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Pyristriatins A and B: Pyridino-Cyathane Antibiotics from the

Basidiomycete Cyathus cf. striatus
Christian Richter,† Soleiman E. Helaly,†,‡ Benjarong Thongbai,§ Kevin D. Hyde,§ and Marc Stadler*,†

Department of Microbial Drugs, Helmholtz Centre for Infection Research; and German Centre for Infection Research (DZIF),
partner site Hannover/Braunschweig, Inhoffenstrasse 7, 38124 Braunschweig, Germany

Department of Chemistry, Faculty of Science, Aswan University, Aswan 81528, Egypt
Institute of Excellence in Fungal Research and School of Science, Mae Fah Luang University, Chiang Rai 57100, Thailand
S Supporting Information

ABSTRACT: Two novel pyridino-cyathane diterpenoids,

pyristriatins A and B (1 and 2), together with striatin C (3)
were isolated from cultures of Cyathus cf. striatus, a
basidiomycete that was found during a field trip in northern
Thailand. The pyristriatins showed antimicrobial effects against
Gram-positive bacteria and fungi. The isolation, structure
elucidation, relative configuration, and biological and cytotoxic
activity are described. Their structures were assigned by
HRMS and NMR spectroscopy. We also describe the first 2D
NMR assignment of striatin C. Pyristriatins A and B are the
first cyathane natural products featuring a pyridine ring.

A ntibiotic-resistant bacteria and emerging infectious dis-

eases are on the rise, new therapeutic agents are needed
more than ever.1 The Basidiomycota represent a relatively
neglected source for promising natural products.2 Cyathane
diterpenoids are a structurally diverse class of secondary
metabolites that are primarily produced by basidiomycetes.
The first compounds of this class of metabolites were isolated
from Cyathus helenae in the 1960s.3 Later, several similar
compounds were isolated from related species of the
Nidulariaceae and in species of other fungal orders.4,5 In
particular, the genus Cyathus is still a promising source for
novel bioactive metabolites.6 Depending on their sources, the
cyathane compounds were named cyathins, striatins, sarcodo-
nins, scabronines, and erinacines. All of these compounds share
a characteristic 5−6−7 tricyclic carbon skeleton.7 Many of these
diterpenoids show biological activity, such as antimicrobial,
anti-inflammatory, and antiproliferative properties, as well as
osteoclast-forming suppressing, nerve growth factor activating,
and agonistic effects toward the kappa-opioid receptor.8
Herein, we report on the isolation, structure determination,
and biological evaluation of two novel cyathane compounds,
pyristriatins A and B (1 and 2), and the known striatin C (3). Figure 1. Pyristriatin A (1), pyristriatin B (2), and striatin C (3).
The new metabolites are members of the cyathane diterpenoid
family; they are related to the striatins but differ by the presence
of a pyridine ring. The antimicrobial and cytotoxic properties of displayed a molecular ion peak at m/z 442.2623 [M + H]+
these metabolites are described. Furthermore, the morpho- (calcd 442.2588) in the HRESIMS spectrum, which was
logical description and the phylogenetic position of the consistent with the molecular formula of C26H35NO5 with 10
producing organism is illustrated and discussed. degrees of unsaturation. The 1H NMR data (Table 1) showed a
Pyristriatin A (1) was obtained as a white, amorphous
powder. Molecular ion peaks at m/z 442.13 [M + H]+ and Received: March 4, 2016
440.17 [M − H]− revealed the molecular mass of 441.13. It
© XXXX American Chemical Society and
American Society of Pharmacognosy A DOI: 10.1021/acs.jnatprod.6b00194
J. Nat. Prod. XXXX, XXX, XXX−XXX
Journal of Natural Products Note

