Spectroscopic data of cerivastatin metabolites derived from biotransformation in dogs, mice, and rats7-a
| Metabolite | Method | Spectroscopic Data |
|---|---|---|
| M-2, silylated | EI-MS | m/z(%): 1067 (1) M+; 585 (15) M-D7-b; 391 (28) A7-b; 375 (19) B7-b; 73 (100) TMS+. |
| M-3, silylated | CI-MS | m/z (%): 1068 (95) [M+H]+. |
| EI-MS | m/z (%): 1052 (0.3) M−CH3 ·; 602 (19) M−C7-b; 391 (19) A7-b; 375 (30) B7-b; 233 (12) TMSO+=CH-CH2-COOTMS; 217 (19) TMSO+=CH-CH=CH-OTMS; 73 (100) TMS+. | |
| M-3 | 1H NMR | (CD3OD): δ = 1.44 (m, 1H) H-4A; 1.75 (m, 1H) H-4B; 2.36 (m, 1H) H-2A; 2.45 (m, 1H) H-2B; 3.88 (m, 1H) H-3; 4.43 (m, 1H) H-5; 4.07 (AB spin system, 2H, JA,B = 10.5 Hz) -CH2O-; 3.15 (s, 3H) CH3O-; 4.02 (d, 1H, J = 7.8 Hz) anomeric H; 5.24 (dd, 1H, J5,6 = 8.0 Hz; J6,7 = 16.2 Hz) H-6; 6.46 (d, 1H) H-7; 7.13–7.22 (m, 4H) aromatic H’s; ppm. |
| M-4, silylated | EI-MS | m/z (%): 1125 (6) M+; 553 (41) M-D7-b-TMSOH; 464 (18) M-D7-b-TMSOH-TMSO·; 375 (16) B7-b; 73 (100) TMS+. |
| M-4 | 1H NMR | (CD3OD): δ = ∼1.3 (superimposed) H-4A; 1.52 (m, 1H) H-4B; 2.18 (m, 1H) H-2A; 2.28 (m, 1H) H-2B; 3.78 (m, 1H) H-3; 4.17 (m, 1H) H-5; 3.99/4.99 (AB spin system, 2H, JA,B = ∼11 Hz) -CH2O-; 3.97 (d, 1H, J = 7.8 Hz) anomeric H; 5.30 (dd, 1H, J5,6 = 6.8 Hz; J6,7 = 16.0 Hz) H-6; 6.30 (d, 1H) H-7; 7.08–7.40 (m, 4H) aromatic H’s; ppm. |
| M-5, silylated | EI-MS | m/z (%): 1111 (1) M+; 553 (18) M-H7-b-TMSOH; 464 (20) M-H7-b-TMSOH-TMSO·; 377 (9) E7-b; 361 (11) F7-b; 331 (68) F7-b-CH2O; 73 (100) TMS+. |
| M-5 | 1H NMR | (CD3OD): δ = 3.77 (m, broad, 1H) H-3; 4.18 (m, 1H) H-5; 4.08/4.81 (AB spin system, 2H, JA,B = 10.5 Hz) -CH2O-; 4.01 (d, 1H, J = 7.8 Hz) anomeric H; 3.63/3.79 (ABX spin system, 2H, JAB = 12.0 Hz, JAX = 5.5 Hz, JBX = 2.2 Hz, X-part superimposed) H-6A/H-6B (glucoside); 5.30 (dd, 1H, J5,6 = 6.5 Hz; J6,7 = 16.0 Hz) H-6; 6.30 (d, 1H) H-7; 7.08–7.35 (m, 4H) aromatic H’s; ppm. |
| M-6, silylated | EI-MS | m/z (%): 1067 (0.3) M+; 602 (10) M-C7-b; 585 (10) M-D7-b; 428 (12) Aryl-CH=CH-CH=O+TMS; 375 (100) B7-b; 73 (79) TMS+. |
