Adventures in Silicon-Organic Chemistry
Adventures in Silicon-Organic Chemistry
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DOI：
10.1021/ar00060a007
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发表时间：
1995-12
影响因子：
18.3
通讯作者：
H. Vorbrueggen
中科院分区：
文献类型：
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作者：
H. Vorbrueggen
1.氯化锡存在下的硅基-希尔伯特-约翰逊反应1966年加入先灵公司的药物研究实验室后，我开始了抗病毒化学疗法的研究计划，并因此对核苷的合成和修饰产生了兴趣。在当时可用的所有核苷合成方法中，由Birkofer 1· 2引入并由Nishimura 3· 4和Wittenburg 5· 6进一步发展的甲硅烷基-Hilbert-约翰逊方法似乎是最实用的一种。极性和相当不溶性的杂环嘧啶碱如尿嘧啶（Ia）、胸腺嘧啶（Ib）或β-乙酰基-胞嘧啶（Ic）通过用六甲基二硅氮烷（HMDS）和痕量的酸性催化剂如三甲基氯硅烷（TCS）进行甲硅烷基化转化为亲脂性、热相当稳定的碱性和挥发性双（甲硅烷基）化合物2（方案1）。由于三甲基甲硅烷基的迁移性，总是形成最稳定的O-三乙基甲硅烷基化芳族杂环2，其被水快速水解成起始碱1。甚至极性更大的嘌呤碱N，N-苯甲酰基腺嘌呤（3a）或N-乙酰基鸟嘌呤（3b）类似地产生稳定的亲脂性和挥发性甲硅烷基化合物4。
1. Silyl-Hilbert-Johnson Reaction in the Pres-ence of SnCL. On joining the pharmaceutical re-search laboratoriesof Schering AG in 1966, 1 started a research program in antiviral chemotherapy and became thus interested in the synthesis and modifica-tion of nucleosides. From all the methods of nucleo-side synthesis available at that time the silyl-Hilbert-Johnson method introduced by Birkofer1· 2 and further developed by Nishimura3· 4 and Wittenburg5· 6 seemed to be the most practical one. Polar and rather insoluble heterocyclic pyrimidine bases such as uracil (la), thymine (lb), or^-acetyl-cytosine (lc) are converted by silylation with hexa-methyldisilazane (HMDS) andtraces of acidic cata-lysts such as trimethylchlorosilane (TCS) into the lipophilic, thermally quite stable basic and volatile bis-(silyl) compounds 2 (Scheme 1). Due to the mobility of the trimethylsilyl groups the most stable O-trim-ethylsilylated aromatic heterocycles 2 are always formed, which are rapidly hydrolyzed by water to the starting bases 1. The even more polar purine bases A^-benzoyladenine (3a) or iW-acetylguanine (3b) af-ford analogously the stable lipophilic and volatile silyl compounds 4.