On the structure of penipratynolene and WA

Article abstract of DOI:10.1016/j.tet.2009.11.073

The antipode of the structure proposed for the natural product penipratynolene in the literature was synthesized in high enantiopurity via an chiron approach and fully characterized. However, substantial differences were observed between the physical and

Full text of DOI:10.1016/j.tet.2009.11.073

Tetrahedron 66 (2010) 637–640
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
On the structure of penipratynolene and WA
*
Ya-Jun Jian, Yikang Wu
State Key Laboratory of Bio-organic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The antipode of the structure proposed for the natural product penipratynolene in the literature was
synthesized in high enantiopurity via an chiron approach and fully characterized. However, substantial
differences were observed between the physical and spectroscopic data of the synthetic sample and
those reported for the natural penipratynolene. Possible causes for the discrepancies are proposed on the
basis of acquisition and comparison of additional data. The present work also provides the only piece of
synthetic evidence for an antifungal natural product WA, the corresponding acid of the antipode of
natural penipratynolene.
Received 2 September 2009
Received in revised form 24 October 2009
Accepted 17 November 2009
Available online 7 December 2009
Keywords:
Natural products
Phenol ether
Coupling
Ó 2009 Elsevier Ltd. All rights reserved.
Acetylene
Propargylic alcohol
1. Introduction
2. Results and discussions
Penipratynolene (1, Fig. 1) was isolated from Penicillium bilaiae
Chalabuda by Kimura and co-workers.1 The structure of 1 was
established on the basis of its spectroscopic data, with the absolute
configuration determined by the method of Mosher.1 Compound 1
has been shown to possess nematicidal activity. Up to now, no
synthetic records can be found in the literature.
Our initial route to 2 is outlined in Scheme 1. We expected that
after Cu(I)-mediated Ullmann coupling of the known2 diol 4 with
methyl p-iodobenzoate 5a, the resulting alcohol 6a would be
readily converted into the target structure 2 via the corresponding
chloride 7. Unfortunately, such attempts led to no 6 but only the
unexpected ester 8 in 50% yield under the well-established and
broadly employed Me2NCH2CO2H$HCl/Cs2CO3/DMF3 conditions.
Use of tert-butyl p-iodobenzoate (5b) in place of 5a did not result in
any improvement. Again, ester 8 was obtained (18%), along with
unreacted starting materials.
OH
OH
OH
3'
1'
2'
4'
2
3
2
3
1
O
O
O
4
5
O
CO2Me
1
CO2Me
CO2H
a
O
O
6
7
8
OH
O
O
OH
OH
OR
+
Figure 1. The structures of the proposed structure for penipratynolene (1), its anti-
pode (2), and WA (3).
I
O
a R = Me
5
4
b R = t-Bu
6
As an extension of another projects currently undergoing in our
labs, we synthesized the antipode of 1 (i.e., 2) to confirm the
structure proposed for the natural product. Initially, such an en-
deavor was expected to be straightforward and uneventful because
of the simplicity of the structure. However, the outcome turned out
to be more complicated than we had expected. Not only the identity
of the title itself, but also that of the corresponding carboxylic acid
appears to need re-examination as detailed below.
O
O
RO
O
O
Cl
RO
O
I
7
OH
OH
O
O
MeO
O
O
O
2
8
O
* Corresponding author. Fax: þ86 21 64166128.
E-mail address: yikangwu@mail.sioc.ac.cn (Y. Wu).
Scheme 1. (a) Me2NCH2CO2H$HCl/CuI/Cs2CO3/DMF/100ꢀC/18 h.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.073

638
Y.-J. Jian, Y. Wu / Tetrahedron 66 (2010) 637–640
Then, we tried the Me4Phen/CuI/Cs2CO3/toluene4a–b conditions
The 1H NMR data (Table 2) of 2 (the antipode of 1) are consistent
with those reported1 for the natural penipratynolene (1). However,
subsequent acquired 13C NMR, also in CD3COCD3 as reported in the
literature,1 showed irrefutable differences from that in the litera-
ture (Table 3). Because 13C NMR is usually more sensitive to
structural changes than 1H NMR, these discrepancies seemingly
suggested natural penipratynolene might have a structure different
from 1.
on 5a. Again, no desired 6a but 8 (31%) was formed. However, ap-
plication of the same set of conditions on 5b gave the corre-
sponding coupling product 6b in 26% yield (along with 8% of 8,
entry 1, Table 1). Encouraged by the above result, we next tried to
improve the yield of 6b by varying the reactions conditions.