| M-9, silylated | EI-MS | m/z(%); 821 (1.5) M+; 731 (3) M-TMSOH; 641 (3) M-2 TMSOH; 512 (30) I7-c; 486 (8) L7-c; 73 (100) TMS+. |
| M-9 | 1H NMR | (CD3OD) δ = 4.31 (s, 2H) -CH2O-; 4.19 (m) H-5; 5.36 (dd, 1H, J5,6 = 6.5 Hz; J6,7 = 16.0 Hz) H-6; 6.22 (d, 1H) H-7; 7.10–7.20 (m, 4H) aromatic H’s; ppm. |
| M-10, silylated | EI-MS | m/z (%): 1199 (4) M+; 890 (2) I7-c; 864 (2) M7-c; 377 (15) E7-b; 361 (19) F7-b; 331 (100) F7-b-CH2O; 73 (79) TMS+. |
| M-11, silylated | CI-MS | m/z (%): 1214 (26) [M+H]+; 90 (100) TMSOH·+. |
| EI-MS | m/z (%): 904 (1) K7-c; 673 (7); 391 (15) A7-b; 375 (13) B7-b; 73 (100) TMS+. | |
| M-15 | FAB-MS | m/z (%): 491 (100) [M−H]−; 124 (26) [NH2CH2CH2SO3]−; 80 (55) [SO3]·−. |
| 1H NMR | (CD3OD): δ = 3.56 (t, 2H, J = 6.7 Hz) -NHCH2-; 2.93 (t, 2H, J = 6.7 Hz) -CH2SO3H; 2.07 (m, 2H) H-2; 2.22 (m, 2H) H-3; 4.31 (s, 2H) -CH2O-; 5.31 (dt, 1H, J4,5 = 16.0 Hz; J3,4 = 6.9 Hz) H-4; 6.09 (ddd, 1H, J3a,5 = 1.6 Hz; J3b,5 = 1.6 Hz) H-5; 7.09–7.17 (m, 4H) aromatic H’s; ppm. | |
| M-16 | FAB-MS | m/z(%): 489 (84) [M−H]−; 124 (100) [NH2CH2CH2SO3]−; 80 (87) [SO3]·−. |
| 1H NMR | (CD3OD): δ = 3.64 (t, 2H, J = 6.7 Hz) -NHCH2-; 2.93 (t, 2H, J = 6.7 Hz) -CH2SO3H; 4.33 (s, 2H) -CH2O-; 5.82 (d, 1H, J2,3 = 15.2 Hz) H-2; 6.99 (ddd, 1H, J3,4 = 11.0 Hz, J3,5 = 0.7 Hz) H-3; 5.99 (dd, 1H, J4,5 = 16.0 Hz, J2,4 = 0.7 Hz) H-4; 6.63 (d, 1H) H-5; 7.10–7.21 (m, 4H) aromatic H’s; ppm. | |
| M-17 | FAB-MS | m/z (%): 489 (88) [M−H]−; 124 (100) [NH2CH2CH2SO3]−; 80 (59) [SO3]·−. |
| 1H NMR | (CD3OD): δ = 3.59 (m, 3H) -NHCH2- and CH (isopropyl); 2.93 (t, 2H, J = 6.7 Hz) -CH2SO3H; 4.67 (AB spin system, 2H, JA,B = 11.5 Hz) -CH2O-; 5.88 (d, 1H, J2,3 = 15.5 Hz) H-2; 6.73 (dd, 1H, J2,3 = 15.5 Hz, J3,4 = 7.5 Hz) H-3; 3.68 (m, 1H) H-4; ∼2.9 (m, 2H) H-5A/H-5B; 7.11 (ddd, 1H, J5”,F = 8.5 Hz, J5”,6” = 8.7 Hz, J3”,5” = 2.5 Hz) H-5”; 7.06 (dd, 1H, J3”,F = 9.0 Hz) H-3”; 8.17 (dd, 1H, J6”,F = 5.7 Hz) H-6”; ppm. | |
