阿卡波糖的核磁共振数据解析

doi:10.11938/cjmr20243125

摘要/Abstract

摘要：

阿卡波糖是一种α-葡萄糖苷酶抑制剂，凭借其独特的作用机制，目前已被广泛应用于II型糖尿病的治疗中. 本文利用DEPT-135、¹H-¹H COSY、¹H-¹³C HSQC和¹H-¹³C HMBC等核磁共振（NMR）技术，以DMSO-d₆为溶剂，对阿卡波糖的¹H NMR、¹³C NMR信号进行了全归属，获得了在重水溶剂中无法获得的羟基¹H NMR信号，补充了C环α、β双信号氢谱和碳谱数据，确证了其分子结构，为阿卡波糖药品安全及质量控制提供了可靠的数据基础.

关键词: 液体核磁共振, 结构归属, 二维核磁共振, 阿卡波糖

Abstract:

Acarbose, an α-glucosidase inhibitor, has been widely used in the treatment of type-II diabetes due to its unique mechanism of action. In this study, comprehensive and accurate ¹H and ¹³C NMR data of acarbose in DMSO-d₆, including ¹H NMR data of all hydroxyl groups of acarbose as well as ¹H and ¹³C NMR data of the dual signal of C-ring α and β, were reported for the first time. The assignment of ¹H and ¹³C NMR data was conducted using DEPT-135, ¹H-¹H COSY, ¹H-¹³C HSQC, and¹H-¹³C HMBC techniques. The molecular structure of acarbose was confirmed, providing a reliable data basis for the safety and quality control of acarbose drugs.

Key words: liquid-state NMR, structural assignment, 2D NMR, acarbose

中图分类号:

O656.4

李玉江, 赵伟, 陶乐, 路博华, 郑果, 张海艳, 郭晓河, 赵天增. 阿卡波糖的核磁共振数据解析[J]. 波谱学杂志, 2025, 42(2): 184-194.

LI Yujiang, ZHAO Wei, TAO Le, LU Bohua, ZHENG Guo, ZHANG Haiyan, GUO Xiaohe, ZHAO Tianzeng. NMR Data Analysis of Acarbose[J]. Chinese Journal of Magnetic Resonance, 2025, 42(2): 184-194.

图/表 8

图1

图2

图3

图4

图5

图6

表1

阿卡波糖的1H NMR数据（DMSO-d6，400 MHz）

原子编号		δ_H	J/Hz	¹H-¹H COSY	文献[11][δ_H (J/Hz), D₂O]
A	1	3.28	m	H-2, NH, H-7	A	3.50(4.5)
	2	3.38	m	H-1, H-3, OH-2		3.62
	OH-2	5.07	d(6.4)	H-2
	3	3.58	m	H-2, H-4, OH-3		3.72
	OH-3	4.68	d(4.0)	H-3
	4	3.66	m	H-3, OH-4		4.00(7.0)
	OH-4	4.56	d(6.8)	H-4
	6	3.94	m	OH-6		4.07(13.5),4.18(13.5)
	OH-6	4.60	t(5.2, 5.2)	H-6
	7	5.59	d(3.6)	H-1		5.86(4.5)
B	1'	4.92	d(3.2)	H-2'	B	5.25(3.0)
	2'	3.28	m	H-1', OH-2'		3.57
	OH-2'	5.45	d(6.0)	H-2'
	3'	3.28	m	H-4', OH-3'		3.56
	OH-3'	5.51	d(6.4)	H-3'
	4'	2.13	t(9.2, 9.2)	H-3', H-5'		2.43(9.0,9.5)
	NH	5.48	d(2.8)	H-1
	5'	3.58	m	H-6'		3.71
	6'	1.16	d(6.4)	H-5'		1.30
Cα	1''	5.00	d(5.2)	H-2''	C	5.34
	2''	3.28	m	H-1'', OH-2''		3.59
	OH-2''	5.52^*	d(8.0)	H-2''
	3''	3.28	m	OH-3''		3,90
	OH-3''	5.01^**	d(6.8)	H-3''
	4''	3.28	m			3.60
	5''	3.28	m	H-6''α, H-6''β		3.79
	6''α	3.58	m	H-6''β, OH-6''		3.74
	6''β	3.66	m	H-6''α, OH-6''		3.88
	OH-6''	4.57	t(6.4, 6.4)	H-6''α, H-6''β
Cβ	1'''	5.00	d(5.2)	H-2'''
	2'''	3.28	m	H-3''', H-1''', OH-2'''
	OH-2'''	5.53^*	d(6.0)	H-2'''
	3'''	3.58	m	H-2''', 4'''
	OH-3'''	4.58^**	d(6.4)	H-3'''
	4'''	3.28	m	H-3'''
	5'''	3.28	m	H-6'''α, H-6'''β
	6'''α	3.58	m	H-5''', H-6'''β, OH-6'''
	6'''β	3.66	m	H-5''', H-6'''α, OH-6'''
	OH-6'''	4.57	t(6.4, 6.4)	H-6'''α, H-6'''β
Dα	1''''	4.91	t(4.4, 4.4)	H-2'''', OH-1''''	Dα	5.19(4.0)
	OH-1''''	6.37	d(4.4)	H-1''''
	2''''	3.19	m	H-3'''', H-1'''', OH-2''''		3.56
	OH-2''''	4.65	d(6.4)	H-2''''
	3''''	3.66	m	H-2'''', H-4'''', OH-3''''		3.92
	OH-3''''	5.32	d(3.6)	H-3''''
	4''''	3.28	m	H-3'''', 5''''		3,60
	5''''	3.66	m	H-4'''', H-6''''α		3.88
	6''''α	3.58	m	H-5'''', 6''''β, OH-6''''		3.78
	6''''β	3.66	m	H-6''''α, OH-6''''		3.89
	OH-6''''	4.42	t(5.6, 5.6)	H-6''''α, H-6''''β
Dβ	1'''''	4.31	dd(6.4, 7.6)	H-2''''', OH-1'''''	Dβ	4.60(8.0)
	OH-1'''''	6.70	d(6.4)	H-1'''''
	2'''''	2.95	ddd(8.0, 7.6, 5.2)	H-3''''', H-1''''', OH-2'''''		3.23(9.0,8.0)
	OH-2'''''	4.99	d(5.2)	H-2'''''
	3'''''	3.38	m	H-2''''', H-4''''', OH-3'''''		3.73
	OH-3'''''	5.47	d(6.4)	H-3'''''
	4'''''	3.28	m	H-5''''', H-3'''''		3.55
	5'''''	3.19	m	H-4''''', H-6'''''α, H-6'''''β		3.54
	6'''''α	3.58	m	H-5''''', H-6'''''β, OH-6'''''		3.78
	6'''''β	3.66	m	H-5''''', H-6'''''α, OH-6'''''		3.89
	OH-6'''''	4.52	t(5.6, 5.6)	H-6'''''α, H-6'''''β

