Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
J Org Chem. 2011 Dec 16;76(24):9962-74. doi: 10.1021/jo201565h. Epub 2011 Nov 15.
The first psico-oxetanocin analogue of the powerful antiviral natural product, oxetanocin A, has been readily synthesized from cis-2-butene-1,4-diol. Key 2-methyleneoxetane precursors were derived from β-lactones prepared by the carbonylation of epoxides. F(+)-mediated nucleobase incorporation provided the corresponding nucleosides in good yield but with low diastereoselectivity. Surprisingly, attempted exploitation of anchimeric assistance to increase the selectivity was not fruitful. A range of 2-methyleneoxetane and related 2-methylenetetrahydrofuran substrates was prepared to explore the basis for this. With one exception, these substrates also showed little stereoselectivity in nucleobase incorporation. Computational studies were undertaken to examine if neighboring group participation involving fused [4.2.0] or [4.3.0] intermediates is favorable.
已从顺式-2-丁烯-1,4-二醇中轻易合成出具有强大抗病毒天然产物奥昔他宁 A 的首个精神氧杂环丁烷类似物。关键的 2-亚甲氧基氧杂环丁烷前体是由环氧化物羰基化制备的β-内酰胺衍生而来的。F(+)-介导的碱基掺入提供了相应的核苷，收率良好，但非对映选择性低。令人惊讶的是，尝试利用亲核体辅助来提高选择性并没有成功。合成了一系列 2-亚甲氧基氧杂环丁烷和相关的 2-亚甲基四氢呋喃底物，以探究其原因。除一个例外，这些底物在碱基掺入中也几乎没有立体选择性。进行了计算研究，以检查涉及稠合[4.2.0]或[4.3.0]中间体的邻基参与是否有利。