| M-18 | FAB-MS | m/z (%): 505 (100) [M−H]−; 124 (27) [NH2CH2CH2SO3]−; 80 (51) [SO3]·−. |
| 1H NMR | (CD3OD): δ = 3.56 (m, 2H) -CH2NH-; 2.93 (t, 2H, J = 6.7 Hz) -CH2SO3H; 4.08 (s, 2H) -CH2O-; 3.15 (s, 3H) CH3O-; 2.07 (m, 2H) H-2; 2.22 (m, 2H) H-3; 5.32 (dt, 1H, J4,5 = 16.0 Hz, J3,4 = 6.8 Hz) H-4; 6.10 (dt, 1H, J3,5 = 1.5 Hz) H-5; 7.10–7.14 (m, 4H) aromatic H’s; ppm. | |
| M-19 | ESI-MS | m/z: 527, [M+Na]+; 522, [M+NH4]+; 505, [M+H]+; 473, [M+H−CH3OH]+; 380, [M+H−NH2CH2CH2SO3H]+; 348, [M+H−CH3OH−NH2CH2CH2SO3H]+; 311, [M+NH4−CH3OH−CH2=CHCONHCH2CH2SO3H]+. |
| 1H NMR | (CD3OD): δ = 3.64 (t, 2H, J = 6.7 Hz) -NHCH2-; 2.97 (t, 2H, J = 6.7 Hz) -CH2SO3H; 3.16 (s, 3H) CH3O-; 4.09 (s, 2H) -CH2O-; 5.82 (d, 1H, J2,3 = 15.1 Hz) H-2; 6.99 (ddd, 1H, J3,4 = 10.8 Hz, J3,5 = 0.7 Hz) H-3; 5.99 (dd, 1H, J4,5 = 16.0 Hz, J2,4 = 0.7 Hz) H-4; 6.65 (d, 1H) H-5; 7.15–7.17 (m, 4H) aromatic H’s; ppm. | |
| M-20 | ESI-MS | m/z: 527, [M+Na]+; 505, [M+H]+; 473, [M+H−CH3OH]+. |
| 1H NMR | (CD3OD): δ = 3.59 (m, 3H) -CH2NH- and CH (isopropyl); 2.93 (t, 2H, J = 6.7 Hz) -CH2SO3H; 3.51 (s, 3H) CH3O-; 4.39 (AB spin system, 2H, JA,B = 10.3 Hz) -CH2O-; 5.86 (d, 1H, J2,3 = ∼15 Hz) H-2; 6.72 (dd, 1H, J2,3 = 15.5 Hz, J3,4 = 7.5 Hz) H-3; 3.69 (m, 1H) H-4; ∼2.9 (m, 2H) H-5A/H-5B; 7.12 (ddd, 1H, J5”,F = 8.5 Hz, J5”,6” = 8.7 Hz, J3”,5” = 2.8 Hz) H-5”; 7.07 (dd, 1H, J3”,F = 9.0 Hz) H-3”; 7.92 (dd, 1H, J6”,F = 5.8 Hz) H-6”; ppm. | |
| M-21 | FAB-MS | m/z (%): 406 (75) [M−2H+Na]−; 384 (100) [M−H]−; 340 (15) [M−H−CO2]−; 310 (77) [M−H−CO2−CH2O]−. |
| 1H NMR | (CD3OD): δ = 4.31 (s, 2H) -CH2O-; 2.05 (m, 2H) H-2; 2.21 (m, 2H) H-3; 5.36 (dt, 1H, J4,5 = 16.0 Hz, J3,4 = 6.7 Hz) H-4; 6.04 (dt, 1H, J3,5 = 1.5 Hz) H-5; 7.10–7.17 (m, 4H) aromatic H’s; ppm. | |
| M-25 | ESI-MS | m/z: 537, [M+H]+. |
| 1H NMR | (CD3OD): δ = 3.59 (t, 2H, J = 6.7 Hz) -CH2NH-; 2.96 (t, 2H, J = 6.7 Hz) -CH2SO3H; 4.31 (AB spin system, 2H, JA,B = 11.4 Hz) -CH2O-; 2.09 (t, 2H, J = 7.4 Hz) H-2; ∼1.1–1.4 (m, 4H, broad) H-3 and H-4; 3.92 (m, 1H) H-5; 5.30 (dd, 1H, J6,7 = 16.2 Hz, J5,6 = 6.3 Hz) H-6; 6.24 (dd, 1H, J5,7 = 1.5 Hz) H-7; 7.09–7.20 (m, 4H) aromatic H’s; ppm. | |
