Enantioselective synthesis and stereochemical revision of communiols A-C, antibacterial 2,4-disubstituted tetrahydrofurans from the coprophilous fungus Podospora communis

Article abstract of DOI:10.1271/bbb.80173

The enantioselective synthesis of the originally proposed structure of communiol C, an antibacterial 2,4-disubstituted tetrahydrofuran natural product from the coprophilous fungus Podospora communis, and its epimer via the Sharpless asymmetric dihydroxylation as the source of chirality led us to propose that the genuine stereochemistry of communiol C should be 3R, 5R, and 6S. The synthesis of the (3R,5R,6S)-isomer of communiol C and its good accordance with natural communiol C in every respect enabled us to confirm the newly proposed (3R,5R,6S)-stereochemistry for communiol C. The stereochemistries of structurally-related natural products (communiols A and B) of the same microbial origin were also revised through their total synthesis.

Full text of DOI:10.1271/bbb.80173

Biosci. Biotechnol. Biochem., 72 (7), 1921–1928, 2008
Enantioselective Synthesis and Stereochemical Revision
of Communiols A–C, Antibacterial 2,4-Disubstituted Tetrahydrofurans
from the Coprophilous Fungus Podospora communis
y
Masaru ENOMOTO and Shigefumi KUWAHARA
Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science,
Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
Received March 17, 2008; Accepted April 10, 2008; Online Publication, July 7, 2008
[doi:10.1271/bbb.80173]
The enantioselective synthesis of the originally pro-
posed structure of communiol C, an antibacterial 2,4-
disubstituted tetrahydrofuran natural product from the
coprophilous fungus Podospora communis, and its
epimer via the Sharpless asymmetric dihydroxylation
as the source of chirality led us to propose that the
genuine stereochemistry of communiol C should be 3R,
5R, and 6S. The synthesis of the (3R,5R,6S)-isomer of
communiol C and its good accordance with natural
communiol C in every respect enabled us to confirm the
newly proposed (3R,5R,6S)-stereochemistry for commu-
niol C. The stereochemistries of structurally-related
natural products (communiols A and B) of the same
microbial origin were also revised through their total
synthesis.
O
H
8
HO2C
HO2C
5
7
OH
O
H
communiol A
(5R,7S,8S)-1
6
HO2C
3
5
OH
O
H
communiol C
(3S,5S,6S)-3
OH
communiol B
(5R,7S,8S)-2
Fig. 1. Structures of Communiols A–C Proposed by Gloer et al.
of natural products,1) displaying a clear difference in
substitution pattern from 2,5-disubstituted tetrahydro-
furans which are frequently found in annonaceous
acetogenins or ionophores.4,5) The structural uniqueness
of communiols A–C coupled with their interesting
biological activity prompted our efforts to synthesize
communiols A–C, which recently culminated in our new
proposal on the stereochemistries of communiols A–C
and the confirmation of the newly proposed stereo-
chemistries by total synthesis,6) as well as the enantio-
selective synthesis of communiols D–F and H with
revised stereochemistries.7,8) Herein, we describe the full
details of our synthetic studies on communiols A–C,
which led to the revision of their stereochemistries.6)
Key words: communiol; antibacterial; enantioselective
synthesis; asymmetric dihydroxylation; ster-
eochemical revision
In the course of screening for bioactive natural
products from coprophilous (dung-colonizing) fungi,
Gloer and coworkers isolated three novel tetrahydrofur-
anyl carboxylic acids from the culture broth of Podo-
spora communis as substances exhibiting significant
antibacterial activity against Bacillus subtilis and Staph-
ylococcus aureus, and named them communiols A, B,
and C (Fig. 1).1) They also isolated five new structur-
ally-related compounds (communiols D–H), apparently
of the same biosynthetic origin, from the culture broth
of P. communis.1,2) The structures of communiols A–C
were proposed to be (5R,7S,8S)-1, (5R,7S,8S)-2 and
(3S,5S,6S)-3, respectively, based mainly on NMR analy-
ses including Mosher’s MTPA methodology.3) The 2,4-
disubstituted tetrahydrofuran substructure incorporated
in communiols A–C is relatively rare as a structural unit
Results and Discussion
Our retrosynthetic analysis of the originally proposed
structure of communiol C [(3S,5S,6S)-3)], chosen as our
first synthetic target due to its structural simplicity, is
shown in Scheme 1. Bearing in mind that the 5,6-threo
y
To whom correspondence should be addressed. Fax: +81-22-717-8783; E-mail: skuwahar@biochem.tohoku.ac.jp
Abbreviations: DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; DEAD, diethyl azodicarboxylate; DIBAL, diisobutylaluminum hydride; DMAP,
4-(dimethylamino)pyridine; LDA, lithium diisopropylamide; MTPA, ꢀ-methoxy-ꢀ-(trifluoromethyl)phenylacetate; PNB, p-nitrobenzoate; TBAF,
tetrabutylammonium fluoride; TBDPSCl, tert-butyldiphenylsilyl chloride; TBSCl, tert-butyldimethylsilyl chloride

