Synthesis and configurations of YF-0200R A and B

Article abstract of DOI:10.1016/j.tet.2016.04.033

Two natural unsaturated fatty acids with aspargyl protease inhibition activity were synthesized for the first time. The stereogenic centers were installed by using Brown asymmetric allylation or chiral building blocks derived from d-glucose, respectively. The conjugate diene unit was introduced via an HWE reaction. The geometry of the C-C double bonds was clearly shown to be (E) by ¹H NMR in C₆D₆. The spectroscopic data for the synthetic samples were in excellent consistency with those reported for the corresponding natural ones. The optical rotations were also compatible with those for the natural ones. The absolute configurations for natural YF-0200R A and B thus could be reliably assigned as (8S) and (8S,10S), respectively.

Full text of DOI:10.1016/j.tet.2016.04.033

Tetrahedron 72 (2016) 3177e3184
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Tetrahedron
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Synthesis and configurations of YF-0200R A and B
,
,
a,
*
Xiao-Dan Wang a b, Ze-Jun Xu b, Shijun Zhu b, Yikang Wu b , Yan-Jun Hou
*
a School of Chemistry and Materials, Heilongjiang University, Harbin 150080, China
b State Key Laboratory of Bioorganic and 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:
Two natural unsaturated fatty acids with aspargyl protease inhibition activity were synthesized for the
first time. The stereogenic centers were installed by using Brown asymmetric allylation or chiral building
blocks derived from D-glucose, respectively. The conjugate diene unit was introduced via an HWE re-
Received 14 March 2016
Received in revised form 8 April 2016
Accepted 12 April 2016
action. The geometry of the CeC double bonds was clearly shown to be (E) by 1H NMR in C6D6. The
spectroscopic data for the synthetic samples were in excellent consistency with those reported for the
corresponding natural ones. The optical rotations were also compatible with those for the natural ones.
The absolute configurations for natural YF-0200R A and B thus could be reliably assigned as (8S) and
(8S,10S), respectively.
Available online 19 April 2016
Keywords:
Diene
Allylation
Fatty acid
Diol
Ó 2016 Elsevier Ltd. All rights reserved.
Inhibitor
1. Introduction
and 2, respectively). However, the previous investigators did not
seem to have made any attempts to determine the absolute con-
Unsaturated fatty acids YF-0200R A and B were isolated from
the culture broth of Streptomyces sp. YF-0200R, a fungus found in
a soil sample from South Sumatra, Indonesia, by Sato1 and co-
workers. In preliminary tests on aspartyl protease inhibition ac-
tivity both 1 and 2 showed an IC50 of ca. 6ꢀ10ꢁ4 M activity against
Candida albicans, with, demonstrating the first examples of un-
saturated fatty acids possessing this activity.
figurations for both compounds. And the critical stereochemical
information remains missing to date, clearly calling for an enan-
tioselective synthesis to complete the long-pending full charac-
terization of these potentially useful natural products. As an
extension of our studies on enantioselective synthesis and absolute
configuration of naturally occurring diols,2 we synthesized both 1
and 2 in optically active forms; the configurations of their natural
counterparts were also hence elucidated. Details are given below.
On the basis of extensive spectroscopic analyses, the gross
structures for YF-0200R A and B were assigned as shown in Fig. 1 (1
2. Results and discussion
Our study began with a synthesis of (R)-1 as shown in Scheme 1.
The known3 aldehyde 3 was subjected to Brown4 asymmetric
allylation to afford alcohol 45 as reported by Menche. The hydroxyl
group in 4 was then protected6 with TBSCl to give 5, which on
treatment with BH3$SMe2 followed by H2O2/NaOH gave alcohol 6
in 70% overall yield (from 3). The terminal alcohol was then oxi-
dized under the standard Swern conditions to result in the corre-
sponding aldehyde 7. It is noteworthy that the Ipc2BOMe related
species in the asymmetric allylation were very difficult to remove
from 4, 5 and 6; complete elimination of such species was possible
only after conversion of 6 into 7.
Fig. 1. The gross structures of YF-0200R A (1) and B (2).
A HornereWadswortheEmmons reaction with 87 then de-
livered the desired ester 9 in 71% yield; the (E,E) CeC double bond
configuration was confirmed by 1H NMR in C6D6.8 The final
* Corresponding authors. E-mail address: yikangwu@sioc.ac.cn (Y. Wu).
http://dx.doi.org/10.1016/j.tet.2016.04.033
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

3178
X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
gave diol 13, which was then converted into 14 by reaction with
1,1-thiocarbonyldiimidazole13 to set the stage for the subsequent
deoxygenation.
Scheme 1. a) (i) (ꢁ)-Ipc2BOMe, CH2]CHCH2MgBr, Et2O, (ii) H2O2, 3 N NaOH, ꢁ78 ꢂC,
5 h; b) TBSCl, imidazole, DMAP, DMF, 16 h; c) (i) BH3$SMe2,THF, (ii) H2O2, 3 N NaOH,
5 h, 70% overall from 3; d) oxalyl chloride, DMSO, CH2Cl2, e78 ꢂC, 1 h, 81%; e) LiHMDS,
THF, e78 ꢂC, 3 h, 71% from 7; f) LiOH, EtOHeH2O (5:1, v/v), 1 N HCl, 16 h, 60%.
(ꢁ)-Ipc2BOMe¼(ꢁ)-B-Methoxydiisopino-campheylborane.
TBS¼tert-Butyldime-
thylsilyl. LiHMDS¼Lithium hexamethyldisilazide. DMAP¼4-N,N0-Dimethylaminopyr-
idine. DMSO¼Dimethylsulfoxide.
deprotection was effected using LiOH in aqueous EtOH9a and 1 N
HCl,10 respectively. The end product (R)-1 showed 1H and 13C NMR
in full consistency with those reported for natural 1.11 However, the
optical rotation for (R)-1 was determined to be ꢁ4.65, indicating
that what we obtained must be the mirror image of natural YF-
0200R A.
A synthesis of (S)-1 was then performed. Using the same route
but with (þ)-Ipc2BOMe to replace (ꢁ)-Ipc2BOMe (Scheme 2), the
desired (S) isomer was attained without any complications. The
optical rotation for (S)-1 was measured to be þ5.66, confirming that
natural YF-0200R A indeed possesses the same configuration as
(S)-1.
Scheme 3. a) CH2]CHCH2MgBr, CuI, THF, e20 ꢂC, 3 h, 82%; b) TBSCl, imidazole, DMAP,
DMF, 16 h, 89% for 12, 98% for 18; c) 50% CF3CO2H, CH2Cl2, 1 h, 82%; d) 1,1-
thiocarbonyldi-imidazole, toluene, 110 ꢂC,
1
h, 93%; e) AIBN, nBu3SnH, toluene,
100 ꢂC, 5 h, 47%; f) (i) O3, CH2Cl2, e78 ꢂC, 20 min, (ii) PPh3, 95% from 18; g) LiHMDS,
THF, e78 ꢂC,
h, 73%; h) (i) LiOH, aq EtOH, 16 h, (ii) HCl, 16 h, 85%.
AIBN¼azodiisobutyronitrile.
3
1 N
A radical mediated deoxygenation of 14 was then carried out
under the AIBN/nBu3SnH/toluene/100 ꢂC14 conditions. As expected,
the reaction was complicated by concurrent side reactions, which
led to formation of 16, 17 and 15’. Although chromatographic sep-
aration of 16 and 17 from 15 was feasible, Removal of 15’ could be
realized only by chromatography on AgNO3-treated15 silica gel.
The hydroxyl group in the purified 15 was then protected with
TBS. The resulting 18 was converted into aldehyde 19 by ozonol-
ysis16 followed by Ph3P reduction. The conjugate diene motif was
installed through a HornereWadswortheEmmons reaction with 8
as in the synthesis of 1. The ethyl ester was then hydrolyzed with
LiOH. The crude intermediate carboxylic acid was directly desily-
lated with aq HCl to afford end product (8R,10R)-2.
The synthetic (8R,10R)-2 showed 1H and 13C NMR (in CD3OD)
in excellent consistency with those reported for natural 2 (cf.
Supplementary data). Like 1, 2 is also insoluble in CDCl3, strongly
suggesting that the previous NMR data were actually recorded in
CD3OD (at least a mixture of CD3OD and CDCl3) rather than CDCl3
as reported in the literature. Normally, such excellent agreements
of the NMR data would allow for concluding that natural 2 and
synthetic (8R,10R)-2 shared the same relative configuration.
However, in a previous2a study we observed that syn and anti
isomers of a linear 1,3-diol showed identical 13C NMR. To exclude
this rare yet not always excludable possibility in the present case,
Scheme 2. a) (i) CH2]CHCH2MgBr, (þ)-Ipc2BOMe, Et2O, (ii) H2O2, 3 N NaOH, e78 ꢂC,
5 h; b) TBSCl, imidazole, DMAP, DMF, 16 h; c) (i) BH3$SMe2,THF, (ii) H2O2, 3 N NaOH,
5 h, 70% overall from 3; d) (COCl)2, DMSO, CH2Cl2, e78 ꢂC, 1 h, 72%; e) LiHMDS, THF,
e78 ꢂC, 3 h, 60% from ent-7; f) (i) LiOH, aq EtOH, (ii) 1 N HCl, 16 h, 64%.
YF-0200R B has two stereogenic centers. In principle its relative
configuration might be either syn or anti. We arbitrarily chose to
begin with the anti-isomer. As shown in Scheme 3, treatment of the
known2e epoxide 10 with CH2]CHCH2MgBr in the presence of CuI
led to 11 in 82% yield. Protection of the newly formed OH with TBS
12
followed by hydrolysis of the acetonide in 50% CF3CO2H/CH2Cl2

X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
3179
we decided to synthesize (8S,10R)-2 (a syn isomer) for
comparison.
each other (vide infra), an (8S,10S) configuration can be reliably
assigned to natural 2.
The synthetic route leading to (8S,10R)-2 is shown in Scheme 4.
