Chiral Recognition Mechanism of Benzyltetrahydroisoquinoline Alkaloids: Cyclodextrin-Mediated Capillary Electrophoresis, Chiral HPLC, and NMR Spectroscopy Study
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthetic Procedures
2.2. Analytical and Semi-Preparative Chiral HPLC Studies
2.3. Enantioseparation of the Benzyltetrahydroisoquinoline Alkaloids by CE
2.4. Enantiomer Migration Order Reversal Determination by CE
2.5. Characterization of the Inclusion Complexes by NMR Spectroscopy
3. Materials and Methods
3.1. Materials
3.2. Syntheses of Benzyltetrahydroisoquinoline Alkaloids
3.2.1. Synthesis of Racemic NOR
3.2.2. Synthesis of Racemic LAU
3.2.3. Synthesis of Racemic PROP
3.2.4. Synthesis of Racemic Br-LAU
3.3. Chiral HPLC
3.4. CD Spectroscopy
3.5. Capillary Electrophoresis
3.6. NMR Spectroscopy
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Column | Mobile Phase | LAU | NOR | Br-LAU | PROP | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
t1 | Rs | EEO | t1 | Rs | EEO | t1 | Rs | EEO | t1 | Rs | EEO | ||
Chiral CD-Ph | ACN | 5.39 | - | - | 5.76 | - | - | 9.21 | - | - | 5.79 | - | - |
MeOH | 11.85 | - | - | 12.17 | 0.8 | S,R | 9.53 | 8.16 | - | - | |||
Cyclobond I | ACN | 7.79 | - | - | 8.48 | - | - | 6.34 | - | - | 5.04 | - | - |
MeOH | 5.11 | - | - | 5.10 | - | - | 4.97 | - | - | 4.79 | - | - | |
Nucleodex β-CD | ACN | 2.68 | - | - | 2.69 | - | - | 2.70 | - | - | 2.68 | - | - |
MeOH | 2.87 | - | - | 3.21 | - | - | 2.88 | - | - | 2.88 | - | - | |
Chiralcel OD | ACN | 5.44 | 2.7 | S,R | 7.33 | 2.9 | S,R | 5.68 | 2.4 | S,R | 5.17 | 0.8 | S,R |
MeOH | 7.00 | 3.2 | S,R | 7.74 | 1.0 | S,R | 7.17 | 2.8 | S,R | 6.89 | 1.8 | S,R | |
Chiralpak AD | ACN | 4.87 | - | - | 5.91 | 3.7 | S,R | 5.00 | - | - | 4.80 | - | - |
MeOH | 5.92 | 0.6 | S,R | 6.98 | 4.7 | S,R | 5.87 | 1.9 | S,R | 6.50 | 1.9 | R,S | |
Chiralpak IA | ACN | 5.10 | 0.5 | S,R | 6.37 | 3.6 | S,R | 5.28 | - | - | 5.03 | - | - |
MeOH | 6.37 | - | - | 6.72 | 3.0 | S,R | 6.45 | - | - | 6.39 | 0.9 | R,S |
CyD | LAU | NOR | Br-LAU | PROP | |||
---|---|---|---|---|---|---|---|
Neutral CyDs | Randomly substituted | HP-β-CyD | EMO | - | - | R,S | - |
Rs | - | - | 0.8 (30 mM) | - | |||
HP-γ-CyD | EMO | S,R | - | S,R | S,R | ||
Rs | 0.4 (30 mM) | - | 0.4 (30 mM) | 1.3 (30 mM) | |||
Anionic CyDs | S-α-CyD | EMO | R,S | R,S | R,S | S,R | |
Rs | 2.6 (10 mM) | 2.1 (10 mM) | 0.9 (10 mM) | 0.4 (10 mM) | |||
S-β-CyD | EMO | R,S | R,S | R,S | R,S | ||
Rs | 3.4 (10 mM) | 7.5 (10 mM) | 0.7 (10 mM) | 5.4 (10 mM) | |||
S-γ-CyD | EMO | S,R | R,S | S,R | - | ||
Rs | 10.5 (10 mM) | 5.4 (10 mM) | 7.3 (10 mM) | - | |||
SP-α-CyD | EMO | - | - | - | S,R | ||
Rs | - | - | - | 0.7 (10 mM) | |||
SP-β-CyD | EMO | - | - | - | S,R | ||
