Immobilized phosphoramidites

The readily prepared immobilized phosphoramidite could be used to efficiently synthesize oligodeoxyribonucleotides with modified thymidine residues. Whereas the effect of microwave irradiation on the deprotection by exposing the strand to tet-rakis-triphenylphosphine palladium(O) and diethylammonium bicarbonate was only small using dichloromethane as solvent, complete removal of the alloc group was achieved in N,N-dimethylformamide within 10 min at 80 °C (Scheme 7.30). After the reaction, the solid-supported product was washed with N,N-dimethylformamide and dichloromethane and dried, before being subjected to acylation. The coupling... 

Scheme 8.8 Immobilized phosphoramidites and their rhodium catalysts.

There is one more report on the synthesis of a library of phosphorus ligands on solid phase. Waldmann et al. prepared a library of phosphoramidites on beads (Fig. 36.5), but these were only applied in enantioselective C-C-bond formation. In fact, as two ligands need to be bound to the catalyst, the use of an immobilized monodentate ligands should most likely be avoided unless the proximity between the ligands is sufficiently close. In addition, crosslinking by the metal may have a negative impact on the permeability of the polymer for the substrate. 

A last possibility to obtain probes grafted onto beads is to directly synthesize the oligonucleotide probes onto glass beads via phosphoramidite reaction [18] (Fig. 6). The synthesis reaction sequence is composed of a coupling step between a protected nucleotide immobilized onto the bead and a tetra-zole activated and protected nucleotide (step C). This is followed by a capping and a de-blocking of the newly added nucleotide (step D and B). The cycle is then repeated until the desired sequence is obtained. 

Another instance for this linker class is the safety-catch linker by Lyttle, which was developed for the synthesis of nucleic acids on solid supports [62]. Starting from a resin carrying an Alloc-protected amino group fragment, conventional phosphoramidite chemistry was carried out to build up the desired immobilized nucleotide 57. Removal of the Alloc group via palladium catalysis under neutral conditions produces a polymer-bound intermediate 58 with a free amino functionality that can intramolecularly attack activated phosphonates and liberate the nucleotide 59 from the solid support (Scheme 16.14). More examples of safety-catch linkers that use the deprotection of an N-functionality as the activation step are listed in Table 16.1 (resins 61-65) [63-68]. 

The total synthesis of yeast tRNA has been reviewed and the total synthesis of a 77-nucleotide RNA sequence with methionine acceptor activity has also been described.l A solid-phase procedure for RNA synthesis has been described wherein the nucleoside is attached covalently to the silica support, through the 5 -OH group via an ester bond, and then treated with excess bisdiisopropylaminomethoxyphosphine and isopropylammonium tetrazolide to form the immobilized nucleoside 3 -phosphoramidite in situ. Treatment with a base-protected 2 -0-tetrahydropyranylnucleoside and tetrazole followed by oxidation... 

The phosphoramidites 37 and 38 have been prepared and were converted into phosphate esters by condensing with alcohols (including some carbohydrate derivatives) and oxidation. The synthesis of 6-0-palmitoyl-L-ascorbic acid was achieved in a non-aqueous medium with an immobilized lipase from Candida antartica, while use of palmitoyl chloride on L-ascorbic acid gave the same product. ... 

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