A Simulation Approach to Cost Estimation in the Project Contracting Industry

In the project contracting industry (particularly in Third World and developing economies) one of the basic requirements for a company to produce a bid is an accurate estimate of the overall costs. A typical contract will involve several hundred quotes from different suppliers, and some of the figures will be inherently more risky than others.This paper looks at the effect of component price uncertainties on the overall cost of a project and develops a company-based simulation model to evaluate this. The basic data is derived from the individual expertise existing within the company, and this is statistically tested for consistency.The application of the simulation model is demonstrated, and it is also used to test some simple hypotheses about the existing modus operandi.     

An alkylsilyl-tethered, high-capacity solid support amenable to diversity-oriented synthesis for one-bead, one-stock solution chemical genetics

The synthesis and use of an alkylsilyl-tethered large (500-600 microm) polystyrene resin (1) are disclosed. An optimized Suzuki coupling of bromine-functionalized polystyrene and a silicon-functionalized alkylborane generates the silicon-substituted polystyrene 1 in large scale (>100 g). Resin loading is accomplished by activation as the silyl triflate, which can accommodate even sterically encumbered secondary alcohols and phenols. Treatment with HF/pyridine for linker cleavage is mild, efficient, and amenable to an automated, large-scale distribution system. This platform delivers, minimally, 50 nmol of each small molecule derived from a diversity-oriented, split-pool synthesis on a per bead basis for use in both forward and reverse chemical genetic assays. This technology satisfies many requirements of a one bead-one stock solution approach to chemical genetics.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 2: The use of esters in place of nitriles in standard DPP syntheses: Claisen-type acylations and furopyrrole intermediates

Ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates react with esters or acyl halides in the presence of a strong base to give 4-acyl derivatives, which exist predominantly as either E- or Z-enols. These are cyclised, either in solution at temperatures >200 °C or by microwave irradiation, to 3,6-disubstituted 1H-furo[3,4-c]pyrrolediones which, after N-protection, are convertible by reaction with primary amines into novel N,N′-disubstituted DPP derivatives.     

Controlling the outcome of an N-alkylation reaction by using N-oxide functional groups

Covalent modifiers of proteins are of importance in chemical proteomics, an emerging chemical technology used to assign protein function. In this study, high-field (1)H NMR techniques were used to analyze the reaction of the bioactive compound, 2,3-bis(bromomethyl)quinoxaline 1,4-dioxide, with amines (a model system for proteins containing nitrogen-based nucleophiles). Unexpectedly, the results show that a double nucleophilic substitution reaction involving 2 equiv of the amine is preferred to an intramolecular cyclization pathway. A direct comparison with the reaction carried out on a substrate lacking the N-oxide functional groups is also provided. X-ray crystal structures and computational studies are used to rationalize the observed differences in reactivity between the two systems.     

The microwave spectrum of bromine isocyanate,Brnco: Determination of rotational constants from quadrupole hyperfine structure

A novel method has been developed to evaluate accurate rotational constants from the microwave spectrum of the unstable molecule bromine isocyanate, using perturbations in nuclear quadrupole hyperfine structure. It has been applied to this prolate near-symmetric rotor to determine A_v and x_ab accurately, entirely from a-type R branches. The method has been made possible by the development of a special computer program for global léast-squares fitting to rotational and centrifugal distortion constants, along with all components of the Br nuclear quadrupole coupling tensor.     

Copper-Mediated Conversion of Complex Ethers to Esters: Enabling Biopolymer Depolymerisation under Mild Conditions

Selective processing of the β-O-4 unit in lignin is essential for the efficient depolymerisation of this biopolymer and therefore its successful integration into a biorefinery set-up. An approach is described in which this unit is modified to incorporate a carboxylic ester with the goal of enabling the use of mild depolymerisation conditions. Inspired by preliminary results using a Cu/TEMPO/O₂ system, a protocol was developed that gave the desired β-O-4-containing ester in high yield using certain dimeric model compounds. The optimised reaction conditions were then applied to an oligomeric lignin model system. Extensive 2D NMR analysis demonstrated that analogous chemistry could be achieved with the oligomeric substrate. Mild depolymerisation of the ester-containing oligomer delivered the expected aryl acid monomer.     

GC–FID as a primary method for establishing the purity of organic CRMs used for drugs in sport analysis

The National Analytical Reference Laboratory has synthesized and characterized 67 anabolic steroid marker metabolites, both unlabelled and deuterated, and 37 key glucuronide and sulfate steroid conjugate pure substance reference materials. Work is also in process to establish their full traceability so that they can be issued as certified and primary reference materials. Both identity and purity have been rigorously characterized using a number of techniques and a primary method for purity assessment developed, based gas chromatography combined with flame ionization detection for the parent steroids and HPLC with evaporative light scattering detection for non-volatile steroid conjugates. Strategies for establishing traceability and for estimating measurement uncertainty are reported. The strategies described are considered applicable to a wide range of organic pure substance reference materials.     

Isothiourea‐Catalysed Acylative Kinetic Resolution of Aryl–Alkenyl (sp2 vs. sp2) Substituted Secondary Alcohols

The non‐enzymatic acylative kinetic resolution of challenging aryl–alkenyl (sp² vs. sp²) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl–alkenyl substituted alcohols has been evaluated, with either electron‐rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (S=2–1980). The use of this protocol for the gram‐scale (2.5 g) kinetic resolution of a model aryl–vinyl (sp² vs. sp²) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 e.r.