P-手性核苷酸间键的立体特异性形成研究：通过格氏试剂活化偶联合成全-Rp和全-Sp甲基膦酸酯五核苷酸d(MMTrAPMeTPMeTPMeCPMeTAc)

Studies on stereospecific formation of P-chiral internucleotide linkage: synthesis of all-Rp and all-Sp methylphosphonate pentanucleotide d(MMTrAPMeTPMeTPMeCPMeTAc) via Grignard activated coupling.

作者信息

Jaworska-Maslanka M M, Kacperczyk W, Korczynski D, Lesnikowski Z

机构信息

Polish Academy of Sciences, Department of Bioorganic Chemistry, Lodz, Poland.

出版信息

Antisense Nucleic Acid Drug Dev. 1997 Feb;7(1):23-30. doi: 10.1089/oli.1.1997.7.23.

DOI:10.1089/oli.1.1997.7.23

PMID:9055035

Abstract

Synthesis of stereoregular 3',5'-protected all-Rp and all-Sp methylphosphonate heterooligonucleotides d(MMTrAPMeTPMeTPMeCPMeTAc) (12) complementary to the fragment of HIV-1 splicing acceptor site was achieved via stereo-controlled formation of internucleotide linkage. The coupling was based on the transesterification of P-stereodefined monomer type of 5'-O-monomethoxytrityl-2'-O-deoxynucleoside 3'-O-[O-(4-nitrophenyl)methylphosphonate]. The nucleophile was a t-butylmagnesium chloride activated 5'-terminal hydroxyl function of the growing oligonucleotide chain. This and other P-homochiral oligomers will be used as building blocks for the synthesis of biologically significant, longer stereoregular oligonucleotides.

摘要

通过核苷酸间键合的立体控制形成，合成了与HIV-1剪接受体位点片段互补的立体规整的3'，5'-保护的全-Rp和全-Sp甲基膦酸酯杂合寡核苷酸d(MMTrAPMeTPMeTPMeCPMeTAc)(12)。偶联反应基于5'-O-单甲氧基三苯甲基-2'-O-脱氧核苷3'-O-[O-(4-硝基苯基)甲基膦酸酯]的P-立体定义单体类型的酯交换反应。亲核试剂是叔丁基氯化镁活化的正在生长的寡核苷酸链的5'-末端羟基官能团。这种以及其他P-同手性寡聚物将用作合成具有生物学意义的更长立体规整寡核苷酸的构建模块。