Total synthesis of (-)-petrosiol e

Article abstract of DOI:10.1016/j.tet.2014.09.030

(-)-Petrosiol E, a metabolite of sponge Petrosia strongylata, has been synthesized in 32% overall yield from cheap natural d-xylose in 10 steps. Our strategy provides an efficient way for the total synthesis of other petrosiol members, featuring the three

Full text of DOI:10.1016/j.tet.2014.09.030

Tetrahedron xxx (2014) 1e5
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Total synthesis of (ꢀ)-petrosiol E
Linlin Wang , Xing Zhang , Jun Liu ,*, Yuguo Du a
a
,
b
a
,
b
a
,b,
*
a
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences,
Beijing 100085, China
b
School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2014
Received in revised form 31 August 2014
Accepted 9 September 2014
Available online xxx
(ꢀ)-Petrosiol E, a metabolite of sponge Petrosia strongylata, has been synthesized in 32% overall yield
from cheap natural D-xylose in 10 steps. Our strategy provides an efficient way for the total synthesis of
other petrosiol members, featuring the three contiguous stereogenic centers are easily constructed from
-xylose chiral template.
D
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Petrosiol E
Total synthesis
Petrosiols
Natural products
OH OH
OH
1
. Introduction
Me
Diyne polyol backbone is a unique unit found in a number of
HO
HO
1
1
Petrosiol A ( )
biologically active natural products. Petrosiols AeE (1e5), natu-
rally occurring novel neurotrophic diyne tetraols, have been iso-
lated recently from an Okinawan marine sponge Petrosia
strongylata by Ojika’s group and found to induce nerve growth
OH OH
OH
Me
Me
2
factor (NGF-like) neuronal differentiation of PC12 cells. The
Petrosiol B (2)
Petrosiol C (3)
structures of petrosiols were elucidated based on extensive spec-
troscopic analyses. The petrosiols AeE (1e5) are comprised of the
similar unusual diyne tetraol skeletons with different side-chain
lengths. The consistent sign of their specific optical rotations, the
similar NMR data around the triol moieties, and the chemical de-
rivatization studies indicated that all the petrosiols share the same
stereochemistry. The relative stereochemistry of the petrosiols was
OH OH
OH
HO
OH OH
OH
2
Me
established by derivatization of petrosiol C (3), and the absolute
configurations were examined by the modified Mosher’s method.
Detailed biological analyses demonstrated that petrosiols may be
useful for the prevention and treatment of vascular diseases such as
HO
Petrosiol D (4)
Petrosiol E (5)
OH OH
OH
Me
Me
3
restenosis and atherosclerosis (Fig. 1).
Because of their unique structures, interesting biological activ-
ities, and limited availability, petrosiols represent attractive targets
for total synthesis. In continuation of our efforts toward the total
synthesis of biologically active natural products based on carbo-
HO
Fig. 1. Structures of petrosiol AeE (1e5).
4
hydrate skeletons, we launched a stereoselective total synthesis of
our efforts, Srihari et al. reported the first total synthesis of petro-
siol D (4). In their report, petrosiol D (4) was prepared from
5
natural petrosiols, taking petrosiol E (5) as our first target. During
(
þ)-diethyl
L-tartrate with an overall yield of 4.7% in 17 steps,
employing Sharpless asymmetric epoxidation, base-induced elim-
*
Corresponding authors. E-mail address: duyuguo@rcees.ac.cn (Y. Du).
ination of chiral epoxy halides, and CadioteChodkiewicz coupling
http://dx.doi.org/10.1016/j.tet.2014.09.030
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
0
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2
L. Wang et al. / Tetrahedron xxx (2014) 1e5
ꢁ
3
neat PPh at 100 C to deliver the phosphonium salt 9 in 96% overall
yield for three steps.
as the key steps. We realized that the chiron approach represents
probably the better way for making biologically active petrosiols if
the characteristic three contiguous oxy-stereocenters in petrosiols
could be derived from natural carbohydrate chiral templates. Here,
we report the first total synthesis of petrosiol E using readily
The known MOM-protected -xylose derivative 8 was prepared
D
6
from D-xylose according to a published procedure in 62% of overall
yield for three steps. Wittig olefination of the hemiacetal 8 and the
phosphonium salt 9 was thus pursued. However, the expecting
available D-xylose as the chiral template.