Using another known epoxy building block 212c we have in hand as
the source of the stereogenic centers, the desired (8S,10R)-2 was
obtained in comparable yields. It is noteworthy that at the radical-
mediated deoxygenation step, the CeC double migration appeared
to occur to a negligible extent compared with the same reaction of
14; in this case a second chromatography on AgNO3-silica gel was
thus no longer necessary.
The optical rotation for the (8R,10R)-2 was measured to be be-
tween ꢁ2.28 and ꢁ0.67 in MeOH at different time points17 (or
between ꢁ3.69 and ꢁ0.74 in CD3OD, cf. Supplementary data),
which is apparently closer in magnitude to that for natural 2 (þ6.5)
than (8S,10R)-2 (ꢁ15.1). This, together with the appearance of the
two diastereomers (one was a solid like the natural 2, while the
other was an oil), provided additional support for the anti relative
configuration assigned to natural 2 on the basis of 13C NMR.
In efforts to understand the discrepancy between the magni-
tudes of the optical rotations for natural 2 and (8R,10R)-2 we also
explored potential causes, such as sample purity and sample con-
centration18 employed in the determination of optical rotations.
The (8R,10R)-2 was homogenous on 1H and 13C NMR. Besides, the
chiral building block 10 employed was definitely free from any
isomers.19 Therefore, the sample purity could be reasonably ex-
cluded as the cause for the small magnitude of the optical rotation
for (8R,10R)-2. Next, we measured the [
tion (c¼0.5, MeOH). The results appeared to be time-dependent. At
26 min after preparation of the sample, the [
D was ꢁ1.71. But over
the next few minutes, the magnitude of [ D decreased by ca. half.
a] at a higher concentra-
D
a]
a
]
(cf. Table S-6, Supplementary data). It thus appears that (8R,10R)-2
may indeed have a rather small magnitude for optical rotation
(when the reading fluctuation finally reduced, ca. 25 min after
preparation of the sample solution),20 which was not mentioned by
previous investigators1 but definitely deserves particular attention
in data comparisons of similar compounds if one wishes to avoid
unnecessary confusions. Finally, it is interesting to note that the two
closely related natural unsaturated fatty acids have different C-8
configurations, although both are (8S) as a result of changes in the
substituents sequence.
3. Conclusion
Scheme 4. a) CH2]CHCH2MgBr, CuI, THF, e20 ꢂC, 3 h, 85%; b) TBSCl, imidazole, DMAP,
DMF, 16 h, 97% for 23, 91% for 27; c) 50% CF3CO2H, CH2Cl2, 30 min, 83%; d) 1,1-
thiocarbonyldiimidazole, toluene, 110 ꢂC, 1 h, 93%; e) AIBN, nBu3SnH, toluene, 110 ꢂC,
5 h, 50%; f) (i) O3, CH2Cl2, e78 ꢂC, 20 min, (ii) PPh3, 91% from 27; g) 8, LiHMDS, THF,
e78 ꢂC, 3 h, 64%; h) (i) LiOH, aq EtOH, 18 h, (ii) 1 N HCl, 16 h, 78%.
YF-0200R A and B, two natural unsaturated fatty acids with
aspargyl protease inhibition activity, were synthesized for the first
time. The optically active synthetic samples (synthesized via chiral
pool based routes) showed spectroscopic data fully consistent with
those reported for their natural counterparts. The so far missing
1He1H coupling constants for YF-0200R A and B are thus made
known. The absolute configurations of the natural products were
signed on the basis of comparison of the 1H and 13C NMR as well as
optical rotations. The tricky optical rotation of the anti triol is also
revealed.
The 1H NMR for (8S,10R)-2 was essentially the same as that for
(8R,10R)-2. However, significant differences were indeed found
between the two diastereomers in the signals for the C-8 and C-10
(Table 1), which definitely excluded the possibility for natural 2 to
be a syn isomer. Therefore, natural 2 must have the anti relative
configuration. As for the absolute configuration, because the signs
for the optical rotations for natural 2 and (8R,10R)-2 are opposite to
4. Experimental
4.1. General methods
Table 1
Comparison of the13C NMR for the natural 2, (8R,10R)-2 (anti 2) and (8S,10R)-2 (syn 2)
The NMR spectra were recorded on an Agilent 500/54 (operat-
ing at 500 MHz for 1H) or a Bruker Avance (operating at 400 MHz
for 1H) NMR spectrometer with TMS as the internal standard. IR
spectra were measured on a Nicolet 380 Infrared spectrophotom-
eter. ESI-MS data were acquired on a Shimadzu LCMS-2010EV mass
spectrometer. HRMS data were obtained with a Bruker APEXIII 7.0
Tesla FT-MS spectrometer. Optical rotations were measured on
a Jasco P-1030 polarimeter. Melting points were uncorrected
(measured on a hot stage melting point apparatus equipped with
Natural 2a
(8R,10R)-2b
(8S,10R)-2b
170.9 (C-1)
170.9 (C-1)
146.7 (C-3)
145.3 (C-5)
129.9 (C-4)
120.7 (C-2)
68.5 (C-8)
66.9 (C-10)
60.2 (C-12)
45.9 (C-9)
41.5 (C-11)
38.1 (C-7)
30.2 (C-6)
171.6 (C-1)
147.2 (C-3)
145.8 (C-5)
130.5 (C-4)
121.5 (C-2)
71.2 (C-8)
69.6 (C-10)
60.7 (C-12)
45.9 (C-9)
41.5 (C-11)
38.1 (C-7)
30.6 (C-6)
146.9 (C-3)
145.5 (C-5)
129.9 (C-4)
120.6 (C-2)
68.6(C-8)
67.0 (C-10)
60.2 (C-12)
45.9 (C-9)
41.5 (C-11)
38.1 (C-7)
30.2 (C-6)
ꢀ
a microscope). CH2Cl2 was dried with activated 4 A MS (molecular
ꢀ
sieves). Deaerated toluene was obtained by bubbling N2 into 4 A MS
dried toluene for 20 min. All chemicals were reagent grade and
used as purchased. Column chromatography was performed on
silica gel (230e400 mesh) under slightly positive pressure. Petro-
leum ether refers to the fraction boiling between 60 and 90 ꢂC.
AgNO3-treated silica gel for column chromatography was prepared
a
Taken with assignments from Ref. 1; reported to be measured at 125 MHz ‘in
CDCl3’. However, we observed that neither (8R,10R)-2 nor (8S,10R)-2 was soluble in
CDCl3.
b
This work, measured at 125 MHz in CD3OD; the assignments were made with
the aid of 2D NMR.

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X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
by stirring 40 g of silica gel (230e400 mesh) with aq AgNO3 (12 g of
AgNO3 in 120 mL of distilled water) for 10 min, evacuating the flask
under membrane pump vacuum, and heated in a 120 ꢂC oven
(covered with aluminum foil to exclude light) for 4 h before use.
The AgNO3-treated TLC plates were prepared by dipping commer-
cially available TLC plates into a solution of AgNO3 (2.5 g) in MeCN
(50 mL) for 5 min and dried in a 120 ꢂC oven for 1 h.
9 H), 0.045 (s, 9 H), 0.039 (s, 3 H). 13C NMR (125 MHz, CDCl3):
d
¼202.6, 71.1, 63.0, 39.7, 36.8, 33.0, 28.9, 26.0, 25.9, 21.6, 18.4, 18.1,
e4.4, e4.5, e5.28e5.29; FTIR (film): 2954, 2930, 2895, 2858, 2711,
1729, 1472, 1463, 1361, 1255, 1101, 1005, 939, 836, 774 cmꢁ1. (For
other data, cf. those for ent-7 below).
4.3. Condensation of 7 with 8 to afford 9
4.2. Synthesis of aldehyde 7
LiHMDS (1.0 M, in THF, 343 mL, 0.343 mmol) was added drop-
wise to a solution of phosphate 8 (96 mg, 0.429 mmol) in dry THF
(0.5 mL) stirred at ꢁ78 ꢂC under argon (balloon). The stirring was
continued for 1 h before a solution of aldehyde 7 (111.2 mg,
0.286 mmol) in dry THF (0.2 mL) was added. The mixture was
stirred at the same temperature for 15 min, then at 0 ꢂC for 30 min,
and finally at ambient temperature for 2 h (TLC showed completion
of the reaction). Aq NH4Cl was added. The mixture was extracted
with EtOAc (5 mLꢀ3). The combined organic layers were washed
with water and brine and dried over anhydrous Na2SO4. Removal of
the solvent by rotary evaporation and column chromatography
A solution of CH2]CHCH2MgBr (1.0 M, in Et2O, 0.65 mL,
0.65 mmol) was added to a solution of (ꢁ)-B-methoxy-diisopino-
campheylborane (2.0 M, in Et2O, 0.35 mL, 0.694 mmol) in dry Et2O
(3.3 mL) stirred at ꢁ78 ꢂC under argon (balloon). The resulting dark
mixture was then stirred at ambient temperature for 1 h to give
a white suspension. The bath was recooled to ꢁ78 ꢂC and a solution
of aldehyde 3 (100 mg, 0.434 mmol) in dry Et2O (1 mL) was in-
troduced. Stirring was continued at the same temperature for 5 h
(TLC showed completion of the reaction). Aq NaOH (3 N, 0.8 mL)
was added, followed by H2O2 (30%, 0.8 mL). The mixture was stirred
at ambient temperature for 12 h before being extracted with Et2O
(10 mLꢀ4). The combined organic layers were washed with water
and brine, and dried over anhydrous Na2SO4. Removal of the sol-
vent by rotary evaporation and column chromatography (5:1 pe-
troleum ether/EtOAc) on silica gel gave the known allyl alcohol 4 as
a colorless oil (120.3 mg, 0.465 mmol), which was dissolved in dry
DMF (0.5 mL). To this solution were added imidazole (317 mg,
4.65 mmol), DMAP (37 mg, 0.465 mmol) and TBSCl (280.6 mg,
1.86 mmol). The mixture was stirred at ambient temperature for
12 h (TLC showed completion of the reaction). Water was added.