Table 1
Results of coupling between 4 and 5ba
Table 3
Comparison of 13C NMR of 1and 2
Entry
4 (equiv)b
Conditions
Yield of 6b and 8
1
2
3
4
1.0
2.0
3.0
3.0
Cs2CO3 (1.0 equiv)/80 ꢀC/30 h
Cs2CO3 (1.2 equiv)/110 ꢀC/41 h
Cs2CO3 (2.0 equiv)/110 ꢀC/24 h
Cs2CO3 (2.0 equiv)/110 ꢀC/18 h
26% (6b), 8% (8)
21% (6b), 3% (8)
41% (6b), 8% (8)
61% (6b), 11% (8)
1 (67.5 MHz, CD3COCD3)
2 (75 MHz, CD3COCD3)
2 (75 MHz, CDCl3)
51.9 (q, C-8)
51.9
61.0
72.6
74.6
83.3
115.1
123.6
132.1
163.2
166.7
51.9
61.1
71.3
74.6
80.8
114.2
123.3
131.6
161.8
166.7
61.1(d, C-20)
71.4 (t, C-10)
a
74.6 (d, C-40)
All runs were performed in toluene under argon in the presence of CuI (5 mol %
with respect to 5a) and Me4Phen (10 mol % with respect to 5a) with the concen-
tration of 5a being 2.0 M.
80.8 (s, C-30)
114.3 (d, C-3 and C-5)
123.5 (s, C-1)
131.7 (d, C-2 and C-6)
161.9 (s, C-4)
b
Molar equivalents with respect to 5a.
Increase the molar ratio of the diol 4 in the reaction appeared to
be a straightforward choice. However, application of more forcing
conditions (entry 2) at the same time did not seem to yield any
improvements. Further increase of the amount of added 4 and
Cs2CO3 but shortening the reaction time raised the yield of 6b to
41% (entry 3), suggesting that too long reaction time might cause
hydrolysis of the products. Indeed, when shortening the reaction
time to 18 h, the desired 6b could be isolated in 61% yield (entry 4).
With 6b in hand, we proceeded along the route shown in
Scheme 2. The terminal hydroxyl group was converted into a chlo-
ride using NCS/Ph3P.4c The resulting 7 was treated5 with LDA to
afford the propargyl alcohol 8, which was of 99% ee as determined
by chiral HPLC. The tert-butyl ester was then hydrolyzed with
F3CCO2H in CH2Cl2 before further elaboration into the corre-
sponding methyl ester 2 by reaction4d with CH2N2.
166.7 (s, C-7)
We noticed that Kimura did not mention why their NMR spectra
were recorded in CD3COCD3 rather than the more commonly
employed CDCl3. To exclude any possibility of typographic errors in
their paper, we also recorded 1H and 13C NMR of 2 in CDCl3 for
comparison.
As shown in Table 2, the 1H NMR of 2 in CDCl3 is apparently
different from that of Kimura’s, confirming that their 1H NMR was
indeed acquired in CD3COCD3. However, the 13C NMR of 2 taken in
CDCl3 turned out to be essentially identical to that of 1 in CD3COCD3
(Table 3). As the two sets of data agree so well with each other, it
seems highly likely that Kimura’s 13C NMR was actually recorded in
CDCl3 but somehow by mistake CD3COCD3 was reported in the
paper. Consequently, the structure originally assigned to natural
penipratynolene seemingly remained to stand.
Then, disproving information turned up: The melting point of 2
was determined to be 113–115 ꢀC (white powder, re-crystallized
from benzene), while that for natural penipratynolene 1 is 246–
O
O
O
O
a
O
O
248 ꢀC (white needles, re-crystallized from benzene). The optical
O
O
26
O
OH
O
Cl
rotation ([
a
]
D
þ3.88 (c 0.2, EtOH)) for 2 is also incompatible with
20
that1 for 1 ([
a
]
ꢁ11.2 (c 0.2, EtOH)). As 2 is supposed to be the
6b
7
D
b
antipode of 1, a value around þ11 would be expected.
