Total synthesis of zaragozic acid A (squalestatin S1). Synthesis of the relay compound
Total synthesis of zaragozic acid A (squalestatin S1). Synthesis of the relay compound
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DOI：
10.1021/jo961534e
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发表时间：
1996-12-27
影响因子：
3.6
通讯作者：
Heathcock, CH
中科院分区：
文献类型：
--
作者：
Caron, S;Stoermer, D;Heathcock, CH
化合物2由1，6-脱水吡喃己糖3制备。制备萨拉戈萨酸的1，7-二氧杂双环[3.2.1]辛烷核的关键过程是将有机金属试剂加入内酯6中，并用酸处理所得的1，2，3-三羟基-6-氧代乙缩醛。在该方法中使用4-溴-1-丁烯的铈（III）试剂以优异的产率提供7，而不伴随异构的1，6-脱水吡喃糖异构体。通过将8的烯醇化锂加成到甲醛中，得到9，并通过铈（III）介导的乙烯基锂加成到酮10中，来加入萨拉戈萨酸核的剩余两个羧基。后一种添加通过2D H-1 NMR实验显示，以提供在萨拉戈萨酸中发现的相对构型。用2-呋喃基锂和（5-甲基-2-呋喃基）-锂观察到类似的立体选择性加成，但所得加合物耐臭氧分解。2的合成完成了萨拉戈萨酸A（角鲨烯抑制素S1）的全合成（1）。
Compound 2 has been prepared from the 1,6-anhydropyranohexose 3. The key process for elaborating the 1,7-dioxabicyclo[3.2.1]octane core of the zaragozic acids is addition of an organometallic reagent to lactone 6 and treatment of the resulting 1,2,3-trihydroxy-6-oxo ethylene acetal with acid. Use of the cerium(III) reagent of 4-bromo-1-butene in this process provided 7 in excellent yield, unaccompanied by the isomeric 1,6-anhydropyranose isomer. The remaining two carboxy groups of the zaragozic acid core were added by addition of the lithium enolate of 8 to formaldehyde, to obtain 9, and cerium(III)-mediated addition of vinyllithium to ketone 10. The latter addition was shown by 2D H-1 NMR experiments to provide the relative configuration found in the zaragozic acids. Similar stereoselective additions were observed with 2-furyllithium and (5-methyl-2-furyl)-lithium, but the resulting adducts are resistant to ozonolysis. The synthesis of 2 completes a total synthesis of zaragozic acid A (squalestatin S1) (1).