The mixture was extracted with EtOAc (10 mLꢀ3). The combined
organic layers were washed with water and brine, and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (10:1 petroleum ether/EtOAc) on
silica gel gave 5 as a colorless oil (160 mg, 0.429 mmol), which was
dissolved in dry THF (2.8 mL) and stirred in an ice-water bath under
argn (balloon). A solution of BH3$SMe2 (2.0 M, in THF, 1.1 mL,
2.2 mmol) was added. Stirring was continued firt at 0 ꢂC for 30 min
and then at ambient temperature for 3 h (TLC showed completion
of the reaction). Aq NaOH (3 N, 1 mL) was added, followed by fol-
lowed by H2O2 (30%, 0.8 mL). The mixture was stirred at ambient
temperature for 12 h before being extracted with Et2O (10 mLꢀ4).
The combined organic layers were washed with water and brine,
and dried over anhydrous Na2SO4. Removal of the solvent by rotary
evaporation and column chromatography (8:1 petroleum ether/
EtOAc) on silica gel afforded the known alcohol 6 as a colorless oil
(124 mg, 0.316 mmol).
(25:1 petroleum ether/EtOAc) on silica gel furnished 9 as a colorless
27
oil (98 mg, 0.202 mmol, 71%). [
(500 MHz, CDCl3):
a]
ꢁ3.4 (c 1.02, CHCl3). 1H NMR
D
d
¼7.26 (dd, J¼15.4, 10.0 Hz, 1 H), 6.20e6.09 (m,
2 H), 5.78 (d, J¼15.4 Hz, 1 H), 4.20 (q, J¼7.1 Hz, 2 H), 3.67 (quint,
J¼5.6 Hz, 1 H), 3.60 (t, J¼6.5 Hz, 2 H), 2.27e2.14 (m, 2 H), 1.57e1.47
(m, 4 H), 1.46e1.42 (m, 2 H), 1.41e1.32 (m, 2 H), 1.29 (t, J¼7.1 Hz,
3 H), 0.893 (s, 9 H), 0.886 (s, 9 H), 0.05e0.04 (several unresolved
singlets, 12 H altogether). 13C NMR (125 Hz, CDCl3):
d¼167.4, 145.1,
144.6, 128.5, 119.4, 71.7, 63.3, 60.3, 37.0, 36.0, 33.2, 28.9, 26.13,
26.06, 21.7, 18.5, 18.3, 14.5, e4.2, e4.3, e5.1. 1H NMR (500 MHz,
C6D6):
d
¼7.49 (dd, J¼15.3, 11.0 Hz, 1 H), 5.97 (dd, J¼15.0, 11.2 Hz,
1 H), 5.90 (d, J¼15.4 Hz, 1 H), 5.75 (dt, J¼15.2, 7.0 Hz, 1 H), 4.08 (q,
J¼7.1 Hz, 2 H), 3.58 (t, J¼6.1 Hz, 2 H), 3.59e3.54 (m, 1 H), 2.09e1.95
(m, 2 H), 1.55e1.49 (m, 2 H), 1.48e1.35 (m, 6 H), 1.01 (t, J¼7.2 Hz,
3 H),1.00 (s,18 H), 0.084 (s, 6 H), 0.078 (s, 3 H), 0.05 (s, 3 H). 13C NMR
(125 MHz, C6D6):
d
¼166.8, 145.0, 144.0, 128.8, 120.2, 72.0, 63.2, 60.1,
37.2, 36.3, 33.5, 29.0, 26.21, 26.18, 22.1, 18.6, 18.4, 14.4, -4.1, e4.2,
e5.1. FTIR (film): 2953, 2930, 2857, 1717, 1644, 1472, 1388, 1367,
1255, 1099, 1000, 835, 774 cmꢁ1. (For other data, cf. those for ent-9
below).
4.4. Conversion of 9 into (R)-1
A solution of 9 (40 mg, 0.0825 mmol) and LiOH (monohydrate,
22.5 mg, 0.536 mmol) in EtOHeH2O (5:1 v/v, 4.1 mL) was stirred at
ambient temperature for 12 h (TLC showed completion of the re-
action). Aq HCl (1 N) was added to bring the mixture to pH 1. The
mixture was stirred for another 2 h and then was extracted with
EtOAc (10 mLꢀ5). The combined organic layers were washed with
water and brine and dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatography (5:1
CH2Cl2/MeOH) on silica gel afforded (R)-1 as a white solid (11.1 mg,
Dry DMSO (55 mL, 1.04 mmol) was added to a solution of (COCl)2
(0.44 mL, 0.521 mmol) in dry CH2Cl2 (0.5 mL) stirred at ꢁ78 ꢂC
under argon (balloon). The mixture was stirred at he same tem-
perature for 35 min. A solution of the above obtained alcohol 6
(102 mg, 0.26 mmol) in dry CH2Cl2 (0.2 mL) was then introduced
slowly. Stirring was continued at ꢁ78 ꢂC for 1 h (TLC showed
completion of the reaction). Dry Et3N (0.22 mL, 1.56 mmol) was
added slowly. The mixture was stirred for another 45 min while the
bath was allowed to warm to ambient temperature. Water was then
added. The mixture was stirred for 15 min and extracted with
CH2Cl2 (10 mLꢀ3). The combined organic layers were washed with
water and brine, and dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatography (5:1
petroleum ether/EtOAc) afforded the known aldehyde 7 as a color-
less oil (free from the boron-containing impurities, 86 mg,
0.0486 mmol, 60%). Mp 87e90 ꢂC. [
(500 MHz, CD3OD):
J¼15.3, 10.6 Hz,1 H), 6.20 (dt, J¼15.2, 6.6 Hz, 1 H), 5.78 (d, J¼15.3 Hz,
1 H), 3.56 (t, J¼6.4 Hz, 2H), 3.54 (quint, J¼4.2 Hz, 1H), 2.38e2.31 (m,
1 H), 2.29e2.21 (m, 1 H), 1.63e1.37 (m, 8 H). 13C NMR (125 MHz,
a
]
26 ꢁ4.7 (c 0.2, MeOH). 1H NMR
D
d
¼7.25 (dd, J¼15.3, 10.5 Hz, 1 H), 6.28 (dd,
CD3OD):
d
¼170.1, 146.2, 144.9, 129.1, 119.8, 71.0, 62.2, 37.5, 36.7,
33.0, 29.6, 22.4. (For other data, cf. those for (R)-1 below).
4.5. Synthesis of ent-7
The same procedure given above for synthesis of aldehyde 7 was
employed, except (ꢁ)-B-methoxydiisopinocampheylborane was
replaced by (þ)-B-methoxydiisopinocampheylborane. ent-7 was
0.221 mmol, 57% overall from aldehyde 3). [
a
]
27 ꢁ4.0 (c 2.0, CHCl3).
D
1H NMR (500 MHz, CDCl3):
d
¼9.78 (t, J¼1.7 Hz, 1 H), 3.74e3.70 (m,
1 H), 3.60 (t, J¼6.4 Hz, 2 H), 2.48 (td, J¼7.5, 1.6 Hz, 2 H), 1.87e1.80
(m, 1 H), 1.74e1.69 (m, 1 H), 1.53e1.30 (m, 6 H), 0.89 (s, 9 H), 0.88 (s,
obtained as a colorless oil (439 mg, 1.13 mmol, 50% overall from 3).
27
[a
]
þ3.5 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3):
¼9.78 (t,
d
D

X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
3181
J¼1.7 Hz, 1 H), 3.74e3.70 (m, 1 H), 3.60 (t, J¼6.4 Hz, 2 H), 2.48 (dt,
alcohol 11 as a colorless oil (1.215 g, 3.53 mmol, 82%). [
a
]
22 þ7.6 (c
D
J¼1.6, 7.5 Hz, 2 H), 1.87e1.80 (m, 1 H), 1.74e1.67 (m, 1 H), 1.53e1.30
(m, 6 H), 0.89 (s, 9 H), 0.88 (s, 9 H), 0.05e0.04 (several unresolved
1.26, CHCl3). 1H NMR (500 MHz, CDCl3):
d¼5.88e5.80 (m, 1 H), 5.04
(dq, J¼17.1, 1.6 Hz, 1 H), 4.97e4.95 (m, 1 H), 4.10e4.05 (m, 2 H),
3.93e3.86 (m, 2 H), 3.83e3.77 (m, 1 H), 3.24 (s, 1 H), 2.25e2.09 (m,
2 H), 1.76 (dq, J¼14.6, 2.2 Hz, 1 H), 1.68 (dq, J¼14.6, 5.0 Hz, 1 H),
1.62e1.55 (m, 1 H), 1.53e1.47 (m, 1 H), 1.41 (s, 3 H), 1.35 (s, 3 H), 0.89
(s, 9 H), 0.12 (s, 3 H), 0.10 (s, 3 H). 13C NMR (125 MHz, CDCl3):
singlets, 12 H altogether). 13C NMR (125 MHz, CDCl3):
d 202.7, 71.1,
63.1, 39.7, 36.8, 33.0, 28.9, 26.0, 25.9, 21.6, 18.4, 18.1, e4.4, e4.5,
e5.27, e5.28. FTIR (film): 2954, 2930, 2895, 2858, 2711, 1729, 1472,
1463, 1361, 1255, 1101, 1005, 939, 836, 774 cmꢁ1. ESI-MS m/z 389.4
[MþH]þ. ESI-HRMS: calcd for C20H45O3Si2 [MþH]þ 389.2902;
d
¼138.5,114.6,109.3, 78.1, 72.8, 68.0, 67.5, 41.6, 37.2, 29.9, 26.7, 25.8,
found 389.2910,
411.2728.