Retrosynthetic analysis of (ꢀ)-petrosiol E is shown in Scheme 1.
The crucial diyne tetraol skeleton could be installed by coupling of
the 1-bromoalkyne 6 with propargyl alcohol via copper-catalyzed
CadioteChodkiewicz reaction. The key intermediate 6 could be
obtained from alkene 7 via a multi-step sequence: hydrogenation
of alcohol 7, followed by oxidation, Wittig reaction, and base-
induced elimination would furnish the desired 1-bromoalkyne 6.
chain elongation at the anomeric carbon of D-xylose turned out to
be more difficult than we expected. As summarized in Table 1,
treatment of 8 with the phosphonium salt 9 in the presence of
various strong bases (t-BuOK, n-BuLi, t-BuLi, LHMDS), resulted in
the recovery of starting material (entries 1, 2, 4) or led to the de-
composition of 8 (entry 3). The best result for the chain elongation
was finally achieved through a reaction of 8 with the ylide, gener-
ated in situ by 9 and lithium hexamethyldisilazide (LHMDS) in
Alkene 7 could be obtained by chain elongation of the known
6
ꢁ
MOM-protected
D
-xylose 8 with the phosphonium salt 9, which
anhydrous toluene at 0e50 C (entry 5), afforded the desired alkene
could be accessible readily from
D-xylose and 11-bromoundecanol,
7 in 92% yield.
respectively. Taking advantages of its excellent stabilities under
strong base treatment and Pd-catalyzed hydrogenation conditions,
methoxymethyl (MOM) was selected to protect hydroxyl groups of
Table 1
a
Reagents and conditions for the formation of 7
D-xylose and could be removed eventually under acid conditions.
Entry
Base
Temperature
Solvent
Yield (%)
ꢁ
1
2
3
4
5
t-BuOK
n-BuLi
n-BuLi
LHMDS
LHMDS
0
C to rt
THF
No reaction
No reaction
Decomposition
No reaction
92
ꢁ
ꢀ78 C to rt
Toluene
Toluene
Toluene
Toluene
ꢁ
ꢁ
C
0
C to 50
ꢁ
ꢀ78 C to rt
ꢁ
ꢁ
C
0
C to 50
a
Detailed procedures are provided in Experimental section.
Pd-catalyzed hydrogenation of alkene 7 in methanol at room
temperature saturated the double bond in excellent yield. The
resulted alcohol 12 was oxidized with pyridinium dichromate
(
PDC) to yield aldehyde 13 smoothly. It should be noted that
8
DesseMartin periodinane oxidation of 12 under various condi-
tions resulted in the recovery of starting material. Possibly, the
steric hindrance of the tri-MOM groups shielded the free hydroxyl
group from the bulky periodinane attacking.
Transformation of aldehyde 13 to 1-bromoalkyne 6 also proved to
be more challenging than we initially anticipated. The CoreyeFuchs
9
dibromoolefination was first explored. Unfortunately, treatment of
1
1
3 with CBr
,1-dibromoalkene was formed. Apparently, an in situ generated
dibromotriphenylphosphine (Ph PBr caused aldehyde de-
composition. The SeyfertheGilbert homologation strategy was also
4 3
/PPh led to the decomposition of 13, and no detectable
3
2
)
10
11
examined, but fruitless. Thus, an alternative strategy of making 6
wasdesignedwiththehelpofHBrelimination. Thedibromoalkene14
was obtained in good yield through a Wittig-type reaction of alde-
hyde 13 and dibromomethyltriphenylphosphonium bromide
12
Scheme 1. Retrosynthetic analysis of (ꢀ)-petrosiol E (5).
