Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil Streptomyces sp. S2236

Article abstract of DOI:10.1016/j.cclet.2016.03.018

Neopeapyran (1), an unusual furo[2,3b]pyran analogue, together with a new cyclopeptide, turnagainolide C (2), were isolated from Streptomyces sp. S2236 associated with the rhizosphere soil of Panax notoginseng. The planar structure and relative configuration of neopeapyran (1) were elucidated on the basis of spectroscopic techniques, while the absolute configuration was determined by TDDFT calculation. The absolute configuration of turnagainolide C (2) was determined by partial hydrolysis, together with the advanced Marfey's method and spectroscopic analysis. The antimicrobial activities of these two compounds were also investigated.

Full text of DOI:10.1016/j.cclet.2016.03.018

G Model
CCLET 3637 1–4
Chinese Chemical Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
1
2
Original article
3
4
Neopeapyran, an unusual furo[2,3b]pyran analogue and
turnagainolide C from a soil Streptomyces sp. S2236
5
6
Q1 Hao Zhou a,1, Ya-Bin Yang a,1, Rong-Ting Duan a, Xue-Qiong Yang a, Ju-Cheng Zhang a,
Xiao-Guang Xie a, Li-Xing Zhao b, Zhong-Tao Ding a,
*
7
8
9
a Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University,
Kunming 650091, China
b Yunnan Institute of Microbiology, Yunnan University, Kunming 650091, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Neopeapyran (1), an unusual furo[2,3b]pyran analogue, together with a new cyclopeptide, turn-
againolide C (2), were isolated from Streptomyces sp. S2236 associated with the rhizosphere soil of Panax
notoginseng. The planar structure and relative configuration of neopeapyran (1) were elucidated on the
basis of spectroscopic techniques, while the absolute configuration was determined by TDDFT
calculation. The absolute configuration of turnagainolide C (2) was determined by partial hydrolysis,
together with the advanced Marfey’s method and spectroscopic analysis. The antimicrobial activities of
these two compounds were also investigated.
Received 1 December 2015
Received in revised form 4 March 2016
Accepted 7 March 2016
Available online xxx
Keywords:
Streptomyces sp.
ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Furo[2,3b]pyran analogue
Cyclopeptide
Structure elucidation
Antimicrobial activity
10
11
1. Introduction
novel natural products with significant biological activity, such as 29
the rhizosphere soil of hosts [8,10], saltern [3], sulphur mine [11], 30
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
The actinomycetes of genus Streptomyces have attracted the
attention of the scientific community due to their enormous
biosynthetic capabilities of producing secondary metabolites
showing novel scaffolds and biologically actives [1–3]. In particu-
lar, terrestrial soil-derived Streptomyces species have been
extensively studied because they can potentially provide bioactive
natural products [1,4]. They have been ascertained to afford
clinically useful antibiotics, such as streptomycin and neomycin
[5,6]. Although actinomycetes are a major source of microbial
compounds, the chemical redundancy of compounds isolated from
these actinomycetes has become one of the current challenges in
the discovery of novel secondary metabolites with biologically
actives [7]. Investigation of unique niches harbouring chemically
new actinomycetes, rather than typical environments, is one
approach to overcome this problem [8,9]. Many recent investiga-
tions have exposed compelling evidence that the Streptomyces
species derived from unique habitats might lead to the discovery of
and so on.
31
As part of our programme to discover structurally unique and 32
biologically active secondary metabolites from Streptomyces 33
associated with the rhizosphere soil of medicine plants, Strepto- 34
myces sp. S2236 had drawn the most interest of us which was 35
isolated from the rhizosphere soil of Panax notoginseng in 36
Wenshan, Yunnan Province, China. The strain was most likely a 37
Streptomyces sp. based on the 99.22% 16S rRNA sequence similarity 38
with the Streptomyces neopeptinius KNF 2047T (EU258679). Our 39
chemical investigation of this strain yielded two new natural 40
products, neopeapyran (1), an unusual furo[2,3b]pyran analogue, 41
and a new cyclopeptide, turnagainolide C (2) (Fig. 1). The planar 42
structure and relative configuration of compound
1 were 43
elucidated on the basis of spectroscopic techniques, while the 44
absolute configuration was determined by TDDFT calculation. The 45
planar structure of compound 2 was determined by spectroscopic 46
analysis, and the absolute configuration of constituent amino acid 47
residues was determined by the advanced Marfey’s method. 48
Differentiation of L-Val and D-Val in the sequence was established 49
by the advanced Marfey’s analysis of fragment peptides obtained 50
from the partial hydrolysate. In the antimicrobial assays, 51
compound 2 displayed moderate antimicrobial activities against 52
*
Corresponding author.
