Scopuquinolone B, a new monoterpenoid dihydroquinolin-2(1H)-one isolated from the coral-derived Scopulariopsis sp. fungus

Article abstract of DOI:10.1080/14786419.2017.1359177

Further chemical investigation of the secondary metabolites of the fungus Scopulariopsis sp. led to the discovery of a new alkaloid, scopuquinolone B (1). The structure of compound 1 was elucidated by extensive NMR spectroscopic data, CD spectrum and analysis of its Dess-Martin oxidation derivative. Compound 1 was evaluated for antilarval settlement activity of barnacle Balanus amphitrite and showed promising antifouling activity with an EC₅₀ value of 0.103?μM and a high therapeutic ratio of 222.

Full text of DOI:10.1080/14786419.2017.1359177

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
Scopuquinolone B, a new monoterpenoid
dihydroquinolin-2(1H)-one isolated from the coral-
derived Scopulariopsis sp. fungus
Xiao-Feng Mou, Xin Liu, Ru-Fang Xu, Mei-Yan Wei, Yao-Wei Fang & Chang-Lun
Shao
To cite this article: Xiao-Feng Mou, Xin Liu, Ru-Fang Xu, Mei-Yan Wei, Yao-Wei Fang &
Chang-Lun Shao (2017): Scopuquinolone B, a new monoterpenoid dihydroquinolin-2(1H)-one
isolated from the coral-derived Scopulariopsis sp. fungus, Natural Product Research, DOI:
10.1080/14786419.2017.1359177
To link to this article: http://dx.doi.org/10.1080/14786419.2017.1359177
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Date: 09 August 2017, At: 02:34

Natural Product research, 2017
https://doi.org/10.1080/14786419.2017.1359177
Scopuquinolone B, a new monoterpenoid dihydroquinolin-
2(1H)-one isolated from the coral-derived Scopulariopsis sp.
fungus
Xiao-Feng Moua, Xin Liub, Ru-Fang Xua, Mei-Yan Weia,c, Yao-Wei Fanga,d and
Chang-Lun Shaoa
aKey laboratory of Marine drugs, school of Medicine and Pharmacy, ocean university of china, Qingdao, the
b
People’s republic of china; technical center, Beijing entry-exit Inspection and Quarantine Bureau, Beijing,
the People’s republic of china; cschool of Pharmacy, Guangdong Medical university, dongguan, the People’s
republic of china; dcollege of Marine life and Fisheries, huanghai Institute of technology, lianyungang, the
People’s republic of china
ABSTRACT
ARTICLE HISTORY
received 2 June 2017
accepted 15 July 2017
Further chemical investigation of the secondary metabolites of the
fungus Scopulariopsis sp. led to the discovery of a new alkaloid,
scopuquinolone B (1). The structure of compound 1 was elucidated
by extensive NMR spectroscopic data, CD spectrum and analysis of
its Dess-Martin oxidation derivative. Compound 1 was evaluated
for antilarval settlement activity of barnacle Balanus amphitrite and
showed promising antifouling activity with an EC50 value of 0.103 μM
and a high therapeutic ratio of 222.
KEYWORDS
Scopulariopsis sp.;
dihydroquinolin-2(1H)-one;
alkaloids; marine natural
products; antifouling activity
1. Introduction
Marine-derived microorganisms have proved to be a rich and important source of drug
candidates (Gerwick and Moore 2012; Blunt et al. 2016). The dihydroquinolin-2(1H)-one
alkaloids constitute an important alkaloid family which has attracted great interest of numer-
ous chemists (Mieriņa et al. 2016; Simonetti et al. 2016). A variety of biological activities of
the compounds from this family were found through oriented bioactivities screening
CONTACT Yao-Wei Fang
fangyw@hhit.edu.cn; chang-lun shao
shaochanglun@163.com
supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2017.1359177.
© 2017 Informa uK limited, trading as taylor & Francis Group