(Scheme 3). It was reported that TBAF was an efficient base for this
13
dehydrobromination in polar aprotic solvents. Accordingly, treat-
ment of 14 with an excessive of TBAF in DMF should give the corre-
sponding 1-bromoalkyne 6. However, in our case, TBAF led to the
terminal alkyne instead of the desired 1-bromoalkyne 6. To our de-
light, NaH in THF was found more reliable, furnishing the 1-
2
. Results and discussion
The synthetic sequence commenced with the coupling of iso-
butylmagnesium bromide and commercially available 11-
14
bromoalkyne 6 in excellent yield. CadioteChodkiewicz coupling
of 6 with propargyl alcohol produced the desired conjugated diyne
bromoundecanol in the presence of dilithium tetrachlorocuprate
7
(
Li
2
CuCl
4
). The primary alcohol 10 was transformed into alkyl io-
15
15. Finally, globaldeprotectionof15 with3 NHClaffordedthetarget
dide 11 (Scheme 2) and then the intermediate was treated with
16
natural product petrosiol E (5) (Scheme 4). All the spectroscopic
data and the specific optical rotation for our synthetic petrosiol E
were in good agreement with those reported for the natural product
2
5
25
2
{
[
a]
D
ꢀ2.0 (c 0.06, MeOH); Ref. 2: [
a]
D
ꢀ1.0 (c 0.06, MeOH)} (see
Supplementary data).
3. Conclusions
Scheme 2. Reagents and conditions: (a) Me
2
CHCH
2
MgBr, Li
2
CuCl
4
, anhydrous THF,
ꢁ
ꢁ
In conclusion, we have achieved the first total synthesis of
(ꢀ)-petrosiol E starting from the chiral template -xylose in 10
ꢀ
78 C to rt, overnight; (b) I
2
, PPh
3
, imidazole, anhydrous toluene, 0e60 C, 2 h; (c)
ꢁ
PPh
3
, 100 C, 2 h, 96% (for three steps).
D
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L. Wang et al. / Tetrahedron xxx (2014) 1e5
3
OMOM
OMOM
HO
OMOM
Me
Me
MOMO
a
3
steps
b
D-Xylose
MOMO
9
6
2%
O
OH
OMOM
8
7
Br
HO
O
OMOM
Me
Me
OMOM
Me
Me
Br
MOMO
OMOM
Me
c
d
MOMO
MOMO
11 Me
1
1
11
OMOM
OMOM
OMOM
14
1
2
13
ꢁ
ꢀ
Scheme 3. Reagents and conditions: (a) 9, LHMDS, anhydrous toluene, 0e50 C, overnight; (b) Pd/C, H
2
, MeOH, rt, overnight, 89% (for two steps); (c) PDC, AcONa, MS-4 A, CH
2
Cl
2
,
ꢁ
reflux, 3 h; (d) (Ph
3
PCHBr
2
)Br, t-BuOK, anhydrous THF, 0 C to rt, 2 h, 81% (for two steps).
Br
Br
Br
OMOM
Me
Me
OMOM
Me
Me
a
b
MOMO
MOMO
1
1
11
OMOM
OMOM
1
4
6
OH
OH OH
OH
Me
Me
OMOM
Me
Me
c
MOMO
1
1
HO
OMOM
1
5
(-)-petrosiol E (5)
ꢁ
2 2
OH$HCl, Et O, n-BuNH , H O, 0 C to rt, 30 min, 76% (for two steps); (c)
Scheme 4. Reagents and conditions: (a) NaH, anhydrous THF, rt, overnight; (b) propargyl alcohol, CuCl, NH
2
2
ꢁ
3
N HCl, EtOH, 80 C, 3 h, 95%.
steps with an overall yield of 32%. The current work also confirmed
the absolute stereochemistry of 5 based on physical data agree-
ments from both synthetic and natural samples. Because of its
compactness and efficiency, our strategy is attractive for the facile
preparation of structurally similar natural products. Further efforts
on the total synthesis of other petrosiols and the bioactivity eval-
uations are currently underway in our laboratory.
with EtOAc (3ꢂ30 mL). The combined organic layers were washed
with water, saturated aq NaHCO and brine, then dried over
Na SO , and concentrated under reduced pressure to give the crude
alcohol 10 as a white solid, which was used for the next reaction
without further purification.