C
20H44NaO3Si2 [MþNa]þ: 411.2721; found:
25.4, 17.9, e4.1, e4.6. FTIR (film): 3488, 2984, 2953, 2930, 2857,
1640, 1472, 1462, 1379, 1370, 1255, 1072, 837, 776, 668 cmꢁ1. ESI-MS
m/z 367.3 [MþNa]þ. ESI-HRMS: calcd for C18H36NaO4Si [MþNa]þ
367.2275; found 367.2271.
4.6. Condensation of ent-7 with 8 to afford ent-9
The same procedure given above for synthesis of 9 was
4.9. TBS protection of 11 to afford 12
employed. ent-9 was obtained as a colorless oil (328.2 mg,
27
0.677 mmol, 60%). [
CDCl3):
a
]
D
þ1.5 (c 2.03, CHCl3). 1H NMR (500 MHz,
A solution of alcohol 11 (1.20 g, 3.48 mmol), imidazole (2.34 g,
34.83 mmol), DMAP (425 mg, 3.48 mmol) and TBSCl (2.10 g,
13.93 mmol) in dry DMF (3.5 mL) was stirred at ambient tem-
perature for 12 h (TLC showed completion of the reaction). Water
was added. The mixture was extracted with EtOAc (10 mLꢀ4).
The combined organic layers were washed with water and brine
and dried over anhydrous Na2SO4. Removal of the solvent by
rotary evaporation and column chromatography (50:1 petroleum
d
¼7.26 (dd, J¼15.4,10.0 Hz,1 H), 6.20e6.09 (m, 2 H), 5.78 (d,
J¼15.4 Hz, 1 H), 4.20 (q, J¼7.1 Hz, 2 H), 3.67 (quint, J¼5.5 Hz, 1 H),
3.60 (t, J¼6.4 Hz, 2 H), 2.27e2.14 (m, 2 H), 1.57e1.47 (m, 4 H),
1.46e1.42 (m, 2 H), 1.41e1.32 (m, 2 H), 1.29 (t, J¼7.1 Hz, 3 H), 0.89
(m, 9 H), 0.89 (m, 9 H), 0.05e0.04 (several unresolved singlets, 12 H
altogether). 13C NMR (125 MHz, CDCl3):
d
¼167.3, 145.0, 144.5, 128.3,
119.3, 71.6, 63.1, 60.2, 36.9, 35.9, 33.1, 28.8, 26.0, 25.9, 21.6, 18.4, 18.1,
14.3, e4.3, e4.4, e5.3. 1H NMR (500 MHz, C6D6):
d
¼7.50 (dd, J¼15.3,
ether/EtOAc) on silica gel gave 12 as a colorless oil (1.422 g,
21
11.0 Hz, 1 H), 5.97 (dd, J¼14.8, 11.2 Hz, 1 H), 5.91 (d, J¼15.4 Hz, 1 H),
5.74 (dt, J¼15.2, 7.0 Hz, 1 H), 4.08 (q, J¼7.1 Hz, 2 H), 3.58 (t, J¼6.1 Hz,
2 H), 3.59e3.54 (m, 1 H), 2.09e1.95 (m, 2 H), 1.55e1.49 (m, 2 H),
1.48e1.35 (m, 6 H), 1.01 (t, J¼7.1 Hz, 3 H), 1.00 (s, 18 H), 0.09 (s, 6 H),
3.10 mmol, 89%). [
CDCl3):
a
]
þ11.2 (c 1.13, CHCl3). 1H NMR (500 MHz,
D
d
¼5.85e5.77 (m, 1 H), 5.03e4.94 (m, 2 H), 4.04e3.96 (m,
2 H), 3.89 (quint, J¼5.8 Hz, 1 H), 3.84e3.80 (m, 2 H), 2.12e2.06
(m, 2 H), 1.68e1.50 (m, 4 H), 1.39 (s, 3 H), 1.33 (s, 3 H), 0.89 (s,
9 H), 0.88 (s, 9 H), 0.08 (s, 6 H), 0.074 (s, 3 H), 0.067 (s, 3 H). 13C
0.08 (s, 3 H), 0.05 (s, 3 H). 13C NMR (125 MHz, C6D6):
d¼166.8, 145.0,
144.0, 128.8, 120.2, 72.0, 63.2, 60.1, 37.2, 36.3, 33.5, 29.0, 26.21,
NMR (125 MHz, CDCl3):
d
¼138.6, 114.4, 109.0, 79.4, 70.4, 69.1,
26.18, 22.1, 18.6, 18.4, 14.4, e4.1, e4.2, e5.1. FTIR (film): 2954, 2930,
66.0, 43.4, 37.1, 29.3, 26.5, 25.93, 25.89, 25.4, 18.10, 18.09, e3.96,
e4.03, e4.1. FTIR (film): 2955, 2929, 2887, 2858, 1641, 1472, 1369,
1255, 1074, 1004, 836, 774 cmꢁ1. ESI-MS m/z 481.5 [MþNa]þ. ESI-
HRMS: calcd for C24H51O4Si2 [MþH]þ 459.3320; found 459.3313.
ESI-HRMS: calcd for C24H50NaO4Si2 [MþNa]þ 481.3140; found
481.3139.
2857, 1717, 1644, 1472, 1388, 1367, 1255, 1099, 1000, 835, 774 cmꢁ1
.
ESI-MS m/z 485.6 [MþH]þ, m/z 507.6 [MþNa]þ. ESI-HRMS: calcd for
C
26H53O4Si2 [MþH]þ 485.3477; found 485.3476.
4.7. Conversion of ent-9 into (S)-1
The same procedure given above for synthesis of (R)-1 was
employed. (S)-1 was obtained as a white solid (9 mg, 0.0394 mmol,
4.10. Hydrolysis of the acetonide in 12 to afford 13
64%). Mp 88e91 ꢂC (mp data for natural 1 was reported in Ref. 1).
A solution of 12 (385.6 mg, 0.839 mmol) in CH2Cl2 (17 mL)
containing aq CF3CO2H (50% v/v, 1.25 mL) was stirred in an ice-
water bath for 1 h (TLC showed completion of the reaction). Aq
saturated NaHCO3 was added to neutralize the acid (pH¼7). The
mixture was extracted with EtOAc (10 mLꢀ4). The combined or-
ganic layers were washed with water and brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (3:1 petroleum ether/EtOAc) on sil-
25
[
a
]
23 þ5.7 (c 0.2, MeOH) (lit.1 [
a
]
¼þ4.0 (c¼0.2, MeOH)). 1H NMR
D
D
(500 MHz, CD3OD):
d
¼7.24 (dd, J¼15.3, 10.5 Hz, 1 H, H-3), 6.28 (dd,
J¼15.2, 10.8 Hz, 1 H, H-4), 6.20 (dt, J¼15.2, 6.6 Hz, 1 H, H-5), 5.78 (d,
J¼15.3 Hz, 1 H, H-2), 3.56 (t, J¼6.4 Hz, 2H, H-12), 3.54 (quint,
J=4.2 Hz, 1H, H-8), 2.38e2.31 (m, 1 H, H-6), 2.29e2.21 (m, 1 H, H-6),
1.63e1.37 (m, 8 H, H-7, H-9, H-10 and H-11). 13C NMR (125 MHz,
CD3OD):
d
¼170.2, 146.1, 144.8, 129.1, 120.0, 71.0, 62.2, 37.5, 36.7,
33.0, 29.6, 22.4. FTIR (KBr): 3334, 2935, 2860, 2628, 1688, 1640,
1412, 1259, 1001, 669 cmꢁ1. ESI-MS m/z 229.1 [MþH]þ, m/z 251.1
[MþNa]þ. ESI-HRMS: calcd for C12H21O4 [MþH]þ 229.1434; found
229.1433.
ica gel afforded diol 13 as a colorless oil (287.5 mg, 0.686 mmol,
21
82%). [
d
a
]
D
ꢁ3.1 (c 1.32, CHCl3). 1H NMR (500 MHz, CDCl3):
¼5.83e5.75 (m, 1 H), 5.04e4.95 (m, 2 H), 3.89 (dd, J¼10.0, 5.7 Hz,
1 H), 3.81 (quint, J¼5.7 Hz, 1 H), 3.76 (dd, J¼11.4, 5.3 Hz, 1 H), 3.67
(dd, J¼11.4, 3.5 Hz, 1 H), 3.62e3.59 (m, 1 H), 2.14e2.02 (m, 2 H),
1.72e1.69 (m, 2 H), 1.62e1.57 (m, 2 H), 0.90 (s, 9 H), 0.89 (s, 9 H),
0.12 (s, 3 H), 0.10 (s, 3 H), 0.089 (s, 3 H), 0.085 (s, 3 H). 13C NMR
4.8. Reaction of epoxide 10 with CH2]CHCH2MgBr to afford
alcohol 11
(125 MHz, CDCl3):
d
¼138.2, 114.8, 74.2, 73.0, 70.2, 63.2, 41.8, 37.0,
CH2]CHCH2MgBr (1.0 M, in Et2O, 6.5 mL, 6.5 mmol) was added
to a white suspension of CuI (123 mg, 0.65 mmol) in dry THF
(20 mL) stirred in an ꢁ20 ꢂC bath under argon (balloon). The
resulting dark-gray mixture was stirred for another 15 min before
a solution of epoxide 10 (1.30 g, 4.3 mmol) in dry THF (30 mL) was
introduced. The mixture was stirred at ꢁ20 ꢂC for 1 h and then at
ambient temperature for 2 h. Aq saturated NH4Cl was added. The
mixture was extracted with EtOAc (50 mLꢀ3). The combined or-
ganic layers were washed with water and brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (8:1 petroleum ether/EtOAc) gave
29.2, 25.9, 25.8, 18.04, 17.96, e3.9, -4.1, e4.3, e4.5. FTIR (film):
3404, 3078, 2954, 2929, 2886, 2857, 1641, 1472, 1360, 1255, 1086,
938, 910, 835, 774 cmꢁ1. ESI-MS m/z 419.5 [MþH]þ, m/z¼441.4
[MþNa]þ. HRMS (EI): calcd for C21H46NaO4Si2 [MþNa]þ 441.2827;
found 441.2821.
