嘌呤2',3'-二脱氧-2',3'-二氟-D-阿拉伯呋喃糖基核苷的合成及其抗病毒活性
Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides.
作者信息
Sivets Grigorii G, Kalinichenko Elena N, Mikhailopulo Igor A, Detorio Mervi A, McBrayer Tami R, Whitaker Tony, Schinazi Raymond F
机构信息
Institute of Bioorganic Chemistry, National Academy of Sciences, Minsk, Belarus.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):519-36. doi: 10.1080/15257770903053979.
9-(2',3'-Dideoxy-2',3'-difluoro-beta-D-arabinofuranosyl)adenine (20), 2-chloro-9-(2',3'-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)adenine (22), as well as their respective alpha-anomers 21 and 23, were synthesized by the nucleobase anion glycosylation of intermediate 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-alpha-D-arabinofuranosyl bromide (13) starting from methyl 5-O-benzyl-3-deoxy-3-fluoro-alpha-D-ribofuranoside (3) and methyl 5-O-benzoyl-alpha-D-xylofuranoside (10). These compounds were evaluated as potential inhibitors of HIV-1 and hepatitis C virus in human PBM and Huh-7 Replicon cells, respectively. The adenosine analog 20 demonstrated potent activity against HIV-1 in primary human lymphocytes with no apparent cytotoxicity. Conformation of pentofuranose ring of nucleoside 20 in solution was studied by PSEUROT calculations.
9-(2',3'-二脱氧-2',3'-二氟-β-D-阿拉伯呋喃糖基)腺嘌呤(20)、2-氯-9-(2',3'-二脱氧-2,3-二氟-β-D-阿拉伯呋喃糖基)腺嘌呤(22)以及它们各自的α-异构体21和23，是从5-O-苄基-3-脱氧-3-氟-α-D-呋喃核糖苷(3)和5-O-苯甲酰基-α-D-呋喃木糖苷(10)出发，通过中间体5-O-苯甲酰基-2,3-二脱氧-2,3-二氟-α-D-阿拉伯呋喃糖基溴(13)的核碱基阴离子糖基化反应合成的。这些化合物分别在人外周血单核细胞和Huh-7复制子细胞中作为潜在的HIV-1和丙型肝炎病毒抑制剂进行了评估。腺苷类似物20在原代人淋巴细胞中表现出对HIV-1的强效活性，且无明显细胞毒性。通过PSEUROT计算研究了核苷20在溶液中戊呋喃糖环的构象。
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