An interesting protocol for stereoselective synthesis of (−)-cytoxazone and its unnatural stereoisomer (+)-5-epi-cytoxazone from d-4-hydroxyphenylglycine in overall yields of 10% and 16%, respectively, is described. The stereoselective addition of cyanide to an N-Boc protected aminoaldehyde (tert-butyl ((R)-1-(4-methoxyphenyl)-2-oxoethyl)carbamate) (5) constitutes the key step in this approach, producing a mixture of cyanohydrins 6a and b (1,2-anti and 1,2-syn tert-butyl (2-cyano-2-hydroxy-1-(4-methoxyphenyl)ethyl)carbamate) in 89% yield, with reasonable stereoselectivity (1.0:1.8) in favor of the anti-Felkin product (1,2-syn). A one-pot sequence of three successive steps from this mixture produced the oxazolidinone isomers 9a and b ((4R,5R)- and (4R,5S)-4-(4-methoxyphenyl)-2-oxooxazolidine-5-carboxylate). Chromatographic column separation and reduction of the ester function of both precursors led to (−)-cytoxazone and (+)-5-epi-cytoxazone.

中文翻译：

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(-)-cytoxazone 及其非天然同源物 (+)-5-epi-cytoxazone 的立体选择性合成

描述了从d -4-羟基苯基甘氨酸以 10% 和 16% 的总产率立体选择性合成 (-)-cytoxazone 及其非天然立体异构体 (+)-5- epi -cytoxazone 的有趣方案。氰化物立体选择性加成到N- Boc 保护的氨基醛（叔丁基（（R）-1-（4-甲氧基苯基）-2-氧乙基）氨基甲酸酯）（5）构成了该方法的关键步骤，产生了混合物氰醇6a和b（1,2-反和 1,2-合成-丁基（2-氰基-2-羟基-1-（4-甲氧基苯基）乙基）氨基甲酸酯），产率为 89%，具有合理的立体选择性（1.0:1.8），有利于抗Felkin 产物（1,2- syn） . 由该混合物的三个连续步骤的一锅序列产生恶唑烷酮异构体9a和b ((4 R ,5 R )- 和 (4 R ,5 S )-4-(4-甲氧基苯基)-2-氧恶唑烷-5 -羧酸盐）。色谱柱分离和两种前体的酯功能降低导致 (-)-胞嘧啶和 (+)-5- epi-胞恶酮。