Synthetic Method for 2'-Amino-LNA Bearing Any of the Four Nucleobases via a Transglycosylation Reaction

Hiroaki Sawamoto; Yuuki Arai; Shuhei Yamakoshi; Satoshi Obika; Eiji Kawanishi

doi:10.1021/acs.orglett.8b00476

Synthetic Method for 2'-Amino-LNA Bearing Any of the Four Nucleobases via a Transglycosylation Reaction

Org Lett. 2018 Apr 6;20(7):1928-1931. doi: 10.1021/acs.orglett.8b00476. Epub 2018 Mar 12.

Authors

Hiroaki Sawamoto¹, Yuuki Arai², Shuhei Yamakoshi², Satoshi Obika³, Eiji Kawanishi²

Affiliations

¹ Research Unit/Innovative Medical Science, Sohyaku. Innovative Research Division , Mitsubishi Tanabe Pharma Corporation , 1000, Kamoshida-cho , Aoba-ku , Yokohama 227-0033 , Japan.
² Research Unit/Immunology & Inflammation, Sohyaku. Innovative Research Division , Mitsubishi Tanabe Pharma Corporation , 1000, Kamoshida-cho , Aoba-ku , Yokohama 227-0033 , Japan.
³ Graduate School of Pharmaceutical Sciences , Osaka University , 1-6 Yamadaoka , Suita , Osaka 565-0871 , Japan.

PMID: 29528240
DOI: 10.1021/acs.orglett.8b00476

Abstract

A transglycosylation reaction of 2'-amino-locked nucleic acid (LNA) from thymine (T) to other nucleobases adenine (A), guanine (G), and 5-methylcytosine (^mC) has been developed. This reaction proceeds in high yield and with high β-selectivity. The mild reaction conditions enable the coexistence of acid-labile protecting groups, including a 4,4'-dimethoxytrytyl (DMTr) group. 2'-Amino-LNAs bearing any nucleobase can now be easily synthesized.