1922
M. ENOMOTO and S. KUWAHARA
93.5% by converting the alcohol into the corresponding
1
oxidative
cleavage
(R)- and (S)-MTPA esters (7) and analyzing their H-
reduction
NMR spectra.7) Prior to the introduction of an allyl
substituent to the lactone, the protection of the hydroxyl
group of 6 was attempted by treating 6 with trityl
chloride (TrCl) and DBU in dichloromethane at room
temperature,16) in the hope that the very bulky protective
group (trityl) of product 8 would effectively hamper the
approach of the allylating agent from the bottom face of
the lactone ring and thereby help enhance the trans-
selectivity in the allylation step (B ! A, Scheme 1).
Unexpectedly, however, the protection did not proceed
at all, resulting in the recovery of 6, although the
tritylation conditions (TrCl, DBU, CH2Cl2) have been
known to effectively protect a variety of secondary
alcohols. Other reaction conditions (TrCl, Et3N, DMAP,
CH2Cl2, room temperature to 40 ꢁC; and TrCl, DBU,
DMAP, DMF, 100 ꢁC) brought about the formation of
complex mixtures. On the other hand, silylation of the
hydroxyl group using TBSCl or TBDPSCl as silylating
agents gave the corresponding TBS- or TBDPS-protect-
ed products (9 or 10, respectively) in almost quantitative
yields. Quite fortunately, the TBDPS-protected lactone
(10) was obtained as a crystalline solid, which suggested
the possibility that lactone 10 might be enantiomerically
enriched by recrystallization from an appropriate solvent
(vide infra). The good crystallinity of 10 coupled with
the bulkier nature of TBDPS as compared to TBS led us
to select 10 as the substrate for the next allylation step.
Allylation of the lithium enolate of 10 prepared by
treating TBDPS-protected lactone 10 with LDA gave a
8.3:1 mixture of 11a and its C3-epimer in 90% yield
favoring the desired 3,5-trans-isomer 11a, while the
corresponding prenylation with prenyl bromide exhib-
ited a slightly better trans-selectivity of 10:1 (74%
combined yield) (Scheme 3).11,12) When the allylation
and prenylation were conducted using the TBS-ether (9)
(see Scheme 2), the trans/cis ratio was 2.3:1 for the
allylation and 4.2:1 for the prenylation. After careful
purification of 11a by silica gel column chromato-
graphy, the trans-allylation product isolated in 64%
yield was reduced with DIBAL to give lactol 12 as a
3:1 anomeric mixture, which was further reduced with
O
O
O
H
H
6
HO2C
3
5
OH
(3S,5S,6S)-3
A
OR1
allylation
O
Sharpless
CO2R2
AD reaction
O
H
B
OR1
C
Scheme 1. Retrosynthetic Analysis of (3S,5S,6S)-3.
EtO2C
EtO2C
OH
AD-mix-α
OH
4
5
TsOH
(94%,
+
2 steps)
O
O
a) TrCl
b) TBSCl
O
O
H
H
c) TBDPSCl
OR1
OR2
8: R2 = Tr
6: R1 = H
9: R2 = TBS (96%)
7: R1 = MTPA
10: R2 = TBDPS (quant)
(93.5% ee)
Scheme 2. Preparation of Protected Lactone Intermediates 8–10.
stereochemistry of (3S,5S,6S)-3 would readily be in-
stalled using the Sharpless asymmetric dihydroxylation
(AD) reaction,9,10) we planned to synthesize the target
molecule from lactone intermediate A, which possesses
an allyl substituent with the desired stereochemistry at
the C3 position, via reduction of the lactone ring to the
tetrahydrofuran ring followed by oxidative cleavage of
the double bond. The lactone (A) with 3,5-trans relative
stereochemistry could be prepared by applying the well-
documented trans-selective alkylation of ꢁ-substituted
ꢁ-lactones to B,11,12) which in turn should be derivable
from olefinic ester C by the Sharpless AD reaction and
subsequent lactonization.
Our synthesis of (3S,5S,6S)-3 began with the exposure
of known olefinic ester 413,14) to the AD reaction
conditions using AD-mix-ꢀ as the chiral catalyst to
give a mixture of dihydroxy ester 5 and monohydroxy
lactone 6 (Scheme 2).9,10) Treatment of the mixture with
p-toluenesulfonic acid cleanly transformed 5 into 6,
.
triethylsilane in the presence of BF3 OEt2 to afford
tetrahydrofuran derivative 13.17,18) The prenylation
product (11b) was also converted into tetrahydrofuran
derivative 14 by the same two-step sequence of
reactions. Oxidative cleavage of the double bond of 13
was performed using RuCl3 and NaIO4,19) and the
resulting carboxylic acid intermediate was deprotected
with aqueous HF to afford (3S,5S,6S)-3, the structure
proposed by Gloer for communiol C, while the prenyl-
ated derivative 14 gave a complex mixture when
subjected to the same oxidative cleavage conditions
(RuCl3/NaIO4). Unexpectedly, direct comparison of the
1H-NMR spectrum of (3S,5S,6S)-3 with that of natural
communiol C revealed several clear differences, espe-
cially in the chemical shifts for 5-H, 6-H, and 9-H2. In
1
whose H-NMR spectrum was in good agreement with
that reported for an authentic sample of 6 previously
prepared from L-glutamic acid.15) The absolute stereo-
chemistry of 6 was confirmed by comparing its specific
22
rotation (½ꢀꢀ
+40.3 (c 2.25, CH2Cl2)) with the
22
D
literature value (½ꢀꢀ
+46.0 (c 2.0, CH2Cl2)),15) and
the enantiomeric excess (ee) of 6 was determined to be
D

