Scheme 1.
Synthesis of 2-[(naphthalen-2-yloxy)methyl]oxirane.
Scheme 2.
Synthesis of (2RS)-1-(2-naphthyloxy)-3-(substituted amino)propan-2-ols.
Table 1.
List of the studied compounds.
| Compound | R | Compound | R |
|---|---|---|---|
| I | -NHCH(CH3)2 | X |  |
| II | -NHC(CH3)3 | XI |  |
| III | -N(CH3)2 | XII |  |
| IV |  | XIII |  |
| V |  | XIV |  |
| VI |  | XV |  |
| VII |  | XVI |  |
| VIII |  | XVII |  |
| IX |  |
[i] Forms of the substances: Ia–XIIa salts with fumaric acid, Ib–XIIb salts with HCl
Table 2.
Screening of antioxidant activities of salts and free bases of the prepared compounds.
| Compound | Working label | Inhibition of ABTS (%) ± SD |
|---|---|---|
| I | B2N IZP | 90.90 ±1.90 |
| Ib | H2NIZP | 31.66 ±2.73 |
| II | B2N4t | 81.97 ±1.94 |
| IIa | F2N4t | 9.33 ±3.77 |
| IIIa | F2NDMA | 8.12 ±3.20 |
| IVa | F2N-CH | 33.51 ±3.30 |
| VIIa | F2N pyrr | 11.71 ±0.64 |
| VIIb | H2N pyrr | 21.99 ± 0.81 |
| VIII | B2N-IMI | 52.18 ±1.5 |
| IX | B2N-2IMI | 57.10 ±6.60 |
| Xa | F2Npiper | 6.01 ±1.09 |
| XIa | F2Nmorph | 17.76 ±0.94 |
| XII | B2NCH3piper | 92.92 ±1.16 |
| XIIIa | F2NMFP | 41.71 ±9.50 |
| XVI | Imidazole | Inactive |
| XVII | 2-methylimidazole | 5.42 ±1.30 |
| XIV | Naphthalen-1-ol | 99.64 ±0.16 |
| XV | Naphthalen-2-ol | 99.63 ±0.30 |
| Propranolola | Standard | 97.48 ± 2.34 |
Figure 1.
HPLC chromatograms for enantioseparation of the compounds I (a) and VII (b) on Chiralpak AD-H column with the mobile phase B.
Figure 2.
HPLC chromatogram for enantioseparation of the compound VIa on Chiralpak AD-H column with the mobile phase B.
Figure 3.
HPLC chromatogram for enantioseparation of the compound VIIIa on Chiralpak AD-H column with the mobile phase D.
Table 3.
Chromatographic parameters of the derivatives of 2-naphthol on the chiral column Chiralpak AD-H.
| Compound | Mobile phase | t1 | t2 | k1 | k2 | α | Rs |
|---|---|---|---|---|---|---|---|
| I | B | 7.88 | 13.83 | 1.11 | 2.71 | 2.44 | 14.88 |
| III | B | 10.41 | 12.90 | 1.70 | 2.35 | 1.38 | 4.15 |
| IVa | A | 12.26 | 21.14 | 1.97 | 4.13 | 2.09 | 12.96 |
| IVa | B | 10.44 | 17.77 | 1.69 | 3.58 | 2.12 | 12.01 |
| V | A | 49.08 | 84.03 | 11.37 | 20.17 | 1.77 | 12.83 |
| V | B | 37.82 | 64.31 | 8.49 | 15.13 | 1.78 | 12.32 |
| VIa | B | 29.48 | 65.29 | 6.59 | 15.82 | 2.40 | 14.32 |
| VII | B | 11.20 | 12.91 | 1.33 | 1.69 | 3.85 | 1.27 |
| VIIIa | D | 17.72 | 20.87 | 4.54 | 5.52 | 0.82 | 3.50 |
| VIIIa | B | 27.97 | 33.75 | 6.32 | 7.83 | 1.24 | 4.21 |
| IX | B | 56.58 | -- | - | - | - | - |
| IX | D | 41.44 | - | - | - | - | - |
| XII | B | 13.45 | 18.05 | 2.60 | 3.80 | 6.35 | 1.46 |
| XIIIa | B | 8.55 | - | - | - | - | - |
| XIIIa | C | 7.75 | - | - | - | - | - |
| XIIIa | A | 9.75 | - | - | - | - | - |
Table 4.
Chromatographic parameters of the derivatives of 2-naphthol on the chiral column Chirobiotic T.
| Compound | Mobile phase | t1 | t2 | k1 | k2 | α | Rs |
|---|---|---|---|---|---|---|---|
| III | E | 15.20 | 15.60 | 3.93 | 4.06 | 1.03 | 0.77 |
| IV | E | 15.98 | 17.04 | 3.32 | 3.61 | 1.09 | 1.18 |
| V | E | 3.18 | - | - | - | - | - |
| VI | E | 17.53 | 19.80 | 3.74 | 4.36 | 1.17 | 2.67 |
[i] E: MeOH:acetonitrile:acetic acid:diethylethanamine = 45:55:0.3:0.2 (v/v/v/v)