Achieving maximum ROI from corporate databases: exploiting your databases with integrated querying for better decision-making

In order to increase the rate of drug discovery, pharmaceutical and biotechnology companies spend billions of dollars a year assembling research databases. Current trends still indicate a falling rate in the discovery of New Molecular Entities (NMEs). It is widely accepted that the data need to be integrated in order for it to add value. The degree to which this must be achieved is often misunderstood. The true goal of data integration must be to provide accessible knowledge. If knowledge cannot be gained from these data, then it will invalidate the business case for gathering it. Current data integration solutions focus on the initial task of integrating the actual data and to some extent, also address the need to allow users to access integrated information. Typically the search tools that are provided are either restrictive forms or free text based. While useful, neither of these solutions is suitable for providing full coverage of large numbers of integrated structured data sources. One solution to this accessibility problem is to present the integrated data in a collated manner that allows users to browse and explore it and also perform complex ad-hoc searches on it within a scientific context and without the need for advanced Information Technology (IT) skills. Additionally, the solution should be maintainable by 'in-house' administrators rather than requiring expensive consultancy. This paper examines the background to this problem, investigates the requirements for effective exploitation of corporate data and presents a novel effective solution.     

On the understanding of the results of NMR spectra prediction using spectroscopic databases

Using spectroscopic databases for spectra prediction has become popular. Although most of the shifts predicted may be used as displayed there are some practical limitations. Some of these are suitable to distort results that are used without further consideration. Reasons and consequences of the most common aspects in this respect are discussed throughout this paper. Most critical effects are expected to rise from the presence of unrecognised data gaps and violation of the conventions used for structure coding for the database used. Any high standard deviation of predicted shift values or wide range of shift distributions indicate the need of further investigation. Looking up the reference data for the focus atom concerned can easily clarify most situations.     

Convenient method to access new 4,4-dialkoxy- and 4,4-diaryloxy-diaza-s-indacene dyes: Synthesis and spectroscopic evaluation

A straightforward method for the synthesis of original 4,4-dialkoxy- or 4,4-diaryloxy-diaza-s-indacenes (BODIPY) derivatives obtained by treatment of BODIPY 1 with various alcohols in the presence of AlCl3 is described. The novel compounds are characterized by spectroscopic properties similar to those of the parent BODIPY 1, absorption and emission spectra with similar band shapes, high molar absorption coefficients (epsilon lambda max approximately 80,000 M(-1) cm(-1)), and for most of them high fluorescence quantum yields (Phi exp from 0.52 to 0.71). Among all of the new compounds synthesized, the dye 2 h exhibits higher fluorescence quantum yield (0.71) and lifetime (4.09 ns) than compound 1 and a good chemical stability toward conditions compatible with biological cell-based assays.     

Development of an access route to the c31-c52 central core of amphidinol 3

[reaction: see text] An asymmetric synthesis of the heavily oxygenated inner sector of amphidinol 3 constituted of C31-C52 is described. The successful pathway highlights construction of the pair of identical tetrahydropyran subunits from a common intermediate.     

Easy access to phosphonothioates

A new and particularly mild method for the formation of phosphorus-sulfur bonds has been achieved through base-catalyzed addition of thiocyanate to the corresponding H-phosphine oxide, phosphinate, or phosphonate. This reaction procedure offers many advantages: the use as starting material of a stable and not oxygen-sensitive phosphorus(v) species, particularly mild and nonaqueous reaction conditions and workup (a pivotal point for these sensitive phosphonothioates), and, through optimized access to thiocyanates, a wider scope of substrates. This method has been applied to achieve the synthesis of substrate analogues for the study of antibody-catalyzed hydrolysis of acetylcholinesterase inhibitor PhX (11).     

