Ion Ghiviriga

Radical cascade transformations of tris(o-aryleneethynylenes) into substituted benzo[a]indeno[2,1-c]fluorenes.

Oligomeric o-aryleneethynylenes with three triple bonds undergo cascade radical transformations in reaction with a Bu 3SnH/AIBN system. These cascades involve three consecutive cycle closures with the formation of substituted benzo[ a]indeno[2,1- c]fluorene or benzo[1,2]fluoreno[4,3- b]silole derivatives. The success of this sequence depends on regioselectivity of the initial attack of the Bu 3Sn radical at the central triple bond of the o-aryleneethynylene moiety. The cascade is propagated through the sequence of 5-exo-dig and 6-exo-dig cyclizations which is followed by either a radical attack at the terminal Ar substituent or radical transposition which involves H-abstraction from the terminal TMS group and 5-endo-trig cyclization. Overall, the transformation has potential to be developed into an approach to a new type of graphite ribbons.

Comparative and functional genomics of Rhodococcus opacus PD630 for biofuels development.

The Actinomycetales bacteria Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 bioconvert a diverse range of organic substrates through lipid biosynthesis into large quantities of energy-rich triacylglycerols (TAGs). To describe the genetic basis of the Rhodococcus oleaginous metabolism, we sequenced and performed comparative analysis of the 9.27 Mb R. opacus PD630 genome. Metabolic-reconstruction assigned 2017 enzymatic reactions to the 8632 R. opacus PD630 genes we identified. Of these, 261 genes were implicated in the R. opacus PD630 TAGs cycle by metabolic reconstruction and gene family analysis. Rhodococcus synthesizes uncommon straight-chain odd-carbon fatty acids in high abundance and stores them as TAGs. We have identified these to be pentadecanoic, heptadecanoic, and cis-heptadecenoic acids. To identify bioconversion pathways, we screened R. opacus PD630, R. jostii RHA1, Ralstonia eutropha H16, and C. glutamicum 13032 for growth on 190 compounds. The results of the catabolic screen, phylogenetic analysis of the TAGs cycle enzymes, and metabolic product characterizations were integrated into a working model of prokaryotic oleaginy.

Rhodostreptomycins, antibiotics biosynthesized following horizontal gene transfer from Streptomyces padanus to Rhodococcus fascians.

Two antibiotics have been isolated from a strain of Rhodococcus fascians that emerged from a competitive co-culture with Streptomyces padanus. The structures of these compounds were elucidated by d...

Chemoenzymatic Synthesis of Amaryllidaceae Constituents and Biological Evaluation of their C-1 Analogues. The Next Generation Synthesis of 7-Deoxypancratistatin and trans-Dihydrolycoricidine†

An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.

An OCO3– Trianionic Pincer Tungsten(VI) Alkylidyne: Rational Design of a Highly Active Alkyne Polymerization Catalyst

Synthesis, characterization, and catalytic alkyne polymerization results for the first trianionic pincer alkylidyne complex, [(t)BuOCO]W≡CC(CH(3))(3)(THF)(2) (6), are described. Complex 6 is a highly active catalyst for the polymerization of acetylenes and exhibits a high turnover number (4371), activity (1.05 × 10(6) g(PPA) mol(cat)(-1) h(-1)),and yield (87%) for the polymerization of 1-ethynyl-4-fluorobenzene.

In Search of Efficient 5-Endo-dig Cyclization of a Carbon-Centered Radical: 40 Years from a Prediction to Another Success for the Baldwin Rules

Despite being predicted to be stereoelectronically favorable by the Baldwin rules, efficient formation of a C-C bond through a 5-endo-dig radical cyclization remained unknown for more than 40 years. This work reports a remarkable increase in the efficiency of this process upon beta-Ts substitution, which led to the development of an expedient approach to densely functionalized cyclic 1,3-dienes. Good qualitative agreement between the increased efficiency and stereoselectivity for the 5-endo-dig cyclization of Ts-substituted vinyl radicals and the results of density functional theory analysis further confirms the utility of computational methods in the design of new radical processes. Although reactions of Br atoms generated through photochemical Ts-Br bond homolysis lead to the formation of cyclic dibromide side products, the yields of target bromosulfones in the photochemically induced reactions can be increased by recycling the dibromide byproduct into the target bromosulfones through a sequence of addition/elimination reactions at the exocyclic double bond. Discovery of a relatively efficient radical 5-endo-dig closure, accompanied by a C-C bond formation, provides further support to stereoelectronic considerations at the heart of the Baldwin rules and fills one of the last remaining gaps in the arsenal of radical cyclizations.

