Production process optimization of vitamin U and its thermal decomposition mechanism

doi:10.16085/j.issn.1000-6613.2023-1465

Abstract

Abstract:

In order to improve the yield of vitamin U and the purity of the final product and reduce the influence of the thermal decomposition products on the quality of the final product, the production process of vitamin U was optimized, and the thermal decomposition products were analyzed. Firstly, through the optimization of the three processes of vitamin U, including synthesis, decolorization, and concentration, the optimal production conditions of vitamin U were obtained as follows: The synthesis temperature was 54℃, the molar ratio of methionine to chloromethane was 1∶2.6, the amount of activated carbon was 2g/L, the decolorization time was 8min, the concentration temperature was controlled at 55℃, and the concentration time was 8h. Then the thermal decomposition products of vitamin U were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS). The main thermal decomposition products compositions and the possible degradation pathways of vitamin U in an aqueous solution were determined. Molecular simulation calculations corroborated that methanol could be used as a refining solvent to remove thermal decomposition products generated during vitamin U production. The average yield of the optimized process was increased by 8.5 percentage points, the average purity was increased by 0.8 percentage points, the average error was reduced by 5.1 percentage points and 0.33 percentage points, respectively, the average melting range was reduced by 0.8℃, the stability of the process was significantly improved, and the purity of the vitamin U was further improved on the basis of meeting the national standards. This work has reference significance for further optimization of the vitamin U production process.

Key words: vitamin U, production, decomposition products, molecular simulation, optimization

摘要：

为提高维生素U收率和最终产品纯度，并减少其热分解产物对最终产品质量的影响，对维生素U生产工艺优化和热分解产物分析。首先，通过对维生素U合成、脱色和浓缩等3个工序的优化，得到最佳维生素U生产条件为：合成温度为54℃，蛋氨酸与氯甲烷的投料摩尔比为1∶2.6，脱色时活性炭用量为2g/L，脱色时间为8min，浓缩温度控制在55℃，浓缩时间为8h。然后再对维生素U的热解产物进行高效液相色谱-质谱联用和气相色谱-质谱联用分析，确定了维生素U在水溶液中的主要热分解产物组成和可能的降解路径。最后，通过分子模拟计算印证甲醇可作为精制溶剂去除维生素U生产过程中产生的热解产物。优化后的工艺平均收率提高了8.5百分点，平均纯度提高了0.8百分点，平均误差分别减少了5.1百分点和0.33百分点，平均熔程减小了0.8℃，工艺稳定性显著提升，所得维生素U的纯度在满足国家标准的基础上进一步提高。该工作对进一步优化维生素U生产工艺具有借鉴意义。

关键词: 维生素U, 生产, 分解产物, 分子模拟, 优化

CLC Number:

TQ466.7

WANG Yucheng, GUO Xiong, LUAN Xinqi, ZHOU Jian, LI Xiang, XING Linguang, ZHOU Xueyun, LIU Ying, WANG Deyong, WU Xuejuan, PAN Qi, LIU Jianxin, ZHAO Zhenxia, ZHAO Zhongxing. Production process optimization of vitamin U and its thermal decomposition mechanism[J]. Chemical Industry and Engineering Progress, 2024, 43(9): 5157-5167.

王禹程, 郭雄, 栾昕奇, 周健, 李想, 幸林广, 周雪芸, 刘颖, 汪德勇, 吴雪娟, 潘琦, 刘建新, 赵祯霞, 赵钟兴. 维生素U生产工艺优化及其热分解机理[J]. 化工进展, 2024, 43(9): 5157-5167.

