An up-to-date in-depth review of the current virtues and limitations in the realm of carbonyl addition reactions with allenyl-, propargyl-, and vinylsilicon reagents, encompassing numerous practical as well as pedagogical principles is presented. Comparisons of chemo-, regio-, and stereoselectivity and reactivity are drawn. Synthetic applications and challenges associated with each class of organosilane are discussed threading together the prospects of these green carbanion surrogates.

Indium halides or bismuth halides catalyzed the coupling of various alcohols with alkenylsilanes to give the corresponding alkenes stereospecifically without any other activators.

Racemic and scalemic PTC-protected alpha-hydroxystannanes cross-couple with alkenyl/aryl/heteroaryl iodides in moderate to good yields using copper(I) thiophene-2-carboxylate (CuTC) in THF at or below room temperature. Simple aryl iodides and 1-iodocyclohexene, two classes of electrophiles that typically react sluggishly, are also good substrates. Cross-couplings proceed with retention of configuration at the alkenyl- and stannyl-substituted stereocenters.

[reaction: see text] An enantio- and diastereoselective Sakurai-Hosomi reaction, catalyzed by chiral scandium pyridyl-bis(oxazoline)(pybox) complexes, has been developed. Both alkyl- and aryl-substituted allylsilanes are effective coupling partners with N-phenylglyoxamide. Applications of this reaction to the asymmetric syntheses of N-Boc D-alloisoleucine and D-isoleucine are described.

We present a general model for understanding the stereochemical course of intramolecular Michael reactions. We show that the addition of beta-ketoester enolates to alpha,beta-unsaturated esters and imides bearing adjacent stereocenters X and Y leads to high levels of asymmetric induction. Reinforcing and non-reinforcing (X-Y, syn, anti) stereochemical relationships are present. On the basis of synthetic, spectroscopic, and computational studies, we propose that the outcomes of these reactions may be rationalized by a dipole-minimized chair transition state model.

Triapine® (3-AP) is a drug in Phase-II trials. One of its established cellular targets is the β2 subunit of ribonucleotide reductase (RNR) that requires a diferric-tyrosyl-radical [(FeIII2-Y·)(FeIII2)] cofactor for de novo DNA biosynthesis. Several mechanisms for 3-AP inhibition of β2 have been proposed: one involves direct Fe-chelation from β2,while a second involves Y· destruction by reactive oxygen species (ROS) formed in situ, in the presence of O2 and reductant, by Fe(II)-(3-AP). Inactivation of β2 can thus arise from cofactor destruction by loss of iron or Y·. In vitro kinetic data on the rates of 55Fe and Y· loss from [(55FeIII2- Y·)(55FeIII2)]-β2 under aerobic and anaerobic conditions reveal that Y· loss alone is sufficient for rapid β2 inactivation. OxyblotTM and mass spectrometric analyses of trypsin-digested, inhibited β2, and lack of Y· loss from H2O2 and O2·(-) treatment, together preclude ROS involvement in Y· loss. Three mammalian cell lines treated with 5 μM 3-AP reveal Y· loss and β2 inactivation within 30-min of 3-AP-exposure, analyzed by whole-cell EPR and lysate assays, respectively. Selective degradation of apo- over [(FeIII2-Y·)(FeIII2)]-β2 in lysates, similar Fe-content in β2 immunoprecipitated from 3-AP-treated and untreated [55Fe]-pre-labeled cells, and prolonged (12 h) stability of the inhibited β2 are most consistent with Y· loss being the predominant mode of inhibition, with β2 remaining iron-loaded and stable. A model consistent with in vitro and cell-based biochemical studies is presented in which Fe(II)-(3-AP), which can be cycled with reductant, directly reduces Y· of the [(FeIII2- Y·)(FeIII2)] cofactor of β2.