Modeling Biological Copper Clusters: Synthesis of a Tricopper Complex, and Its Chloride- and Sulfide-Bridged Congeners

The synthesis and characterization of a family of tricopper clusters housed within a tris(β-diketimine) cyclophane ligand (H3L) that bear structural similarities to biological copper clusters are reported. In all complexes, each Cu atom is held within the N2-chelate of a single β-diketiminate arm. Reaction of L(3-) with CuCl affords an anionic complex containing a μ3-chloride donor in the central cavity, whereas there is no evidence for bromide incorporation in the product of the reaction of L(3-) with CuBr (Cu3L). Cu3L reacts with elemental sulfur to generate the corresponding air-stable mixed-valent (μ3-sulfido)tricopper complex, Cu3(μ3-S)L, which represents the first example of a sulfide-bridged copper cluster in which each metal center is both coordinatively unsaturated and held within a N-rich environment. The calculated LUMO is predominantly Cu-S π* in character and delocalized over all three metal centers, which is consistent with the isotropic ten-line absorption (g ∼ 2.095, A ∼ 33 G) observed at room temperature in EPR spectra of the one-electron chemically reduced complex, [Cu3(μ3-S)L](-).

Characterization of Streptomyces MITKK-103, a newly isolated actinomycin X2-producer

A new actinomycete strain designated MITKK-103 was isolated from the soil of a flowerpot using a humic acid agar medium. The newly isolated strain was able to produce a large amount of actinomycin X2 even under nonoptimized growing conditions and serves as a promising source of this antibiotic. Actinomycin X2 has higher cytotoxicity toward cultured human leukemia (HL-60) cells than does actinomycin D, and it induces cell death via apoptosis. A nearly complete 16S ribosomal DNA (rDNA) sequence from the isolate was determined and found to have high identity (98.5–100%) with Streptomyces galbus, Streptomyces griseofuscus, and Streptomyces padanus, indicating that MITKK-103 belongs to the genus Streptomyces. The isolate clustered with species belonging to the S. padanus clade in a 16S-rDNA-based phylogenetic tree and showed 75% overall homology to S. padanus ATCC 25646 in DNA–DNA relatedness analysis. Although the growth of the isolate was somewhat different from the three species mentioned, the strain MITKK-103 most closely resembles S. padanus on the basis of the morphological and phenotypic characteristics, phylogenetic analysis, and genotypic data. As such, this is the first report of a strain of S. padanus capable of producing actinomycins.

Hydrogen Bonding and Tautomerism in Anils of Salicylaldehydes and Related Compounds. A Study of Deuterium Isotope Effects on13C Chemical Shifts

Deuterium‐induced chemical shift differences on the 13C (DIS) are reported for a series of Schiff bases of salicylaldehydes, 1‐(phenyliminomethyl)naphthalen‐2‐ol and 4‐chloro‐1,7‐phenanthrolin‐10‐ol. Provided that corrections for the hydrogen donor atom and diamagnetic effects of the surrounding groups are made, plots of logarithms of two bond DIS vs. the chemical shift of the exchangeable proton are linear for compounds in which tautomeric equilibria are absent or strongly displaced in favor of one form. Molecules with comparably populated tautomers in fast exchange fall off this correlation. By this method, anils of salicylaldehydes were found to exist as hydroxy forms with localized hydrogen bonds while 1‐(phenyliminomethyl)naphthalen‐2‐ol and 4‐chloro‐1,7‐phenanthrolin‐10‐ol were found to be tautomeric mixtures dominated by the hydroxy forms. DIS also revealed that 4‐chlor‐1,7‐phenanthrolin‐10‐ol exists in solution as an aggregate of two molecules.

Steric hindrance to the solvation of melamines and consequences for non-covalent synthesis

Steric hindrance to solvation disfavors structures like 1 synanti in which the melamine exposes to the solvent faces, such as tBu-H, for whom binding to the ring nitrogen is hindered but not blocked; steric hindrance to solvation lowers the barriers to rotation in solvents which bind the triazine nitrogens, therefore these solvents display the fastest rates for assembling/disassembling processes.