表1

表2

阿卡波糖的13C NMR数据（DMSO-d6，400 MHz）

原子编号		δ_C	DEPT	HSQC	HMBC(δ_H)	文献[12][δ_C, D₂O]
A	1	56.0	CH	3.28	H-2,3, OH-2, H-7	A	58.7
	2	70.8	CH	3.38	H-3, OH-4, OH-3, OH-2, H-7		75.2
	3	72.5	CH	3.58	H-1, H-4, OH-4, OH-3, OH-2		75.2
	4	71.2	CH	3.66	H-3, H-6, OH-4, OH-3, OH-2, H-7		74.1
	5	140.3	C		H-3, H-4, H-6, OH-4, OH-6, H-7		143.2
	6	61.3	CH₂	3.94	H-4, OH-6, H-7		64.1
	7	121.4	CH	5.59	H-4, H-6		124.3
B	1'	101.1	CH	4.92	H-2', 3', OH-2'	B	102.5
	2'	72.0	CH	3.28	OH-2', OH-3'		73.8
	3'	73.7	CH	3.28	H-4', H-2', H-1', OH-2', NH, OH-3'		75.7
	4'	64.9	CH	2.13	H-6', H-2', 3', H-5', NH, OH-3'		67.1
	5'	69.5	CH	3.58	H-6', H-4', H-1'		72.5
	6'	18.3	CH₃	1.16	H-5'		20.0
Cα	1''	100.5	CH	5.00	H-2'', 3'', 5'', OH-2''	C	102.3
	2''	71.9	CH	3.28	H-3'', 4'', H-1'', OH-3'', OH-2''		74.5
	3''	72.8	CH	3.28	H-2'', 4'', 5'', H-1'', OH-3'', OH-2''		75.9
	4''	79.6^*	CH	3.28	H-6''α, H-6''β		79.7
	5''	73.3	CH	3.28	H-3'', 4'', H-6''β, OH-6''		74.0
	6''	60.3	CH₂	3.58, 3.66	H-4'',OH-5'',OH-6''		63.1
Cβ	1'''	100.5	CH	5.00	H-2''', 5''', OH-2'''
	2'''	71.9	CH	3.28	H-4''', OH-3''', H-1''', OH-2'''
	3'''	72.1	CH	3.58	H-2''', 4''', OH-3''', OH-2'''
	4'''	79.7^*	CH	3.28	H-6'''α, H-6'''β
	5'''	73.3	CH	3.28	H-4''', H-6'''β, OH-6'''
	6'''	60.3	CH₂	3.58, 3.66	H-4''', H-5''',OH-6'''
Dα	1''''	92.1	CH	4.91	OH-2'''', OH-1''''	Dα	94.5
	2''''	71.8	CH	3.19	H-4'''', OH-2'''', OH-1''''		74.0
	3''''	73.1	CH	3.66	H-4'''', OH-2'''', OH-3''''		75.7
	4''''	80.5	CH	3.28	H-6''''α, H-3'''', 5'''', 6'''', 6''''β, H-1'', OH-3''''		80.00
	5''''	70.2	CH	3.66	H-4'''', OH-6'''', H-1''''		73.6
	6''''	60.6	CH₂	3.58, 3.66	H-4'''', H-5'''', OH-6''''		63,3
Dβ	1'''''	96.8	CH	4.31	H-2''''', H-5''''', OH-2''''', OH-1'''''	Dβ	98.3
	2'''''	74.3	CH	2.95	H-4''''', OH-2''''', OH-3''''', OH-1'''''		76.5
	3'''''	76.4	CH	3.38	H-2''''', H-4''''', OH-2''''', OH-3'''''		78.7
	4'''''	80.0	CH	3.28	H-5''''', H-3''''', H-6'''''α, H-6'''''β, H-1''', OH-3'''''		79.9
	5'''''	75.0	CH	3.19	H-4''''', OH-6''''', OH-1'''''		77.1
	6'''''	60.7	CH₂	3.58, 3.66	H-4''''', H-5''''', OH-6'''''		63.1

表2

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