Enantioseparation of Seventeen Kinds of β-Lactams on Carboxymethyl-β-cyclodextrin Chiral Stationary Phase and Research on Enantioseparation Mechanism

doi:10.7503/cjcu20170810

Abstract

Abstract:

A reversed phase high performance liquid chromatographic method was developed using carboxymethyl-β-cyclodextrin chiral stationary phase for enantioseparation of seventeen kinds of cis-β-lactams enantiomers. Most of the compounds could get base-line separation. The effects of mobile phase pH, salt type and concentration, as well as mobile phase proportion were discussed. The results showed that(0.10% NH₄Ac+FA)(pH=5.0)-MeOH(70∶30, volume ratio)was the optimum condition for most of chiral compound. Under the optimum condition, the 7 compounds for CA series could get base-line separation except for compound 18CA, the best resolution values for compounds 15CA and 17CA were 1.71 and 1.74, respectively. The resolution values for seven EA compounds were between 1.00 and 1.50 which was nearly close to base-line separation except for compounds 18EA and 22EA. The resolution values for three BA compounds were close to 1.00. Structures of analytes also played important role in chiral separation. The results indicated that better resolution could be obtained if the analyte with proper size matching cyclodextrin cavity. Hydrogen bond interaction between the substituents on the cyclodextrin derivative and the analytes and smaller steric hindrance were also good for enantioseparation. Smaller steric hindrance making analytes easily penetrate into cyclodextrin cavity was beneficial to enantioseparation. A tentative chiral recognition mechanism was proposed after a comprehensive analysis of the influencing factors for enantioseparation using compound 15CA as example. Inclusion interaction, hydrogen bond interaction, dipole-dipole interaction and steric hindrance were found to exert synergistic effects on enantioseparation. However, the inclusion interaction between the analytes and the cyclodextrin was the primary role for enantioselective recognition. In comparison with native β-CD CSP, CM-β-CD CSP exhibited enhanced enantioseparation.

Key words: Carboxymethyl-β-cyclodextrin;, β-Lactam;, Enantioseparation, High performance liquid chromatography

CLC Number:

O657

TrendMD:

ZHOU Min, XU Xiaoying, LONG Yuande. Enantioseparation of Seventeen Kinds of β-Lactams on Carboxymethyl-β-cyclodextrin Chiral Stationary Phase and Research on Enantioseparation Mechanism[J]. Chem. J. Chinese Universities, 2018, 39(6): 1164.

Figures/Tables 9

References 27

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pH	Additive	15CA			15EA			15BA
pH	Additive	k₁	α	R_s	k₁	α	R_s	k₁	α	R_s
7.5	NH₃·H₂O	2.91	1.16	1.11	2.40	1.11	0.68	2.05	1.00	0.00
	TEA	2.67	1.15	1.05	2.16	1.11	0.61	1.91	1.00	0.00
	DEA	2.49	1.16	1.04	2.12	1.11	0.61	1.86	1.00	0.00
6.0	HAc	3.90	1.15	1.16	3.17	1.11	0.72	2.59	1.05	0.06
	TFA	4.17	1.15	1.20	3.51	1.11	0.77	2.84	1.05	0.09
	FA	3.52	1.16	1.15	3.07	1.11	0.75	2.60	1.05	0.07
5.0	HAc	5.49	1.15	1.27	4.73	1.10	0.81	3.78	1.05	0.15
	TFA	5.89	1.15	1.29	5.12	1.10	0.80	4.19	1.00	0.00
	FA	4.77	1.18	1.30	4.92	1.10	0.85	4.02	1.06	0.17
4.0	HAc	4.37	1.13	1.12	3.70	1.09	0.68	3.23	1.00	0.00
	TFA	5.31	1.13	1.10	4.64	1.08	0.52	3.22	1.00	0.00
	FA	4.34	1.15	1.23	3.53	1.10	0.65	3.22	1.00	0.00

pH	Additive	15CA			15EA			15BA
pH	Additive	k₁	α	R_s	k₁	α	R_s	k₁	α	R_s
7.5	NH₃·H₂O	2.91	1.16	1.11	2.40	1.11	0.68	2.05	1.00	0.00
	TEA	2.67	1.15	1.05	2.16	1.11	0.61	1.91	1.00	0.00
	DEA	2.49	1.16	1.04	2.12	1.11	0.61	1.86	1.00	0.00
6.0	HAc	3.90	1.15	1.16	3.17	1.11	0.72	2.59	1.05	0.06
	TFA	4.17	1.15	1.20	3.51	1.11	0.77	2.84	1.05	0.09
	FA	3.52	1.16	1.15	3.07	1.11	0.75	2.60	1.05	0.07
5.0	HAc	5.49	1.15	1.27	4.73	1.10	0.81	3.78	1.05	0.15
	TFA	5.89	1.15	1.29	5.12	1.10	0.80	4.19	1.00	0.00
	FA	4.77	1.18	1.30	4.92	1.10	0.85	4.02	1.06	0.17
4.0	HAc	4.37	1.13	1.12	3.70	1.09	0.68	3.23	1.00	0.00
	TFA	5.31	1.13	1.10	4.64	1.08	0.52	3.22	1.00	0.00
	FA	4.34	1.15	1.23	3.53	1.10	0.65	3.22	1.00	0.00