3
2
4
To a vigorously stirred solution of the crude alcohol 10, triphe-
nylphosphine (15.72 g, 60 mmol), and imidazole (8.16 g, 120 mmol)
in anhydrous toluene (300 mL) was added iodine (15.24 g,
ꢁ
ꢁ
4
4
. Experimental section
60 mmol) at 0 C. The resulting mixture was stirred at 60 C for 2 h.
After TLC showed that all the starting alcohol had disappeared, to
the mixture was added methanol (5 mL). After full consumption of
triphenylphosphine judged via TLC, the mixture was cooled to
.1. General
All commercially available reagents were used without further
room temperature, washed with saturated aq Na
2 2 3
S O , and
purification. All anhydrous solvents were purified according to stan-
dard procedures before use. Reactions were monitored by thin-layer
chromatography (TLC) on silica gel F254 plates. Flash chromatography
extracted with Et O. The combined organic layer was washed with
2
brine, dried, and concentrated under reduced pressure. The residue
was eluted with petroleum ether on a short silica gel column to give
the colorless crude iodide 11 as oil, which was used for the next
reaction without further purification.
(
FC) was performed using silica gel (200e300 mesh) according to the
1
13
standard protocol. H and C NMR spectrawere recorded on a Bruker
AVANCE-III 400 MHz (100 MHz for 13C NMR) spectrometer. High-
resolution mass spectrometry (HRMS) data were measured with
a Bruker microTOF-Q II mass spectrometer. Optical rotations were
recorded in either a 5-cm microcell or a 2.5-cm microcell.
A mixture of the above iodide 11 and triphenylphosphine
ꢁ
(83.84 g, 320 mmol) was fused at 100 C under N
2
atmosphere.
After being stirred for 2 h at the same temperature, the reaction
mixture was cooled to room temperature, dissolved in MeCN
(
300 mL), and washed with petroleum ether (450 mLꢂ12 times).
4
.2. Iodo(13-methyltetradecyl)triphenylphosphorane (9)
The MeCN layer was concentrated under reduced pressure to give
the crude phosphonium salt 9 (23.1 g, 96% for three steps) as
To a stirred solution of 11-bromoundecanol (10 g, 40 mmol) in
a yellow solid, which could be used for the next reaction without
1
anhydrous THF (100 mL) was added
a
solution of iso-
further purification; H NMR (400 MHz, CDCl
3
):
d
7.78e7.87 (m,
butylmagnesium bromide (1 mol/L in THF, 148 mL, 148 mmol),
9H), 7.68e7.73 (m, 6H), 3.74 (m, 2H), 1.64 (m, 5H), 1.46e1.56 (m,
13
followed by a solution of Li
2
CuCl
4
(0.1 mol/L in THF, 5 mL, 0.5 mmol)
1H), 1.11e1.22 (m, 17H), 0.85 (d, J¼6.4 Hz, 6H); C NMR (100 MHz,
ꢁ
at ꢀ78 C under N
2
atmosphere. The resulting mixture was warmed
CDCl ): 135.3 (3C), 133.9 (3C), 133.8 (3C), 130.8 (3C), 130.7 (3C),
3
d
to room temperature and stirred overnight. After the reaction
mixture was quenched with saturated aq NH Cl, it was extracted
118.7 (2C), 117.8, 39.2, 29.3e30.7 (10C), 28.1, 27.5, 22.8, 22.7; ESI-
þ
4
HRMS calcd for C33
H
46P ([MꢀI] ) 473.3331, found 473.3346.