Table 1. NMR Spectroscopic Data (700 MHz, CD3OD) for Pyristriatin A (1), Pyristriatin B (2), and Striatin C (3)
1 2 3
pos. δC, type δH (J in Hz) δC, type δH (J in Hz) δC, type δH (J in Hz)
1a 39.9, CH2 1.56, m 39.9, CH2 1.56, m 40.7, CH2 1.52, m
1b 1.64, m 1.64, m 1.72, m
2 29.3, CH2 2.35, m 29.4, CH2 2.35, m 29.5, CH2 2.33, m
3 140.4, qC 140.4, qC 140.7, qC
4 139.1, qC 139.0, qC 138.1, qC
5 47.9, CH 2.24, brs 48.5, CH 2.19, brs 48.2, CH 2.23, brs
6 47.5, qC 47.8, qC 41.4, qC
7a 33.1, CH2 1.18, m 32.1, CH2 0.89, m 30.3, CH2 1.44, m
7b 1.48, m 1.55, m 1.72, m
8a 38.5, CH2 1.40, m 38.4, CH2 1.38, m 38.4, CH2 1.56, m
8b 1.54, m 1.52, m
9 50.5, qC 50.4, qC 50.6, qC
10 68.8, CH 4.73, brd (4.3) 68.7, CH 4.72, brd (4.3) 70.2, CH 4.63, d (7.0)
11a 43.4, CH2 3.14, d (19.2) 43.5, CH2 3.14, d, (18.9) 133.4, CH 6.09, m
11b 3.34, d (16.7) 3.34, d (16.5)
12 135.6, qC 135.9, qC 136.4, qC
13 150.8, qC 150.9, qC 48.6, CH 2.99, d (9.5)
14 90.4, CH 5.85, s 89.3, CH 5.92, s 91.6, CH 4.65, d (9.1)
15 151.9, CH 8.45, s 151.9, CH 8.46, s 99.4, CH 5.24, brs
16 21.1, CH3 1.31, s 21.0, CH3 1.32, s 21.8, CH3 1.22, s
17 24.9, CH3 0.81, s 24.9, CH3 0.79, s 24.5, CH3 1.02, s
18 27.2, CH 3.31, m 27.2, CH 3.31, m 26.9, CH 3.39, m
19 22.5, CH3 1.04, d (6.7) 22.4, CH3 1.04, d (7.0) 22.2, CH3 0.97, d (7.1)
20 22.0, CH3 1.05, d (6.7) 22.0, CH3 1.05, d (6.7) 22.4, CH3 1.02, d (6.4)
1′ 107.9, CH 6.47, s 107.7, CH 6.58, d (2.1) 107.3, CH 4.94, s
2′ 134.5, qC 135.1, qC 81.3, qC
3′ 145.9, qC 146.1, qC 97.9, qC
4′ 200.5, qC 200.5, qC 70.2, CH 3.88, dd (4.9, 9.2)
5a′ 67.2, CH2 4.91, d (19.3) 68.7 4.91, d (19.5) 65.2, OCH2 3.66, dd (4.9, 10.1)
5b′ 5.21, d (19.5) 5.21, d (19.5) 3.75, dd (9.1, 10.7)
6′ 57.4, OCH3 3.59, s 56.6, OCH3 3.50, s 56.7, OCH3 3.56, s

characteristic aromatic singlet (δH 8.45) and together with the

nitrogen atom implied by the molecular formula suggested the
presence of a heterocyclic ring in compound 1. HSQC data
established all 1J1H−13C connectivities. The planar structure of
pyristriatin A was established by comprehensive analysis of the
2D NMR data, particularly COSY and HMBC data (Figure
2A), in which the HMBC correlations network from H-1 to C-
3/C-4/C-9, H-2 to C-4/C-9, H-5 to C-3/C-4/C-7/C-9/C-11/
C-16, H-10 to C-4/C12/C-6, H-11 to C-5/C-12/C-13, H-14 to
C-13/C-6/C-7, H-7 to C-5/C-8/C-14, and H-8 to C-4/C-6/C-
7/C-9 enabled the construction of the characteristic 5−6−7
tricyclic carbon skeleton (rings A, B, and C) in 1. In addition,
HMBC correlations from the methyls H3-16 to C-14/C-5/C-6/
C-7, H3-17 to C-8/C-9/C-1, and H-18 to C-2/C-3/C-4 and
from the two germinal methyls H3-19/H3-20 to C-18/C-3
indicated the presence of 10-hydroxycyathane in compound 1.
The previously mentioned data and biosynthetic reasoning
suggested that 1 was likely a new cyathane derivative containing
a heterocyclic ring. Furthermore, HMBC correlations from H-
15 (δH 8.45) to C-11/C-12/C-13/C-3′ enabled the con-
struction of a pyridine ring attached at C-12/C-13 of the
cyathane skeleton (ring E). The five-membered 2-methoxyte-
trahydrofuran D-ring was established by the HMBC correlation
from H-1′ (δH 6.47) to C-14 and C-13 together with an HMBC Figure 2. Key HMBC (arrows) and COSY (green bonds) correlations
correlation from H-14 (δH 5.85) to C-2′ and a correlation from of 1 and 2 (A) and 3 (B).
the methoxyl group H-6′ to C-1′. Finally, the presence of a 2-
hydroxyethanone moiety was deduced by an HMBC
B DOI: 10.1021/acs.jnatprod.6b00194
J. Nat. Prod. XXXX, XXX, XXX−XXX
Journal of Natural Products Note

