Solid-Phase Chemical Synthesis

Solution-phase oligosaccharide synthesis remains a slow process due to the need for iterative coupling and deprotection steps, with purification at each step along the way. To alleviate the need for repetitive purification events, solid-phase techniques have been developed.29,30 In solid-phase 

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The Reformatsky type of reaction with Zn(0) was performed in situ and led to somewhat unstable phosphonodiamidite (step a) which was coupled with 5 -DMTr-thymidine to give the intermediate mononucleoside phospho-noamidite (step b). The latter was further coupled with 3 -acetyl-thymidine (step c). Couplings described in steps b and c were activated by tetrazole. The intermediate dinucleoside phosphonite was oxidized with (lS)-(+)-(10-camphorsulphonyl)oxaziridine (step d) or sulfurized with Beaucage reagent. The phosphonoamidites mentioned above were used in the solid-phase chemical synthesis of phosphonoacetate and thiophosphonoacetate oligonucleotides. 

SPOT-synthesis is a facile and very flexible technique for the simultaneous parallel solid phase chemical synthesis. Series of compounds or compound... 

Pig. 12. The key steps in solid-phase chemical synthesis of DNA oligonucleotides. Each cycle consists of deprotection, coupling, capping, and oxidation steps and results in addition of one monomer onto the chain. 

Functional RNase Tl and mutant enzymes have also been obtained by total solid-phase chemical synthesis using the method of peptide segment condensations (53,54). 

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