4.11. Conversion of 13 into 14
A solution of diol 13 (1.18 g, 2.81 mmol) and 1,1-thio-
carbonyldiimidazole (600 mg, 3.37 mmol) in dry toluene (29 mL)
was stirred in an 110 ꢂC oil bath under argon (balloon) for 1 h

3182
X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
(TLC showed completion of the reaction). The mixture was con-
centrated on a rotary evaporator. The residue was purified by
column chromatography (8:1 petroleum ether/EtOAc) on silica
[MþH]þ, m/z 539.6 [MþNa]þ. EESI-HRMS: calcd for C27H61NaO3Si3
[MþNa]þ 517.3923; found 517.3912.
gel to give 14 as a colorless oil (1.20 g, 2.60 mmol, 93%). [
a
]
22 ꢁ3.0
4.14. Ozonolysis of alkene 18 to afford aldehyde 19
D
(c 2.21, CHCl3). 1H NMR (500 MHz, CDCl3):
d
¼5.81e5.72 (m, 1 H),
5.08e4.97 (m, 3 H), 4.72 (dd, J¼8.1, 7.2 Hz, 1 H), 4.57 (t, J¼8.5 Hz,
1 H), 4.14e4.11 (m, 1 H), 3.84e3.79 (m, 1H), 2.12e1. 96 (m, 2 H),
1.66e1.57 (m, 2 H), 1.56e1.49 (m, 1 H), 1.41 (dt, J¼14.5, 8.3 Hz,
1 H), 0.891 (s, 9 H), 0.899 (s, 9 H), 0.15 (s, 3 H), 0.11 (s, 3 H), 0.09
Ozone-containing oxygen was bubbled into a solution of 18
(100 mg, 0.193 mmol) in CH2Cl2 (3.8 mL) cooled in an acetone-dry
ice bath (ꢁ78 ꢂC) until a blue color developed. N2 gas was bubbled
into the solution to expel the excess ozone. The resulting colorless
solution was then stirred with Ph3P (76 mg, 0.29 mmol) first at
ꢁ78 ꢂC for 30 min and then at ambient temperature for 4 h. The
mixture was concentrated on a rotary evaporator. The residue was
purified by column chromatography (25:1 petroleum ether/EtOAc)
(s, 3 H), 0.08 (s, 3 H). 13C NMR (125 MHz, CDCl3):
d
¼191.8, 137.7,
115.2, 84.3, 69.7, 69.2, 68.3, 40.8, 37.2, 29.1, 25.9, 25.7, 18.0, 17.8,
e3.9, e4.2, e4.4, e4.6. FTIR (film): 2954, 2929, 2886, 2857, 1641,
1472, 1360, 1292, 1255, 1124, 988, 836, 776 cmꢁ1. ESI-MS m/z
461.4 [MþH]þ, m/z 483.4 [MþNa]þ. ESI-HRMS: calcd for
on silica gel to give aldehyde 19 as a colorless oil (95 mg,
22H45O4SSi2 [MþH]þ 461.2572; found 461.2564.
27
C
0.183 mmol, 95%). [
a
]
þ14.9 (c 1.11, CHCl3). 1H NMR (500 MHz,
D
CDCl3):
d
¼9.78 (t, J¼1.6 Hz, 1 H), 3.88e3.83 (m, 1 H), 3.82e3.77 (m,
1 H), 3.66 (t, J¼6.5 Hz, 2 H), 2.48 (dt, J¼1.4, 7.5 Hz, 2 H), 1.92e1.85
(m, 1 H), 1.73e1.56 (m, 5 H), 0.89 (s, 9 H), 0.88 (s, 18 H), 0.07 (s, 3 H),
0.06 (s, 6 H), 0.05 (s, 3 H), 0.04 (s, 6 H). 13C NMR (125 MHz, CDCl3):
4.12. Deoxygenation of 14 to afford alcohol 15
A solution of 14 (500 mg, 1.09 mmol), n-Bu3SnH (1.75 mL,
6.51 mmol) and AIBN (178 mg, 1.09 mmol) in deaired toluene
(37 mL) was stirred in a 100 ꢂC oil bath under argon (balloon) for 5 h
(TLC showed completion of the reaction). The mixture was con-
centrated on a rotary evaporator. The residue was purified by col-
umn chromatography (8:1 petroleum ether/EtOAc) on silica gel to
remove 16 and 17 (126 mg and 122 mg, respectively, both were
polluted by small amounts of other side products, both were less
polar than 15). The fractions contain 15 (and the inseparable 150)
were combined, concentrated and further purified by column
chromatography (eluting with 15:1, 12:1, 10:1, and 8:1 petroleum
ether/EtOAc) on AgNO3-treated silica gel to give pure 15 as a col-
d
¼202.3, 69.1, 67.2, 59.6, 45.6, 40.8, 39.5, 29.5, 25.94, 25.89, 25.87,
18.3, 18.0, 18.0, e4.1, e4.2, e4.3, e5.3. FTIR (film): 2955, 2929, 2886,
2857, 2711, 1730, 1472, 1388, 1361, 1256, 1098, 1005, 836, 774 cmꢁ1
.
ESI-MS m/z 519.6 [MþH]þ, m/z 541.6 [MþNa]þ. ESI-HRMS: calcd for
C
26H59O4Si3 [MþH]þ 519.3716; found 519.3708.
4.15. Condensation of 19 with 8 to afford 20
LiHMDS (1.0 M, in THF, 161 L, 0.161 mmol) was added dropwise
m
to a solution of phosphate 8 (49 mg, 0.20 mmol) in dry THF (0.1 mL)
stirred at ꢁ78 ꢂC under argon (balloon). The stirring was continued
for 1 h before a solution of aldehyde 19 (69.5 mg, 0.134 mmol) in
dry THF (0.2 mL) was added. The mixture was stirred at ꢁ78 ꢂC for
15 min, then 0 ꢂC for 30 min, and finally ambient temperature for
2 h (TLC showed completion of the reaction). Aq NH4Cl was added.
The mixture was extracted with EtOAc (5 mLꢀ3). The combined
organic layers were washed with water and brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (25:1 petroleum ether/EtOAc) on
silica gel furnished 20 as a colorless oil (60 mg, 0.0976 mmol, 73%),
which was 98.5% pure as shown by HPLC analysis using a Agilent
1260 Infinity LC equipped with an ACE 5 C18 column (4.6ꢀ150 mm,
orless oil (206 mg, 0.512 mmol, 47%). [
NMR (500 MHz, CDCl3):
3.98e3.94 (m, 1 H), 3.84 (dq, J¼10.9, 4.6 Hz, 1 H), 3.74e3.69 (m,
2 H), 2.16e2.04 (m, 2 H), 1.90e1.84 (m, 1 H), 1.72 (t, J¼6.5 Hz, 2 H),
1.67e1.61 (m, 1 H), 1.58e1.47 (m, 2 H), 0.892 (s, 9 H), 0.887 (s, 9 H),
0.10 (s, 3 H), 0.09 (s, 3 H), 0.07 (s, 3 H), 0.06 (s, 3 H). 13C NMR
a
]
25 þ15.4 (c 1.89, CHCl3). 1H
D
d
¼5.85e5.77 (m, 1 H), 5.04e4.94 (m, 2 H),
(125 MHz, CDCl3):
d
¼138.6, 114.5, 69.8, 69.6, 60.1, 44.9, 38.6, 36.7,
29.3, 25.9, 25.8,18.1, 17.9, e4.10, e4.13, e4.3, e4.5. FTIR (film): 3355,
3078, 2954, 2929, 2886, 2857, 1641, 1472, 1462, 1407, 1361, 1255,
1058, 1005, 938, 910, 836, 774 cmꢁ1. EESI-MS m/z 403.4 [MþH]þ, m/
z¼425.4 [MþNa]þ. ESI-HRMS: calcd for C21H47O3Si2 [MþH]þ
403.3058; found 403.3051, C21H46NaO3Si2 [MþNa]þ 425.2878;
found 425.2876.
