Page 190 - 《精细化工》2023年第8期

第 40 卷第 8 期 精 细 化 工 Vol.40, No.8
20 23 年 8 月 FINE CHEMICALS Aug. 2023

食品与饲料用化学品
1,2-二硬脂酰基-sn-甘油-3-磷脂酰丝氨酸的全合成

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黄文静 ，符姜燕 ，谭新佳 ，扈圆舒 ，胡 峰 ，晏日安
（1. 暨南大学 理工学院，广东 广州 510632；2. 广东厨邦食品有限公司，广东 阳江 529800）
摘要：(S)-2-[(苄氧羰基)氨基]-3-羟基丙酸苄酯（Ⅰ）经亚磷酸二苯酯处理得到了(S)-2-[(苄氧羰基)氨基]-2-(苄氧
羰基)乙基膦酸酯（Ⅱ）；化合物Ⅱ经新戊酰氯介导活化后，与(S)-(+)-2,2-二甲基-1,3-二氧戊环-4-甲醇（Ⅲ）缩合，
并由碘氧化得到新化合物(R)-2,3-异亚丙基-sn-甘油基{(S)-2-[(苄氧羰基)氨基]-2-(苄氧羰基)-1-氧乙基}膦酸酯
（Ⅳ）；然后，化合物Ⅳ在三氟乙酸的作用下脱除异丙叉基得到(R)-2,3-二羟基丙基-sn-甘油基{(S)-2-[(苄氧羰基)
氨基]-2-(苄氧羰基)-1-氧乙基}膦酸酯（Ⅴ）；在 1-乙基-(3-二甲氨基丙基)碳酰二亚胺盐酸盐（EDCI）的作用下，
中间体Ⅴ与硬脂酸进一步乙酰化，以 85.8%的产率得到了(R)-2,3-双(硬脂酰基)丙酰基{(S)-2-[(苄氧羰基)氨
基]-2-(苄氧羰基)-1-氧乙基}膦酸酯（Ⅵ）；中间体Ⅵ经氢解得到了 1,2-二硬脂酰基-sn-甘油-3-磷脂酰丝氨酸（Ⅶ）。
对主要合成步骤的反应条件进行了优化，并进行了验证和放大实验。产物Ⅶ共经历 5 步反应，总产率为 57.1%。
采用 FTIR、HRMS 和 NMR 对产物Ⅶ的结构进行了确证。
关键词：磷脂酰丝氨酸；硬脂酸；H-膦酸酯；合成工艺；食品化学品
中图分类号：TQ645.96 文献标识码：A 文章编号：1003-5214 (2023) 08-1804-08

Total synthesis of 1,2-distearoyl-sn-glycero-3-phosphatidylserine

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HUANG Wenjing , FU Jiangyan , TAN Xinjia , HU Yuanshu , HU Feng , YAN Rian
（1. College of Science and Engineering, Jinan University, Guangzhou 510632, Guangdong, China; 2. Guangdong
Chubang Food Company Limited, Yangjiang 529800, Guangdong, China）
Abstract: (S)-2-[(benzyloxycarbonyl)amino]-2-(benzyloxycarbonyl)ethide phosphonate (Ⅱ) was firstly
synthesized from (S)-benzyloxy-2-[(benzyloxycarbonyl)amino]-3-hydroxypropanoate (Ⅰ) and diphenyl
phosphite, activated by pivaloyl chloride, and further reacted with (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-
methanol (Ⅲ) to produce new compound (R)-2,3-isopropylidene-sn-glyceryl{(S)-2-[(benzyloxycarbonyl)amino]-
2-(benzyloxycarbonyl)-1-oxyethyl}phosphonate (Ⅳ) following iodine mediated oxidation. Subsequently, was removed
to obtain (R)-2,3-dihydroxypropoxy-sn-glyceryl{(S)-2-[(benzyloxycarbonyl)amino]-2-(benzyloxycarbonyl)-
1-oxyethyl}phosphonate (Ⅴ). Next, intermediate Ⅴ, which as obtained from removal of the isopropylidene in
compound Ⅳ in the presence of trifluoroacetic acid, was acetylated with stearic acid in the presence of
1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI) to produce (R)-2,3-bis(stearoyloxy)
popyl{(S)-2-[(benzyloxycarbonyl)amino]-2-(benzyloxycarbonyl)-1-oxyethyl}phosphonate (Ⅵ) with a yield
of 85.8%. Finally, 1,2-distearoyl-sn-glycero-3-phosphatidylserine (Ⅶ) was obtained from hydrogenolysis of
intermediate Ⅵ. The reaction conditions for the main synthesis steps were optimized, while validation and
scale-up experiments were performed. Compound Ⅶ with a total yield of 57.1% could be synthesized by
only 5 steps, and its structure was confirmed by FTIR, HRMS and NMR.
Key words: phosphatidylserine; stearic acid; H-phosphonates; synthesis process; food chemicals

收稿日期：2023-02-06; 定用日期：2023-05-05; DOI: 10.13550/j.jxhg.20230071
基金项目：阳西县级科技项目（202101）
作者简介： 黄文静（1998—），女，硕士生，E-mail：13787677367@163.com。联系人：晏日安（1962—），男，教授，E-mail：yanrian813@
163.com。