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4
L. Wang et al. / Tetrahedron xxx (2014) 1e5
ꢁ
4
.3. (2R,3R,4S)-2,3,4-Tris(methoxymethoxy)-18-
hydride (34 mg, 0.86 mmol) as a solid at 0 C. The resulting mixture
was warmed to room temperature and stirred overnight. After the
methylnonadecan-1-ol (12)
4
reaction mixture was quenched with saturated aq NH Cl, it was
The phosphonium salt 9 (4.14 g, 6.90 mmol) was azeotropically
dried with toluene and further dried by heating to 50 C under
vacuum for 4 h. The salt was cooled to room temperature, backfilled
2
with N , and dissolved in anhydrous toluene (30 mL). To the re-
extracted with EtOAc. The combined organic layers were washed
with brine, dried, and concentrated under reduced pressure to give
the crude 1-bromoalkyne 6, which was used for the next reaction
without further purification.
ꢁ
sultant solution was added dropwise LHMDS (1.0 mol/L in THF,
2
To a stirred 30% n-BuNH aqueous solution (5 mL) was added
ꢁ
6
.90 mL, 6.90 mmol) at 0 C under N
2
atmosphere. The resulting red
CuCl (0.2 mg, 0.002 mmol) at room temperature, resulted in the
formation of a blue solution immediately. A few crystals of hy-
droxylamine hydrochloride were added until the blue color dis-
appeared. The resulting colorless solution indicated the present of
mixture was stirred at room temperature for 1 h. To the above
mixture was added a solution of tri-O-methoxymethyl- -xylopyr-
D
anose 8 (778 mg, 2.76 mmol) in anhydrous toluene (10 mL), and the
ꢁ
resulting mixture was stirred at 50 C overnight. At the end of
Cu (I) salt. A solution of propargyl alcohol (50
mL, 0.86 mmol) in
which time, the reaction mixture was quenched with saturated
2
Et O (0.5 mL) was added to the solution at room temperature,
aq NH
4
Cl and extracted with EtOAc (3ꢂ20 mL). The extracts were
yielding a yellow acetylide suspension, which was immediately
ꢁ
washed with brine, dried, and concentrated under reduced pres-
sure to give the crude alkene 7, which was used for next reaction
without further purification.
A mixture of alkene 7 and 10% Pd/C (294 mg, 0.276 mmol) in
methanol (10 mL) was stirred vigorouslyat room temperature under
cooled to 0 C. A solution of the 1-bromoalkyne 6 in Et
2
O (2 mL)
was added dropwise. The resulting mixture was warmed to room
temperature and stirred for 30 min. More crystals of hydroxyl-
amine hydrochloride were added throughout the reaction to
prevent the reaction mixture from turning blue or green. The re-
H
2
atmosphere overnight until all starting materials were con-
action mixture was extracted with Et
organic layers were dried, and concentrated under reduced pres-
sure. The residue was purified by silica gel column chromatogra-
phy (ethyl acetate/petroleum ether 1:6) to give the diyne 15
2
O (3ꢂ15 mL). The combined
sumed. The mixture was filtered and concentrated under reduced
pressure. The residue was purified by silica gel column chromatog-
raphy (ethyl acetate/petroleum ether 1:4) to give the alcohol 12
2
5
1
25
(
1.17 g, 89% for twosteps) as a colorless oil; [