E-mail address: ztding@ynu.edu.cn (Z.-T. Ding).
These authors contributed equally to this work.
1
http://dx.doi.org/10.1016/j.cclet.2016.03.018
1001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: H. Zhou, et al., Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil
Streptomyces sp. S2236, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.03.018

G Model
CCLET 3637 1–4
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H. Zhou et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
2.4. Partial hydrolysis and the advanced Marfey’s analyses of the
fragments
96
97
Each of 2 (0.5 mg) was hydrolyzed in 6 mol/L HCl at 100 8C for
3 h or 4 h. The dried hydrolysates were redissolved in 50 L of
MeOH. 20 L portions were separated by RP-HPLC (Agilent Eclipse
XDB-C18 column 4.6 mm  150 mm 5 m) using a gradient
98
99
m
m
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
m
elution from 10 to 100% MeCN containing 0.2% AcOH. After the
assignments of peptide sequences by extensive MS/MS analyses,
the fractions were identified as Ala-Val-Hppa, Ile-Val-Hppa, Val-
Ile, together with other fragments (Fig. 2). Then 2.0 mg of 2 was
hydrolyzed in 6 mol/L HCl at 100 8C for 3 h. The hydrolysate was
redissolved in 100
separated by RP-HPLC (Agilent Eclipse XDB-C18 column
m) using the same gradient elution, and
mL of MeOH, and each of 20 mL portions was
Fig. 1. Structures of compounds 1, 2.
4.6 mm  150 mm 5
m
53
54
55
Candida albicans, Escherichia coli and Staphylococcus aureus. Herein,
we report the discovery and characterization of these two
compounds and their antimicrobial activities.
the eluate was collected according to the retained time which was
analyzed by the LC–MS/MS data. The fractions of Ala-Val-Hppa, Ile-
Val-Hppa and Val-Ile were hydrolyzed in 6 mol/L HCl at 110 8C
overnight. The solution was dried, converted to the FDLA
derivative, and analyzed as described previously.
56
57
2. Experimental
2.1. Biological material and cultivation
3. Results and discussion
115
58
59
60
61
62
63
64
65
66
67
68
69
70
71
The bacterial strain S2236 was isolated using modified ISP4-
medium from the rhizosphere soil of P. notoginseng in Wenshan,
Yunnan Province, China. The strain was most likely a Streptomyces
sp. based on the 99.22% 16S rRNA sequence similarity with the
S. neopeptinius KNF 2047T (EU258679), and it was identified as
Streptomyces sp. S2236. The strain has been preserved at Yunnan
Institute of Microbiology, Yunnan University, China. This bacteri-
um was cultivated on 40 L scale using 1 L Erlenmeyer flasks
containing 250 mL of the seed medium (yeast extract 0.4%, glucose
0.4%, malt extract 1.0%, decavitamin 0.01%, pH 7.2) and the
fermentation medium (soluble starch 1%, glucose 1%, peptone 0.5%,
yeast extract 0.5%, soybean flour 0.3%, NaCl 0.4%, K2HPO4 0.05%,
MgSO4Á7H2O 0.05%, CaCO3 0.2%, pH 7.0) at 28 8C for 7 d on rotary
shaker (250 rpm).
Neopeapyran (1) was obtained as colourless oil, and the results
of TCL chromogenic reactions certified the inexistence of N in
compound 1. Its molecular formula of C13H20O5 was confirmed on
the basis of a prominent ion peak at m/z 257.1388 [M+H]+ (calcd.
for C13H21O5, 257.1389) observed in the HRESIMS spectrum (Fig.