Clofarabine (ClF) is a drug used in the treatment of leukemia. One of its primary targets is human ribonucleotide reductase (hRNR), a dual-subunit,(α(2))(m)(β(2))(n), regulatory enzyme indispensable in de novo dNTP synthesis. We report that, in live mammalian cells, ClF targets hRNR by converting its α-subunit into kinetically stable hexamers. We established mammalian expression platforms that enabled isolation of functional α and characterization of its altered oligomeric associations in response to ClF treatment. Size exclusion chromatography and electron microscopy documented persistence of in-cell-assembled-α(6). Our data validate hRNR as an important target of ClF, provide evidence that in vivo α's quaternary structure can be perturbed by a nonnatural ligand, and suggest small-molecule-promoted, persistent hexamerization as a strategy to modulate hRNR activity. These studies lay foundations for documentation of RNR oligomeric state within a cell.

The ecosystem services (ES) framework provides a link between changes in a natural system's structure and function and public welfare. This systematic integration of ecology and economics allows for more consistency and transparency in environmental decision making by enabling valuation of nature's goods and services in a manner that is understood by the public. This policy analysis (1) assesses the utility of the ES conceptual framework in the context of setting a secondary National Ambient Air Quality Standard (NAAQS),(2) describes how economic valuation was used to summarize changes in ES affected by NOx and SOx in the review, and (3) uses the secondary NOxSOx NAAQS review as a case study to highlight the advantages and challenges of quantifying air pollutant effects on ES in a decision making context. Using an ES framework can benefit the decision making process by accounting for environmental, ecological, and social elements in a holistic manner. As formal quantitative linkages are developed between ecosystem structure and function and ES, this framework will increasingly allow for a clearer, more transparent link between changes in air quality and public welfare.

A full account of our total synthesis of the galbulimima alkaloids GB 13 and himgaline is provided. Using a strategy adapted from the proposed biosynthesis of the GB alkaloid family, a linear precursor underwent successive intramolecular Diels-Alder, Michael, and imine aldol cyclizations to form the polycyclic alkaloid core. We now show that modification of this strategy can also deliver an advanced intermediate en route to the related alkaloid himandridine. The success of the key imine aldol cyclization is acutely sensitive to substrate structure and solvent, including a case in which cyclization was spontaneous in protic solvents. A detailed computational investigation of the course of the reaction closely correlates with, and suggests a rationale for, the observed patterns of imine aldol reactivity.

The use of cyclic α,β-unsaturated iminium-ion dienophiles is documented in two highly diastereoselective Diels-Alder (DA) reactions. The dienophilic counterion was found to have a significant effect on reactivity.

Human ribonucleotide reductases (hRNRs) catalyze the conversion of nucleotides to deoxynucleotides and are composed of α- and β-subunits that form active α(n)β(m)(n, m = 2 or 6) complexes. α binds NDP substrates (CDP, UDP, ADP, and GDP, C site) as well as ATP and dNTPs (dATP, dGTP, TTP) allosteric effectors that control enzyme activity (A site) and substrate specificity (S site). Clofarabine (ClF), an adenosine analog, is used in the treatment of refractory leukemias. Its mode of cytotoxicity is thought to be associated in part with the triphosphate functioning as an allosteric inhibitor of hRNR. Studies on the mechanism of inhibition of hRNR by ClF di- and triphosphates (ClFDP and ClFTP) are presented. ClFTP is a reversible inhibitor (K(i)= 40 nM) that rapidly inactivates hRNR. However, with time, 50% of the activity is recovered. D57N-α, a mutant with an altered A site, prevents inhibition by ClFTP, suggesting its A site binding. ClFDP is a slow-binding, reversible inhibitor ( K(i)*; t(1/2)= 23 min). CDP protects α from its inhibition. The altered off-rate of ClFDP from E•ClFDP* by ClFTP (A site) or dGTP (S site) and its inhibition of D57N-α together implicate its C site binding. Size exclusion chromatography of hRNR or α alone with ClFDP or ClFTP, ± ATP or dGTP, reveals in each case that α forms a kinetically stable hexameric state. This is the first example of hexamerization of α induced by an NDP analog that reversibly binds at the active site.

