The synthesis of azadirachtin: a potent insect antifeedant

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.     

Numerical solution of certain classes of transport equations in any dimension by Shannon sampling

A method is developed for computing solutions to some class of linear and nonlinear transport equations (hyperbolic partial differential equations with smooth solutions), in any dimension, which exploits Shannon sampling, widely used in information theory and signal processing. The method can be considered a spectral or a wavelet method, strictly related to the existence of characteristics, but allows, in addition, for some precise error estimates in the reconstruction of continuous profiles from discrete data. Non-dissipativity and (in some case) parallelizability are other features of this approach. Monotonicity-preserving cubic splines are used to handle nonuniform sampling. Several numerical examples, in dimension one or two, pertaining to single linear and nonlinear (integro-differential) equations, as well as to certain systems, are given.     

Search for right-handed currents in muon decay

We report new limits on right-handed currents, based on precise measurements of the endpoint of the e⁺ spectrum from ⁺ decay. Highly polarized ⁺ from the TRIUMF surface beam were stopped in pure metal foils within either an 1.1-T spin-holding logitudinal field, or a 70-gauss spin-precessing transverse field. Decay e⁺ emitted within 200 mrad of the beam direction were momentum-analyzed to ±0.2%. For the spin-held data, decay via (V-A) currents requires the e⁺ rate to approach zero in the beam direction at the endpoint. Measurement of this rate sets the 90%-confidence limits P />0.9959 and M(W_R)>380 GeV, where W_R is the possible right-handed gauge boson. For the spin-precessed data we independently determine a 90% confidence limit P />0.9918.We are indebted to the entire TRIUMF management and staff for their splendid support of this experiment. In its early stages we benefited from discussion with J. Brewer, R. Cahn, K. Crowe, and W. Wenzel. Rapid commissioning of the polarimeter was made possible by the superb efforts of the LBL support staff. This research was supported in part by the U.S. Department of Energy, Division of Basic Energy Sciences, Office of Energy Research under contracts W-7405-ENG-48 and AC02-ER02289.     

Process-driven information management system at a biotech company: concept and implementation

While established pharmaceutical companies have chemical information systems in place to manage their compounds and the associated data, new startup companies need to implement these systems from scratch. Decisions made early in the design phase usually have long lasting effects on the expandability, maintenance effort, and costs associated with the information management system. Careful analysis of work and data flows, both inter- and intradepartmental, and identification of existing dependencies between activities are important. This knowledge is required to implement an information management system, which enables the research community to work efficiently by avoiding redundant registration and processing of data and by timely provision of the data whenever needed. This paper first presents the workflows existing at Anadys, then ARISE, the research information management system developed in-house at Anadys. ARISE was designed to support the preclinical drug discovery process and covers compound registration, analytical quality control, inventory management, high-throughput screening, lower throughput screening, and data reporting.