Concise Synthesis of the Anti-HIV Nucleoside EFdA
Concise Synthesis of the Anti-HIV Nucleoside EFdA
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DOI：
10.1271/bbb.120134
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发表时间：
2012-06-01
影响因子：
1.6
通讯作者：
Kuwahara, Shigefumi
中科院分区：
文献类型：
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作者：
Kageyama, Masayuki;Miyagi, Takuho;Kuwahara, Shigefumi
EFdA（4'-乙炔基-2-氟-2'-脱氧腺苷）是一种具有极强抗 HIV 活性的核苷逆转录酶抑制剂，由 (R)-甘油醛丙酮化物通过 12 步序列（涉及 α-烷氧基酮中间体的高度非对映选择性乙酰化）以 18% 的总收率简洁地合成。目前的合成方法在总产率和步骤数方面均优于之前的合成方法，之前的合成方法需要使用昂贵的起始材料进行 18 个步骤，并且总产率适中，为 2.5%。
EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a nucleoside reverse transcriptase inhibitor with extremely potent anti-HIV activity, was concisely synthesized from (R)-glyceraldehyde acetonide in an 18% overall yield by a 12-step sequence involving highly diastereoselective ethynylation of an alpha-alkoxy ketone intermediate. The present synthesis is superior, both in overall yield and in the number of steps, to the previous one which required 18 steps from an expensive starting material and resulted in a modest overall yield of 2.5%.