S7 in Supporting information) and 13C NMR spectra, and that
indicated four degrees of unsaturation. IR spectrum exhibited
absorption at 3433, 2923, 1632, 1450 and 1047 cmÀ1 which
indicated that the structure of compound 1 contained at least one
hydroxyl group and one olefin group. The 1H NMR and 13C NMR
spectra of 1 displayed resonances that were assigned to one methyl
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
(
dC 18.2), one methylene (dC 26.6), three oxygen-bearing methy-
lenes (dC 55.8, 78.0, 77.9), six methines [among them four vinyl
methines (dC 132.1, 130.8, 130.6, 130.3)], and two quaternary
carbons (dC 104.8, 88.4) (Table 1). The 1H–1H COSY correlations
between H-10 and H-11, H-11 and H-12, H-12 and H-13, H-13 and
H-14, revealed the carbon skeletons for C-10 connected to C-11,
C-11 connected to C-12, C-12 connected to C-13, and C-13
72
2.2. Extraction and isolation
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
After 7 days of growth, the mycelia were removed from the
cultures (40 L) by filtration. The filtrate was extracted with ethyl
acetate (EtOAc, 3Â 40 L), and the solvent was removed under
vacuum. The EtOAc extract (31.0 g) was separated into four
fractions (Fr 1–Fr 4) by a chromatographic column (3 cm  50 cm)
on silica gel (200–300 mesh), eluting with stepwise CHCl3/MeOH
gradient (CHCl3, CHCl3/MeOH = 30:1 v/v, CHCl3/MeOH = 10:1 v/v,
A
10
1: MS2
TIC
Ile-Val-Hppa
m/z 405
2.27e
Ala-Val-Hppa
m/z 363
MeOH, 1.5 L each). The Fr
2 (18.5 g, eluted with CHCl3/
Ile-Val
m/z 231
%
MeOH = 30:1 v/v) was placed in a silica gel column (2 cm  30 cm)
cm) and eluted with petroleum ether/ethyl acetate mixture (10:1)
to ethyl acetate, then MeOH, which gave three fractions (Fr 2-1 to
Fr 2-3). Fr 2-1 (3.4 g) was separated by a chromatographic column
(1 cm  150 cm) on Sephadex LH-20 (MeOH) and then subjected
to further elution on a silica gel column (1 cm  15 cm) with
CHCl3/MeOH (50:1–9:1) to afford 2 (10.2 mg). Fr 2-2 (2.1 g) was
subjected to further elution on a silica gel column (1 cm  20 cm)
with CHCl3/MeOH (40:1–9:1) and then separated by a chro-
matographic column (1 cm  150 cm) on Sephadex LH-20 (MeOH)
to give 1 (2.1 mg).
Time
50.0
0
10.0
20.0
30.0
40.0
B
10
Ile-Val-Hppa
Ala-Val-Hppa
%
0
m/z 405
m/z 363
Ile-Val
m/z 231
92
93
2.3. Determination of absolute configuration by the advanced
Marfey’s method
Time
50.0
10.0
20.0
30.0
40.0
94
95
Details may be found in Supporting information and the
references cited therein [12,13].
Fig. 2. Total ion current (TIC) chromatogram of the partial hydrolysate of 2. (A) The
hydrolysis time was 3 h, (B) the hydrolysis time was 4 h.
Please cite this article in press as: H. Zhou, et al., Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil
Streptomyces sp. S2236, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.03.018

G Model
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H. Zhou et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
3
Table 1
Gaussian 09 program to generate its specific rotation. The 169
calculated specific rotation of (4S, 5R, 6R, 9R)-1 was negative, 170
and the calculated specific rotation of (4R, 5S, 6S, 9S)-1 was 171
positive. Therefore, the absolute configuration of 1 was determined 172
NMR data for compound 1 (
d
in ppm, J in Hz).a
dH (mult.; J)
Position
dC
2
3
55.8
4.12 (m, 1H), 3.63 (m, 1H)
1.86 (m, 2H)
as (4S, 5R, 6R, 9R)-1 (Fig. 1) by compared with the experimental 173
26.6
74.7
25
4
4.32 (m, 1H)
specific rotation of 1 which was [
a
]
D
À5.8 (c 0.1, MeOH).
