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Improved synthesis of trinucleotide phosphoramidites and generation of randomized oligonucleotide libraries.

Author information

1
Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland and Metkinen Chemistry, Kuopio, Finland.

Abstract

A new method to produce a set of 20 high quality trinucleotide phosphoramidites on a 5-10 g scale each was developed. The procedure starts with condensation reactions of P-components with N-acyl nucleosides, bearing the 3 '-hydroxyl function protected with 2-azidomethylbenzoyl, to give fully protected dinucleoside phosphates 13. Upon cleavage of dimethoxytrityl group from 13, dinucleoside phosphates 16 are initially transformed into trinucleoside diphosphates 19 and then the 2-azidomethylbenzoyl is selectively removed under neutral conditions to generate trinucleoside diphosphates 5 in excellent yield. Subsequent 3 '-phosphitylation affords target trinucleotide phosphoramidites 7. When mutagenic oligonucleotides are synthesized employing mixtures of building blocks 7 as well as following the new synthetic protocol, representative oligonucleotide libraries are generated in good yields.

PMID:
17578745
DOI:
10.1080/15257770701426260
[Indexed for MEDLINE]

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