1H and 13C NMR Study of Indoloquinolizines obtained from tryptamine and acetylacetaldehyde.

Results and Discussion

Proton NMR Results

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).

Oxidation and ketalization

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.

Treatment with base

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.

Indole and tryptamine

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.

1H NMR chemical shift data in DMSO-d6
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


1H NMR chemical shift data in DMSO-d6 (cont.)
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)
4.28 (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-
All values in ppm and coupling constants in Hz.

*=overlaps with water signal.

Legend

13
indole
14
tryptamine
4
tryptamine hydrochloride
s
singlet
d
doublet
t
triplet
A
H numbering in indole system
B
H numbering in indoloquinolizinium system

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.


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