Rs | - | - | - | 0.7 (10 mM) | |||
SP-γ-CyD | EMO | S,R | - | S,R | S,R | ||
Rs | 1.2 (10 mM) | - | 1.5 (10 mM) | 2.1 (10 mM) | |||
SBE-α-CyD | EMO | - | - | S,R | - | ||
Rs | - | - | 0.5 (10 mM) | - | |||
SBE-β-CyD | EMO | R,S | R,S | ||||
Rs | 1.0 (10 mM) | - | 2.3 (10 mM) | - | |||
SBE-γ-CyD | EMO | - | - | S,R | S,R | ||
Rs | - | - | 1.1 (10 mM) | 1.3 (10 mM) | |||
CM-α-CyD | EMO | S,R | S,R | - | S,R | ||
Rs | 0.6 (10 mM) | 1.0 (10 mM) | - | 4.8 (10 mM) | |||
CM-β-CyD | EMO | S,R | - | - | S,R | ||
Rs | 0.7 (10 mM) | - | - | 1.0 (10 mM) | |||
CM-γ-CyD | EMO | S,R | S,R | S,R | S,R | ||
Rs | 3.2 (7.5 mM) | 1.0 (10 mM) | 3.3 (7.5 mM) | 2.7 (10 mM) | |||
SBX | EMO | S,R | S,R | R,S | - | ||
Single isomer | Rs | 2.6 (7.5 mM) | 3.3 (7.5 mM) | 2.9 (7.5 mM) | - | ||
SGX | EMO | S,R | S,R | S,R | S,R | ||
Rs | 6.7 (5 mM) | 5.7 (5 mM) | 2.2 (2.5 mM) | 7.2 (2.5 mM) | |||
HS-β-CyD | EMO | R,S | R,S | R,S | R,S | ||
Rs | 1.5 (4 mM) | 0.6 (5 mM) | 1.8 (4 mM) | 2.1 (5 mM) | |||
HDAS | EMO | R,S | R,S | R,S | R,S | ||
Rs | 8.3 (2 mM) | 3.2 (2 mM) | 5.0 (2 mM) | 4.7 (2 mM) | |||
HxDMS | EMO | R,S | R,S | R,S | R,S | ||
Rs | 2.2 (5 mM) | 1.0 (5 mM) | 1.9 (5 mM) | 0.5 (5 mM) | |||
HDMS | EMO | R,S | R,S | R,S | R,S | ||
Rs | 7.0 (3 mM) | 6.1 (2 mM) | 5.6 (3 mM) | 8.3 (3 mM) | |||
ODMS | EMO | R,S | R,S | R,S | R,S | ||
Rs | 2.8 (4 mM) | 7.5 (2 mM) | 6.3 (2 mM) | 1.8 (2 mM) |
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Várnagy, E.; Tóth, G.; Hosztafi, S.; Dobó, M.; Fejős, I.; Béni, S. Chiral Recognition Mechanism of Benzyltetrahydroisoquinoline Alkaloids: Cyclodextrin-Mediated Capillary Electrophoresis, Chiral HPLC, and NMR Spectroscopy Study. Molecules 2025, 30, 1125. https://doi.org/10.3390/molecules30051125
Várnagy E, Tóth G, Hosztafi S, Dobó M, Fejős I, Béni S. Chiral Recognition Mechanism of Benzyltetrahydroisoquinoline Alkaloids: Cyclodextrin-Mediated Capillary Electrophoresis, Chiral HPLC, and NMR Spectroscopy Study. Molecules. 2025; 30(5):1125. https://doi.org/10.3390/molecules30051125
Chicago/Turabian StyleVárnagy, Erzsébet, Gergő Tóth, Sándor Hosztafi, Máté Dobó, Ida Fejős, and Szabolcs Béni. 2025. "Chiral Recognition Mechanism of Benzyltetrahydroisoquinoline Alkaloids: Cyclodextrin-Mediated Capillary Electrophoresis, Chiral HPLC, and NMR Spectroscopy Study" Molecules 30, no. 5: 1125. https://doi.org/10.3390/molecules30051125
APA StyleVárnagy, E., Tóth, G., Hosztafi, S., Dobó, M., Fejős, I., & Béni, S. (2025). Chiral Recognition Mechanism of Benzyltetrahydroisoquinoline Alkaloids: Cyclodextrin-Mediated Capillary Electrophoresis, Chiral HPLC, and NMR Spectroscopy Study. Molecules, 30(5), 1125. https://doi.org/10.3390/molecules30051125