCCH has been compared with recently studied related acetylene complexes, including a comparison with (and further structural analysis of) the CHClF(2)···HCCH complex.     

Molybdenum Cofactor Deficiency in Humans

Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic–ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1, MOCS2, MOCS3, and GPHN. Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.     

Chemical constituents of the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity

Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140, associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl-cyclohex-2-enone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1- 6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), and Chagas disease (Trypanosoma cruzi). Cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 microM), T. cruzi (IC50 1.08 and 0.78 microM), P. falciparum (IC50 1.03 and 2.99 microM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 microM). Compounds 3-6 were not active in these assays at a concentration of 10 microg/mL.     

Diastereoselective addition of trimethylsilyl cyanide to chiral O‐, S‐ and N‐heterocyclic aldimines

Systematic investigation of asymmetric trimethylsilylcyanation of heterocyclic azomethines has been realized. The addition of trimethylsilyl cyanide to optically active furan, thiophene and pyridine aldimines, derived from (R)‐ and (S)‐1‐phenylethylamine, was studied in the presence of Lewis acids, and a series of the corresponding α‐amino nitriles was obtained in fair to good yields (up to 91%). Unsaturated nitriles were also formed from pyridine imines. The sense of asymmetric induction and the degree of diastereoselectivity in the synthesis of α‐amino nitriles were determined by means of ¹H NMR. The stereochemical outcome is a result of the same sense of asymmetric induction: Re face attack to the (S)‐imines and Si face addition to the (R)‐imines took place. The (R,R)‐ (up to 81%) or (S,S)‐ (up to 87%) α‐amino nitriles predominated in the products obtained from the all furan, thiophene and pyridine (R)‐ or (S)‐imines respectively. Copyright © 2002 John Wiley & Sons, Ltd.     

161Dy Time‐Domain Synchrotron Mössbauer Spectroscopy for Investigating Single‐Molecule Magnets Incorporating Dy Ions

Time‐domain synchrotron Mössbauer spectroscopy (SMS) based on the Mössbauer effect of ¹⁶¹Dy has been used to investigate the magnetic properties of a Dy^III‐based single‐molecule magnet (SMM). The magnetic hyperfine field of [Dy(Cy₃PO)₂(H₂O)₅]Br₃?2 (Cy₃PO)?2 H₂O?2 EtOH is with B₀=582.3(5) T significantly larger than that of the free‐ion Dy^III with a ⁶H_15/2 ground state. This difference is attributed to the influence of the coordinating ligands on the Fermi contact interaction between the s and 4f electrons of the Dy^III ion. This study demonstrates that ¹⁶¹Dy SMS is an effective local probe of the influence of the coordinating ligands on the magnetic structure of Dy‐containing compounds.     

Covalent‐Allosteric Inhibitors to Achieve Akt Isoform‐Selectivity

Isoforms of protein kinase Akt are involved in essential processes including cell proliferation, survival, and metabolism. However, their individual roles in health and disease have not been thoroughly evaluated. Thus, there is an urgent need for perturbation studies, preferably mediated by highly selective bioactive small molecules. Herein, we present a structure‐guided approach for the design of structurally diverse and pharmacologically beneficial covalent‐allosteric modifiers, which enabled an investigation of the isoform‐specific preferences and the important residues within the allosteric site of the different isoforms. The biochemical, cellular, and structural evaluations revealed interactions responsible for the selective binding profiles. The isoform‐selective covalent‐allosteric Akt inhibitors that emerged from this approach showed a conclusive structure–activity relationship and broke ground in the development of selective probes to delineate the isoform‐specific functions of Akt kinases.     

An Unusual Skeletal Rearrangement in the Biosynthesis of the Sesquiterpene Trichobrasilenol from Trichoderma

The skeletons of some classes of terpenoids are unusual in that they contain a larger number of Me groups (or their biosynthetic equivalents such as olefinic methylene groups, hydroxymethyl groups, aldehydes, or carboxylic acids and their derivatives) than provided by their oligoprenyl diphosphate precursor. This is sometimes the result of an oxidative ring‐opening reaction at a terpene‐cyclase‐derived molecule containing the regular number of Me group equivalents, as observed for picrotoxan sesquiterpenes. In this study a sesquiterpene cyclase from Trichoderma spp. is described that can convert farnesyl diphosphate (FPP) directly via a remarkable skeletal rearrangement into trichobrasilenol, a new brasilane sesquiterpene with one additional Me group equivalent compared to FPP. A mechanistic hypothesis for the formation of the brasilane skeleton is supported by extensive isotopic labelling studies.     

Renewability is not Enough: Recent Advances in the Sustainable Synthesis of Biomass‐Derived Monomers and Polymers

Taking advantage of the structural diversity of different biomass resources, recent efforts were directed towards the synthesis of renewable monomers and polymers, either for the substitution of petroleum‐based resources or for the design of novel polymers. Not only the use of biomass, but also the development of sustainable chemical approaches is a crucial aspect for the production of sustainable materials. This review discusses the recent examples of chemical modifications and polymerizations of abundant biomass resources with a clear focus on the sustainability of the described processes. Topics such as synthetic methodology, catalysis, and development of new solvent systems or greener alternative reagents are addressed. The chemistry of vegetable oil derivatives, terpenes, lignin, carbohydrates, and sugar‐based platform chemicals was selected to highlight the trends in the active field of a sustainable use of renewable resources.