Unable to explain these discrepancies, we looked into the lit-
erature for relevant information. Then, we found that in 1989 Arai6
and co-workers already reported isolation of the same compound
(1, without any trivial name) from Penicillium fructigenum Takeuchi,
though no information about how the absolute configuration was
determined was provided. Their 1H and 13C NMR (both recorded in
CDCl3) and mp data were fully consistent with ours. The specific
OH
OH
c
O
HO
O
O
O
3
O
8
(WA)
OH
d
MeO
O
rotation ([
this work ([
(recorded in EtOH!).
a
]
a
D ꢁ12.3 (c 0.1, CHCl3)) was also compatible with that of
O
]
D
þ12.46 (c 0.1, CHCl3)) and rather close to Kimura’s
2
Scheme 2. (a) Ph3P/NCS/rt/12 h, 91%. (b) LDA/THF/ꢁ78 ꢀC/2 h, then ꢁ40 ꢀC/1 h, 82%.
In efforts to reconcile those incompatible data, we looked into
the literature again and found that the acid 3 in fact is also a natural
(c) F3CCO2H/CH2Cl2/rt/2 h, 100%. (d) CH2N2, 92%.
Table 2
Comparison of 1H NMR of natural penipratynolene 1 (Ref. 1) and its synthetic antipode 2 (this work)
1 (270 MHz, CD3COCD3)
2 (300 MHz, CD3COCD3)
2 (300 MHz, CDCl3)
2.97 (d, J¼1.5 Hz, 1H, H-40)
3.84 (s, 3H, H-8)
2.97 (d, J¼2.4 Hz, 1H)
3.84 (s, 3H)
4.20 (dd, J¼4.8, 10.2 Hz, 1H)
4.15 (dd, J¼3.4, 9.8 Hz, 1H)
4.79–4.70 (m, 1H)
4.96 (br d, J¼6.0 Hz, 1H)
7.06 (d, J¼9.0 Hz, 2H)
7.96 (d, J¼8.0 Hz, 2H)
2.73 (d, J¼4.7 Hz, 1H)
3.89 (s, 3H)
4.24–4.08 (m, 2H)
4.19 (dd, J¼3.5, 6.7 Hz, 2H, H-10)
4.74 (ddd, J¼1.5, 3.5, 6.7 Hz, 1H, H-20)
4.84–4.75 (m, 1H)
4.89 (br s, 1H, H-20 OH)
2.55 (br s, 1H, OH)
6.95 (d, J¼8.2 Hz, 2H)
8.00 (d, J¼8.2 Hz, 2H)
7.07 (d, J¼8.8 Hz, 2H, H-3 and H-5)
7.96 (d, J¼8.8 Hz, 2H, H-2 and H-6)

Y.-J. Jian, Y. Wu / Tetrahedron 66 (2010) 637–640
639
product, which was first isolated in 1998 by Yang7 et al. (without
given any specific rotation data) and later by Gloer8 et al. from
another source with full characterization. It was therefore hoped
that a full agreement of all data could be found between the syn-
thetic and the natural 3, if discrepancy between 1 and 2 could not
be solved (Table 4).