Rietveld refinement and vibrational spectroscopic study of alunite from el Gnater, central Tunisia

The crystal structure of alunite (K_0.72,Na_0.28) Al₃(SO₄)₂(OH)₆ from El Gnater, central Tunisia, is refined by the Rietveld method. Raman and infrared data of this mineral are also given in order to provide some further information about the mineralogy and chemistry of this alunite. The crystal system is trigonal, space group R $ \bar 3 The crystal structure of alunite (K_0.72,Na_0.28) Al₃(SO₄)₂(OH)₆ from El Gnater, central Tunisia, is refined by the Rietveld method. Raman and infrared data of this mineral are also given in order to provide some further information about the mineralogy and chemistry of this alunite. The crystal system is trigonal, space group R m, with a = 6.9834(4) ? and c = 17.0899(11) ?. Final Rietveld refinement converges to R _p = 0.16, R _wp = 0.16, and R _Bragg = 0.07. In the alkalic site, the occupancy of potassium and sodium is refined to 72 and 28%, respectively. The Raman and infrared spectra are investigated in order to improve previous assignments of the observed frequencies, especially for tetrahedral and octahedral vibration and OH group, which are discussed on the basis of unit-cell group analysis and by comparison with previously observed wavenumbers of natrojarosite and synthetic alunite. The text was submitted by the authors in English.     

Improved Ritter reaction with CF3-containing oxirane for an access to central units of protease inhibitors

The influence of fluorinated alcohols on the BF₃·Et₂O-promoted Ritter type reaction has been investigated. Trifluoroethanol/BF₃·Et₂O system allowed access to the central unit of protease inhibitors by the ring opening of fluorinated epoxide 2 with various nitriles.     

Facile access to arsenic-containing triacylglycerides

The previously unknown arsenic-containing triacylglycerides (AsTAGs) 3-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,2-diyl dipalmitate 1 and 2-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,3-diyl dipalmitate 2 have been synthesized. They will serve as model compounds in the search for naturally occurring AsTAGs, recently proposed natural constituents of fish oils.     

Synthetic access to arsenic-containing phosphatidylcholines

We wish to disclose the first synthesis of 1-O-hexadecanoyl-2-O-((15-(dimethylarsinoyl)pentadecanoyl)oxy)-sn-glycero-3-phosphocholine, which belongs to the group of arsenic-containing phosphatidylcholines (AsPCs), recently discovered in herring caviar. The synthesized product will serve as a model compound to study biological and toxicological properties of arsenolipids in food.     

A facile access to indigodianiles

Bis‐imidoylchlorides derived from oxalic acid can easily be transformed into the corresponding bis‐imino benzotriazoles. The fact that benzotriazole is a well‐established leaving group has been exploited for an improved synthesis of indigodianiles. Employing metallic lithium, the benzotriazoles can be converted in a cascade reaction into indigo bis‐arylimines in yields up to 45%. Formation of the reduced form of dimeric isocyanides is suggested as a key step.     

Transition-metal-free access to 7-azaindoles

A novel method for transition-metal-free synthesis of 7-azaindoles is developed through a one-pot synthesis involving amination of pyridine N-oxides and intramolecular enamine formation. Remarkable features of the method include simple operation, mild reaction conditions, wide substrate scope, and easily accessible starting materials.     

Straightforward four-component access to spiroindolines

Spiroindolines could be synthesized via a very convenient one-pot procedure combining a Ugi coupling and a new copper-catalyzed oxidative process at a peptidyl position. Due to the nature of the first step, this method offers a straightforward access to complex alkaloids with four points of molecular diversity.     

Easy access to bismuth catecholates

The reaction of catechols with bismuth (III) acetate in acetic acid solution provides an easy access to the polymeric bismuth catecholate acetate ( 1 ), 4-tert ˙ butylcatecholate hydroxide ( 2 ), and 3,5-di-tert ˙ butylcatecholate hydroxide ( 3 ).     

Stereocontrolled access to optically-enriched oxabispidines

A range of chiral, optically-enriched bicyclic oxabispidines were prepared from (S)-(-)-2,3-epoxypropylphthalimide using an efficient sequence featuring a stereocontrolled intramolecular Mannich reaction as the key transformation.     

New access to azido-substituted alkylnitramines

A new versatile access to azido-substituted N-alkylnitramines is based on ring opening in N-nitrooxazolidines and N-nitroperhydro-1,3-oxazines with thionyl chloride followed by treatment with sodium azide. Representative N,N-bis(azidoalkyl)- and N-azidoalkyl-N-methoxymethyl- containing nitramines were synthesized and characterized.     

A stereocontrolled access to vicinal difluoroalkanes

An expedient method for the preparation of diastereomerically and, by extension, even enantiomerically pure vicinal difluoroalkanes is described. The two fluorine atoms are introduced in two consecutive steps : ring opening of an oxirane by addition of hydrogen fluoride and subsequent treatment of the resulting fluorohydrine with diethylaminosulfur trifluoride.