2
X.-F. MOU ET AL.
strategies, such as cytotoxic (He et al. 2005), antioxidant (Wubshet et al. 2013), herbicidal
(Kusano et al. 2000) and anti-RSV (Chen et al. 2014) activities. A series of dihydroquino-
lin-2(1H)-one alkaloids, including scopuquinolone A (Shao et al. 2016), aniduquinolone A,
aflaquinolone A, aflaquinolone D and 6-deoxyaflaquinolone E (Neff et al. 2012; An et al. 2013;
Shao et al. 2015), showed potent antifouling activity. Further chemical investigation led to
the isolation of another new dihydroquinolin-2(1H)-one alkaloid with a monoterpenoid side
chain, scopuquinolone B (1). Compound 1 was also evaluated for antifouling activity and
showed strong antilarval settlement activity with an EC50 value of 0.103 μM and a high
therapeutic ratio of 222. Herein, we report the structure elucidation and antifouling activity
of scopuquinolone B (1).
2. Results and discussion
Secondary metabolites of the fungus Scopulariopsis sp. were further separated and purified
by a combination of silica gel column chromatography, Sephadex LH-20 and semi-
preparative HPLC to yield 1.
Scopuquinolone B (1) was obtained as pale yellow solid. Its molecular formula of C26H31NO5
was determined by HREIMS (m/z 437.2197), which suggested 12 degrees of unsaturation.
The IR spectrum showed absorption bands for hydroxyl (3361 cm−1) and amide (1685 cm−1)
groups. Detailed analysis of the 1H NMR and 13C NMR data of 1 (Table S1) together with a
literature search revealed that 1 was closely related to aflaquinolone B (Neff et al. 2012). The
most obvious differences were the chemical shifts of C-19, C-20, C-22 and C-24 which were
obviously shifted downfield (δC 37.6, 46.9, 76.7 and 37.7 in 1 vs 30.7, 40.0, 70.0 and 31.7 in
aflaquinolone B) indicating the different configurations of the cyclohexane rings in both
compounds.
To elucidate the relative configurations of the aliphatic ring in 1, the selective 1D NOE
experiment was carried out (Figure S13). When the signal at δH = 3.02 (H-22) was irradiated,
the signal of H3-26 (δH 4.42), H-24ax (δH 1.39) and H-23 eq (δH 1.71) enhanced, indicating that
H-22 and the methyl group of C-26 should be in a cis relationship. When the signal at δH = 1.01
(H3-25) was irradiated, the signal of H-20ax and H-24ax enhanced, indicating that the methyl
group of C-25 and H-20ax, H-24ax should be in a cis relationship. Because the signals of CD
spectrum of 1 mainly reveal the configurations of the 4-phenyl-3,4-dihydroquinolin-2(1H)-one
unit, the absolute configurations of this unit in 1 could be established as 3S,4S by CD spec-
trum (Figure S14) compared with those of aflaquinolones (Neff et al. 2012). Until now, there
are two potential structures 1 and 1a which was shown in Figure S15.
Treatment of 1 with Dess-Martin periodinane in CH2Cl2 afforded a Dess-Martin oxidation
product (Figure 1). Finally, the oxidation product of 1 was identified as aflaquinolone A
Figure 1. chemical transformation of 1 to aflaquinolone a.

NATURAL PRODUCT RESEARCH
3
(Figure S16). Because the relative and absolute configurations of aflaquinolone A have been
previously established, the chemical conversion from 1 to aflaquinolone A allows the deter-
mination of 3S, 4S, 19R, 21S and 22S configuration for 1.
Marine biofouling has major economic impact to all marine industries. Barnacle is one of
the most common marine sessile organisms worldwide, and its strong adhesion causes
seriously fouling problems (Khandeparker and Anil 2007). In the past decades, a variety of
marine natural products have been discovered and proved to show antifouling activity (Qian
et al. 2010; Shao et al. 2011). Compound 1 was also evaluated for antifouling activity against
the larval settlement of the barnacle Balanus amphitrite according to literature procedures
(Thiyagarajan et al. 2003). It showed potent antilarval settlement of B. amphitrite cyprids
with an EC50 value of 0.103 μM and a high therapeutic ratio (LC50/ EC50) of 222, which is
stronger than the positive control SeaNine 211 (EC50 = 4.36 μM, LC50/ EC50 = 20).
3. Conclusion
In summary, We reported the isolation and structure elucidation of a new compound scop-
uquinolone B (1), a 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid with a monoterpenoid
side chain. Compound 1 showed strong antifouling activity and a very high therapeutic
ratio. Ongoing studies are focused on total synthesis and pharmacological activity screening
of this class of compounds.
Supplementary material
Experimental details related to this article along with Figures S1–S16 and Table S1 is available online.
Acknowledgements
We would like to thank Prof. P.-Y. Qian and K.-L. Wang for the evaluation of antifouling activity.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the Programme of National Natural Science Foundation of China [grant num-
ber 41606172], [grant number 41322037]; the Programme of Natural Science Foundation of Shandong
Province of China [grant number JQ201510]; Marine Special Public Welfare Scientific Research, State
Oceanic Administration of China [grant number 201405038]; AoShan Talents Programme Supported
by Qingdao National Laboratory for Marine Science and Technology [grant number 2015ASTP-ES11]
and the Taishan Scholars Programme, China.
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