Analyte	CSP	k₁	α	R_s	P^b
15CA	CM-β-CD	13.64	1.15	1.71	1.00
	Native β-CD	6.12	1.20	—	0.98
16CA	CM-β-CD	10.07	1.14	1.66	1.00
	Native β-CD	5.43	1.18	—	0.92
17CA	CM-β-CD	13.41	1.13	1.57	0.97
	Native β-CD	7.11	1.17	—	0.93
18CA	CM-β-CD	13.06	1.06	0.54	0.28
	Native β-CD	7.14	1.10	—	0.52
20CA	CM-β-CD	12.08	1.14	1.60	1.00
	Native β-CD	5.90	1.19	—	0.90
21CA	CM-β-CD	14.29	1.16	1.74	1.00
	Native β-CD	6.76	1.22	—	0.95
22CA	CM-β-CD	6.49	1.14	1.57	1.00
	Native β-CD	4.88	1.15	—	0.88
15EA	CM-β-CD	10.98	1.12	1.38	0.94
	Native β-CD	5.44	1.13	—	0.72
16EA	CM-β-CD	8.13	1.12	1.34	0.93
	Native β-CD	4.67	1.12	—	0.72
17EA	CM-β-CD	11.28	1.13	1.51	0.96
	Native β-CD	6.61	1.17	—	0.91
Analyte	CSP	k₁	α	R_s	P^b
18EA	CM-β-CD	12.27	1.06	0.54	0.31
	Native β-CD	6.88	1.09	—	0.42
20EA	CM-β-CD	9.52	1.12	1.38	0.94
	Native β-CD	5.12	1.15	—	0.80
21EA	CM-β-CD	13.88	1.11	1.23	0.85
	Native β-CD	5.91	1.11	—	0.59
22EA	CM-β-CD	5.43	1.08	0.74	0.48
	Native β-CD	3.79	1.04	—	0.05
15BA	CM-β-CD	10.43	1.08	0.82	0.55
	Native β-CD	4.29	1.11	—	0.59
16BA	CM-β-CD	8.51	1.08	0.92	0.67
	Native β-CD	4.09	1.10	—	0.45
17BA	CM-β-CD	9.73	1.08	0.91	0.64
	Native β-CD	4.73	1.11	—	0.57

Analyte	CSP	k₁	α	R_s	P^b
15CA	CM-β-CD	13.64	1.15	1.71	1.00
	Native β-CD	6.12	1.20	—	0.98
16CA	CM-β-CD	10.07	1.14	1.66	1.00
	Native β-CD	5.43	1.18	—	0.92
17CA	CM-β-CD	13.41	1.13	1.57	0.97
	Native β-CD	7.11	1.17	—	0.93
18CA	CM-β-CD	13.06	1.06	0.54	0.28
	Native β-CD	7.14	1.10	—	0.52
20CA	CM-β-CD	12.08	1.14	1.60	1.00
	Native β-CD	5.90	1.19	—	0.90
21CA	CM-β-CD	14.29	1.16	1.74	1.00
	Native β-CD	6.76	1.22	—	0.95
22CA	CM-β-CD	6.49	1.14	1.57	1.00
	Native β-CD	4.88	1.15	—	0.88
15EA	CM-β-CD	10.98	1.12	1.38	0.94
	Native β-CD	5.44	1.13	—	0.72
16EA	CM-β-CD	8.13	1.12	1.34	0.93
	Native β-CD	4.67	1.12	—	0.72
17EA	CM-β-CD	11.28	1.13	1.51	0.96
	Native β-CD	6.61	1.17	—	0.91
Analyte	CSP	k₁	α	R_s	P^b
18EA	CM-β-CD	12.27	1.06	0.54	0.31
	Native β-CD	6.88	1.09	—	0.42
20EA	CM-β-CD	9.52	1.12	1.38	0.94
	Native β-CD	5.12	1.15	—	0.80
21EA	CM-β-CD	13.88	1.11	1.23	0.85
	Native β-CD	5.91	1.11	—	0.59
22EA	CM-β-CD	5.43	1.08	0.74	0.48
	Native β-CD	3.79	1.04	—	0.05
15BA	CM-β-CD	10.43	1.08	0.82	0.55
	Native β-CD	4.29	1.11	—	0.59
16BA	CM-β-CD	8.51	1.08	0.92	0.67
	Native β-CD	4.09	1.10	—	0.45
17BA	CM-β-CD	9.73	1.08	0.91	0.64
	Native β-CD	4.73	1.11	—	0.57