Figure S5.2. 13C NMR and DEPT-135 spectra of L-dopa prodrug 8
Figure S5.3. 1H NMR spectra of L-dopa prodrug 9
Figure S5.4. 13C NMR and DEPT-135 spectra of L-dopa prodrug 9
Figure S5.5. 1H NMR spectra of L-dopa prodrug 10
Figure S5.6. 13C NMR and DEPT-135 spectra of L-dopa prodrug 10
Figure S5.7. 1H NMR spectra of L-dopa prodrug 11
Figure S5.8. 13C NMR and DEPT-135 spectra of L-dopa prodrug 11
Table S5.1: Correlation of the NMR spectra with the structure of the L-Dopa prodrug 8.
¹H NMR
The CH2 group at C7 corresponds to the signals at 2.86 and 2.95 ppm (the signals integrate for 1 proton each). The assignment is based on the literature, which reports that the side chain CH2 of L-Dopa appears as two signals at these chemical shifts (Nakonieczna et al., 1994).
The CH group at C8, the α-carbon position of L-Dopa, corresponds to the multiplet at 4.03 ppm (the signal integrate for 1 proton).
The protons of the CH2 group at C12 correspond to the signals at 4.47 and 4.60 ppm (the signals integrate for 1 proton each).
The aromatic protons on the phenyl ring (C1, C4 and C6) correspond to the doublets at 6.64 ppm (C4, 1H) and 6.70 ppm (C1, 1H), and the doublet of doublets at 6.50 ppm (1H). The assignment is based on the literature, which reports that aromatic protons of L-Dopa appear as distinct signals at these chemical shifts (Nakonieczna et al., 1994).
The aromatic protons of C14 and C15 on the pyridyl ring correspond to the two doublets at 7.63 ppm (2H) and 8.75 ppm (1H). As shown by the coupling constants, the protons represented by these signals couple with each other.
The hydrochloric acid of the prodrug contains 6 exchangeable protons (NH, NH3+ and OH groups). These signals are most likely represented by the broad signals observed in the spectrum at 9.45 ppm (1H), and the broad signal at approximately 9 ppm.
Exchangeable protons may also be obscured by the broad water signal at approximately 3.5 ppm.
¹³C NMR
The carbonyl carbon at C10 is represented by the signal at 168.83 ppm.
The methylene and methene carbons C7, C8, and C12 correspond to the signals at 53.91, 41.57 and 36.38 ppm.
Aromatic carbons (9 carbons) on the catechol and pyridyl rings are represented by signals at 158.52, 145.32, 144.57, 141.53, 125.61, 124.64, 120.32, 117.11 and 115.93 ppm.
13C DEPT 135 °
Methylene CH2 groups at C7 and C12 correspond to the signals at 41.57 and 36.38 ppm.
The methene CH group at C8 is represented by the signal at 53.91 ppm
Aromatic CH carbons (5 carbons) are represented by signals at 141.53, 124.64, 120.32, 117.11 and 115.93 ppm.
Aromatic C carbons (4 carbons) are represented by signals at 158.52, 145.32, 144.57 and 125.61 ppm.
Table S5.2: Correlation of the NMR spectra with the structure of the L-Dopa prodrug 9.
¹H NMR
The CH2 group at C7 corresponds to the signals at 2.88 and 3.01 ppm (the signals integrate for 1 proton each). The assignment is based on the literature, which reports that the side chain CH2 of L-Dopa appears as two signals at these chemical shifts (Nakonieczna et al., 1994).
The CH group at C8, the α-carbon position of L-Dopa, corresponds to the signal at 4.11 ppm (the signal integrate for 1 proton).
The protons of the CH2CH2 group at C12 and C13 correspond to the signals at 1.81 (2H) and 2.55 ppm (2H).
The aromatic protons on the phenyl ring (C1, C4 and C6) correspond to the doublets at 6.62 ppm (C4, 1H) and 6.67 ppm (C1, 1H), and the doublet of doublets at 6.46 ppm (C6, 1H). The assignment is based on the literature, which reports that aromatic protons of L- Dopa appear as distinct signals at these chemical shifts (Nakonieczna et al., 1994).
The aromatic protons of C15 and C16 on the pyridyl ring correspond to the two signals at 7.27 ppm (2H) and 7.20 – 7.11 ppm (3H). For the latter signal (3H) two protons are aromatic while the other most likely represents an exchangeable proton (e.g. OH, NH).
The hydrochloric acid of the prodrug contains 6 exchangeable protons (NH, NH3+ and OH groups). These signals are most likely represented by the broad signals observed in
the spectrum at 8.53 ppm (3H), and the signal at 8.96 ppm (2H). As mentioned above one exchangeable proton may also be part of the multiplet at 7.20 – 7.11 ppm.
¹³C NMR
The carbonyl carbon at C10 is represented by the signal at 169.19 ppm.
The methylene and methene carbons C7, C8, C12 and C13 correspond to the signals at 53.53, 35.54, 31.15, 29.50 ppm.
Aromatic carbons (9 carbons) on the catechol and pyridyl rings are represented by signals at 145.34, 144.69, 141.05, 128.37, 125.93, 125.02, 120.16, 116.74 and 115.72 ppm.
13C DEPT 135 °
Methylene CH2 groups at C7, C12 and C13 correspond to the signals at 35.54, 31.15 and 29.50 ppm.
