Encoding techniques

One way out of this dilemma is the so-called frequency encoding technique. It is often referred to as an approach that is very different from phase encoding, but... 

SPRITE is termed a pure phase encode technique because spatial encoding occurs through the application of variable amplitude magnetic field gradients (which yield spatially varying frequencies) applied for fixed periods of time. Variable frequency with a fixed evolution or encoding time yields a variable signal phase. 

We can use some elementary facts from recursive function theory to show that every partially computable or partial recursive function from nonnegative integers to nonnegative integers can be computed by a WHILE program of a particularly simple form. This result can be extended to functions computable over other domains by standard encoding techniques. 

Encoding techniques offer a powerful approach to rapidly dissecting out significant SAR information from an entire library. Among the methods available, the chemically... 

This review will cover encoding techniques for small organic molecule pool libraries, one of the most challenging and powerful techniques in combinatorial chemistry. A short introduction to illustrate briefly the advantages in library encoding and to compare the method with other structure determination techniques will be given, but for a more detailed introduction the reader should look elsewhere in this book [1]. 

Encoding Techniques for Pool Libraries of Small Organic Molecules... 

A comparison between different encoding techniques was never attempted using the same library and building it with two, or more, different codes. While many authors reported or claimed specific advantages for a particular technique, a detailed examination of the available methods reveals a fundamental complementarity, rather than redundancy, of the approaches, such that different libraries may better benefit from different encoding methods. Moreover, variables such as the availability of analytical or synthetic instrumentation, resources, which may be devoted to the assessment for a chosen encoding technique and the expertise of the chemist(s) involved in the project, will also strongly influence the final choice of a particular method. 

It is much easier, though, to compare encoding techniques with direct deconvolution (see elsewhere in this book) [1, 6], The two main classes of structure determination methods for pool libraries are significantly different, and clear distinctions about their usefulness can be made. The example of a 240-member (without considering diastereoisomers) mercaptoacyl pyrrolidine library, which was prepared as an encoded (secondary amine tags) [40] or as a nonencoded library and then submitted to iterative deconvolution [88], will be used for this comparison. The following considerations were either reported by MacLean et al. [40] or derived from the critical analysis of the results obtained. 

A real combinatorial testing of libraries of small compound catalysts is hampered by the problem that the information about which catalyst reacted with the substrate to which product needs to be transferred. In the case of the highly inventive encoding techniques for libraries (e. g. via radio frequencies or bar codes), this problem may be solved in the future [23]. 

Recently several reports highlighting the usefulness of IR and Raman spectroscopy for SP synthesis, especially during the SP chemical assessment, were published a multistep SP scheme was monitored successfully (167) and a new encoding technique (see Section 7.4) was reported (168). Both IR (169) and Raman (170) spectroscopy applications for SP synthesis were recently reviewed. 

A more complex combinatorial strategy based on a natural scaffold was reported by Nicolaou et al. (56) with the synthesis of an epothilone-based SP library L27 (Fig. 4.18). This biased library was prepared asa3x3x5 = 45-member collection, but the final reaction vessels could, theoretically contain 4 different isomeric desoxyepothi-lones (Fig. 4.18), thus leading to a total number of 45 x 4 = 180 components. The library was prepared using a radiofrequency encoding technique (42), and the final... 

In the synthesis of combinatorial libraries, there is a raft of tactical issues that need to be tackled. Will the library be made of mixtures or discrete compounds Prepared by solid-phase or solution-phase Screened in solution or attached to beads What level of purification and characterization is needed Will hits be identified by deconvolution, encoding techniques, or other means These are aU crucial operational aspects of combinatorial chemistry but it is equally important not to concentrate on them to the extent of missing the big picture. At the end of the day, neither a biological assay nor a medicinal chemist care how a compound was made. It is vital, though, that the tactical decisions do not prevent one from making the right compounds. Combinatorial synthesis is a means to an end, not an end in itself. 

Rinars encoding Encoding technique of a libraiy bo.sed on the presence or absence of tags on a bead. Thus, the sequence 01 loot would encrxle the presence of three of six possible mgs. The number of combinations that can be encoded is 2 . whcTc n Is tbc number of positions in the string. 

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