Lewis acid-catalyzed highly diastereoselective asymmetric Friedel-Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)(3) at room temperature, providing a series of enantiomerically enriched α-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel-Crafts alkylation to afford dialkylation product was also investigated.

alpha-Amino-beta-hydroxy-gamma-lactam 1 is a peptide mimic in which the Ser/Thr residue omega-, psi-, and chi-dihedral angle geometry all are constrained by the 5-membered lactam ring. Lactams 1 were made by employing N-(Fmoc)oxiranylglycine 3 as a bis-electrophile in TFE with cat. BzOH to sequentially alkylate and acylate a variety of amino acid derivatives in one pot. Solid-phase synthesis of beta-hydroxy-gamma-lactam 8, an analogue of the IL-1 modulator 101.10, was achieved using this method for studying Ser/Thr geometry.

We have observed true self-starting Kerr-lens mode locking in two distinct solid-state laser systems operating at room temperature by optimizing the cavity geometry to maximize the amplitude modulation with respect to the intracavity power variation. Pulses of 15 ps have been obtained from a Pr(3+):YLF laser system operating at 607 nm, and 53-fs pulses have been obtained from Cr(4+):YAG at 1.54 microm.

The copper(i) ethylene complex [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4))(Dipp = 2,6-diisopropylphenyl) has been synthesized by treating [N{(C(3)F(7))C(Dipp)N}(2)]Cu(NCCH(3)) with ethylene at room temperature.[N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) is an air stable, yellow solid. X-Ray crystallographic data of [N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) show that the 1,3,5-triazapentadienyl ligand coordinates to copper in kappa(2)-fashion. The copper atom adopts a trigonal-planar geometry.[N{(C(3)F(7))C(Dipp)N}(2)]Cu(C(2)H(4)) and [N{(C(3)F(7))C(Dipp)N}(2)]Cu(NCCH(3)) effectively catalyze carbene and nitrene transfer to a variety of substrates in high efficiencies.

The nickel-catalyzed enantioselective addition of allylboronic acid pinacol ester [allylB(pin)] to alpha,beta,gamma,delta-unsaturated aldehydes is described. This reaction results in a remarkable inversion of substrate olefin geometry, providing the Z,E-configured reaction product in good enantioselectivity and olefin stereoselectivity. The reaction appears to proceed by conversion of the dienal to an unsaturated pi-allyl complex followed by reductive elimination via transition state II. Enantioselectivities range from 73-94% ee for a range of delta-substituted dienals when chiral ligand L3 is employed.

A new and concise total synthesis of (-)-zampanolide,(-)-1, and (-)-dactylolide,(-)-2, is described. Synthetic highlights include (i) a mild Horner-Wadsworth-Emmons reaction providing the seco acid,(ii) an unusual stepwise cross-coupling reaction of a 1,1-dibromodiene with inversion of olefin geometry, and (iii) specific O-Michael reaction conditions using catalytic LHMDS with TMEDA for the synthesis of functionalized 2,6-cis-tetrahydropyran. A marine sponge extract was analyzed for the presence of (-)-2 as the biosynthetic precursor of (-)-zampanolide.

We demonstrate operation of a simple and reliable water-cooled femtosecond laser running at 10 kHz suitable for industrial micromachining applications. A laser geometry involving only a regenerative amplifier and delivering 3.5 W average power 60-fs pulses is compared to a more conventional architecture using an additional multi-pass amplifier. Both laser systems require a moderate pumping laser of ~30 W average power and deliver high-quality beams (M2<1.2).

An imaging system in reflection geometry based on a multimode 2.9 THz quantum cascade laser as radiation source is reported. The beating between neighbouring longitudinal modes is detected using a room temperature point-contact Schottky diode as mixing element. We show that the technique can, in principle, give a dynamic range of 60 dB with a time constant of ~ 10 mus.

A finite-difference frequency-domain (FDFD) method is applied for photonic band gap calculations. The Maxwell's equations under generalized coordinates are solved for both orthogonal and non-orthogonal lattice geometries. Complete and accurate band gap information is obtained by using this FDFD approach. Numerical results for 2D TE/TM modes in square and triangular lattices are in excellent agreements with results from plane wave method (PWM). The accuracy, convergence and computation time of this method are also discussed.

Organocatalysts for the asymmetric reduction of ketimines are presented that function well at low catalyst loadings providing chiral amines in good yield and enantioselectivity, the latter appearing to be independent of the ketimine substrate geometry.