synthesized for the first time via an unambiguous route in very
high enantiopurity. The melting point, optical rotation, and 1H as
well as 13C NMR data for these two compounds were thus acquired
with high reliability to clear up the hidden confusions created by
the contradicting data encapsulated in earlier documents. Careful
comparison of the physical and spectroscopic data of the synthetic
samples with the corresponding natural ones reported in the lit-
erature revealed that some of the previous investigators highly
likely misreported the solvents employed for recording the NMR
and specific rotation. While the NMR data for synthetic 2 and 3 are
in excellent consistence with those reported for the natural ones,
unignorable discrepancies are found in melting points and
Table 4
Comparisona of 13C NMR of synthetic and natural 37,8
Yang’s
Gloer’s
This work
(100 MHz, CD3COCD3)
(75 MHz, CDCl3)
(75 MHz, CD3COCD3)
167.3
163.4
132.5
124.1
115.3
83.5
74.7
72.8
61.3
167.3 (C-7)
163.5 (C-4)
132.6 (2C, C-2/C-6)
124.1 (C-1)
167.5
163.3
132.5
123.9
115.2
83.4
74.8
72.7
61.2
specific rotations: The mp and [a
] for 11 (of (R) configuration) are
246–248 ꢀC and ꢁ11.2 (c 0.2, EtOH), respectively, while the corre-
sponding values for the synthetic 2 (of (S) configuration) are
113–115 ꢀC9 and þ3.88 (c 0.2, EtOH) (but þ12.46 (c 0.1, CHCl3)),
respectively. A minor difference also exists in the UV spectrum: the
spectrum of 1 contains an extra shoulder at 271 nm compared with
that of 2, which suggests presence of an additional UV absorption
115.3 (2C, C-3/C-5)
83.5 (C-30)
74.8 (C-40)
72.8 (C-10)
61.3 (C-20)
a
For comparison, the same numbering system for 1 is adopted here.
species in the natural 1. Similarly, the large value of specific rotation
for natural 3 ([
a]
þ80 (c 0.40, MeOH)8) is apparently un-
24
D
Yang’s 1H and 13C NMR (both acquired in CD3COCD3) as well as
mp (126–128 ꢀC) were consistent with ours (128–129 ꢀC; cf. also
Gloer’s 126–127 ꢀC). However, as they did not measure the optical
rotation, complete data comparison hence could be made only with
Gloer’s.
reasonable judging from the value measured on pure synthetic one
þ7.45 (c 0.42, acetone)).10
28
27
([
a]
þ10.85 (c 0.40, MeOH) or [
a]
D
D
4. Experimental
4.1. General
According to Gloer8 both their 1H and 13C NMR were recorded in
CDCl3. However, in our hands the acid 3 turned out to be insoluble
in CDCl3 (or CHCl3). It was therefore impossible for us to collect
similar data in CDCl3. Nevertheless, as the 13C NMR data of 3 and the
natural WA of Yang,7 both acquired in CD3COCD3, are fully consis-
tent with those of Gloer’s,8 it appears that the actual NMR solvent in
Gloer’s experiment was also CD3COCD3. Comparison of the three
sets of 1H NMR data (Table 5) lends strong support for this
deduction.
The 1H NMR and 13C NMR spectra were recorded at ambient
temperature using a Varian Mercury 300 or a Bruke Avance 300
instrument (operating at 300 MHz for proton). The FTIR spectra
were scanned with a Nicolet Avatar 360 FTIR. EIMS and EI-HRMS
were recorded with an HP 5989A and a Finnigan MAT 8430 mass
spectrometer, respectively. The ESI-MS and ESI-HRMS were recor-
Table 5
Comparisona of 1H NMR of synthetic and natural 37,8
Yang’s (400 MHz, CD3COCD3)
Gloer’s (300 MHz, CDCl3)
This work (300 MHz, CD3COCD3)
8.00 (dd, J¼8.8, 4.8 Hz, 2H, H-2 and H-6)
7.07 (dd, J¼8.8, 4.8 Hz, 2H, H-3 and H-5)
4.92 (br s, 1H, OH)
7.99 (distorted d, J¼7.5 Hz, 2H, H-2 and H-6)
8.00 (d, J¼8.4 Hz, 2H)
7.06 (d, J¼8.5 Hz, 2H)
4.97 (br s, OH, 1H)
7.06 (distorted d, J¼7.5 Hz, 2H, H-3 and H-5)
4.75 (m, 1H, H-20)
4.74 (ddd, J¼6.7, 4.7, 2.2 Hz, 1H, H-20)
4.20 (dd, J¼9.7, 4.7 Hz, 1H, H-10)
4.16 (dd, J¼9.7, 6.7 Hz, 1H, H-10)
2.96 (d, J¼2.2 Hz, 1H, H-40)
4.75 (m, 1H)
4.19 (m, 2H, H-10)
4.21 (dd, J¼4.4, 9.6 Hz, 1H)
4.15 (dd, J¼5.8, 9.9 Hz, 1H)
2.98 (d, J¼1.4 Hz, 1H)
2.98 (d, J¼2.2 Hz, 1H, H-40)
a
For comparison, the same numbering system for 1 is adopted here.
