201600030
FULL PAPER
(+)-N-Formylnorglaucine Rotamers from Unonopsis stipitata DIELS
by Felipe M. A. da Silva*
a
), Francinaldo A. da Silva Filho
a
), Bruna R. de Lima
a
), Richardson A. de Almeida
a
), D acio
M. Mendonc ßa
b
), Raimundo C. Pereira Junior
a
), L ıvia M. Dutra
c
), Andersson Barison
c
), Hector H. F. Koolen
d
), Afonso
D. L. de Souza
a
), and Maria L ucia B. Pinheiro
a
)
a
) Department of Chemistry, Federal University of Amazonas, Manaus-AM, 69077-000, Brazil (phone: +55 92 982517341;
e-mail: felipemas@ufam.edu.br)
b
) Amazon Biotechnology Center, Manaus-AM, 69075-351, Brazil
c
) NMR Center, Federal Universisty of Paran a, Curitiba-PR, 81531-990, Brazil
d
) DeMpSter Mass Spectrometry Group, Amazonas State University, Manaus-AM, 69050-010, Brazil
(+)-N-formylnorglaucine (1), an aporphine alkaloid containing a formyl group linked to the heterocyclic nitrogen, was
isolated from the leaves of Unonopsis stipitata, an Amazon medicinal plant. The chemical structure was characterized based
on 1D- and 2D-NMR spectroscopy and HR-ESI-MS. NMR spectra revealed that 1 is composed of two rotamers (1a and
1b) in a ratio of approximately 2:1. In addition, the fragmentation behavior of 1 displayed an unusual fragmentation
pattern compared to regular aporphine alkaloids. Thus, this compound is reported for the first time as a natural product in
this study.
Keywords: Unonopsis stipitata, Aporphine alkaloid, Rotamers, (+)-N-Formylnorglaucine, Annonaceae.
Introduction
Unonopsis (Annonaceae) is a neotropical genus with
broad distribution through the Amazon region [1]. Some
species of Unonopsis have been described due to its
medicinal applications [2][3], including Unonopsis stipitata
whose pulverized leaves are employed in the treatment of
brain disorders [3]. A recent study indicated that U. stipi-
tata is a promising source of aporphine alkaloids [4],
which are extensively explored in synthetic studies due to
promising biological activities observed for several apor-
phinoid structures [5 – 8].
Besides its attractive biological properties, the fast
recognition and dereplication of this class in complex
matrices by mass spectrometry (MS) has accelerated the
research for new compounds [9 – 11]. This favorable sit-
uation is possible due to the advances on the gas-phase
chemistry of aporphines through key fragmentation
recognition via collision-induced dissociation (CID)
experiments [12].
Aiming the discovery of new alkaloids from Amazon
medicinal plants, we carried out a chemical investigation
of the leaves of U. stipitata, which resulted in the isolation
of a new natural aporphine compound. In the present
work, we chemically characterized this substance through
1D- and 2D-NMR techniques and MS. In addition, the
fragmentation behavior by CID was investigated through
high-resolution MS.
Results and Discussion
Structure Elucidation
Compound 1 was obtained as a yellow amorphous solid
with molecular formula C
21
H
24
NO
5
(m/z 370.1627), as
determined by HR-ESI-MS. The
1
H-NMR spectrum indi-
cated duplicate aromatic, CH, methoxyl, and CH
2
signals
in CDCl
3
(Tables 1 and 2) at a ratio of approximately 2:1,
suggesting the presence of two rotameric isomers (1a and
1b) [13 – 15]. This ratio was estimated based on the inte-
gration of aromatic signals. Therefore, each signal of the
two rotamers was individually assigned.
In the
1
H-NMR spectrum, signals of eight deshielded
H-atoms were observed at d(H) 6.62 (s,H–C(3)), 6.80 (s,
H–C(8)), 8.14 (s,H–C(11)), and 8.26 (s,N–CHO), which
are relative to the main rotamer 1a, and at d(H) 6.65 (s,
H–C(3
0
)), 6.77 (s,H–C(8
0
)), 8.15 (s,H–C(11
0
)), and 8.39
(s,N–CHO’) for the minor rotamer 1b. Besides, four
MeO groups were observed at d(H) 3.68 (s, MeO–
C(1)), 3.91 (s, MeO–C(2)), 3.91 (s, MeO–C(10)), and 3.92
(s, MeO–C(9)) for 1a, whereas MeO group signals at d
(H) 3.67 (s, MeO–C(1
0
)), 3.91 (s, MeO–C(2
0
)), 3.92 (s,
MeO–C(10
0
)), and 3.94 (s, MeO–C(9
0
)) were attributed to
1b. A typical CH signal was observed at d(H) 4.92 (dd,
J = 14.2, H–C(6a)) for 1a and d(H) 4.49 (dd, J = 14.4, 4.5,
H–C(6a
0
)) for 1b, suggesting that 1 has an aporphine
skeleton [10][13 – 15]. Through HSQC experiments, it
DOI: 10.1002/hlca.201600030 © 2016 Verlag Helvetica Chimica Acta AG, Z€ urich
Helv. Chim. Acta 2016, 99, 1–5 1