correlation from the oxygenated methylene to the carbonyl C-5, C-6, and C-9, and consequently the tentative absolute
carbon (C-4′); its position attached to C-3′ of the pyridine ring configuration of 1 is assumed to be 5R,6R,9R,10S,14R,1′R.
was determined by a weak HMBC correlation from H-5′ to C- Pyristriatin B (2) was obtained as a white, amorphous
3′. Consequently, compound 1 was established as a novel powder. The EIMS data of 2 were identical with compound 1,
pyridino-cyathane diterpenoid, which was named pyristriatin A, which exhibited a molecular mass of 441.13, and similarly the
representing the first member of the cyathane diterpenoid HRESIMS data (m/z 442.2625, [M + H]+) gave the molecular
family possessing a pyridine ring. formula of C26H35NO5 (calcd 442.2588). Nevertheless,
The relative configuration of 1 was established by compound 2 showed a difference of 0.35 min in the HPLC
examination of its NOESY data (Figure 3A). A strong NOE chromatogram. The 2D NMR data analysis, particularly the
HMBC (Figure 2A) revealed that compound 2 has the same
planar structure as 1. Its 1H and 13C NMR data revealed a high
similarity with those of 1, and the slight differences observed
were closely associated with C-1′, with the H-7 (δH 1.18/1.48,
1; 0.89/1.55, 2), H-14 (δH 5.85, 1; 5.92, 2), H-1′ (δH 6.47, 1;
6.58, 2), and the methoxy group (δH 3.59, 1; δH 3.50, 2)
suggesting that they were C-1′ epimers. The relative
configuration of pyristriatin B was assigned on the basis of its
NOESY spectrum, which showed that the stereocenters from
rings A to C were identical with those of 1. Nevertheless, the
key NOE correlation between H-1′ and H-7a and between H-
7a and H-5 indicated that the plane of rings D and E is vertical
on the cyathane rings and H-1′ is β-oriented (Figure 3B).
Furthermore, on comparing its NMR data with those of 1
(Table 1), H-7a in 2 was significantly more shielded due to the
effect of the methoxy group (H-6′), while H-14 was more
deshielded owing to the absence of the methoxy group (Figure
4), which confirmed the different configurations at C-1′. Thus,

Figure 3. NOESY correlations of 1 (A) and 2 (B).

