SynPhase™ crowns

BAL chemistry is compatible with a wide range of functionalized polymeric supports, including PS, PEG-PS, and Synphase crowns. 

A. M. Seller and S. S. Gerritz, Using one- and two-dimensional NMR techniques to characterize reaction products bound to Chiron SynPhase crowns, J. Comb. Chem., 2000, 2, 127-133. 

SOLID-PHASE ORGANIC SYNTHESIS ON RADIATION-GRAFTED POLYMER SURFACES APPLICATION OF SYNPHASE CROWNS TO MULTIPLE PARALLEL SYNTHESES... 

The advantages of SynPhase crowns over conventional solid-phase syntheses on resin beads are as follows ... 

SynPhase crowns may be used to perform large numbers of optimization reactions in parallel. This library of reaction conditions may be analyzed by assaying product purities after cleavage from the solid phase using high-throughput techniques such as HPLC and ESMS. Overall, this approach can greatly reduce the time required for this critical step of compound library development. 

A wide range of linker groups are currently used with SynPhase crowns. They accommodate formation of the following functional groups upon cleavage carboxylic acids, primary and secondary amides, sulfonamides, alcohols, phenols, amines, anilines, anilides, hydroxymates, aldehydes, ketones, and thiols. 

This section outlines useful strategies for preparing aldehydes and hy-droxamic acids that were developed on SynPhase crowns. 

Figure 6.3. Back (left to right) P-series SynPhase crown l-series SynPhase crown. Front (left to right) polypropylene stem with transponder encapsulated (TranStem) transponder O-series crown attached to TranStem.

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

A Review of Solid-Phase Organic Synthesis on SynPhase Lanterns and SynPhase Crowns... 

Mimotopes has been involved in the development, use, and commercialization of radiation-grafted polymer surfaces for multiple parallel synthesis since the late 1980s.10-12 Although other workers have reported the use of radiation-graft polymers in solid-phase synthesis,13,14 as far as we are aware, the graft polymer devices manufactured and sold by Mimotopes (SynPhase Crowns, SynPhase Lanterns) are the only current commercial products of this type. These products are presented in Fig. 1. The SynPhase Lanterns are the current design for small molecule synthesis. The initial... 

SynPhase Crown SynPhase Lantern Fig. 3. SynPhase Lantern and SynPhase Crown symbols used in this chapter. 

Benzodiazepines were the first class of heterocyclic compounds to be synthesized on the SynPhase surface. In 1994, Ellman and co-workers24 reported a 192 member library of structurally diverse 1,4-benzodiazepines. These compounds were prepared on Mimotopes pins that were grafted with polyacrylic acid, the surface originally used for antibody epitope elucidation.10 Ellman and co-workers25 subsequently synthesized a 1680-member 1,4-benzodiazepine library on SynPhase Crowns that were grafted with a methacrylic acid/dimethylacrylamide copolymer, one of the first SynPhase surfaces designed for solid-phase synthesis. The synthesis was performed on a preformed linker-template system in order to avoid low aminobenzophenone incorporation in this case the HMP acid-labile linker... 

The group of Schultz has synthesized a 406-member purine library on MD grafted SynPhase Crowns with varying substituents at the C2 and C6 positions.29 A common 2-chloropurine derivative was coupled onto... 

In a more recent paper, Schultz and co-workers32 extended the technology on SynPhase Crowns to synthesize more diverse 2,6,9-trisubstituted... 

SynPhase Crowns with a Rink amide linker were used by Linn et al.38 at Glaxo-Wellcome to synthesize a library of 1,3,5-trisubstituted pyridin-2-ones (Scheme 12). The solid bound amide 38 was treated with 3-amino-5-methoxycarbonyl-l/f-pyridin-2-one with CS2CO3 in DMF to afford pyridine-2-one 39. Coupling of diphenylacetic acid FIATU and DIEA in... 

Kurth and co-workers40 (Novartis) prepared a 990-member compound library of hydantoin and isoxazohne containing heterocycles on amine-derived SynPhase Crowns. As shown in Scheme 15, the synthesis was... 

Lambert and co-workers49 (University of Melbourne) synthesized a library of cyclic thioether peptides with a pendant 9-aminoacridine moiety as a DNA-binding agent 81. Diversity in the library was achieved by assembling every permutation of four amino acid residues within the cyclic peptide (Scheme 24). The linear peptides 80 were synthesized in parallel with standard Fmoc chemistry on SynPhase Crowns functionalized with a Rink linker. The acridine moiety was incorporated onto the C-terminal lysine side chain using 9-phenoxyacridine. Cysteine deprotection and peptide cy-clization also took place under the acidic conditions used for the cleavage of 80 from the solid support. The library of cyclic thioether peptides 81 was obtained in high yields and purity (11 of 12 members had purities >95%). 

Lambert and co-workers50 also synthesized a pair of cyclic octapeptides 82 and 83 and studied their propensity to form nanotubular aggregates (Fig. 5). A linear peptide was initially synthesized on SynPhase Crowns with a Rink amide handle by standard Fmoc chemistry. The first residue used was aspartic acid protected as the ct-allyl ester. The support-bound linear peptide was cyclized in a head-to-tail manner by deprotection of... 

Synthesis of the orthogonally diprotected homospermidine 91 and the monoprotected homospermidine 92 was performed on SynPhase Crowns with a carbonate handle. The optimization of the reactions was aided by rapid handling of Crowns and performing reactions in parallel. 

An alternative solution is to produce a solid-phase particle that yields micromolar amount of product. Mimotopes Pty. Ltd. has developed and commercialized the SynPhase Crown and later Lanterns, a rigid polypropylene mold with a grafted layer of polystyrene. The solid-phase synthesis takes place on the derivatized graft.11... 

An alternative method for tracking the chemical history is encoding by spatial address. The identity of each entity is defined by its spatial address. A one-dimensional directed split-and-pool procedure, referred to as necklace coding, has been developed for synthesis carried out on SynPhase Crowns and Lanterns.13 Individual supports are strung on a Teflon thread and the position of a particle on the thread (necklace) encoded the previous chemical history (Fig. 1). A similar concept was later reported by Furka and co-workers14,15 Two-and three-dimensional encoding of the directed split-and-pool synthesis platform has been patented by Selectide Corp.16... 

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