Synthesis of 2′, 3′-dideoxynucleosides for automated DNA synthesis and pyrophosphorolysis activated polymerization

摘要

Methods for preparation of 2′,3′-dideoxynucleotides support structures, such as 2′,3′-dideoxyguanosine, 2′,3′-dideoxyadenosine, and 3′-deoxythymidine support structures are disclosed. Various methods of using such structures are also provided, such as their use for automated DNA synthesis and pyrophosphorolysis activated polymerization.

主权项

1. A method for preparing a 2′,3′-dideoxyguanosine support structure, the method comprising:
(a) reacting 2′,3′-dideoxyguanosine with N,N-dimethylformamide dimethylacetal, to obtain a first intermediate; (b) reacting the first intermediate with 4,4-dimethoxytriphenylmethyl chloride to obtain a second intermediate comprising a dimethylformamide protecting group; (c) cleaving the dimethylformamide protecting group off the second intermediate to obtain a third intermediate; (d) reacting the third intermediate with adipic anhydride to obtain a 2′,3′ dideoxy guanosine derivative; and (e) coupling the 2′,3′ dideoxy guanosine derivative to a solid support,thereby obtaining the 2′,3′-dideoxyguanosine support structure.