Radiofrequency tagging

The resin-bound trienes 83 (Scheme 11) were prepared in a similar fashion to the solution-phase studies (Sect. 2.2.2) and underwent tandem RCM resin-cleavage to liberate four macrolactones 84a,b and 85a,b in a combined yield of 52%. Although, as expected, a large amount of initiator 3 was required to effect this transformation, the procedure constituted a novel and efficient route to the epothilones which paved the way for the generation of a library of epothilone analogs. The library synthesis was achieved using the recently developed SMAR-I9 microreactors (SMART=single or multiple addressable radiofrequency tag) [25] (Scheme 12). 

Each microreactor consists of a polymer-bound substrate and a radiofrequency encoded microchip enclosed within a small porous vessel. The radiofrequency tag allows the identity of the substrate contained within each microreactor to be established readily. Using this technology, the polymer-bound substrates 86 were individually elaborated, within separate microreactors, by sequential reactions with acids 87 and alcohols 88 in a similar way to the solution-phase processes [25c]. Each of the microreactors was then subjected to the tandem RCM resin-cleavage conditions employing initiator 3. The products from each microreactor were obtained as a mixture of four compounds (89-92). The library of analogs prepared by this technique was then screened for biological activity [25c]. 

Figure 6.4. The sort-reaction-combine-wash-resort cycle for I ibrary synthesis using radiofrequency tagging of individual SynPhase crowns.

SMART Microreactors Refer to Radiofrequency tag based chemistry and Products Produced by IRORI Quantum Microchemistry, San Diego, CA. 

An intermediate level of sophistication was achieved by semiautomated sorting of radiofrequency tagged containers (e.g., MicroKans,8 Lanterns11). A simple instrument that integrates the process of one-dimensional necklace encoding by creating a linear sequences of solid-phase particles is the Encore synthesizer. 

Recently two different groups [82, 83] reported the use of radiofrequency tags for the encoding of chemical libraries. While the materials used were different, the coding strategy was rather similar and it is depicted schematically in Figure 9.20. 

The reactors selected were 432 aminomethylated MicroTubes 7.63, which are polystyrene-grafted polypropylene tubes with a 50 xM loading capacity per reactor, that encapsulate a preencoded radiofrequency tag (Fig. 7.38). The tubes were reacted with the Fmoc-protected, acid-labile Knorr linker (step a), the residual amine functions... 

Nanokan Easy readout with radiofrequency tags Peptide library is relatively small ... 

Radiofrequency tags encapsulated in grafted functionalized polymers have recently been reported (53), as have laser optical-encoded ceramics with grafted polystyrene supports (54). These devices have the properties of really big beads that contain the identifying tag and thus combine the features of chemically encoded libraries with the advantages of mechanically encoded libraries. 

A very extensive diversification of l,5-benzodiazepin-2-ones with the help of the radiofrequency tagged IRORI system (Discovery Partners International, San Diego, USA) was reported by Herpin et al. [24]. Here, the strategy of template preformation in solution and subsequent derivatization on a soHd phase was pursued. 

Nearly all suppliers of specific equipment, such as IRORI Kans with radiofrequency tags or Bohdan Mini-Blocks, have excellent descriptions of their tools on-... 

As an alternative, tagging strategies have been developed, in which the active molecule can be identified by placing a tag on the same bead. These procedures are rather tedious and, with the exception of radiofrequency tagging of small polypropylene reactors, have not fulfilled expectations. 

SCHEME 1.3 Benzopyrans synthesized on solid support utilizing a novel selenium linker and IRORI radiofrequency tags, MacroKan technologies, and the NanoKan system. 

Moran, E.J. et al.. Radiofrequency tag encoded combinatorial library method for the discovery of tripeptide-substituted cinnamic acid inhibitors of the protein tyrosine phosphatase PTPIB, J. Am. Chem. Soc., 117, 10787, 1995. 

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