2
K. Ahamada et al. / Tetrahedron Letters xxx (2016) xxx–xxx
Table 1
5
5
N
NMR charts of polyneuridine aldehyde 3 and compound 7
Oβ-D-Glc
O
NH
Polyneuridine aldehyde (3) DMSO-
Product (7) chloroform-d
N
H
H
1
5
d6
N
H
H
2
CO Me
H
16
1
6
dH
dC
dH
dC
HO
corynan alkaloids
2
MeO C
geissoschizine (2)
1
2
3
5
6
10.89 (1H, s)
—
—
—
—
182.5
biosynthetic precursor
—
138.4
48.8
57.1
23.0
strictosidine (1)
- oxidation
Mannich
4.18 (1H, dd, 10.6–2.0 Hz)
4.01 (1H, d br, 4.7 Hz)
2.89 (1H, dd, 15.5–4.7 Hz)
2.97 (1H, dd, 15.5–1.0 Hz)
4.05 (1H, m)
4.04 (1H, m)
1.54 (1H, d, 3.2 Hz)
3.32 (1H, dd, 14.0–
3.2 Hz)
54.9
49.2
31.8
-
a
H
O
OHC CO
2
Me
Me
6b
H
H
5
16
Me
7
8
9
1
1
1
—
—
104.1
125.5
117.7 7.32 (1H, m)
118.6 7.16 (1H, t, 7.4 Hz)
120.9 7.31 (1H, m)
111.1 7.47 (1H, d, 7.8 Hz)
—
—
81.5
N
138.4
130.0
126.4
123.1
121.2
154.0
25.0
O
Me
N
N
H
N
H
7.35 (1H, d, 7.7 Hz)
6.95 (1H, dd, 8.3–7.7 Hz)
7.04 (1H, dd, 8.3–8.0 Hz)
7.28 (1H, d, 8.0 Hz)
—
2.19 (1H, ddd, 13.6–4.2–
2.0 Hz)
1.83 (1H, dd, 13.6, 10.6 Hz)
3.38 (1H, d br, 4.2 Hz)
—
H
0
1
2
sarpagan alkaloids
polyneuridine aldehyde (3)
alstophyllan alkaloids
macroline (4)
13
1
136.5
27.3
—
O
4a
2.53 (1H, t, 13.5 Hz)
H
HO
OMe
Me
1
1
1
1
1
1
2
2
2
2
4b
5
6
7
8
1.80 (1H, d, 13.5 Hz)
3.37 (1H, m)
—
ajmalan alkaloids
quebrachidine (5)
29.0
62.2
32.7
53.3
94.6
12.9
116.9
135.1
54.6
N
N
8.90 (1H, s)
195.2 5.53 (1H, s)
12.6
115.7 5.26 (1H, q, 6.8 Hz)
136.0
54.7
H
H
1.56 (3H, d, 6.9 Hz)
5.25 (1H, q, 6.9 Hz)
—
3.45 (1H, d, 17.0 Hz)
3.55 (1H, d, 17.0 Hz)
—
1.57 (3H, d, 6.8 Hz)
9
0
Scheme 1. Place of polyneuridine aldehyde (3) in the biosynthetic pathways.
—
1a
3.44 (1H, m)
3.58 (1H, s)
—
1b
2
170.5
52.4
172.9
52.1
O
O
H
H
OMe 3.61 (3H, s)
3.64 (3H, s)
HO
OMe
HO
1
6
Me
OMe
Me
15
5
(
a)
N
N
N
H
H
N
H
1
7
OHC
CO
2
Me
9
16
22
ajmalan-form (3')
6
quebrachidine (5)
5
A
15
7
14
C
19
B
N D
21
1
2
O
H
sarpagan-form
N
H
2
3
HO
polyneuridine aldehyde (3)
OMe
OHC
Me
CO Me
2
(
b)
O
Me
Figure 1. Key HMBC correlations of 3.
N
7
N
N
(
c)
N
H
1
)
dehydratation
retro-Mannich
isomerisation
polyneuridine aldehyde (3)
2
)
shielding effect from the indole nucleus. This value can be com-
3
)
5
1
11
4
)
C16 elimination
pared to the aldehyde H NMR of vellosimine at 9.57 ppm.
N
The quinuclidine nucleus of polyneuridine renders the molecule
quite constraint and limits the number of possible conformations.
flavopereirine (6)
Me
N
H
15
a
The observed coupling constants (J3H-14 10.6 Hz, J3H-14b 2.0 Hz,
J
15H-14a
4.2 Hz, J15H-14b < 1 Hz) are coherent with dihedral angles
Scheme 2. Synthesis of polyneuridine aldehyde (3) and degradation by-products.
Reaction conditions: (a) MnO , CH Cl (>95%); (b) CHCl , H O (6: 50%, 7: 20%); (c)
DMSO-D (quant.).
of 10°, 110°, 40°, and 80°, respectively (according to the Karplus
diagram), as predicted after geometry optimization of the
molecule.
2
2
2
3
2
6
1
2
Polyneuridine aldehyde (3) revealed to be unstable in solution
and degradation products could be characterized. After 2 days of
proton signals could be split and coupling constants accessible. The
aerobic stirring in DMSO-d , 3 was completely oxidized into a pol-
6
1
3
predominant sarpagan form was confirmed by the typical
chemical shifts of C2, C7, C8, and C13 of the indole nucleus at
38.4, 104.1, 125.5, and 136.5 ppm, respectively.10 All connectivi-
C
yaromatic compound 6. Compound 6 was identified as being
1
3
flavopereirine known as a natural product from Geissospermum
14
1
sp. Moreover, Geissospermum laeve contains large amounts of vel-
1
1,15
ties in the indole nucleus were completed by heteronuclear HMBC
experiment (Table 1, Fig. 1). HMBC also indicated correlations
between carbon C7 and protons H3, H5, and H6 and between posi-
tions C3 and H5 thus establishing all chemical shifts of the C-ring.
The COSY experiment suggested spin couplings involving H3, H14
and H15. HMBC experiment and also the indicated C3/H21,
C21/H15, and C20/H14 connectivities, completed thereby the attri-
bution of the D-ring of polyneuridine aldehyde (3). Finally the C16
carbon bridge (62.2 ppm) was attributed based on the C5/H15 and
C16/H6, H15 HMBC correlations. Concerning the 1H NMR of the
C17 aldehyde, the low value of 8.90 ppm may be explained by a
losimine, biosynthetically originating from 3.
From our results
we can presume that isolation of 6 in Geissospermum laeve partially
originates from aerobic degradation of polyneuridine aldehyde
during the extraction procedure, rather than an enzymatic process
1
6
in the plant cells. A stable product 7 was also obtained from aer-
obic stirring of 3 in chloroform. Mass spectra indicated the pres-
ence of
a supplementary oxygen atom. Heteronuclear NMR
analysis indicated the conservation of the quinuclidine nucleus
and the presence of a hydroxy-indolenine ring system suggested
by the C2 chemical shift at 182.5 ppm and the C7 unshielded
chemical shift at 81.5 ppm. Furthermore, the chemical shift of