NMR (400 MHz, CDCl ): 4.66e4.80 (m, 6H), 3.69e3.82 (m, 5H), 3.43
s, 3H), 3.42 (s, 3H), 3.39 (s, 3H),1.63e1.72 (m,1H),1.45e1.56 (m, 2H),
a
]
D
20 (c 0.67, CHCl
3
); H
(34 mg, 76% for two steps) as a colorless oil; [
a
]
D
ꢀ122 (c 0.4,
1
3
d
CHCl
3
); H NMR (400 MHz, CDCl
3
):
d
4.92 (dd, J¼6.8, 16.4 Hz, 2H),
(
4.71e4.74 (m, 3H), 4.67 (d, J¼7.2 Hz, 1H), 4.62 (d, J¼6.8 Hz, 1H),
4.33 (s, 2H), 3.85e3.89 (m, 1H), 3.74 (dd, J¼3.2, 7.2 Hz, 1H), 3.43 (s,
3H), 3.40 (s, 3H), 3.38 (s, 3H), 1.95 (br, 1H), 1.44e1.71 (m, 4H), 1.25
1
.38 (m, 2H),1.25 (m, 20H),1.12e1.15 (m, 2H), 0.86 (d, J¼6.4 Hz, 6H);
1
3
3
C NMR (100 MHz, CDCl ): d 98.9, 97.9, 97.3, 80.9, 79.5, 78.6, 62.7,
13
5
6.5, 56.2 (2C), 39.3, 31.0, 29.9e30.2 (9C), 28.3, 27.7, 25.6, 23.0 (2C);
(m, 21H), 1.11e1.15 (m, 2H), 0.85 (d, J¼6.4 Hz, 6H); C NMR
þ
ESI-HRMS calcd for C26
54
H O
7
([MþNa] ) 501.3762, found 501.3775.
(100 MHz, CDCl ): 98.7, 97.1, 95.1, 80.0, 78.0, 76.3, 71.6, 70.0, 68.4,
3
d
56.7, 56.3 (2C), 51.7, 39.4, 31.3, 30.0e30.3 (9C), 28.3, 27.8, 25.7, 23.0
þ
4
.4. 3(5R,6R,7S)-5-(2,2-Dibromovinyl)-6-(methoxymethoxy)-
(2C); ESI-HRMS calcd for C30
549.3774.
54
H O
7
([MþNa] ) 549.3762, found
7
-(14-methylpentadecyl)-2,4,8,10-tetraoxaundecane (14)
To a stirred solution of the alcohol 12 (350 mg, 0.732 mmol) in
4.6. (L)-Petrosiol E (5)
ꢀ
CH
2
Cl
2
(10 mL) was added anhydrous molecular sieves (4 A,
8
26 mg), sodium acetate (180 mg, 2.20 mmol), and pyridinium
To a stirred solution of the diyne 15 (28 mg, 0.053 mmol) in
dichromate (826 mg, 2.20 mmol) at room temperature. After being
stirred under reflux for 3 h, the mixture was eluted from a short
column of silica gel with EtOAc to give aldehyde 13, which was used
for next reaction without further purification.
EtOH (2.5 mL) was added 3 N HCl aqueous solution (0.6 mL) at
ꢁ
room temperature. The mixture was stirred at 80 C for 3 h. After
4
the reaction mixture was quenched with saturated aq NH Cl, it
was extracted with EtOAC. The combined organic layers were
dried, and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (ethyl acetate/pe-
troleum ether 1:1) to give petrosiol E (5) (20 mg, 95%) as a color-
t-BuOK (234 mg, 2.09 mmol) was added to a solution of
ꢁ
(
Ph
3
PCHBr
2
)Br (1.13 g, 2.20 mmol) in anhydrous THF (10 mL) at 0 C
under N
2
atmosphere. The mixture was warmed to room temper-
ature and stirred for 30 min, followed by addition of a solution of 13
in anhydrous THF (2 mL). After 2 h, the reaction mixture was
quenched with brine, and extracted with EtOAc. The combined
organic layers were dried, concentrated under reduced pressure,
and purified by silica gel column chromatography (ethyl acetate/
petroleum ether 1:10) to give the dibromoalkene 14 (374 mg, 81%
2
5
1
less powder; [
CD OD (4:1)):
a
d
]
D
ꢀ2 (c 0.06, MeOH); H NMR (400 MHz, CDCl
3
/
3
4.46 (d, J¼6.4 Hz, 1H), 4.26 (s, 2H), 3.76 (m, 1H),
3
.44 (d, J¼5.6 Hz, 1H), 1.13e1.66 (m, 27H), 0.87 (d, J¼6.4 Hz, 6H);
1
3
3 3
C NMR (100 MHz, CDCl /CD OD (4:1)): d 78.3, 77.6, 76.1, 71.3,
7
2
0.1, 68.9, 64.5, 50.6, 39.2, 34.2, 29.8e30.1 (9C), 28.1, 27.6, 25.9,
þ
2.7 (2C); ESI-HRMS calcd for C24
found 417.2966.
