The reaction of carbanions with 2-substituted-2-nitropropanes : Substitution and dimerization occurring by radical chain processes involving electron transfer

The reaction of mono-enolate anions with O₂NCMe₂X where X = Cl, NO₂, p-MePhSO₂ yield coupling (RCOCH(R′)(CMe₂NO₂) and enolate dimerization products (RCOCH(R′)CH(R′)COR) by free radical chain mechanisms involving bimolecular substitution or electron transfer reactions between the enolate anion and the intermediate nitro alkane radical anion (XCMe₂NO₂^?).     

Tributylgermanium hydride as a replacement for tributyltin hydride in radical reactions

Tributylgermanium hydride (Bu(3)GeH) can be used as an alternative to tributyltin hydride (Bu(3)SnH) as a radical generating reagent with a wide range of radical substrates. Tributylgermanium hydride has several practical advantages over tributyltin hydride, e.g. low toxicity, good stability and much easier work-up of reactions. The reagent can be easily prepared in good yield and stored indefinitely. Suitable substrates include iodides, bromides, activated chlorides, phenyl selenides, tert-nitroalkanes, thiocarbonylimidazolides and Barton esters. Alkyl, vinyl and aryl radicals can be generated in radical reactions including reduction and cyclisation processes. Common radical initiators such as ACCN and triethylborane can be used. The slower rate of hydrogen abstraction by carbon-centred radicals from Bu(3)GeH as compared to Bu(3)SnH facilitates improved cyclisation yields. Polarity reversal catalysis (PRC) with phenylthiol can be used in reactions which generate stable radical intermediates which will not abstract hydrogen from Bu(3)GeH.     

A simple and versatile method for the synthesis of acetals from aldehydes and ketones using bismuth triflate

Acetals are obtained in good yields by treatment of aldehydes and ketones with trialkyl orthoformate and the corresponding alcohol in the presence of 0.1 mol % Bi(OTf)3.4H2O. A simple procedure for the formation of acetals of diaryl ketones has also been developed. The conversion of carbonyl compounds to the corresponding 1,3-dioxolane using ethylene glycol is also catalyzed by Bi(OTf)3.4H2O (1 mol %). Two methods, both of which avoid the use of benzene, have been developed.     

Generic serial and parallel on-line direct-injection using turbulent flow liquid chromatography/tandem mass spectrometry

The development of turbulent flow chromatography (TFC) has enabled considerable growth in the utility of on-line direct-injection technologies. TFC has now become established in a large number of varied analytical environments, particularly drug discovery/pharmacokinetics, metabolite profiling, combinatorial library purification, pre-clinical and clinical GLP applications. The utility of turbulent flow technology for in-house pre-clinical and clinical quantitative applications has necessitated extensive valve-cleaning procedures, and consequently lengthy cycle-times, to effectively remove the system carry-over. In-house requirements for assay validation require carry-over less than 20% of the lowest level of quantification (LLOQ), corresponding to 0.02% carry-over for a linear calibration range incorporating 3 orders. A generic turbulent flow chromatography protocol has been developed for drug discovery that incorporates polymeric turbulent flow extraction (cyclone) with C18-based reverse-phase chromatography. Further, multiple wash steps are incorporated within the methodology to meet in-house requirements for carry-over. Selection of novel switching-valve materials based on polyarylethyl ketone (PAEK) and Hastelloy/Valcon E autosampler injection hardware has enabled us to significantly impact the cycle-time required to reduce carry-over. Consequently, optimal usage of switching valves has enabled parallel operation for a generic on-line direct-injection methodology to successfully reduce the total cycle-time. Overall reductions from 4 min per sample to 90 s per sample are shown with comparable data quality using a proprietary target molecule from 0.1-100 ng/mL. This paper describes the hardware configuration and methodologies utilized to perform generic serial and parallel on-line direct-injection using a Turboflow HTLC 2300 system.     

Exact controllability and stabilizability of the Korteweg-de Vries equation

In this paper, we consider distributed control of the system described by the Korteweg-de Vries equation

 

on the interval , with periodic boundary conditions

 

where the distributed control is restricted so that the ``volume' of the solution is conserved. Both exact controllability and stabilizibility questions are studied for the system. In the case of open loop control, if the control is allowed to act on the whole spatial domain , it is shown that the system is globally exactly controllable, i.e., for given and functions , with the same ``volume', one can alway find a control so that the system (i)--(ii) has a solution satisfying

If the control is allowed to act on only a small subset of the domain , then the same result still holds if the initial and terminal states, and , have small ``amplitude' in a certain sense. In the case of closed loop control, the distributed control is assumed to be generated by a linear feedback law conserving the ``volume' while monotonically reducing . The solutions of the resulting closed loop system are shown to have uniform exponential decay to a constant state. As in the open loop control case, a small amplitude assumption is needed if the control is allowed to act on only a small subdomain. The smoothing property of the periodic (linear) KdV equation discovered recently by Bourgain has played an important role in establishing the exact controllability and stabilizability results presented in this paper.

     

Chemistry and Biology of Cylindrols: Novel Inhibitors of Ras Farnesyl-Protein Transferase from Cylindrocarpon lucidum

Farnesyl-protein transferase (FPTase) is an enzyme responsible for the farnesylation of Ras protein. Farnesylation is required for cell-transforming activity in several tumor-types, and therefore, inhibition of FPTase activity may be a potential target for anticancer drugs. Our continued search for novel inhibitors led to the isolation of a number of bicyclic resorcinaldehyde cyclohexanone derivatives named here cylindrols A(1) to A(4), cylindrols B and B(1), and a number of known compounds, from Cylindrocarpon lucidum. The compounds were isolated by bioassay-guided separation using Sephadex LH-20, silica gel, and reverse phase HPLC. Structures were elucidated by extensive application of 2D NMR and X-ray crystallography. The determination of absolute stereochemistry was accomplished by CD measurements. Chemical transformations of the most abundant compound resulted in a number of key derivatives which were critical for the evaluation of structure activity relationship. These compounds are members of ascochlorin family and showed a wide range of inhibitory activity (0.7 &mgr;M to >140 &mgr;M) against FPTase. The FPTase activity was noncompetitive with respect to both substrates. Isolation, structures, chemical transformations, and FPTase activity are discussed in detail.     

The effect of random restrictions on formula size

We consider the formula size complexity of boolean functions over the base consisting of ∧, ∨, and ¬ gates. In 1961 Subbotovskaya proved that, for any boolean function on n variables, setting all but a randomly chosen ?n variables to randomly chosen constants, reduces the expected complexity of the induced function by at least a factor. This fact was used by Subbotovskaya to derive a lower bound of Ω(n^1.5) for the formula size of the parity function, and more recently by Andreev who exhibited at lower bound of ΩC(n^2.5/log^O(1)(n)) for a function in P. We present the first improvement of Subbotovskaya's result, showing that the expected formual complexity of a function restricted as above is at most an O(?^γ) franction of its original complexity, for This allows us to give an improved lower bound of Ω(n^2.556…) for Andreev's function. At the time of discovery, this was the best formula lower bound known for any function in NP. © 1993 John Wiley & Sons, Inc.