correlation between H-14 and H3-16 showed that they were on Figure 4. Newman projections along C-1′/C-14/C-7 bonds for 1 and
the same side of the cyathane skeleton and were assigned to be 2, describing the deshielding effect of the methoxy group on H-7a and
α-oriented. In addition, NOEs between H-5 and H-10/H3-17/ H-14.
H2-7a and between H-10 and H2-11b/H3-18/H3-20 showed
that H-5, H-10, and H3-17 were cofacial and β-oriented. compound 2 was established as the 1′-epimer of 1 and named
Furthermore, no correlations were observed between H-1′ and pyristriatin B. The absolute stereochemistry of pyristriatin B
H2-7, while a weak correlation between the methoxy group H3- was determined, on the same basis previously argued for
6′ and H-7b was observed, indicating that rings D and E are compound 1, as 5R,6R,9R,10S,14R,1′S.
vertical to the cyathane unit and H-1′ is α-directed. Thus, the Compound 3 was isolated from the same fermentation as a
relative configuration of pyristriatin A was assigned as shown in white powder possessing a molecular formula of C26H38O8 as
(Figure 3A), which was in good accordance with those of the determined by HRESIMS, which showed a peak at m/z
striatal/striatin group.6 Several attempts including crystalliza- 461.2550 [M + H − H2O]+ (calcd 461.2534). A database
tion and Mosher esterification, as well as recording the 1H search revealed that the molecular formula of 3 is identical with
NMR of 1 in the chiral solvent BMBA-p-Me reported by that of striatin C, an antibiotic previously isolated from Cyathus
Kobayashi et al.,9 were unsuccessful in determining the absolute striatus.6 To the best of our knowledge there were no 2D NMR
configuration of 1. The NMR data revealed that the data published for striatin C. Thus, herein we described the first
esterification using (R)- and (S)-MTPA chlorides occurs on 2D NMR assignment of striatin C (3). The 1H NMR spectrum
the less sterically hindered hydroxy 5′-OH rather than the exhibited signals for four methyls (one methoxy), five
targeted hydroxy 10-OH. Nevertheless, the diterpenoid part of methylenes (one oxygenated), and nine methines (five
striatals/striatins is formed via the mevalonate pathway,10 and oxygenated and one olefinic). The 13C NMR data with a
to the best of our knowledge all 105 cyathane diterpenoids DEPT spectrum showed 26 carbon resonances. Furthermore,
hitherto reported proved to have the same absolute comprehensive analysis of the 2D NMR data, particularly
configuration at C-5, C-6, and C-9 of the cyathane scaffold.7 COSY and HMBC correlation networks (Figure 2B),
We assume that the cythane scaffold of pyristriatin A (1) is confirmed the planar structure of 3 to be identical with striatin
formed by the same pathway, as it has been coisolated with the C. In addition, further analysis of the NOESY data in which the
known striatin C (3) from the same strain. Therefore, key correlation between H-5 and H-10/H-13/H3-17 and
compound 1 should have the same absolute configuration at between H-13 and H-5/H2-7a showed that H-5, H-10, H-13,
C DOI: 10.1021/acs.jnatprod.6b00194
J. Nat. Prod. XXXX, XXX, XXX−XXX
Journal of Natural Products Note

Table 2. Antimicrobial and Cytotoxic Activities of Compounds 1 and 2

test strains 1 2 reference
Bacteria MIC (μg/mL)
Bacillus subtilis DSM 10 9.4 9.4 ≤2.3 ciprofloxacin
Chromobacterium violaceum DSM 30191 n.a.a n.a. 2.1 oxytetracycline
Escherichia coli DSM 498 n.a. n.a. ≤2.3 ciprofloxacin
Micrococcus luteus DSM 1790 8.3 16.7 8.3 oxytetracycline
Pseudomonas aeruginosa PA 14 n.a. n.a. 0.5 gentamicin
Staphylococcus aureus DSM 346 8.3 16.7 1 oxytetracycline
Candida albicans DSM 1665 n.a. n.a. 16.7 nystatin
Mucor plumbeus MUCL 49355 150 150 9.4 nystatin
Pichia anomala DSM 6766 n.a. n.a. 16.7 nystatin
Rhodotorula glutinis DSM 10134 8.3 16.7 66.7 nystatin
Schizosaccharomyces pombe DSM 70572 8.3 16.7 66.7 nystatin
Cell Lines IC50 (μM)
Huvec 6.3 5.9 0.00055 epothilone B
KB 3.1 HeLa 12.7 14.7 0.00022 epothilone B
mouse fibroblasts L929 15.4 16.3 0.0038 epothilone A
n.a. no activity.

