Indexed libraries

As in solid-phase synthesis programs, one of the most challenging problems with solution-phase synthesis is to separate products obtained in the reaction mixtures and identify the compound or compounds with biological potency or some other desirable property. An especially effective technique that has been developed to deal with this problem is called indexed libraries, also known as orthogonal libraries. In this process, each product compound is prepared twice. Analysis then permits identification of the positive part of the compound and the negative part of the compound with the greatest potency. Once these have been determined, it is possible to identify the specific compound most active in the mixture. 

In a similar approach, Pimmg and Chen [3] prepared an indexed library of 54 carbamates from a set of nine alcohols and nine isocyanates. The library was prepared as 15 sublibraries in which each of the alcohols and isocyanates was reacted with an equimolar mixture of the other reactants. The product mixtures were tested as inhibitors of acetylcholinesterase and their activities were used as indices to the rows and columns of a two-dimensional matrix reflecting the activities of individual products. An identical approach was used by the same authors in the preparation of a library of 72 tetrahydro-acridines by the condensation of 12 cyclohexanones with six cyanoanilines in 18 sublibraries [4]. 

Retention index library mass chromatography interpretation and search for specific chemical shifts and couplings... 

Retention index library MS, FTIR, and NMR spectral libraries and databases... 

Positional scanning, or 1-D indexing, was reported as a deconvolutive technique by Houghten and coworkers [35] and subsequently applied extensively to solid-phase peptide library synthesis. An example of solid-phase small organic molecule 2-D indexed library synthesis and deconvolution was reported by Berk et al. [36]. Description of this strategy, called spatially arrayed mixture (SpAM), and a comparison with classical positional scanning, are shown in Figure 8.9. 

Positional scanning was repeatedly used by Houghten and coworkers [38] in solid-phase peptide synthesis, but few examples of its application to small molecule libraries have been reported. Smith et al. [39] deconvoluted a solid-phase library of 1600 esters/amides, Andrus et al. [40] deconvoluted a solid-phase library of non-natural polyenes, Leone-Bay et al. [41] deconvoluted the activity of an indexed library in an in vivo assay, while Pirrung et al. reported both a solution phase 54-member carbamate library [42] and a solution-phase 72-member tetrahydroacridine library [43]. 

SPR is used to monitor the concentration of proteins at the surface of a solid support by measuring changes in refractive index. Libraries of functionalized fragments differing by virtue of the spacer length and composition as well as the linker functionality itself have been conjugated to solid support, followed by exposure to target proteins of interest. 

There are many books and other sources that discuss the retention index from theoretical and practical aspects. One comprehensive book is "The Sadtler Standard Gas Chromatography Retention Index Library" [15]. This series of book (from Volume 1 to Volvune 4) provides detailed data on the retention indices for more than 2,000 compoimds under varying isothermal and temperature programming GC conditions for the purpose of the general identification of unknown compoimds. 

The Sadtler Standards Gas Chromatography Retention Index Library, Sadtler and Sanyo, 1985. 

Figure 3.1. A comparison of (a) traditional chemistry with three approaches to combinatorial chemistry (b) array synthesis directly identifies an active compound (c) one-pot simultaneous synthesis necessitates deconvolution and (d) indexed library indirectly indicates active compounds.

For compounds prepared in mixtures, the identification of the active compound(s) from these mixtures is approached in various ways. Methods comprise identification by analytical means, iterative or noniterative strategies, as well as the generation of indexed libraries, or elucidation of the structure by the aid of so-called "tags" that encode for the single building blocks and the synthetic history. 

Anderson, K., 2008b. Dyeing Textiles with Supercritical Carbon Dioxide A Non-Aqueous Dyeing System. [TC]2, NC, USA. Available at http //www.techexchange.com/index library TE articles subcategories.php. 

The Sadtler Capillary GC Standard Retention Index Library, Sadtler, Philadelphia. Computer disk database, contains data on 2000 compounds on four columns. 

Sadder Standard Gas Chromatography Retention Index Library. Vnls. 1-4, Philadelphia Biu-Rad Laboratories, Sadtler Division, 1984-8S, For reviews of two-dimensional GC. see M. Adahehour. J. Beens. R, J. J. Vreuls, U. A. Th. Brinkman. Trends Anal. Chem. (TRAC). 2006.25, 438 2006,25. 540 2066,25, 726,... 

Retention time indices are available for many substances as data collections for a variety of stationary phases [14-15]. Gomputerized retention index libraries are available. Alternative RI systems have recently been reviewed by Gastello [16]. 

Of the more recent works one of the most important is A Guide to the Literature of Chemistry by E. J. Crane, A. M. Patterson and E. B. Marr (Wiley, 1957). Its chapters deal with books, periodicals, patents, government publications, trade literature, other sources, indexes, libraries, and procedure in literature searches. There are also several valuable appendixes. It is a most comprehensive guide which shows how to use each form of the literature, analyses the various kinds of sources of information, and tells the reader how to keep up to date. It is useful as a reference tool and as a textbook, showing the correct way to use libraries and indexes in carrying out literature searches. 

A more recent British publication is the British Technology Index (Library Association, 1962-). This indexes about 400 British technical journals monthly in an alphabetical sequence of subject headings, with an annual cumulation. 

GC method/retention index library Retention index library nist ri 346 757 Kovats RI values for 82,868 compounds... 

The Fiehn Library is a mass spectral and retention index library for comprehensive metabolic profiling. The library comprises over 1000 identified metabohtes that are currently screened by the Fiehn laboratory. The compound list is continually extended. The Fiehn mass spectral library is commercially available for GC-quadrupole mass spectrometers from Agilent Technologies, and for GC-TOF mass spectrometers from Leco Corporation, see http //fiehnlab.ucdavis.edu/Metabolite-Library-2007/... 

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