174
5
52.1
2.40 (d, 1H, 7.6)
Turnagainolide C (2) obtained as a white powder, and its 175
molecular formula of C30H44N4O6 was assigned by positive 176
HRESIMS (m/z 579.3156 for [M+Na]+, calcd. for C30H44N4O6Na: 177
579.3159, Fig. S14 in Supporting information) and 13C NMR data 178
(Table 2). The molecular formula of 2 indicated 11 degrees of 179
unsaturation. IR spectrum exhibited intense N–H and CO absorp- 180
tion at 3392 and 1665 cmÀ1, respectively. The appearance of four 181
amino carbonyl signals (dC 173.1, 172.4, 170.4, and 168.8) in 13C 182
6
88.4
–
7
78.0
4.17 (d, 1H, 9.6), 3.82 (dd, 1H, 9.7, 1.8)
–
9
104.8
130.6
130.8
130.3
132.1
18.2
10
11
12
13
14
15
5.58 (d, 1H, 15.4)
6.39 (dd, 1H, 15.4, 10.5)
6.06 (ddd, 1H, 15.1, 12.2, 3.0)
5.80 (m, 1H)
1.76 (d, 3H, 6.5)
77.9
4.08 (d, 1H, 10.0), 3.71 (dd, 1H, 9.1, 1.6)
NMR spectrum and four NH signals (dH 7.59, 7.73, 8.09, and 8.56) in 183
a
Data in CDCl3 at 400 MHz for 1H NMR and 100 MHz for 13C NMR.
1H NMR spectrum, suggesting the molecule contained a peptide 184
component. The amino acid residues were identified as two valine 185
groups (Vals), one alanine group (Ala), and one isoleucine group 186
(Ile) by 1H–1H COSY, HSQC and HMBC spectra. The sequence of 187
amino acid residues in 2 was determined from HMBC correlations 188
between the carbonyl group and amide of the adjacent residues 189
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
connected to C-14. The HMBC correlations from H-14 to C-12 and
C-13, together with J10,11 = 15.4 Hz and J12,13 = 15.1 Hz for H-10, 11
trans and H-12, 13 trans, respectively, indicated the presence of a
(2E,4E)-pentylene residue. A tetrahydrofuran moiety was deduced
by the HMBC correlations from H-5 to C-6 and C-9, H-7 to C-5, C-6
and C-9, together with the chemical shifts of C-7 (dC 78.0) and
C-9 (dC 104.8). The HMBC correlations from H-15 to C-5, C-6 and
(Fig. 3). HMBC correlations from
aH-Val(I) and NH-Val(I) to CO-Ile, 190
from H-Ile and NH-Ile to CO-Ala, from NH-Ala to CO-Val(II), 191
a
demonstrated the sequence of the four amino acid residues was - 192
Val(I)-Ile-Ala-Val(II)-. Compared with the molecular formula of 2 193
(C30H44N4O6), the molecule still had an elemental composition of 194
C-7, together with the chemical shifts of C-6 (dC 88.4) and C-15 (dC
77.9), indicated that C-6 was substituted by a hydroxymethyl and a
hydroxyl. At the same time, the HMBC correlations from H-10 and
H-11 to C-9, H-10 to C-5, indicated that the (2E,4E)-pentylene
residue was linked to C-9. The 1H–1H COSY correlations between
H-2 and H-3, H-3 and H-4, H-4 and H-5, revealed the carbon
skeletons for C-2 connected to C-3, C-3 connected to C-4, and C-4
C11H10O2 by subtracted the atoms attributed to the four amino 195
acids residues (C19H34N4O4). This fragment was identified as a 3- 196
hydroxy-5-phenylpent-4-enoic acid residue (Hppa) by 1H–1H 197
COSY, HSQC and HMBC spectra (Fig. 3). The 16.0 Hz scalar coupling 198
observed between H-4(Hppa) and H-5(Hppa) deduced the moiety 199
connected to C-5, and the chemical shift of C-4 (dC 74.7) indicated
Table 2
that C-4 was substituted by a hydroxyl. However, the HMBC
correlations from H-2 and H-4 to C-9, along with one additional
degree of unsaturation and the molecular formula of C13H20O5
deduced by the HRESIMS spectrum, indicated the existed of a
tetrahydropyrane moiety (Fig. 3), and the upfield shifts of H-2 (dH
3.63, 4.12) and C-2 (dC 55.8) cased by the shielding effect of the
double bond between C-10 and C-11. Finally, the structure of
compound 1 was deduced as shown in Fig. 1. The skeleton of
furo[2,3b]pyran with a (2E,4E)-pentylene side chain in compound
1 was reported for the first time.