| M-26 | ESI-MS | m/z: 573, [M+Na]+; 551, [M+H]+. |
| 1H NMR | (CD3OD): δ = 3.59 (t, 2H, J = 6.7 Hz) -CH2NH-; 2.96 (t, 2H, J = 6.7 Hz) -CH2SO3H; 4.08 (AB spin system, 2H, JA,B = 10.3 Hz) -CH2O-; 3.15 (s, 3H) CH3O-; 2.10 (t, 2H, J = 7.4 Hz) H-2; ∼1.1–1.5 (m, 4H, broad) H-3 and H-4; 3.91 (m, 1H) H-5; 5.31 (dd, H, J6,7 = 16.0 Hz, J5,6 = 6.2 Hz) H-6; 6.25 (dd, 1H, J5,7 = 1.5 Hz) H-7; 7.11–7.17 (m, 4H) aromatic H’s; ppm. | |
| M-27 | ESI-MS | m/z: 466, [M+Na]+; 444, [M+H]+. |
| 1H NMR | (CD3OD): δ = 4.09 (AB spin system, 2H, JA,B = 10.3 Hz) -CH2O-; 3.16 (s, 3H) CH3O-; 2.09 (m, 2H) H-2; ∼1.1–1.5 (m, 4H, broad) H-3 and H-4; 3.93 (m, 1H) H-5; 5.34 (dd, 1H, J6,7 = 16.2 Hz, J5,6 = 6.4 Hz) H-6; 6.23 (dd, 1H, J5,7 = 1.5 Hz) H-7; 7.1–7.2 (m, 4H) aromatic H’s; ppm. | |
| M-28 | ESI-MS | m/z: 430, [M+H]+. |
| 1H NMR | (CD3OD): δ = 4.32 (AB spin system, 2H, JA,B = 11.5 Hz) -CH2O-; 2.09 (m, 2H) H-2; ∼1.1–1.4 (m, 4H, broad) H-3 and H-4; 3.93 (m, 1H) H-5; 5.33 (dd, 1H, J6,7 = 16.1 Hz, J5,6 = 6.3 Hz) H-6; 6.23 (dd, 1H, J5,7 = 1.5 Hz) H-7; 7.09–7.20 (m, 4H) aromatic H’s; ppm. | |
| M-29 | ESI-MS | m/z: 398, [M+H]+. |
| 1H NMR | (CD3OD): δ = 3.16 (s, 3H) CH3O-; 4.10 (s, 2H) -CH2O-; 5.75 (d, 1H, J2,3 = 15.0 Hz) H-2; 6.88 (ddd, 1H, J3,4 = 10.5 Hz, J3,5 = 0.7 Hz) H-3; 5.98 (dd, 1H, J4,5 = 16.0 Hz, J2,4 = 0.7 Hz) H-4; 6.51 (dd, 1H) H-5; 7.1–7.2 (m, 4H) aromatic H’s; ppm. | |
| M-30 | ESI-MS | m/z: 400, [M+H]+. |
| 1H NMR | (CD3OD): δ = 4.08 (s, 2H) -CH2O-; 3.15 (s, 3H) CH3O-; 2.08 (m, 2H) H-2; 2.22 (m, 2H) H-3; 5.35 (dt, 1H, J4,5 = 16.0 Hz, J3,4 = 6.8 Hz) H-4; 6.08 (dt, 1H, J3,5 = 1.5 Hz) H-5; 7.10–7.14 (m, 4H) aromatic H’s; ppm. | |
| M-32 | ESI-MS | m/z: 416, [M+H]+. |
| 1H NMR | (CD3OD): δ = 4.08 (s, 2H) -CH2O-; 3.15 (s, 3H) CH3O-; 2.09 (m, 2H) H-2; 4.32 (m, 1H) H-3; 5.38 (dd, 1H, J4,5 = 16.0 Hz, J3,4 = 6.8 Hz) H-4; 6.28 (dd, 1H, J3,5 = 1.5 Hz) H-5; 7.10–7.16 (m, 4H) aromatic H’s; ppm. |