氨曲南主环的合成

The synthesis process of(2R,3S)-3-amino-2-methyl-4-oxo-1-azetidine sulfonic acid

以L-苏氨酸为初始原料,通过与甲醇进行酯化、与甲醇氨进行氨解、与氯甲酸苄酯进行氨基保护、与甲烷磺酰氯进行羟基甲磺酰化、与氯磺酸进行磺化,在碱性条件下环合,最后加氢脱保护等7步制备得到氨曲南主环。产品经核磁共振氢谱确证为目标产物,经HPLC检测纯度为98.2%,最终收率为54.6%(以L-苏氨酸计)。该合成工艺对设备要求不高,产品收率较高,易于工业化。

（2R,3S）-3-amino-2-methyl-4-oxo-1-azetidinesufonic acid is synthesized from L-threonine by esterification with methanol,ammonolysis of ester with CH3OH·NH3,protection of amino group with benzyl chloroformate,hydroxyl group by forming methanesulfonate with methane sulfonyl chloride,subsequently sulfonation with chlorosulfonic acid,cyclization under alkaline conditions and deprotection by hydrogenation.The product＇s chemical structure is confirmed by the H-NMR,the purity is 98.2% by HPLC detection and the overall yield is 54.6%.The synthesis process is less demanding on equipment,with higher total yield and more suitable for industrial production.