The relative stereochemistry of 1 was deduced from the ROESY
experiments (Fig. 3). ROESY correlations between H-4, H-5 and
H-15, and no significant correlations between H-10 and H-4/H-5/
H-15, suggested that there were two possible isomers [(4S, 5R, 6R,
9R)-1 and (4R, 5S, 6S, 9S)-1] of compound 1. The absolute
configuration of 1 was determined by comparison of quantum
chemical TDDFT calculated and experimental specific rotations.
Each isomer was optimized using DFT at the B3LYP/6-311 + G(d,p)
level in the Gaussian 09 program. Then, the optimized isomer was
calculated using TDDFT/GIAOs at the B3LYP/6-311 + G(d,p) in the
NMR data for compound 2 (
d
in ppm, J in Hz).a
Residue
Val(I)
Position
dC
dH (mult.; J)
CO
a
b
168.8
58.3
28.5
18.9
19.7
–
–
4.24 (m, 1H)
2.25 (m, 1H)
0.90 (d, 3H, 6.2)
0.90 (d, 3H, 6.2)
7.59 (d, 1H, 8.5)
g
NH
Ile
CO
a
b
170.4
57.3
35.7
23.6
11.9
15.6
–
–
4.26 (m, 1H)
2.04 (m, 1H)
1.23 (m, 2H)
0.81 (m, 3H)
0.82 (m, 3H)
8.09 (d, 1H, 9.4)
g
d
NH
Ala
CO
a
b
173.1
48.9
16.4
–
–
4.32 (m, 3H)
1.18 (d, 3H, 6.6)
8.56 (d, 1H, 5.6)
NH
Val(II)
CO
a
b
172.4
57.6
29.9
18.3
19.4
–
–
4.14 (t, 1H, 7.2)
1.96 (m, 1H)
0.88 (d, 3H, 5.6)
0.88 (d, 3H, 5.6)
7.73 (d, 1H, 8.3)
Val(I)
g
O
9
HO
NH
OH
4
15
OH
HN
O
8
O
6
Hppa
1
2
168.8
40.1
–
4
5
9
3
1
2.88 (dd, 1H, 13.7, 11.4)
2.42 (d, 1H, 13.4)
5.50 (m, 1H)
Hppa
7
1
2
Ile
COSY
O
HN
O
O
O
3
73.0
126.8
132.5
135.8
126.6
128.8
128.2
NH
4
6.28 (dd, 1H, 16.0, 7.0)
6.68 (d, 1H, 15.9)
–
10
11
HMBC
5
N
H
6
O
Ala
ROESY
Val(II)
7, 11
8, 10
9
7.45 (d, 2H, 9.0)
7.35 (t, 2H, 7.3)
7.28 (t, 1H, 7.3)
14
1
2
a
Fig. 3. Key COSY, HMBC and ROESY correlations of 1 and 2.
NMR data in DMSO-d6 at 400 MHz for 1H and 100 MHz for 13C.
Please cite this article in press as: H. Zhou, et al., Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil
Streptomyces sp. S2236, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.03.018

G Model
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H. Zhou et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
Table 3
S2236. The skeleton of furo[2,3b]pyran with a (2E,4E)-pentylene
side chain has never been reported from natural resources or
synthesis. The skeleton of 1 was reported for the first time. The
245
246
247
248
249
250
251
252
MICs of the extract and compounds from Streptomyces sp. S2236 (
m
g/mL).
Sample
C. albicans
E. coli
S. aureus
relative configuration of
1 was elucidated by spectroscopic
Extract
128
128
32
128
64
32
–
256
128
32
–
techniques, while the absolute configuration was determined by
TDDFT calculated specific rotation. Compound 2 showed moderate
antimicrobial activities against C. albicans, E. coli and S. aureus all
1
2
Nystain
Kanamycin
16
–
8
4
with the MIC of 32
mg/mL.