particle size 5 mM) eluting with MeCN/H2O (initially 90:10 and then
from 15 min to the end 10:90 v/v) at a flow rate of 1.0 mL (column
temperature: 25 ꢂC) with the UV detector set 210 nm). [
a
]
27 þ10.3
D
(c 1.01, CHCl3). 1H NMR (500 MHz, CDCl3):
d
7.25 (dd, J¼15.4,
4.13. TBS protection of 15 to afford 18
10.2 Hz, 1 H), 6.19e6.08 (m, 2 H), 5.78 (d, J¼15.4 Hz, 1 H), 4.20 (q,
J¼7.1 Hz, 2 H), 3.89e3.84 (m, 1 H), 3.77e3.72 (m, 1 H), 3.66 (t,
J¼6.5 Hz, 2 H), 2.29e2.15 (m, 2 H), 1.69e1.57 (m, 5 H), 1.56e1.48 (m,
1 H), 1.29 (t, J¼7.1 Hz, 3 H), 0.89 (s, 18 H), 0.88 (s, 9 H), 0.062 (s, 3 H),
0.059 (s, 6 H), 0.050 (s, 3 H), 0.04 (s, 6H). 13C NMR (125 Hz, CDCl3):
A solution of alcohol 15 (206 mg, 0.512 mmol), imidazole
(348 mg, 5.11 mmol), DMAP (62 mg, 0.51 mmol) and TBSCl (309 mg,
2.05 mmol) in dry DMF (0.5 mL) was stirred at ambient tempera-
ture for 12 h (TLC showed completion of the reaction). Water was
added. The mixture was extracted with EtOAc (10 mLꢀ3). The
combined organic layers were washed with water and brine and
dried over anhydrous Na2SO4. Removal of the solvent by rotary
evaporation and column chromatography (50:1 petroleum ether/
d
167.3, 144.9, 144.2, 128.4, 119.3, 69.5, 67.2, 60.2, 59.6, 45.9, 40.9,
36.5, 28.6, 25.94, 25.91, 25.90, 18.3, 18.08, 18.06, 14.3, e4.07, e4.15,
e4.2, e5.30, e5.31. 1H NMR (500 MHz, C6D6):
d
¼7.49 (dd, J¼15.3,
11.0 Hz, 1 H), 6.02 (dd, J¼15.1, 11.1 Hz, 1 H), 5.91 (d, J¼15.4 Hz, 1 H),
5.80 (dt, J¼15.2, 7.0 Hz, 1 H), 4.07 (q, J¼7.1 Hz, 3 H), 3.85 (quint,
J¼5.9 Hz,1 H), 3.79e3.74 (m,1 H), 3.70e3.66 (m,1 H), 2.19e2.06 (m,
2 H), 1.81e1.70 (m, 4 H), 1.61e1.49 (m, 2 H), 1.01 (t, J¼7.2 Hz, 3 H),
1.00 (s, 9 H), 0.995 (s, 9 H), 0.988 (s, 9 H), 0.151 (s, 3 H), 0.146 (s, 3 H),
0.13 (s, 3 H), 0.09 (s, 3 H), 0.084 (s, 3 H), 0.081 (s, 3 H). 13C NMR
EtOAc) on silica gel gave 18 as a colorless oil (260 mg, 0.503 mmol,
25
98%). [
d
a
]
D
þ13.8 (c 1.23, CHCl3). 1H NMR (500 MHz, CDCl3):
¼5.85e5.77 (m, 1 H), 5.03e4.92 (m, 2 H), 3.89e3.84 (m, 1 H),
3.76e3.72 (m, 1 H), 3.67 (t, J¼6.6 Hz, 2 H), 2.16e2.02 (m, 2 H),
1.71e1.45 (m, 1 H), 0.889 (s, 9 H), 0.885 (s, 9 H), 0.880 (s, 9 H),
0.06e0.04 (several unresolved singlets, 18 H altogether). 13C NMR
(125 MHz, C6D6):
d
¼166.7, 144.9, 143.7, 129.0, 120.3, 70.0, 67.6, 60.1,
59.7, 46.3, 41.6, 37.1, 28.9, 26.21, 26.20, 26.19, 18.5, 18.4, 14.4, e3.80,
e3.82, e3.85, e3.88, e5.1. FTIR (film): 2955, 2929, 2886, 2857, 1718,
1644, 1472, 1388, 1367, 1256, 1097, 1002, 836, 774 cmꢁ1. ESI-MS m/
z¼615.6 [MþH]þ, m/z 637.6 [MþNa]þ. ESI-HRMS: calcd for
(125 MHz, CDCl3):
d
¼138.8, 114.3, 69.6, 67.2, 59.7, 46.0, 40.9, 36.8,
29.4, 25.96, 25.94, 25.92, 18.3, 18.1, 18.0, e4.09, e4.12, e4.14, e4.3,
e5.29, e5.30. FTIR (film): 3078, 2955, 2929, 2895, 2857, 1642, 1472,
1388, 1361, 1255, 1095, 1005, 939, 835, 774 cmꢁ1. ESI-MS m/z 517.5
C
32H67O5Si3 [MþH]þ 615.4291; found 615.4287.

X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
3183
4.16. Conversion of 20 into (8R,10R)-2
774 cmꢁ1
C
.
ESI-MS m/z 481.5 [MþNa]þ. ESI-HRMS: calcd for
24H51O4Si2 [MþH]þ 459.3320; found 459.3314.
A solution of 20 (50 mg, 0.0813 mmol) and LiOH (monohydrate,
25 mg, 0.59 mmol) in EtOHeH2O (5:1 v/v, 3.1 mL) was stirred at
ambient temperature for 12 h (TLC showed completion of the re-
action). Aq HCl (1 N) was added to bring the mixture to pH 1. The
mixture was stirred for another 2 h. The mixture was concentrated
on a rotary evaporator. The residue was purified by reverse-phase
chromatography (eluting first H2O, then 9:1 H2O/MeOH and fi-
nally 2:1 H2O/MeOH) on C-18 alkyl modified silica gel to give
4.19. Hydrolysis of the acetonide in 23 to afford 24
The same procedure given above for the conversion of 12 into 13
was employed. After chromatography (3:1 petroleum ether/EtOAc)
diol 24 was obtained as a colorless oil (940 mg, 2.24 mmol, 83%).
[a]
24 þ48.9 (c 0.83, CHCl3). 1H NMR (500 MHz, CDCl3):
d
¼5.84e5.76
D
(m, 1 H), 5.05e4.96 (m, 2 H), 3.93e3.88 (m, 2 H), 3.74e3.68 (m, 2 H),
3.60 (dd, J¼9.5, 5.2 Hz, 1 H), 2.08 (dd, J¼14.6, 7.7 Hz, 2 H), 1.84 (dq,
J¼14.6, 4.6 Hz, 1 H), 1.67 (dq, J¼14.6, 4.0 Hz, 1 H), 1.64e1.59 (m, 2 H),
0.91 (s, 9 H), 0.89 (s, 9 H), 0.10 (s, 6 H), 0.091 (s, 3 H), 0.085 (s, 3 H).
13C NMR (125 MHz, CDCl3): 138.1, 114.8, 73.6, 71.5, 69.1, 63.6, 41.4,
36.1, 29.5, 25.85, 25.81, 18.0, 17.9, e4.36, e4.39, e4.41, e4.7. FTIR
(film): 3414, 3078, 2954, 2929, 2887, 2857, 1642, 1472, 1361, 1255,
1084,1004, 938, 910, 837, 775 cmꢁ1. ESI-MS m/z 441.4 [MþNa]þ. ESI-
HRMS: calcd for C21H46NaO4Si2 [MþNa]þ 441.2827; found 441.2828.
(8R,10R)-2 as a white solid (16.8 mg, 0.0688 mmol, 85%). Mp
25
141e143 ꢂC (lit.1 mp 143e145 ꢂC for natural 2). [
a]
ꢁ1.3 (c 0.2,
D
25
MeOH),
[
a
]
¼ꢁ3.7 (c¼0.2, CD3OD) (for more data, cf.
D
25
Supplementary data) (lit.1 [
a
]
¼þ6.5 (c¼0.2, MeOH) for natural 2).
D
1H NMR (500 MHz, CD3OD):
d
¼7.25 (dd, J¼15.3, 10.5 Hz, 1 H, H-3),
6.28 (dd, J¼15.2,10.6 Hz,1 H, H-4), 6.20 (dt, J¼15.2, 6.7 Hz,1 H, H-5),
5.78 (d, J¼15.3 Hz, 1 H, H-2), 4.01e3.96 (m, 1 H, H-10), 3.86e3.81
(m, 1 H, H-8), 3.70 (t, J¼6.6 Hz, 2 H, H-12), 2.38e2.31 (m, 1 H, H-6),
2.31e2.23 (m, 1 H, H-6), 1.67 (dd, J¼13.0, 6.5 Hz, 2 H, H-11),
1.60e1.56 (m, 2 H, H-7 or H-9), 1.54e1.51 (m, 2 H, H-9 or H-7). 13
C
4.20. Conversion of 25 into 26
NMR cf. Table 1. FTIR (KBr): 3353, 2940, 2611,1698,1641,1408,1258,
1060, 1003, 669 cmꢁ1. ESI-MS m/z 243.2 [MꢁH]e. ESI-HRMS: calcd
for C12H19O5 [MꢁH]e 243.1238; found 243.1237.
The same procedure given above for the conversion of 14 into 15
was employed, except the second chromatography on AgNO3-silica
gel was skipped. After chromatography (8:1 petroleum ether/
EtOAc) alcohol 26 was obtained as a white solid (175 mg,
4.17. Reaction of epoxide 21 with CH2]CHCH2MgBr to afford
alcohol 22
22
0.435 mmol, 50%). [
CDCl3):
1 H), 3.86e3.82 (m, 1 H), 3.74e3.68 (m, 2 H), 2.08 (dd, J¼14.4,
7.6 Hz, 2H), 1.93e1.86 (m, 1 H), 1.76e1.70 (m, 1 H), 1.69e1.60 (m,
2 H), 1.58e1.52 (m, 2 H), 0.90 (s, 9 H), 0.89 (s, 9H), 0.10 (s, 3 H), 0.09
(s, 3 H), 0.05 (s, 3 H), 0.04 (s, 3H). 13C NMR (125 MHz, CDCl3):
a
]
þ18.5 (c 0.67, CHCl3). 1H NMR (500 MHz,
D
d
¼5.84e5.76 (m, 1 H), 5.03e4.94 (m, 2 H), 4.11e4.06 (m,
CH2¼CHCH2MgBr (1.0 M, in Et2O, 0.5 mL, 0.5 mmol) was added
to a white suspension of CuI (9.44 mg, 0.049 mmol) in dry THF
(1 mL) stirred in an ꢁ20 ꢂC bath under argon (balloon). The
resulting dark-gray mixture was stirred for another 15 min before
a solution of epoxide 21 (100 mg, 0.33 mmol) in dry THF (3.0 mL)
was introduced. The mixture was stirred at ꢁ20 ꢂC for 1 h and then
at ambient temperature for 2 h. Aq saturated NH4Cl was added. The
mixture was extracted with EtOAc (10 mLꢀ3). The combined or-
ganic layers were washed with water and brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (8:1 petroleum ether/EtOAc) gave
d
¼138.6, 114.5, 69.4, 69.0, 60.2, 43.8, 37.4, 36.9, 29.2, 25.9, 25.8, 18.0,
17.9, e4.2, e4.4, e4.5, e4.7. FTIR (film): 3415, 3078, 2955, 2929,
2857, 1641, 1472, 1463, 1361, 1255, 1055, 1005, 938, 910, 836,
774 cmꢁ1. ESI-MS m/z 403.5 [MþH]þ, m/z 425.5 [MþNa]þ. ESI-
HRMS: calcd for C21H47O3Si2 [MþH]þ 403.3058; found 403.3052.