The methene CH group at C8 is represented by the signal at 53.53 ppm
Aromatic CH carbons (5 carbons) are represented by signals at 128.37, 125.93, 120.16, 116.74 and 115.72 ppm.
Aromatic C carbons (4 carbons) are represented by signals at 145.34, 144.69, 141.05 and 125.02 ppm.
Table S5.3: Correlation of the NMR spectra with the structure of the L-Dopa prodrug 10.
¹H NMR
The CH2 group at C7 corresponds to the signals at 2.75 and 2.81 ppm (the signals integrate for 1 proton each). The assignment is based on the literature, which reports that the side chain CH2 of L-Dopa appears as two signals at these chemical shifts (Nakonieczna et al., 1994).
The CH group at C8, the α-carbon position of L-Dopa, corresponds to the multiplet at 3.80 ppm (the signal integrate for 1 proton).
The protons of the CH2CH2 group at C12 and C13 correspond to the multiplets at 3.14 (2H), 3.46 (1H) and 3.52 ppm (1H).
The aromatic protons on the phenyl ring (C1, C4 and C6) correspond to the doublets at 6.59 ppm (C4, 1H) and 6.64 ppm (C1, 1H), and the doublet of doublets at 6.41 ppm (1H). The assignment is based on the literature, which reports that aromatic protons of L-Dopa appear as distinct signals at these chemical shifts (Nakonieczna et al., 1994).
The aromatic protons of C15–C18 on the pyridyl ring correspond to the signals at 7.81 ppm (1H), 7.85 (1H), 8.40 (1H) and 8.73 (1H).
The hydrochloric acid of the prodrug contains 6 exchangeable protons (NH, NH3+ and OH groups). These signals are most likely represented by the broad signals observed in the spectrum at 8.84 ppm (1H), and the broad signal at 8.33 ppm (3H). Exchangeable protons may also be obscured by the broad water signal at approximately 3.75 ppm, and the broad signal at approximately 9 ppm.
¹³C NMR
The carbonyl carbon at C10 is represented by the signal at 168.31 ppm
The methylene and methene carbons C7, C8, C12 and C13 correspond to the signals at 54.00, 38.08, 36.33 and 32.96.ppm
Aromatic carbons (11 carbons) on the catechol and pyridyl rings are represented by signals at 154.46, 145.38, 145.17, 144.48, 141.78, 127.42, 125.62, 124.94, 120.27, 116.99 and 115.82 ppm.
13C DEPT 135 °
Methylene CH2 groups at C7, C12 and C13 correspond to the signals at 38.08, 36.33 and 32.96 ppm.
The methene CH group at C8 is represented by the signal at 54.00 ppm
Aromatic CH carbons (7 carbons) are represented by signals at 145.38, 141.78, 127.42, 124.94, 120.27, 116.99 and 115.82 ppm.
Aromatic C carbons (4 carbons) are represented by signals at 154.46, 145.17, 144.48 and 125.62 ppm.
Table S5.4: Correlation of the NMR spectra with the structure of the L-Dopa prodrug 11.
¹H NMR
The CH2 group at C7 corresponds to the signal at 2.85 ppm (the signal integrates for 2 protons). The assignment is based on the literature, which reports that the side chain CH2 of L-Dopa appears as two signals at these chemical shifts (Nakonieczna et al., 1994).
The CH group at C8, the α-carbon position of L-Dopa, corresponds to the signal at 3.83 ppm (the signal integrate for 1 proton).
The protons of the (CH2)3 group at C12–C14 correspond to the signals at 1.64 (2H), 2.85 (2H), 2.97 – 3.10 (2H) and 3.35 (1H).
The aromatic protons on the phenyl ring (C1, C4 and C6) correspond to the two doublets, noted as a multiplet at 6.66 ppm (C4 and C1, 2H), and the doublet of doublets at 6.49 ppm (1H). The assignment is based on the literature, which reports that aromatic protons of L-Dopa appear as distinct signals at these chemical shifts (Nakonieczna et al., 1994).
The aromatic protons of C15–C18 on the phenyl ring correspond to the signals at 7.17 ppm (3H) and 7.26 (2H).
The hydrochloric acid of the prodrug contains 6 exchangeable protons (NH, NH3+ and OH groups). These signals are most likely represented by the broad signals observed in the spectrum at 8.54 ppm (1H), and the broad signal at 8.91 ppm (2H). Exchangeable protons may also be obscured by the broad water signal at approximately 3.5 ppm, and the broad signal at approximately 8.25 ppm.
¹³C NMR
The carbonyl carbon at C10 is represented by the signal at 168.10 ppm
The methylene and methene carbons C7, C8, C12–C14 correspond to the signals at 54.05, 38.22, 36.70, 32.35 and 30.50 ppm.
Aromatic carbons (10 carbons) on the catechol and phenyl rings are represented by signals at 145.18, 144.46, 141.62, 128.40, 128.32, 125.81, 125.77, 120.24, 117.00 and 115.65 ppm.
13C DEPT 135 °
Methylene CH2 groups at C7 and C12–C14 correspond to the signals at 38.22, 36.70, 32.35 and 30.50 ppm.
The methene CH group at C8 is represented by the signal at 54.05 ppm
Aromatic CH carbons (6 carbons) are represented by signals at 128.40, 128.32, 125.77, 120.24, 117.00 and 115.65 ppm.
Aromatic C carbons (4 carbons) are represented by signals at 145.18, 144.46, 141.62 and 125.81, ppm.