(2S,3R,4S)-4-羟基异亮氨酸的不对称合成

Asymmetric Synthesis of (2S,3R,4S)-4-Hydroxyisoleucine

对甲氧基苯胺和乙醛酸乙酯依次经缩合、(S)-脯氨酸催化不对称Mannich反应和DBU不对称转化制得(2S,3R)-2-(4-甲氧基苯胺基)-3-甲基-4-氧代戊酸乙酯,再经CAN氧化脱保护、硼氢化钠还原和氢氧化锂水解得(2S,3R,4S)-4-羟基异亮氨酸,总收率约30%。

（2S,3R,4S）-4-Hydroxyisoleucine was synthesized from p-anisidine and ethyl glyoxalate with an overall yield of about 30% by condensation,（S）-proline-catalyzed asymmetric Mannich reaction,DBU-catalyzed asymmetric transformation to afford ethyl（2S,3R）-2-（4-methoxyphenylamino）-3-methyl-4-oxo-pentanoate,which was subjected to deprotection with ceric ammonium nitrate,reduction with NaBH4 and then hydrolysis with lithium hydroxide.