Tetrahedron Letters
Determination of the absolute configuration of picrasidine Y,
a naturally occurring b-carboline alkaloid
a,
⇑
a
b
a
a
Kazuo Koike , Hiroshi Yoshino , Hong-yu Li , Tatsunori Sasaki , Wei Li
a
Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan
College of Pharmacy, Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85721, USA
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The absolute configuration of picrasidine Y, a b-carboline alkaloid isolated from Picrasma quassioides
Simaroubaceae), has not been determined. To determine the absolute configuration of picrasidine Y,
Received 26 June 2015
Accepted 29 July 2015
Available online 1 August 2015
(
we synthesized stereoisomers of picrasidine Y through 7-step chemical reactions using tartaric acid as
a starting material. Moreover, we extended the scope of application of this synthetic method to
canthin-5,6-dione compounds. The absolute configuration of natural picrasidine Y was elucidated based
Keywords:
Absolute configuration
Picrasidine Y
b-Carboline alkaloid
Canthin-5,6-dione
Picrasma
1
13
on comparisons of chemically synthesized isoforms with the naturally occurring compound in H and
C
NMR spectra, specific optical rotation, HPLC analysis with chiral columns, computational molecular
simulation, and analysis with the CD exciton chirality method.
Ó 2015 Elsevier Ltd. All rights reserved.
Picrasma quassioides and other plants in the Picrasma genus of
the Simaroubaceae family are used as bitter stomachics for gastritis,
loss of appetite, and indigestion in Chinese and Japanese traditional
medicine. In addition to limonoids, a large number of b-carboline
and canthinone alkaloids have been isolated from these
L-tartaric acid (2a) was treated with acetic anhydride to yield
the O-protected acid anhydride 3a in one step, which was then
converted to the half-ester 4a with methanol. The carboxylic acid
was converted to the acid chloride 5a with thionyl chloride. The
1
production of 5a was monitored by H NMR spectroscopy.
1
–19
plants.
Furthermore, these alkaloids have been reported to
Specifically, after the 2 h reaction, a broad signal at d
two doublet signals at d 5.72 and 5.75 assignable, respectively,
to the carboxylic acid and two methine protons in 4a disappeared,
and the new methine proton signals shifted to lower field (d 5.83
and 5.91) were observed. Next, 5a was allowed to react with bub-
bling hydrogen in the presence of 5% Pd-BaSO in a xylene reflux to
H
9.84 and
have a variety of biological activities, including PTP1B-inhibition,
anti-inflammatory activity, cAMP-phosphodiesterase inhibition,
H
6
,14,17–19
and cytotoxicity.
Picrasidine
Y
(1) isolated from
H
P. quassioides is a b-carboline alkaloid, and the absolute configura-
tion of the propionic acid side chain at position 1 of the backbone
structure has not been determined (Fig. 1).16 In the present study,
we synthesized stereoisomers of picrasidine Y through 7-step
chemical reactions using tartaric acid as a starting material. We
then determined the absolute configuration of natural picrasidine
Y (1) by comparing chemically synthesized isoforms with the
4
obtain aldehyde 6a through the Rosenmund reduction. The struc-
ture of 6a was confirmed by the appearance of a low-field signal
1
at d
H
9.45 for the aldehyde moiety in the H NMR spectrum and
C
the downfield shift of a carbonyl signal at d C
194.7 in the 13
NMR spectrum.
1
13
naturally occurring compound in H and C NMR spectra, specific
optical rotation, HPLC analysis with chiral columns, computational
molecular simulation, and analysis with the CD exciton chirality
method.
Next, 6a was treated with tryptamine in the presence of triflu-
oroacetic acid (TFA) to construct the b-carboline backbone through
Stereoisomers of picrasidine Y were synthesized from
acid (2R,3R, 2a), -tartaric acid (2S,3S, 2b), and meso-tartaric acid
2c) (Scheme 1). The synthetic methods for these compounds are
L-tartaric
D
N
N
H
HO
1
(
1'
2'
COOH
explained using the one starting from
representative.
L-tartaric acid (2a) as a
OH
Picrasidine Y (1)
⇑
Figure 1. Chemical structure of natural occurring picrasidine Y.
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0