An efficient procedure has been developed for the synthesis of 3‘-fluoro-2‘,3‘-dideoxy-2‘,3‘-didehydro-4‘-ethynyl d- and l-furanosyl nucleosides (1 and 2) starting from 2,3-O-isopropylidene-d-glyceraldehyde. The key intermediate 1-O-benzoyl-3E-fluoro-3,4-unsaturated-5,6-di(tert-butyldimethylsilyloxy)-2-hexanone 8 was obtained in nine steps with the overall yield of 22%. The α,β-unsaturated ketone 8 was then treated with ethynylmagnesium bromide in a typical Grignard reaction procedure to afford the two intermediates 9 and 10, which after deprotection, oxidation, and acetylation gave the corresponding 4-ethynyl-substituted d- and l-sugar moieties 15 and 16, respectively. A series of d- and l-pyrimidine and purine nucleosides were prepared by the coupling of the sugar moieties with various silylprotected bases. The anomeric mixtures were obtained after condensation. After separation, the β-isomers were further deprotected to yield the target nucleosides. All the newly synthesized 4‘-substituted nucleosides were tested for their activities against HIV, among which the d-adenine derivative showed moderate anti-HIV activity (EC₅₀ = 25.1 μM) without significant cytotoxicity.

中文翻译：

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3'-氟-2'，3'-二脱氧-2'，3'-二氢-4'-乙炔基-d-和-1-呋喃糖基核苷的合成

已经开发了一种有效的方法，用于合成从2开始的3'-氟-2'，3'-二脱氧-2'，3'-二氢-4'-乙炔基d-和1-呋喃糖基核苷（1和2） ，3- ø异亚丙基d甘油醛。关键中间体1- ö苯甲酰基3 é氟-3,4-不饱和-5,6-二（叔-butyldimethylsilyloxy）-2-己酮8在九个步骤22％的总产率得到。然后在典型的格利雅德反应程序中，用乙炔基溴化镁处理α，β-不饱和酮8，得到两种中间体9和参见图10，其在脱保护，氧化和乙酰化后分别得到相应的4-乙炔基取代的d-和l-糖部分15和16。通过将糖部分与各种甲硅烷基保护的碱基偶联来制备一系列的d-和1- y-嘧啶和嘌呤核苷。缩合后得到异头混合物。分离后，将β-异构体进一步脱保护，得到目标核苷。测试了所有新合成的4'-取代核苷的抗HIV活性，其中d-腺嘌呤衍生物显示出中等的抗HIV活性（EC ₅₀ = 25.1μM），而没有明显的细胞毒性。