The seemingly excellent match of the data between the syn-
thetic and the natural 3 was then challenged by a large difference in
ded with a PE Mariner API-TOF and an APEX III (7.0 Tesla) FTMS
mass spectrometer, respectively. The melting point was un-
corrected. Dry THF was distilled from Na/Ph2CO under N2. Dry
CH2Cl2 was distilled over CaH2 and kept over 4 Å molecular sieves.
All other solvents and reagents were commercially available and
used as received without any further purification.
27
specific rotation: the former is [
a]
þ10.85 (c 0.40, MeOH) while
D
24
the latter is [
a
]
D
þ80 (c 0.40, MeOH). In the beginning we thought
a wrong solvent might be mentioned here. As CHCl3, the most
common one for measuring optical rotation, is not applicable here
(because 3 is insoluble in it), acetone seemed to be the most likely
one they used. Unfortunately, the specific rotation in acetone turned
4.2. Coupling of diol 4 with iodide 5b leading to 6b
27
out to be even smaller ([
a
]
þ7.45 (c 0.40, acetone)). As we do not
D
have the access to the natural 1 and 3, it appears that a complete
solution to the puzzling structural problem of these compounds
embedded in the literature data in several papers published over
some 10 years can be eventually found only in the future.
A mixture of 4 (162 mg, 1.00 mmol), 5b (90 mg, 0.29 mmol), CuI
(3 mg, 0.015 mmol), Me4Phen (7 mg, 0.03 mmol), and Cs2CO3
(198 mg, 0.67 mmol) in toluene (0.5 mL) under argon was vigor-
ously stirred in an oil bath (100 ꢀC) for 18 h. After being cooled to
ambient temperature, the mixture was diluted with EtOAc, washed
with water, and dried over anhydrous Na2SO4. Removal of the
solvent on a rotary evaporator and column chromatography (3:1
3. Conclusions
In efforts to confirm the structures of the corresponding natural
products proposed in the literature, compounds 2 and 3 were
PE/EtOAc) on silica gel gave 6b as a colorless oil (60 mg, 0.18 mmol,
27
61%): [
a
]
D
þ10.49 (c 0.84, CHCl3). 1H NMR (300 MHz, CDCl3)
d 7.95

640
Y.-J. Jian, Y. Wu / Tetrahedron 66 (2010) 637–640
(d, J¼8.8 Hz, 2H), 6.93 (d, J¼8.9 Hz, 2H), 4.32 (dt, J¼7.6, 4.9 Hz, 1H),
4.22 (dd, J¼5.0, 9.9 Hz, 1H), 4.17–4.09 (m, 2H), 3.93 (dd, J¼3.9,
12.2 Hz, 1H), 3.77 (dd, J¼4.2, 11.9 Hz, 1H), 2.16 (br s, 1H, OH), 1.60 (s,
gel (15:1 CH2Cl2/MeOH) to afford acid 3 as a white solid (13 mg,
0.063 mmol, 100%): mp 128–129 ꢀC (lit.7 126–128 ꢀC; lit.8 126–
28
27
127 ꢀC), [
a
]
þ10.85 (c 0.40, MeOH), [
a
]
þ7.45 (c 0.42, acetone)
D
24
9H), 1.49 (s, 3H), 1.48 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
165.5,
(lit.8
[a]
Dþ80 (c 0.40, MeOH)). EIMS m/z (%) 206 (Mþ, 38), 191
D
161.7, 131.4, 125.0, 113.9, 109.9, 80.7, 78.9, 75.2, 68.3, 62.1, 28.2, 27.1,
26.9; FTIR (film) 3491, 2983, 2934, 1708, 1606, 1510, 1369, 1295,
1252, 1161, 849, 772 cmꢁ1. ESI-MS m/z 361.1 ([MþNa]þ); ESI-HRMS
calcd for C18H26O6Na ([MþNa]þ) 361.16216, found 361.16220.
(14), 151 (45), 138 (34), 133 (23), 121 (100), 105 (19), 65 (53); EI-
HRMS calcd for C11H10O4 (Mþ) 206.0579, found 206.0576.