Acknowledgments
253
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
was (E)-3-hydroxy-5-phenylpent-4-enoic acid residue. Finally, the
HMBC correlations from H-Val(II) and NH-Val(II) to CO-Hppa,
from H-3(Hppa) to CO-Val(I) established that 2 was cyclo(Val(I)-
Ile-Ala-Val(II)-Hppa).
1H NMR and 13C NMR spectra of 2 displayed the similar
resonances as EGM-556 [14] and turnagainolides A-B [15], but the
absolute stereochemistry of the amino acid residues in 2 were
a
The work was funded by grants from the National Natural Q2 254
Science Foundation of China (Nos. 81360480, 81460536 and
81560571).
255
256
Appendix A. Supplementary data
257
identified as
method. There was no correlations between
H-Ala and H-Val(II) in ROESY spectrum, but observed the
correlations between H-Ile and H-Val(I), H-Ile(CH2) and H-
Val(I), H-Ala and H-Val(II) in ROESY spectrum, together with
contrasting the NMR spectra of with turnagainolide A,
L
-Val,
D-Val,
L-Ile and
D
-Ala by the advanced Marfey’s
a
H-Ile and H-Val(I),
a
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2016.03.
018.
258
259
260
a
a
b
a
g
a
b
a
2
References
261
established the configurations of Val(I), Val(II) and Ile as (R)-
Val(I), (S)-Val(II) and (2S,3S)-Ile (Fig. 3). In the same way, the
configuration of Hppa was determined as (3R)-Hppa by comparing
the chemical shifts of Hppa residue with turnagainolide A, and
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there was no ROESY correlation between H-3(Hppa) and aH-Val(I).
Therefore, the structure of 2 was determined as cyclo((R)-Val(I)-
(2S,3S)-Ile-(R)-Ala-(S)-Val(II)-(3R)-Hppa), which had a different
stereochemical structure from turnagainolides A-B, named as
turnagainolide C.
In order to confirm the configuration elucidation of 2, we used
LC–MS/MS analysis to set up proper hydrolysis conditions and get
suitable peptide fragments by partial hydrolysis [16]. We hoped to
isolate peptides to determine the chirality of each Val in the peptide
sequence. To do this we chose harsher conditions of 6 mol/L HCl at
100 8C and set the hydrolysis time for 3 h on the basis of the LC–MS
data. The LC–MS/MS data allowed us to identify fragments that
contain Val residues of specific position, i.e., Ala-Val-Hppa, Ile-Val-
Hppa and Val-Ile, together with other fragments (Fig. 2). Marfey’s
analysis of fragment Ala-Val-Hppa indicated that the Val(II) was a
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L-Val. Due to the little amount of 2, we did not get enough fragments
of Ile-Val-Hppa or Val-Ile to determined the absolute stereochemis-
try of Val(I). However, the Marfey’s analysis result of partial
hydrolysis of 2 was consistent with the determined structure.
The extract of Streptomyces sp. S2236 and the isolates (1 and 2)
were tested for their antimicrobial activity against C. albicans, E. coli,
and S. aureus. The results were showed in Table 3. Both 1 and 2
showed activity against E. coli with MICs of 64 and 32
mg/mL,
ˇ
´
respectively. At the same time, 2 also showed moderate antimicro-
bial activities against C. albicans and S. aureus.
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produced in culture by a Bacillus sp.: isolation, structure elucidation, and synthe-
sis, J. Nat. Prod. 74 (2011) 1093–1099.
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with four D-amino acid residues, from a marine Streptomyces sp.: LC–MS-aided
inspection of partial hydrolysates for the distinction of D-and L-amino acid
residues in the sequence, J. Org. Chem. 78 (2013) 6746–6750.
242
4. Conclusion
243
244
Two new compounds, neopeapyran (1) and turnagainolide C (2)
were isolated from the fermentation broth of Streptomyces sp.
Please cite this article in press as: H. Zhou, et al., Neopeapyran, an unusual furo[2,3b]pyran analogue and turnagainolide C from a soil
Streptomyces sp. S2236, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.03.018