4.21. TBS protection of 26 to afford 27
alcohol 22 as a colorless oil (96.7 mg, 0.281 mmol, 85%). [
a
]
23 þ19.0
D
The same procedure given above for the conversion of 15 into 18
was employed. After chromatography (50:1 petroleum ether/
(c 2.01, CHCl3). 1H NMR (500 MHz, CDCl3):
d¼5.88e5.80 (m, 1 H),
5.04 (dq, J¼17.1, 1.7 Hz, 1 H), 4.98e4.95 (m, 1 H), 4.11e4.04 (m, 2 H),
3.92e3.87 (m, 2 H), 3.79 (dd, J¼7.8, 6.6 Hz, 1 H), 2.60 (s, 1 H),
2.25e2.09 (m, 2 H), 1.76 (dq, J¼14.4, 5.1 Hz, 1 H), 1.66 (dq, J¼14.4,
2.9 Hz, 1 H), 1.61e1.47 (m, 2 H), 1.41 (s, 3 H), 1.35 (s, 3 H), 0.88 (s,
9 H), 0.094 (s, 3 H), 0.092 (s, 3 H). 13C NMR (125 MHz, CDCl3):
EtOAc) 27 was obtained as a colorless oil (29 mg, 0.056 mmol, 91%).
22
[a
]
þ1.8 (c 1.15, CHCl3). 1H NMR (500 MHz, CDCl3):
d 5.85e5.77
D
(m, 1 H), 5.02e4.92 (m, 2 H), 3.89 (quint, J¼6.2 Hz, 1 H), 3.78 (quint,
J¼5.9 Hz, 1 H), 3.71e3.63 (m, 2 H), 2.15e2.02 (m, 2 H), 1.74e1.54 (m,
5 H), 1.51e1.43 (m, 1 H), 0.89 (s, 27 H), 0.05e0.04 (several un-
resolved singlets, 18 H altogether). 13C NMR (125 MHz, CDCl3):
d
¼138.5,114.6,109.4, 78.7, 71.4, 67.6, 67.3, 42.7, 37.0, 29.9, 26.6, 25.8,
25.4, 17.9, e4.1, e4.5. FTIR (film): 3483, 3077, 2984, 2930, 2887,
2857, 1641, 1472,1462, 1380, 1371, 1255,1074, 837, 776 cmꢁ1. ESI-MS
m/z 367.3 [MþNa]þ. ESI-HRMS: calcd for C18H36NaO4Si [MþNa]þ
367.2275; found 367.2278.
d
139.0, 114.4, 69.2, 67.0, 60.1, 45.3, 40.7, 36.7, 29.5, 26.2, 26.08,
26.07, 18.5, 18.20, 18.19, e4.1, e4.17, e4.24, e4.3, e5.1, e5.2. FTIR
(film): v¼3078, 2955, 2929, 2895, 2857, 1642, 1472, 1388, 1361,
1255,1095,1005, 939, 836, 774 cmꢁ1. ESI-MS m/z 517.6 [MþH]þ, m/z
539.6 [MþNa]þ. ESI-HRMS: calcd for C27H61O3Si3 [MþH]þ
517.3929; found 517.3914.
4.18. TBS protection of 22 to afford 23
The same procedure given above for the conversion of 11 into 12
4.22. Ozonolysis of alkene 27 to afford aldehyde 28
was employed. After chromatography (50:1 petroleum ether/
EtOAc) 23 was obtained as a colorless oil (125 mg, 0.273 mmol,
The same procedure given above for the conversion of 18 into 19
was employed. After chromatography (25:1 petroleum ether/
EtOAc) aldehyde 28 was obtained as a colorless oil (291 mg,
24
97%). [
a]
þ15.9 (c 1.03, CHCl3). 1H NMR (400 MHz, CDCl3):
D
d
¼5.87e5.76 (m, 1 H), 5.04e4.93 (m, 2 H), 4.06e4.01 (m, 1 H), 3.95
(dd, J¼7.5, 6.3 Hz, 1 H), 3.91e3.86 (m, 2 H), 3.79 (t, J¼7.6 Hz, 1 H),
2.17e2.02 (m, 2 H), 1.71e1.63 (m, 1 H), 1.63e1.56 (m, 2 H), 1.54e1.45
(m, 1 H), 1.40 (s, 3 H), 1.33 (s, 3 H), 0.893 (s, 9 H), 0.886 (s, 9 H), 0.08
(s, 3 H), 0.07 (s, 3 H), 0.06 (s, 3 H), 0.05 (s, 3 H). 13C NMR (100 MHz,
0.193 mmol, 91%). [
CDCl3):
a
]
D
ꢁ5.5 (c 1.38, CHCl3). 1H NMR (500 MHz,
21
d
¼9.78 (s, 1 H), 3.89e3.85 (m, 2 H), 3.70e3.63 (m, 2 H), 2.48
(t, J¼7.3 Hz, 2 H), 1.93e1.87 (m, 1 H), 1.72e1.64 (m, 4 H), 1.58e1.53
(m, 1 H), 0.89 (s, 9 H), 0.88 (s, 18 H), 0.06e0.04 (several unresolved
CDCl3):
d
¼138.8, 114.4, 108.9, 78.9, 69.4, 68.5, 65.9, 42.7, 36.5, 29.3,
singlets,18 H altogether). 13C NMR (125 MHz, CDCl3):
d
¼202.4, 68.2,
26.6, 25.9, 25.4, 18.0, e4.2, e4.27, e4.30, e4.5. FTIR (film): 3078,
66.8, 59.7, 44.7, 40.6, 39.4, 28.9, 26.0, 25.9, 18.3, 18.0, e4.35, e4.38,
e4.40, e4.5, e5.31, e5.33. FTIR (film): 2955, 2929, 2886, 2857, 2711,
2955, 2930, 2887, 2858, 1641, 1472, 1369, 1255, 1073, 1005, 837,

3184
X.-D. Wang et al. / Tetrahedron 72 (2016) 3177e3184
1730, 1472, 1388, 1361, 1256, 1098, 1005, 836, 774 cmꢁ1. ESI-MS m/z
519.6 [MþH]þ, m/z 541.6 [MþNa]þ. ESI-HRMS: calcd for
References and notes
C
26H59O4Si3 [MþH]þ 519.3716; found 519.3706.
1. Sato, T.; Nagai, K.; Shibazaki, M.; Abe, K.; Takebayashi, Y.; Lumanau, B.; Ran-
tiatmodjo, R. M. J. Antibiot. 1994, 47, 566e570.
2. See: e. g., (a) Gao, J.; Zhen, Z.-B.; Jian, Y.-J.; Wu, Y.-K. Tetrahedron 2008, 64,
9377e9383; (b) Wu, J.-Z.; Wu, Y.-K.; Jian, Y.-J.; Zhang, Y.-H. Chin. J. Chem. 2009,
27, 13e15; (c) Wu, J.-Z.; Gao, J.; Ren, G.-B.; Zhen, Z.-B.; Zhang, Y.-H.; Wu, Y.-K.
Tetrahedron 2009, 65, 289e299; (d) Cui, S.; Wu, Y.-K.; Gao, P. Chin. J. Chem. 2011,
29, 2759e2762; (e) Jiang, P.; Zhang, S.-M.; He, L.; Wu, Y.-K.; Li, Y. Tetrahedron
2011, 67, 2651e2660; (f) Chen, C.-Y.; Zhang, S.-M.; Wu, Y.-K.; Gao, P. Eur. J. Org.
Chem. 2013, 348e355; (g) Chen, C.-Y.; Han, W.-B.; Chen, H.-J.; Wu, Y.-K.; Gao, P.
Eur. J. Org. Chem. 2013, 4311e4318; (h) Wan, Z.-L.; Zhang, G.-L.; Chen, H.-J.; Wu,
Y.-K.; Li, Y. Eur. J. Org. Chem. 2014, 2128e2139; (i) Zhu, S.-J.; Wu, Y.-K. Synlett
2014, 261e264; (j) Wu, W.-J.; Chen, H.-J.; Wu, Y.-K.; Liu, B. Tetrahedron 2014, 70,
92e96; (k) Wang, X.-L.; Yang, Y.-Y.; Chen, H.-J.; Wu, Y.-K.; Gao, P. Tetrahedron
2014, 70, 4571e4579; (l) He, T.-J.; Zhu, S.-J.; Lu, X.-W.; Wu, Y.-K.; Li, Y. Eur. J. Org.
Chem. 2015, 647e654.
4.23. Condensation of 28 with 8 to afford 29
The same procedure given above for the condensation of 19 with
8 to afford 20 was employed. After chromatography (25:1 petro-
leum ether/EtOAc) 29 was obtained as a colorless oil (22.8 mg,
22
0.0371 mmol, 64%). [
CDCl3):
a
]
D
ꢁ2.7 (c 0.85, CHCl3). 1H NMR (400 MHz,
d
¼7.25 (dd, J¼15.4, 9.8 Hz, 1 H), 6.20e6.08 (m, 2 H), 5.78 (d,
J¼15.4 Hz, 1 H), 4.20 (q, J¼7.1 Hz, 2 H), 3.87 (quint, J¼6.1 Hz, 1 H),
3.80 (quint, J¼6.2 Hz, 1 H), 3.69e3.63 (m, 2H), 2.30e2.13 (m, 2 H),
1.71e1.45 (m, 6 H), 1.29 (t, J¼7.1 Hz, 3 H), 0.89 (s, 18 H), 0.88 (s, 9 H),
0.06 (s, 3 H), 0.05 (s, 3 H), 0.045 (s, 3 H), 0.040 (s, 9 H). 13C NMR
3. Frankowski, K. J.; Golden, J. E.; Zeng, Y.; Lei, Y.; Aube, J. J. Am. Chem. Soc. 2008,
130, 6018e6024.
4. (a) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401e404; (b) Jadhav, P. K.;
Bhat, K. S.; Perumal, P. T.; Brown, H. C. J. Org. Chem. 1986, 51, 432e439.