4.6. Conversion of 3 into 2
4.3. Conversion of alcohol 6b into chloride 7
A solution of acid 3 (66 mg, 0.32 mmol) in Et2O (2 mL) was
treated with an excess of CH2N2 (ethereal solution, freshly prepared
from aq KOH and N-nitroso-N-methyl-urea in Et2O) at 0 ꢀC. When
TLC showed completion of the reaction (ca.10 min), the solvent was
evaporated on a rotary evaporator. The residue was chromato-
graphed on silica gel (4:1 n-hexane/EtOAc) to give methyl ester 2 as
a white solid (65 mg, 0.29 mmol, 91% yield): mp 113–115 ꢀC (lit.1
mp 246–248 ꢀC for 1) (lit.6 mp 111–112 ꢀC for 1), UV lmax (MeOH)
254 nm (without any shoulder at 271 nm) (lit.1 UV lmax (MeOH)
NCS (51 mg, 0.38 mmol) and PPh3 (100 mg, 0.38 mmol) were
added in turn to a solution of alcohol 6b (85 mg, 0.25 mmol) in dry
CH2Cl2 (1.5 mL) stirred in an ice-water bath. After completion of the
addition, the mixture was stirred at ambient temperature overnight
before being diluted with EtOAc, washed with water and brine, and
dried over anhydrous Na2SO4. Rotary evaporation and column
chromatography (15:1 PE/EtOAc) gave the chloride 7 as a colorless
28
þ11.11 (c 1.10, CHCl3). 1H NMR
254, 271 (sh) nm for 1). [
a
]
þ3.88 (c 0.2, EtOH) (lit.1 [
a
]
ꢁ11.2
26
26
oil (81 mg, 0.23 mmol, 91%): [
a
]
D
D
D
(c 0.2, EtOH) for 1); [
a
]Dþ 12.46 (c 0.1, CHCl3) (lit.6 [
]Dþ 12.3 (c 0.1,
a
(300 MHz, CDCl3)
d
7.94 (d, J¼9.3 Hz, 2H), 6.92 (d, J¼8.7 Hz, 2H),
4.34–4.17 (m, 4H), 3.75 (dd, J¼4.7, 11.7 Hz, 1H), 3.70 (dd, J¼5.4,
CHCl3)). The ee value was determined to be 99.1% by HPLC on
a CHFT-IRALPAK IC column (0.46 cmꢂ25 cm) eluting with 80:20 n-
hexane/i-PrOH at a flow rate of 0.7 mL/min with the UV detector set
to 214 nm (tR¼14.68 and 16.09 min for the major and minor iso-
mers, respectively). FTIR (KBr) 3458, 3234, 2948, 2927, 2849, 2118,
11.5 Hz, 1H), 1.58 (s, 9H), 1.48 (s, 3H), 1.47 (s, 3H); 13C NMR (75 MHz,
CDCl3)
d 165.4, 161.7, 131.4, 125.2, 113.9, 110.6, 80.6, 77.8, 77.5, 68.5,
44.3, 29.7, 28.2, 27.1; FTIR (film) 2982, 2932, 1709, 1606, 1510, 1369,
1294, 1251, 1161, 1115, 849, 771 cmꢁ1. ESI-MS m/z 379.1 ([MþNa]þ);
ESI-HRMS calcd for C18H25ClO5Na ([MþNa]þ) 379.12827, found
379.12718.
1693, 1607, 1510, 1437, 1323, 1291, 1259, 1170, 1038, 850, 773 cmꢁ1
.
EIMS m/z (%) 220 (Mþ) (29),165 (41),135 (43),121 (87), 43 (100); EI-
HRMS calcd for C12H12O4 (Mþ) 220.0736, found 220.0737.
