Synthesis of nucleotide analogues, EFdA, EdA and EdAP, and the effect of EdAP on hepatitis B virus replication

Kamata, Mai; Takeuchi, Toshifumi; Hayashi, Ei; Nishioka, Kazane; Oshima, Mizuki; Iwamoto, Masashi; Nishiuchi, Kota; Kamo, Shogo; Tomoshige, Shusuke; Watashi, Koichi; Kamisuki, Shinji; Ohrui, Hiroshi; Sugawara, Fumio; Kuramochi, Kouji

doi:10.6084/m9.figshare.9944795.v1

tbbb_a_1673696_sm2864.docx (4.9 MB)

Synthesis of nucleotide analogues, EFdA, EdA and EdAP, and the effect of EdAP on hepatitis B virus replication

journal contribution

posted on 2019-10-07, 13:05 authored by Mai Kamata, Toshifumi Takeuchi, Ei Hayashi, Kazane Nishioka, Mizuki Oshima, Masashi Iwamoto, Kota Nishiuchi, Shogo Kamo, Shusuke Tomoshige, Koichi Watashi, Shinji Kamisuki, Hiroshi Ohrui, Fumio Sugawara, Kouji Kuramochi

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) and 4′-ethynyl-2′-deoxyadenosine (EdA) are nucleoside analogues which inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. EdAP, a cyclosaligenyl (cycloSal) phosphate derivative of EdA, inhibits the replication of the influenza A virus. The common structural feature of these compounds is the ethynyl group at the 4′-position. In this study, these nucleoside analogues were prepared by a common synthetic strategy starting from the known 1,2-di-O-acetyl-D-ribofuranose. Biological evaluation of EdAP revealed that this compound reduced hepatitis B virus (HBV) replication dose-dependently without cytotoxicity against host cells tested in this study.

Synthesis of nucleotide analogues, EFdA, EdA and EdAP, and the effect of EdAP on hepatitis B virus replication.