and H3-17 are cofacial and were assigned to be in a β- Collection and Characteristics of the Strain. The fungal
configuration. In addition, H-14, H3-16, and H-4′ were assigned material was collected in August 2014 in the tropical rainforest near
to the α-configuration due to strong correlations between H-14 the MRC (, Chiang Mai
Province, Thailand. A voucher specimen and the corresponding
and H3-16/H-4′. Finally correlations between H-10 and H-11, culture have been deposited at the mycological herbarium of Mae Fah
and H-11 and H-15, revealed that H-15 is α-oriented. Luang University, Chiang Rai (MFLU15-1416 and MFLUCC14-0770,
Consequently, our 2D NMR assignment including NOESY respectively). Sequences of the rDNA (5.8S gene region, the internal
data confirmed that compound 3 is striatin C, and this is the transcribed spacer 1 and 2 (ITS) and part of the large subunit (LSU))
first report of the 2D NMR assignment. are deposited in GenBank with acc. nos. KU865513 (ITS) and
The producing organism is named Cyathus cf. striatus based KU865514 (LSU).
on morphological and molecular data of the specimen and DNA extraction was performed with the EZ-10 Spin Column
Genomic DNA Miniprep kit (Bio Basic Canada Inc., Markham,
culture (Supporting Information). To the best of our
Ontario, Canada). A Precellys 24 homogenizer (Bertin Technologies,
knowledge, pyristriatins A and B are the first cyathane France) was used for cell disruption at a speed of 6000 rpm for 2 × 40
diterpenoids featuring a pyridine ring and therefore also s. The gene regions were amplified with primers ITS 1f and ITS4
constitute the first members of a novel heterocyclic diterpene (ITS) and LR0R and LR7 (LSU). According to the BLAST search
carbon skeleton. We assume that the pyristriatins are descend results of the submitted sequences, the fungal culture belongs to the
from the striatals/striatins biosynthetic pathway.10 In addition, striatum group within the genus Cyathus and is closely related to
the incorporation of ammonia may lead to the formation of the Cyathus striatus and C. stercoreus.12 A morphological investigation of
the specimen confirmed a close relationship of the first-mentioned
pyridine ring.
species, but also revealed differences. For a detailed description of the
Pyristriatins A and B were tested for antimicrobial and producer strain and the morphological characterization and compar-
cytotoxic properties against various bacteria, fungi, and ison of the specimen see the Supporting Information.
mammalian cell lines (Table 2). They showed antibacterial Fermentation, Extraction, and Isolation. Small pieces from
effects exclusively against Gram-positive bacteria such as the well-grown YMG agar were used to inoculate 200 mL of YM medium
pathogenic Staphylococcus aureus, antifungal effects against contained in eight 500 mL Erlenmeyer flasks, which were shaken on a
filamentous fungi as well as yeasts, and moderate cytotoxic rotary shaker at 23 °C and 140 rpm. After 20 days the free glucose was
activities. The striatins are known to possess broad-spectrum used up and the cultures were harvested. The mycelium was separated
from the culture broth by using gauze and filtration. The mycelium
antimicrobial activities, but compared to the pyristriatins also was extracted two times with acetone in an ultrasonic bath at 40 °C for
act against some Gram-negative bacteria.11 30 min, and the solvent was evaporated in vacuo (40 °C). The

remaining aqueous residue was diluted with the same amounts of ethyl
EXPERIMENTAL SECTION acetate and water and extracted three times. The extracts were
combined, dried over sodium sulfate, and again evaporated in vacuo
General Experimental Procedures. Optical rotations were (40 °C) to dryness. After filtration using an RP solid-phase cartridge
determined with a PerkinElmer 241 polarimeter. NMR data were (Strata-X 33 μm, polymeric reversed phase; Phenomenex, Aschaffen-
recorded on a Bruker 500 MHz Avance III spectrometer with a burg, Germany) 1 g of crude product was obtained.
BBFO(plus) SmartProbe (1H 500 MHz, 13C 125 MHz) and a Bruker Preparative HPLC. The crude mycelial extract was fractionated by
700 MHz Avance III spectrometer with a 5 mm TCI cryoprobe (1H preparative RP-MPLC [column 480 × 30 mm (Kronlab), ODS-AQ
700 MHz, 13C 175 MHz). HRESIMS mass spectra were obtained with C18, 15 μm; solvent A: deionized water (Milli-Q), solvent B:
an Agilent 1200 series HPLC-UV system combined with an ESI-TOF- methanol; gradient system: 30% B for 5 min increasing to 100% B
MS (Maxis, Bruker) [column 2.1 × 50 mm, 1.7 μm, C18 Acquity in 170 min, holding at 100% B for 20 min; flow rate 15 mL/min, UV
UPLC BEH (Waters), solvent A: H2O + 0.1% formic acid; solvent B: detection at 254 nm]. RP-HPLC [VP 250/21 Nucleodur100-5 C18 ec
AcCN + 0.1% formic acid, gradient: 5% B for 0.5 min, increasing to column (Macherey−Nagel) equipped with a Kromasil 100 precolumn
100% B in 19.5 min, maintaining 100% B for 5 min, RF = 0.6 mL (50 × 20 mm, 7 μm; AkzoNobel); acetonitrile−water gradient with
min−1, UV detection 200−600 nm]. 0.05% trifluoroacetic acid, 5 min at 80% to 100% solvent B in 20 and 5