Figures/Tables 12

References 14

1	Yu-Ra SON, CHOI Eun-Hye, KIM Goon-Tae, et al. Bioefficacy of graviola leaf extracts in scavenging free radicals and upregulating antioxidant genes[J]. Food & Function, 2016, 7(2): 861-871.
2	安息香, 韩英. 维生素U卷土重来[J]. 医药世界, 2008(3): 82.
	AN Xixiang, HAN Ying. Vitamin U comeback[J]. Pharmaceutical World, 2008(3): 82.
3	周力, 刘琦, 佃雪辉, 等. 国产胃仙-U治疗消化性溃疡的近期疗效观察[J]. 贵阳医学院学报, 1996, 21(4): 316-317.
	ZHOU Li, LIU Qi, DIAN Xuehui, et al. Recent curative effect of domestic Weixian-U on peptic ulcer[J]. Journal of Guiyang Medical College, 1996, 21(4): 316-317.
4	田乃中, 张祖坪, 王文仲. 维生素U治疗胃及十二指肠溃疡的临床观察[J]. 天津医药杂志, 1962(7): 426-427.
	TIAN Naizhong, ZHANG Zuping, WANG Wenzhong. Clinical observation of vitamin U in the treatment of gastric and duodenal ulcer[J]. Tianjin Journal of Medicine, 1962(7): 426-427.
5	YAVIR Kateryna, KONIECZNA Karolina, Łukasz MARCINKOWSKI, et al. Ionic liquids in the microextraction techniques: The influence of ILs structure and properties[J]. TrAC Trends in Analytical Chemistry, 2020, 130: 115994.
6	LEUNG C P, LEUNG W K H. Determination of vitamin U and its degradation products by high-performance liquid chromatography with fluorescence detection[J]. Journal of Chromatography A, 1989, 479: 361-367.
7	STEKOL Jakob A. Preparation and determination of sulfur amino acids and related compounds[M]//Methods in Enzymology. Amsterdam: Elsevier, 1957: 578-600.
8	南京药学院. 维生素U加压合成法[J]. 医药工业, 1974(5): 8-10.
	Nanjing pharmaceutical institute. Pressure synthesis of vitamin U[J]. Pharmaceutical Industry, 1974(5): 8-10.
9	张俊萍. 一种医药级维生素U的制备方法: CN113336685A[P]. 2021-09-03.
	ZHANG Junping. A preparation method of pharmaceutical grade vitamin U: CN113336685A[P]. 2021-09-03.
10	冯颖, 赵孟杰, 崔倩, 等. 分子模拟技术在壳聚糖功能材料开发和应用中的研究进展[J]. 化工进展, 2022, 41(8): 4241-4253.
	FENG Ying, ZHAO Mengjie, CUI Qian, et al. Research progress of molecular simulation technology in the development and application of chitosan functional materials[J]. Chemical Industry and Engineering Progress, 2022, 41(8): 4241-4253.
11	郭鹏坤, 李攀, 常春, 等. 计算机模拟技术在生物质转化中的应用研究进展[J]. 化工进展, 2020, 39(8): 3027-3040.
	GUO Pengkun, LI Pan, CHANG Chun, et al. Advances in the application of computer simulation technology in biomass conversion[J]. Chemical Industry and Engineering Progress, 2020, 39(8): 3027-3040.
12	朱碧云, 秦博文, 马霞. 维生素U含量测定方法的研究进展[J]. 食品工业, 2020, 41(8): 227-230.
	ZHU Biyun, QIN Bowen, MA Xia. Research progress on determination methods of vitamin U content[J]. The Food Industry, 2020, 41(8): 227-230.
13	TANAKA Kazuko, NAKAMURA Keiji. Metabolism of S-methylmethionine: Ⅰ. Bacterial degradation of S-methylmethionine[J]. The Journal of Biochemistry, 1964, 56(2): 172-176.
14	TIAN Zeyu, MA Yu, ZHANG Chengpan. Alkylation reactions with alkylsulfonium salts[J]. Synthesis, 2022, 54(6): 1478-1502.

次数	优化前^①			优化后
次数	总收率/%	产品纯度/%	熔点/℃	总收率/%	产品纯度/%	熔点/℃
1	76.5	98.2	134.2~136.8	81.7	99.4	134.5~135.8
2	68.9	98.7	134.1~135.9	83.2	99.6	134.3~135.7
3	73.2	98.6	134.1~136.2	80.6	99.1	134.1~135.7
4	71.2	98.2	134.2~136.5	82.5	99.5	134.2~135.3
5	78.3	99.1	134.5~136.1	81.4	99.3	134.5~135.4
平均值	74.4±6.7	98.6±0.55	2.1（熔程）	82.9±1.6	99.4±0.22	1.3（熔程）