4.4. Conversion of chloride 7 into alkyne 8
Acknowledgements
A solution of chloride 7 (266 mg, 0.75 mmol) in THF (2 mL) was
added to a solution of LDA (freshly prepared from i-Pr2NH (0.73 mL,
5.2 mmol) and n-BuLi (2.5 M, 2 mL, 5.0 mmol)) in THF (5 mL) stir-
red at ꢁ78 ꢀC under argon. Stirring was then continued at the same
temperature for 2 h and ꢁ40 ꢀC for 1 h. Aq satd NH4Cl was added,
followed by EtOAc. The phases were separated. The organic layer
was washed with water and brine, and dried over anhydrous
Na2SO4. Rotary evaporation and column chromatography (5:1 PE/
This work was supported by the National Natural Science
Foundation of China (20025207, 20272071, 20372075, 20321202,
20672129, 20621062, 20772143), and the Chinese Academy of
Sciences (‘Knowledge Innovation’ project, KGCX2-SW-209,
KJCX2.YW.H08).
References and notes
EtOAc) gave alkyne 8 as a colorless oil (177 mg, 0.68 mmol, 82%):
26
[
a]
þ12.12 (c 1.00, CHCl3). 1H NMR (300 MHz, CDCl3)
d 7.94 (d,
D
1. Nakahara, S.; Kusano, M.; Fujioka, S.; Shimada, A.; Kimura, Y. Biosci. Biotechnol.
Biochem. 2004, 68, 257–259.
J¼8.7 Hz, 2H), 6.93 (d, J¼8.8 Hz, 2H), 4.79 (br s, 1H), 4.19 (dd, J¼3.9,
9.9 Hz, 1H), 4.13 (dd, J¼3.0, 9.9 Hz, 1H), 2.79 (d, J¼3.8 Hz, 1H, OH),
2. Hungerbuehler, E.; Seebach, D. Helv. Chim. Acta 1981, 64, 687–702.
3. Zhang, H.; Ma, D.; Cao, W. Synlett 2007, 243–246 and references cited therein.
4. (a) Wolter, M.; Nordmann, G. E.; Buchwald, S. L. Org. Lett. 2002, 4, 973–976; (b)
Altman, R. A.; Shafir, A.; Choi, A.; Lichtor, P. A.; Buchwald, S. L. J. Org. Chem.
2008, 73, 284–286; (c) Chun, J.; Byun, H.-S.; Bittman, R. J. Org. Chem. 2003, 68,
348–354; (d) Arndt, F. Org. Synth. 1935, 5, 3–5.
5. (a) Yadav, J. S.; Chander, M. C.; Joshi, B. V. Tetrahedron Lett. 1988, 29, 2737–2740;
(b) Yadav, J. S.; Deshpande, P. K.; Sharma, G. V. M. Tetrahedron 1990, 46,
7033–7046.
2.55 (d, J¼1.8 Hz,1H), 1.58 (s, 9H); 13C NMR (75 MHz, CDCl3)
d 165.5,
161.4, 131.4, 125.2, 114.0, 80.8, 80.7, 74.5, 71.3, 61.1, 28.2; FTIR (film)
3440, 3295, 2977, 2933, 2119, 1705, 1606, 1582, 1510, 1369, 1297,
1255, 1161, 849, 772 cmꢁ1. ESI-MS m/z 285.1 ([MþNa]þ); ESI-HRMS
calcd for C15H18O4Na ([MþNa]þ) 285.10973, found 285.10994.
6. Arai, K.; Kimura, K.; Mushiroda, T.; Yamamoto, Y. Chem. Pharm. Bull. 1989, 37,
2937–2939.
4.5. Conversion of 8 into 3
7. Yang, J.; Qi, X.-L.; Li, W.; Shao, G.; Yao, X.-S.; Kitanaka, S. Chin. Chem. Lett. 1998, 9,
539–540.
8. Oh, H.; Swenson, D. C.; Gloer, J. B.; Shearer, C. A. J. Nat. Prod. 2003, 66, 73–79.
9. Note that the melting point for natural 1 isolated by Arai (Ref. 6) is 111–112 ꢀC,
rather close to ours (113–115 ꢀC).
A solution of CF3CO2H (0.48 mL, 6.4 mmol) and 8 (14 mg,
0.064 mmol) in dry CH2Cl2 (3 mL) was stirred at ambient temper-
ature for 2 h. The solvent was removed on a rotary evaporator. The
residue was diluted with toluene and evaporated again (repeating
three times). The remainder was then chromatographed on silica
10. Note that as the ee value for synthetic 2 (and consequently 3) is already as high
as 99.1%, the [
a
] for 3 in any case does not seem likely to be as large as þ80.