Starting from the dihydroindoloquinolizinium chloride, 5, dehydrogenation with o-chloranil yields compound 6, bearing a fully aromatized C ring. Both 5 and 6 yield the corresponding ketal (7 and 8, respectively) after a two-phase reaction (suspension in toluene and treatment with ethyleneglycol and aqueous hydrochloric acid).
Treatment of chlorides 5 to 8 with base produces dihydro-indoloquinolizines and indoloquinolizines (9-12). We will later submit these to bioassays to examine their antitumor activity.
The NMR determinations indicate that compound 9 does not present a zwitterionic structure, but a structure devoid of localized charges, with methylenedenyl group exo to the pyridinic ring.
In order to confirm the assignments of the 13C NMR signals of the indoloquinolizine compounds (5-12), we first measured their 1H NMR of indole, 13, tryptamine, 14, and tryptamine hydrochloride, 4, in DMSO-d6.
The proton signal assignments were confirmed by the HH-chemical shift correlation spectroscopy (COSY) and the nuclear Overhauser effect difference spectroscopy (DIFNOE) methods. The results are summarized in table I.
| A | Indole
|
Tryptamine
|
Tryptamine.HCl
|
5
|
6
|
B |
|---|---|---|---|---|---|---|
| RESET | ||||||
| 8.27 (s) | 8.96 (s) | 1 | ||||
| 9.43 (s) | 10.07 | 4 | ||||
| Nb | 3.33 (s)* | 8.32 (s) | 5 | |||
| 3''-CH2- | 2.81 (t, 6.33) | 3.07 (s) | 4.93 (t, 7.15) | 9.11(d, 6.90) | 6 | |
| 3'-CH2- | 2.75 (t, 6.33) | 3.07 (s) | 3.43 (t, 7.15) | 8.86 (d, 6.90) | 7 | |
| 3 | 6.42 (s, 2.65) | 7a | ||||
| 4 | 7.53 (d, 7.82) | 7.51 (d, 7.81) | 7.58(d, 7.81) | 7.76 (d, 8.05) | 8.46 (d, 8.03) | 8 |
| 5 | 6.98 (t, 7.37) | 6.96 (t, 7.29) | 7.00 (t, 7.16) | 7.20 (t, 7.46) | 7.50 (t, 7.51) | 9 |
| 6 | 7.07 (t, 7.52) | 7.05 (t, 7.42) | 7.09 (t, 7.51) | 7.41 (t,7.58) | 7.77 (t, 7.65) | 10 |
| 7 | 7.39 (d, 8.06) | 7.33 (d, 8.10) | 7.39 (t, 8.5) | 7.57 (d, 8.30) | 7.89 (d, 8.34) | 11 |
| 1 | 11.08 (s) | 10.77 (s) | 11.10 (s) | 12.61 (s) | 13.80 (s) | 12 |
| 2 | 7.33 (t, 2.65) | 7.11 (s) | 7.25 (d, 2.0) | 12a | ||
| 2.73 (s) | 2.81 (s) | 2'-CH3 | ||||
| 2.70 (s) | 2.81 (s) | 3''-CH3 |
| A | 7
|
8
|
9
|
10
|
11
|
12
|
B |
|---|---|---|---|---|---|---|---|
| RESET | |||||||
| 8.34 (s) | 8.61 (s) | 6.38 (s) | 8.78 (s) | 8.02 (s) | 8.74 (s) | 1 | |
| 8.77 (s) | 9.31 (s) | 7.80 (s) | 9.75 (s) | 8.37 (s) | 9.03 (s) | 4 | |
| Nb | 5 | ||||||
| 3''-CH2- | 4.89 (t, 7.23) | 9.05 (d, 6.43) | 3.92 (t, 5.82) | 8.52 (d, 6.5) | 4.64 (t, 7) | 8.52 (d, 6) | 6 |
| 3'-CH2- | 3.37(t,7.23) | 8.64 (d, 6.95) | 2.99 (t, 5.82) | 8.55 (d, 6.5) | 3.19 (t, 7) | 8.35 (d, 6) | 7 |
| 3 | 7a | ||||||
| 4 | 7.71 (d, 8.04) | 8.30 (d, 8.01) | 7.51 (d, 7.83) | 8.21 (d, 7.87) | 7.33 (d, 7.86) | 8.12 (d, 7.50) | 8 |
| 5 | 7.16 (t, 7.19) | 7.36 (t, 7.50) | 7.03 (t, 7.40) | 7.10 (d, 7.21) | 6.64 (t, 7.26) | 7.01 (t, 7.15) | 9 |
| 6 | 7.36 (t, 7.57) | 7.62 (t, 7.60) | 7.16 (t, 7.48) | 7.40 (t, 7.43) | 6.80 (t, 7.38) | 7.27 (t, 7.36) | 10 |
| 7 | 7.54 (d, 8.31) | 7.73 (d, 8.33) | 7.35 (d, 8.11) | 7.77 (d, 8.52) | 7.27 (d, 8.34) | 7.67 (d, 8.13) | 11 |
| 1 | 12.70 (s) | 13.20 (s) | 11.39 (s) | 12 | |||
| 2 | 12a | ||||||
| 2.72 (s) | 2.71 (s) | 5.52 (d, 3) | 2.73 (s) | 2.60 (s) | 2.68 (s) | 2'-CH3 | |
| 1.70 (s) | 1.72 (s) | 2.28 (s) | 2.73 (s) | 1.66 (s) | 1.68 (s) | 3''-CH3 | |
| 4.10 (t, 7.0)
3.85 (t, 7.0) |
4.07 (t, 6.9)
3.80 (t, 6.9) |
4.04 (t, 6.8)
3.82 (t, 6.8) |
4.0 (t, 8.5)
3.77 (t, 8.5) |
CH2-O-
CH2-O- |
*=overlaps with water signal.
Legend
These data are essentially in agreement with those previously reported[6],[7], but these are more precise.
Next, we measured the 13C NMR spectra of compounds 4-14 in DMSO-d6.