H
42
O
4
([MþNa] ) 417.2975,
2
5
1
for two steps) as a colorless oil; [
a]
D
ꢀ111 (c 0.93, CHCl
3
); H NMR
(
(
1
3
400 MHz, CDCl ): d
6.57 (d, J¼8.8 Hz, 1H), 4.74e4.82 (m, 3H), 4.69
dd, J¼3.2, 6.8 Hz, 2H), 4.59 (d, J¼6.8 Hz, 1H), 4.51 (dd, J¼4.0, 8.8 Hz,
H), 3.75e3.79 (m, 1H), 3.68e3.70 (m, 1H), 3.44 (s, 3H), 3.40 (s, 3H),
.39 (s, 3H),1.67e1.76 (m,1H),1.46e1.64 (m, 3H),1.39e1.41 (m, 2H),
Acknowledgements
3
13
1
.25 (m, 19H), 1.14e1.15 (m, 2H), 0.86 (d, J¼6.4 Hz, 6H); C NMR
This work was supported in partial by the Strategic Priority
Research Program of the Chinese Academy of Sciences (Grant No.
XDB14040201), the National Basic Research Program of China
(Grants 2012CB822101 and 2011CB936001), and National Natu-
ral Science Foundation of China (Projects 21372254 and
21202193). We thank Dr. Min Li for mass spectra measurements.
Special thanks to Dr. Yi-Xian Li (Key Laboratory of Molecular
Recognition and Function, Institute of Chemistry, Chinese
Academy of Sciences) for measuring the optical rotation of
synthetic petrosiol E.
(
100 MHz, CDCl ): 137.0, 98.4, 97.6, 94.9, 92.7, 79.8, 78.7, 76.4, 56.6,
3
d
5
6.4, 56.2, 39.3, 31.3, 29.9e30.2 (9C), 28.2, 27.7, 25.3, 22.9 (2C); ESI-
þ
HRMS calcd for C27
H52Br
2
O
6
([MþNa] ) 655.2005, found 655.2006.
4
.5. (6R,7R,8S)-6,7,8-Tris(methoxymethoxy)-22-
methyltricosa-2,4-diyn-1-ol (15)
To a stirred solution of the dibromoalkene 14 (54 mg,
.086 mmol) in anhydrous THF (1 mL) was added 60% sodium
0
Please cite this article in press as: Wang, L.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.09.030

L. Wang et al. / Tetrahedron xxx (2014) 1e5
5
Supplementary data
(h) Cai, C.; Liu, J.; Du, Y.; Linhardt, R. J. J. Org. Chem. 2010, 75, 5754e5756; (i) Du,
Y.; Liu, J.; Linhardt, R. J. J. Org. Chem. 2006, 71, 1251e1253; (j) Du, Y.; Chen, Q.;
Linhardt, R. J. J. Org. Chem. 2006, 71, 8446e8451.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.09.030.
5
. Sathish Reddy, A.; Srihari, P. Tetrahedron Lett. 2013, 54, 6370e6372.
6. Kireev, A. S.; Nadein, O. N.; Agustin, V. J.; Bush, N. E.; Evidente, A.; Manpadi, M.;
Ogasawara, M. A.; Rastogi, S. K.; Rogelj, S.; Shors, S. T.; Kornienko, A. J. Org.
Chem. 2006, 71, 5694e5707.
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