A six-step synthesis of (S)-5-ethenyl-3-(1-methyl-2-pyrrolidinyl)pyridine (SIB-1508Y) from (S)-nicotine

The anti-Parkinson’s agent SIB-1508Y was prepared in six steps from (S)-nicotine in 20% overall yield. The strategy involves a regioselective formylation at C-5 of a 1,4-dihydronicotine intermediate.     

Pure adaptive search in monte carlo optimization

Pure adaptive search constructs a sequence of points uniformly distributed within a corresponding sequence of nested regions of the feasible space. At any stage, the next point in the sequence is chosen uniformly distributed over the region of feasible space containing all points that are equal or superior in value to the previous points in the sequence. We show that for convex programs the number of iterations required to achieve a given accuracy of solution increases at most linearly in the dimension of the problem. This compares to exponential growth in iterations required for pure random search.     

Discontinuity in decision-making when objectives conflict: a military command decision case study

In previous work, we considered the representation of human decision-making processes in closed-form simulation models of conflict. An important element of this representation is the rapid planning process that embodies the processing of information for situation assessment to support a course of action decision (eg in a military headquarters). The application of this work is in support of operational analysis models for defence procurement and balance of investment. This paper describes the application of non-linear multi-attribute utility theory in conflict scenarios in order to extend the representation of the rapid planning process to account for a wider set of subjective attributes of the decision-maker. The results show, through examination of experimental data, that decision-making can be modelled through a particular class of utility functions. These utilities embody a geometry which allows us to classify the types of decision being made when there are conflicting objectives and when decision-makers adopt very different and subjective appraisals of constraints and beliefs in outcome. The experimental results help to demonstrate that the subjective nature of the situation assessment, and the personality, training, experience and history of the decision-maker are central to the functional representations. This paper presents a way to capture this deeper representation of human decision-making in a way that is potentially useful for quantitative modelling using the rapid planning process as a basis.     

Towards a fully optimised organic LED device: Analysis of surface synthesis using coupling reactions by ToF-SIMS

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and polarisation-modulation reflection-absorption infrared spectroscopy (PM-RAIRS) have been used to monitor the surface synthesis of self-assembled aromatic π-conjugated molecular wires on gold substrates as a step towards a novel structure for organic electroluminescent devices (OLEDs). The wires have been synthesised using a series of Schiff's base coupling reactions in solution on a self-assembled monolayer of an aromatic thiolate anchor. ToF-SIMS and PM-RAIRS measurements have demonstrated that: (i) the anchor molecules self-assemble at the gold surface, (ii) the anchor molecules selectively react through imino coupling reactions with additional wire units with high efficiency and (iii) the wire-like structure is predominantly orientated normal to the surface.     

Synthetic DNA and Biology (Nobel Lecture)

Most of the significant work has been summarized in a number of reviews and articles. In these there was, of necessity, a good deal of simplification and omission of detail…. With the passage of time, even I find myself accepting such simplified accounts. F Sanger^[1]     

Pure adaptive search in global optimization

Pure adaptive seach iteratively constructs a sequence of interior points uniformly distributed within the corresponding sequence of nested improving regions of the feasible space. That is, at any iteration, the next point in the sequence is uniformly distributed over the region of feasible space containing all points that are strictly superior in value to the previous points in the sequence. The complexity of this algorithm is measured by the expected number of iterations required to achieve a given accuracy of solution. We show that for global mathematical programs satisfying the Lipschitz condition, its complexity increases at mostlinearly in the dimension of the problem.This work was supported in part by NATO grant 0119/89.