Tetrahedron Letters
Homopetasinic acid isolated from Diaporthe sp. strain 1308-05
Atsushi Ito a, Ikuya Kumagai b, Miku Maruyama c, Hayato Maeda b, Akio Tonouchi b, Tatsuo Nehira d,
Ken-ichi Kimura a,c, Masaru Hashimoto a,b,
⇑
a The United Graduate School of Agricultural Science, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Japan
b Faculty of Agriculture and Bioscience, Hirosaki University, 3-Bunkyo-cho, Hirosaki 036-8561, Japan
c Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, Japan
d Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1, Kagamiyama, Higashi-Hiroshima 739-8521, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Homopetasinic acid (1) was isolated from fungi of the Diaporthe sp. strain 1308-05. NMR spectroscopic
structural analysis revealed a petasol (3) substructure and a (4E,6E)-7-carboxy-3-hydroxy-2-methyl-
hepta-4,6-dienoate side chain. The absolute configuration of the petasol moiety was established by the
specific rotation value after basic hydrolysis. The (20S,30S)-configuration of the side chain was determined
by NMR empirical methods as well as comparison of the spectral data with related model compounds.
The absolute structure of the side chain moiety was established on the basis of ECD spectral analyses
involving theoretical calculations. The biological activities of 1 are also discussed.
Received 16 December 2015
Revised 21 January 2016
Accepted 27 January 2016
Available online 28 January 2016
Keywords:
Homopetasinic acid
Chemical correlation
Electron circular dichroism analysis
Cytotoxicity
Ó 2016 Elsevier Ltd. All rights reserved.
Introduction
1308-05. Homopetasinic acid (1) afforded a protonated molecular
ion at m/z = 417.2296. The mass spectrum also showed the sodium
Petasin, an eremophilane-type sesquiterpenoid, was first iso-
lated from roots of Petasites hybridus (L.) in 1955.1 S-Petasin is
the (Z)-3-(methylthio)acrylate derivative found in P. officinalis2 as
well as P. formosanus Kitamura.3 The latter has been used as a folk
medicine in Taiwan.4 Since S-petasin exhibits remarkable biologi-
cal properties, such as inhibition of cumulative histamine,3 spas-
molytic activity,2 and anti-inflammatory activity,5 it is
anticipated to be a novel drug. Although these were isolated from
plant resources, we herein report homopetasinic acid (1), a 3-O-
[(4E,6E,2S,3S)-3-hydroxy-2-methylocta-4,6-dienedioate] analogue
of petasol (3), from the filamentous fungus Diaporthe sp. strain
1308-05. The structure was elucidated by ESIMS, 1H and 13C
NMR, chemical derivatizations, and ECD analyses.
adduct ion at m/z = 439.2115, which was helpful to establish the
molecular formula of 1 as C24H32O6 ([M+H]+: 417.2277, [M+Na]+:
439.2097). This molecule also gave a dehydrated ion at m/z =
399.2187, suggesting a hydroxy group ([MꢀOH]+: 399.2171).
The NMR spectral data of 1 in CDCl3 are summarized in Table 1.
The 1H-decoupling 13C NMR and HMQC spectra reveal 24 carbon
atoms comprising four methyl, four methylene (involving an exo-
methylene), ten methine, and six quaternary carbons (involving
three carbonyls). These analyses also reveal 30 hydrogen atoms
directly linked with carbons. The 13C NMR signal at 198.46 ppm
is assigned as a ketone, while signals appearing at 169.76 and
174.79 ppm suggest carboxy groups. These were supported by
broad but strong absorption found at 1650–1720 cmꢀ1 in the IR
spectrum. Treatment of 1 with trimethylsilyldiazomethane in
methanol gave the monomethyl ester 2 (m/z = 431.2434), revealing
a carboxylic acid functionality in the molecule. Detailed NMR anal-
Results and discussion
yses disclosed that
1 comprises a (4E,6E,2S,3S)-3-hydroxy-2-
Isolation and structural elucidation
methylocta-4,6-dienedioate side chain unit and a petasol substruc-
ture. Relative configuration of the petasol moiety was determined
by NOEs found at Hb-1/H-3, Hb-1/H3-14, H-7/H3-14, and H3-14/H3-
15. The (E,E)-configuration for the C40,C60-diene component was
In the course of exploring novel and bioactive secondary
metabolites from fungi in the Shirakami mountainous area Japan,
homopetasinic acid (1) was isolated along with phomolide C6
and UCS1025A7 from the culture broth of Diaporthe sp. strain
2
established by observing large spin couplings at JH-4/H-5 and
2JH–6/H-7 (15.5 Hz for both).
As shown in Figure 1, alkaline hydrolysis of 1 gave an approxi-
mate 1:1 mixture of petasol (3) and isopetasol (4) as well as
⇑
Corresponding author. Tel./fax: +81 172 39 3782.
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.