次数	优化前^①			优化后
次数	总收率/%	产品纯度/%	熔点/℃	总收率/%	产品纯度/%	熔点/℃
1	76.5	98.2	134.2~136.8	81.7	99.4	134.5~135.8
2	68.9	98.7	134.1~135.9	83.2	99.6	134.3~135.7
3	73.2	98.6	134.1~136.2	80.6	99.1	134.1~135.7
4	71.2	98.2	134.2~136.5	82.5	99.5	134.2~135.3
5	78.3	99.1	134.5~136.1	81.4	99.3	134.5~135.4
平均值	74.4±6.7	98.6±0.55	2.1（熔程）	82.9±1.6	99.4±0.22	1.3（熔程）

编号	模式	保留时间/min	加合离子	分子式	质荷比(m/z)	名称
U	Neg	0.85	[M-H-C₄H₁₀ClS+Cl₃]^-, [M-H C₄H₁₀ClS+Cl₄]^-	C₆H₁₄ClNO₂S	160.84 197.81	维生素U
P1 P2	Poz	0.85	[M+H-H₂O]⁺ [M+H]⁺	C₄H₉NO₃	102.06 120.07	高丝氨酸、苏氨酸
P1 P2	Neg	0.85 1.12 1.37 3.72	[M-C₂H₅-H]^- [M-H]^-	C₄H₉NO₃	89.02 118.05	高丝氨酸、苏氨酸
P3	Poz	1.47	[M+H]⁺	C₆H₁₃NO₂S	150.06	四氢噻吩-2-羧酸
P4	Poz	1.06	[M+H]⁺	C₅H₈O₂S	164.07	乙硫氨酸
P5	Poz	1.02	[M+H]⁺	C₅H₁₁NO₃S	166.05	蛋氨酸亚砜
P6	Neg	1.03	[M-H]^- [M+Cl]^-	C₅H₁₁NO₂S	148.04 184.02	蛋氨酸
P6	Poz	1.03	[M+H-C₂H₄O₃]⁺	C₅H₁₁NO₂S	74.06	蛋氨酸
P7	Poz	0.57	[M+H]⁺	C₅H₁₁NO₃	134.08	高丝氨酸甲酯
P8	Neg	1.12 1.37	[M-H]^-	C₉H₁₈N₂O₄S	249.09	苏氨酸-蛋氨酸
P9 P10	Neg	9.82	[M-H]^-	C₄H₈ClNO₂	134.90	4-Cl-2-氨基丁酸 3-Cl-2-氨基丁酸

编号	模式	保留时间/min	加合离子	分子式	质荷比(m/z)	名称
U	Neg	0.85	[M-H-C₄H₁₀ClS+Cl₃]^-, [M-H C₄H₁₀ClS+Cl₄]^-	C₆H₁₄ClNO₂S	160.84 197.81	维生素U
P1 P2	Poz	0.85	[M+H-H₂O]⁺ [M+H]⁺	C₄H₉NO₃	102.06 120.07	高丝氨酸、苏氨酸
P1 P2	Neg	0.85 1.12 1.37 3.72	[M-C₂H₅-H]^- [M-H]^-	C₄H₉NO₃	89.02 118.05	高丝氨酸、苏氨酸
P3	Poz	1.47	[M+H]⁺	C₆H₁₃NO₂S	150.06	四氢噻吩-2-羧酸
P4	Poz	1.06	[M+H]⁺	C₅H₈O₂S	164.07	乙硫氨酸
P5	Poz	1.02	[M+H]⁺	C₅H₁₁NO₃S	166.05	蛋氨酸亚砜
P6	Neg	1.03	[M-H]^- [M+Cl]^-	C₅H₁₁NO₂S	148.04 184.02	蛋氨酸
P6	Poz	1.03	[M+H-C₂H₄O₃]⁺	C₅H₁₁NO₂S	74.06	蛋氨酸
P7	Poz	0.57	[M+H]⁺	C₅H₁₁NO₃	134.08	高丝氨酸甲酯
P8	Neg	1.12 1.37	[M-H]^-	C₉H₁₈N₂O₄S	249.09	苏氨酸-蛋氨酸
P9 P10	Neg	9.82	[M-H]^-	C₄H₈ClNO₂	134.90	4-Cl-2-氨基丁酸 3-Cl-2-氨基丁酸

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