5. Zimmermann, N.; Pinard, P.; Carboni, B.; Gosselin, P.; Gaulon-Nourry, C.; Du-
jardin, G.; Collet, S.; Lebreton, J.; Mathe-Allainmat, M. Eur. J. Org. Chem. 2013,
2303e2315.
(100 MHz, CDCl3):
d
¼167.3, 145.0, 144.4, 128.4, 119.3, 68.9, 66.8,
60.2, 59.8, 45.0, 40.5, 36.1, 28.6, 26.0, 25.90, 25.88, 18.3, 18.03, 18.01,
14.3, e4.3, e4.4, e4.38, e5.30, e5.32. 1H NMR (500 MHz, C6D6):
d
¼7.46 (dd, J¼15.3, 11.0 Hz, 1 H), 5.97 (dd, J¼15.2, 11.0 Hz, 1 H), 5.87
6. Aiguade, J.; Hao, J.; Forsyth, C. J. Org. Lett. 2001, 3, 979e982.
(d, J¼15.3 Hz, 1 H), 5.76 (dt, J¼15.1, 7.0 Hz, 1 H), 4.03 (q, J¼7.1 Hz,
2 H), 4.00e3.96 (m, 1 H), 3.81 (quint, J¼6.1 Hz, 1 H), 3.73e3.66 (m,
2 H), 2.14e2.01 (m, 2 H), 1.82e1.77 (m, 1 H), 1.73 (dd, J¼12.5, 6.3 Hz,
2 H), 1.65e1.60 (m, 1 H), 1.57e1.50 (m, 1 H), 1.47e1.40 (m, 1 H), 0.98
(s, 9 H), 0.97 (s, 9 H), 0.949 (s, 9 H), 0.947 (t, J¼7.3 Hz, 3 H), 0.11 (s,
3 H), 0.10 (s, 6 H), 0.053 (s, 3 H), 0.046 (s, 6 H). 13C NMR (125 MHz,
7. (a) Baeckstroem, P.; Jacobsson, U.; Norin, T.; Unelius, C. R. Tetrahedron 1988, 44,
2541e2548; (b) Mohapatra, D. K.; Sahoo, G.; Gurjar, M. K. Tetrahedron: Asym-
metry 2006, 17, 2609e2616.
8. The configuration of the conjugate CeC double bonds in such compounds
cannot be shown in CDCl3 because of the serious overlap of the olefinic protons.
However, in C6D6 the signals are well separated and allowed for unambigous
assignment of the geometry of the double bonds; cf. Zhu, S.-J.; Wu, Y.-K. Synlett
2014, 261e263 and references cited therein.
9. For hydrolysis of the ethyl ester using LiOH/EtOH, cf.: (a) Ogby, C. O.; Kim, H.-O.;
Blaskovich, M. A. US patent Assigned to Myriad Pharmaceuticals; US2004/
14763; 2004; (A1) English; WO 2003068237 (CAN 139:197496); for use of KOH/
EtOH to hydrolyze a similar ethyl ester: (b) Jiao, Y.; Yoshihara, T.; Ichihara, A.
Biosci. Biotechnol. Biochem. 1995, 59, 1032e1035.
10. For desilylation: (a) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190e6191; (b) Cunico, R. F.; Bedell, L. J. Org. Chem. 1980, 45, 4797e4798.
11. It should be noted that in the Ref. 1 above the solvent employed in measuring
NMR of both 1 and 2 was reported to be CDCl3. However, in our hands neither 1
nor 2 was soluble in CDCl3; measuring their NMR in CDCl3 was impossible. The
1H and 13C NMR in CD3OD were in full consistency with those in the ref 1 above,
suggesting that the NMR solvent therein must also be CD3OD.
C6D6):
d
¼166.7, 145.0, 143.8, 128.9, 120.3, 69.3, 67.2, 60.1, 60.0, 45.6,
41.1, 36.6, 28.8, 26.22, 26.18, 26.17, 18.6, 18.30, 18.29, 14.4, e4.0,
e4.08, e4.13, e5.09, e5.14. FTIR (film): 2954, 2929, 2886, 2857,
1718, 1644, 1472, 1388, 1366, 1256, 1096, 1001, 836, 774 cmꢁ1. ESI-
MS m/z 615.6 [MþH]þ, m/z 637.6 [MþNa]þ. ESI-HRMS: calcd for
C
32H67O5Si3 [MþH]þ 615.4291; found 615.4278.
4.24. Conversion of 29 into (8S,10R)-2
The same procedure given above for the conversion of 20 into
(8R,10R)-2 was employed. After reverse phase chromatography
(eluting with first H2O, then 9:1 H2O/MeOH and finally 2:1 H2O/
12. Smith, A. B., III; Doughty, V. A.; Sfouggatakis, C.; Bennett, C. S.; Koyanagi, J.;
Takeuchi, M. Org. Lett. 2002, 4, 783e786.
13. (a) Barret, A. G. M.; Prokopiou, P. A.; Barton, D. H. R. J. Chem. Soc., Perkin Trans. 1
1981, 1510e1515; (b) Adiyaman, M.; Li, H.; Lawson, J. A.; Huang, S.-W.; Kha-
napure, S. P.; FitzGerald, G. A.; Rokach, J. Tetrahedron Lett. 1997, 38, 3339e3342;
(c) Vidari, G.; Di Rosa, A.; Castronovo, F.; Zanoni, G. Tetrahedron: Asymmetry
2000, 11, 981e989; (d) Yang, Z.; Kim, H.-D. Tetrahedron: Asymmetry 2014, 25,
305e309; (e) Rokach, J.; Khanapure, S. P.; Hwang, S.-W.; Adiyaman, M.; Schio,
L.; FitzGerald, G. A. Synthesis 1998, 569e580.
MeOH) on C-18 alkyl modified silica gel to (8S,10R)-2 was obtained
25
as a colorless oil (5.1 mg, 0.021 mmol, 72%). [
a
]
ꢁ15.1 (c 0.2,
D
MeOH). 1H NMR (500 MHz, CD3OD):
d
¼7.24 (dd, J¼15.3, 10.6 Hz,
1 H), 6.28 (dd, J¼15.2, 10.7 Hz, 1 H), 6.20 (dt, J¼15.2, 6.7 Hz, 1 H),
5.79 (d, J¼15.3 Hz, 1 H), 3.95e3.90 (m, 1 H), 3.81e3.76 (m, 1 H), 3.70
(t, J¼6.6 Hz, 2 H), 2.38e2.31 (m, 1 H), 2.30e2.22 (m, 1 H), 1.75e1.69
(m, 1 H), 1.68e1.58 (m, 4 H), 1.57e1.51 (m, 1 H). 13C NMR (125 MHz,
ꢁ
14. (a) Alibes, R.; Bourdlande, J. L.; Font, J.; Parella, T. Tetrahedron 1996, 52,
1279e1292; (b) Liang, D.; Pauls, H. W.; Fraser-Reid, B.; Beoges, M.; Mubarak, A.
M.; Jarosz, S. Can. J. Chem. 1986, 64, 1800e1809; (c) Nicolaou, K. C.; Sarlah, D.;
Wu, T. R.; Zhan, W. Angew. Chem., Int. Ed. 2009, 48, 6870e6874.
15. For a comprehensive review of chromatographic separation using AgNO3-silica
gel, see Williams, C. M.; Mander, L. N. Tetrahedron 2001, 57, 425e447.
16. Hollister, K. A.; Conner, E. S.; Zhang, X.; Spell, M.; Bernard, G. M.; Patel, P.; de
Carvalho, A. C. G. V.; Butcher, R. A.; Ragains, J. R. Bioorg. Med. Chem. 2013, 21,
5754e5769.
17. In a previous study, we observed that in some cases optical rotations might be
time-dependent; see: Wu, W.-J.; Chen, H.-J.; You, J.; Wu, Y.-K.; Liu, B. Eur. J. Org.
Chem. 2015, 5817e5825.
18. Epoxides 10 and 21 showed several base-line separated signals; even traces of
one diastereomer in anther would be readily spotted on 1H NMR. The config-
uration of the C-10 never has any possibility to invert. Pollution of 10 (also 21)
by either epimers or antipodes was practically impossible.
19. In some cases, optical rotations may also be concentration-dependent, see, for
example: (a) Consiglio, G.; Pino, P.; Flowers, L. I.; Pittman, C. U., Jr. J. Chem. Soc.,
Chem. Commun. 1983 612e612; (b) Ref. 2j above; (c) Mori, K.; Uenishi, K. Liebigs
Ann. Chem. 1994, 41e48.
20. Some known compounds structurally related to the 2’s in one way or the other
did not seem to show such complications in optical rotation measurement, see
(a) Romeyke, Y.; Keller, M.; Kluge, H.; Grabley, S.; Hammann, P. Tetrahedron
1991, 47, 3335e3346; (b) Blechert, S.; Dollt, H. Liebigs Ann. Chem. 1996,
2135e2140; (c) Mori, K.; Maemoto, S. Liebigs Ann. Chem. 1987, 863e869; (d)
Schmidt, B.; Kunz, O. Eur. J. Org. Chem. 2012, 1008e1018.
CD3OD):
d
¼171.6, 147.2, 145.8, 130.5, 121.5, 71.2, 69.6, 60.7, 45.9,
41.5, 38.1, 30.6. FTIR (film of a solution in MeOH): 3358, 2939, 2362,
1699, 1641, 1381, 1257, 1054, 881, 669 cmꢁ1. ESI-MS m/z 245.2
[MþH]þ, m/z 267.2 [MþNa]þ. ESI-HRMS: calcd for C12H21O5
[MþH]þ 245.1384; found 245.1382.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21532002, 21372248) and the Chinese
Academy of Sciences.
Supplementary data
Supplementary data (Copies of the 1H and 13C NMR spectra, FTIR
spectra for all new compounds. Time-dependent optical rotations
data for (8R,10R)-2) related to this article can be found, in the online
version at http://dx.doi.org/10.1016/j.tet.2016.04.033.