D DOI: 10.1021/acs.jnatprod.6b00194
J. Nat. Prod. XXXX, XXX, XXX−XXX
Journal of Natural Products Note

min at 100%, flow 15 mL/min] provided 4.5 mg of 1 and 5.3 mg of 2. (6) Hecht, H.-J.; Höfle, G.; Steglich, W.; Anke, T.; Oberwinkler, F. J.
The compounds eluted at 14−15 min (1) and 16−17 min (2), Chem. Soc., Chem. Commun. 1978, 15, 665−666.
respectively. (7) Tang, H.-Y.; Yin, X.; Zhang, C.-C.; Jia, Q.; Gao, J.-M. Curr. Med.
Pyristriatin A (1): white powder; [α]25D −185 (c 0.1, MeOH); 1H Chem. 2015, 22, 2375−2391.
NMR and 13C NMR see Table 1; LCMS m/z 442.17 [M + H]+ (100), (8) De Silva, D. D.; Rapior, S.; Sudarman, E.; Stadler, M.; Xu, J.;
440.12 [M − H]− (93), 486.09 [M − H + HCOOH]− (100), 422 Aisyah Alias, S.; Hyde, K. D. Fungal Divers. 2013, 62, 1−40.
(23), 390 (16); HRESIMS m/z 442.2623 [M + H]+ (calcd for (9) Kobayashi, Y.; Hayashi, N.; Kishi, Y. Org. Lett. 2002, 4, 411−414.
C26H35NO5, 442.2588). (10) Anke, T.; Rabe, U.; Schu, P.; Eizenhöfer, T.; Schrage, M.;
Pyristriatin B (2): white powder; [α]25D −100 (c 0.07, MeOH); 1H Steglich, W. Z. Naturforsch., C: J. Biosci. 2002, 57, 263−271.
NMR and 13C NMR see Table 1; LCMS m/z 442.13 [M + H]+ (100), (11) Anke, T.; Oberwinkler, F.; Stegich, W.; Höfle, G. J. Antibiot.
440.17 [M − H]− (87), 486.11 [M − H + HCOOH]− (100), 422 1977, 30, 221−225.
(20), 390 (17); HRESIMS m/z 442.2625 [M + H]+ (calcd for (12) Zhao, R.-L.; Desjardin, D. E.; Soytong, K.; Hyde, K. D. Persoonia
C26H35NO5, 442.2588). - Mol. Phylogeny Evol. Fungi 2008, 21, 71−76.
Striatin C (3): white powder; [α]25D −15 (c 1, MeOH); 1H NMR (13) Surup, F.; Thongbai, B.; Kuhnert, E.; Sudarman, E.; Hyde, K.
and 13C NMR see Table 1; LCMS m/z 447.20 [M + H − CH3OH]+ D.; Stadler, M. J. Nat. Prod. 2015, 78, 934−938.
(69), 461.22 [M + H − H2O]+ (19), 429 (100), 411 (15), 445.05 [M
− H − CH3OH]− (100), 491.03 [M − H + HCOOH]−, 385 (10),
373 (13); 357 (22), 339 (19); HRESIMS m/z 461.2550 [M + H −
H2O]+ (calcd for C26H38O8, 461.2534).
Serial Dilution Assay and Cytotoxicity Assay. The MIC and
the in vitro cytotoxicity (IC50) were determined according to our
previously reported procedure.13

S Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.jnat-
Experimental procedures, 1D and 2D NMR data, LCMS
data, morphological and phylogenetic details of the
producing organism (PDF)

Corresponding Author
*Tel: +49 531 6181-4240. Fax: +49 531 6181 9499. E-mail:
The authors declare no competing financial interest.

We are grateful to W. Collisi for conducting the bioassays and
C. Kakoschke, A. Gollasch, C. Schwager, and H. Steinmetz for
recording NMR and HPLC-MS data. Financial support by the
German Academic Exchange Service (DAAD) and the Thai
Royal Golden Ph.D. Jubilee-Industry program (RGJ) for a joint
TRF-DAAD PPP (2012−2014) academic exchange grant to
K.D.H. and M.S. and the RGJ for a personal grant to B.T. (No.
Ph.D/0138/2553 in 24.S.MF/53/A.3) is gratefully acknowl-
edged. K.D.H. would like to thank the Thailand Research Fund
for a grant (BRG5580009). S.E.H. would like to thank the
Alexander von Humboldt Foundation for funding through a
Georg Forster research fellowship (HERMES).

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E DOI: 10.1021/acs.jnatprod.6b00194
J. Nat. Prod. XXXX, XXX, XXX−XXX