2-Butyl-4-iodoimidazole-5-carboxaldehyde: A Versatile Intermediate for the Synthesis of Highly Functionalized Imidazoles

The facile preparation of 2-butyl-4-iodoimidazole-5-carboxaldehyde 1 is described. The versatility of this intermediate in the synthesis of highly tunctionalized imidazoles is demonstrated with the synthesis of two potent and selective angiotensin II receptor antagonists.     

Conformational Transmission in DNA

Abstract

This poster presents our recent results on DNA dimers in which a stable trigonal bipyramidal pentacoordinated phosphorus (P^v) structure forms the internucleoside linkage. Conformational analysis of the systems 1-4 with 300 and 500 ¹H NMR has shown that the P^v structure results in a distorted conformation of the backbone structuE (1).     

SYNTHESIS AND CONFORMATIONAL STUDIES OF A NUMBER OF SATURATED BICYCLIC SIX-MEMBERED RING PHOSPHITES

Abstract

An ¹H NMR study of the conformation of the dioxaphosphorinane ring of a number of diastereoisomeric bicyclic saturated six-membered ring phosphites (3ab-10ab) has been performed. The dioxaphosphorinane ring of these phosphites is transannelated with a tetrahydrofuran, cyclopen-tane, tetrahydropyran or cyclohexane ring. The substituent on the phosphorus atom is a methoxy or phenoxy group. It is shown that the cis isomers 3a-10a prefer a chair conformation of the dioxaphosphorinane ring, independent of the substituent on the phosphorus atom and of the nature of the transannelated ring. In contrast, for the trans isomers 3b-10b a twist rather than a chair conformation of the dioxaphosphorinane ring is preferred. The fraction of the twist conformer in the trans isomers is mainly determined by the substituent on phosphorus. The size and composition of the transannelated ring are relatively unimportant in this respect. For both cis and trans isomers the preferred geometry is solvent-independent. The measured ^3JPOCH couplings of the cis isomers 3a-10a are used to formulate an expression for the dependence of such couplings upon dihedral angles in bicyclic phosphites.     

Performance monitoring of a mammalian cell based bioprocess using Raman spectroscopy

Being able to predict the final product yield at all stages in long-running, industrial, mammalian cell culture processes is vital for both operational efficiency, process consistency, and the implementation of quality by design (QbD) practices. Here we used Raman spectroscopy to monitor (in terms of glycoprotein yield prediction) a fed-batch fermentation from start to finish. Raman data were collected from 12 different time points in a Chinese hamster ovary (CHO) based manufacturing process and across 37 separate production runs. The samples comprised of clarified bioprocess broths extracted from the CHO cell based process with varying amounts of fresh and spent cell culture media. Competitive adaptive reweighted sampling (CoAdReS) and ant colony optimization (ACO) variable selection methods were used to enhance the predictive ability of the chemometric models by removing unnecessary spectral information. Using CoAdReS accurate prediction models (relative error of predictions between 2.1% and 3.3%) were built for the final glycoprotein yield at every stage of the bioprocess from small scale up to the final 5000 L bioreactor. This result reinforces our previous studies which indicate that media quality is one of the most significant factors determining the efficiency of industrial CHO-cell processes. This Raman based approach could thus be used to manage production in terms of selecting which small scale batches are progressed to large-scale manufacture, thus improving process efficiency significantly.     

Approaches to the Synthesis of Gibberellic Acid. Construction of the B,C and D Ring System

One of the most challenging aspects of the synthesis of gibberellic acid² and structurally related compounds such as steviol³ is the construction of the bicyclo[3.2.1]octane system with the unusual features of an exocyclic methylene group adjacent to a bridgehead tertiary hydroxyl group. In gibberellic acid this structural feature comprises the C, D ring system, which is fused to the five-membered B ring.     

Improving neutron activation analysis accuracy for the measurement of gold in the characterization of heterogeneous catalysts using a TRIGA reactor

To measure the gold content of a catalyst accurately, neutron activation analysis (NAA) is one of the methods of choice. NAA is preferred for such heterogeneous catalysts because: (1) it requires minimal sample preparation; (2) NAA provides consistent and accurate results; and (3) in most cases results are obtained much quicker than competing methods. NAA is also used as a referee for the other elemental techniques when results do not fall within expected statistical uncertainties. However, at very high gold concentrations, applying NAA to determine the gold in a heterogeneous catalyst is more challenging than a routine NAA procedure. On the one hand, the neutron absorption cross section for gold is very high, resulting in significant self-shielding related errors. On the other hand, gold exhibits low energy resonance neutron absorptions. In this application the self-shielding minimization effort was handled more rigorously than the classic suppression of neutron flux within a specimen. This non-routine approach was used because: (1) for most applications, high accuracy, <3 % relative, is desired, (2) the low energy resonances of gold make its neutron reaction rate complex and (3) the TRIGA reactor flux profile used in this study contains both thermal and significant epithermal neutron fluxes. Accuracy and precision, using this new approach, are expected to improve from 15 % to better than 3 % relative uncertainty. This has been accomplished through a rigorous assessment of the observed effects of low energy resonance on the neutron flux spectral shape within the sample and designing an experiment to minimize the effects.     

Input,flux, and persistence of six select pesticides in San Francisco Bay

Temporal patterns of pesticide inputs to San Francisco Bay were identified and correlated with timing of application and transport mechanism. Fluxes were calculated from measured concentrations and estimated flow. Persistence of the pesticides under typical riverine or estuarine conditions were estimated from laboratory experiments. Simazine was detected most frequently and had the highest flux into the Bay, which could be explained by its continuous use and long half-life. In comparison, diazinon was detected at lower concentrations and had a lower flux which corresponded to its lower use and shorter half-life. The order-of-magnitude lower fluxes of carbofuran and methidathion corresponded to their lower use and expected hydrolysis. Molinate was detected at the highest concentration but its flux was lower than expected, considering its very high use and persistence in the laboratory experiments. Additional loss of molinate is likely to occur from volatilization and photodegradation on the rice fields. Although thiobencarb had the second highest use, it had the lowest flux of the six pesticides, which can be attributed to its loss via hydrolysis, photodegradation, volatilization, and sorption to sediments. Fluxes into San Francisco Bay were equal to or greater than those reported for other estuaries, except for the Gulf of Mexico.