Synthesis of Communiols A–C
1923
when the C2/C10-relative stereochemistry is threo,
while that of the corresponding erythro-isomer appears
at ca. 72 ppm. The observed chemical shift (73.7 ppm)
for the C6 carbon of natural communiol C led Gloer
et al. to propose its 5,6-relative stereochemistry to be
threo as shown in Fig. 1. To the best of our knowledge,
however, Born’s rule has never been applied to the
determination of the C2/C10-relative stereochemistry of
2,4-disubstituted tetrahydrofurans like communiol C.
This led us to presume that the genuine 5,6-relative
stereochemistry of communiol C might not be threo, but
erythro, judging from the fact that the 3,5-trans-stereo-
chemistry was determined by the well-established
NOESY methodology.1)
According to our presumption that the genuine
5,6-relative stereochemistry of cmmuniol C might be
erythro, we set about the synthesis of (3S,5S,6R)-3
possessing 3,5-trans-5,6-erythro stereochemistry from
intermediate 13 used in the synthesis of (3S,5S,6S)-3
(Scheme 4). Deprotection of the TBDPS-ether gave
alcohol 14, which was then exposed to the Mitsunobu
inversion conditions to afford PNB-ester 15 with
inversion of the absolute configuration at the C6
position.23,24) Oxidative cleavage of the double bond of
15 gave a carboxylic acid intermediate, the PNB-ester
group of which was deprotected by alkaline hydrolysis
to furnish (3S,5S,6R)-3. As expected, the 1H-NMR
spectrum of (3S,5S,6R)-3 was exactly the same as that of
natural communiol C, which enabled us to establish the
relative stereochemistry of communiol C as 3,5-trans
O
a) LDA
allyl bromide
O
H
10
R
3
5
b) LDA
prenyl bromide
OTBDPS
R
11a: R = H (90%)
11b: R = Me (74%)
HO
O
Et3SiH
DIBAL
H
11a
BF3·OEt2
(86%, 2 steps)
OTBDPS
12
1) RuCl3
NaIO4
9
3
O
O
H
H
6
HO2C
2) aq HF
(42%,
5
R
OTBDPS
13: R = allyl
OH
(3S,5S,6S)-3
2 steps)
O
H
OTBDPS
14
Scheme 3. Synthesis of (3S,5S,6S)-3.
the synthetic sample, the signals for 5-H, 6-H, and 9-H2
appeared at ꢂ 3.85, 3.34, and 4.06/3.49, respectively,
while the corresponding signals for natural commu-
niol C were observed at ꢂ 3.90, 3.68, and 4.09/3.41. In
their report on the structural determination of commu-
niols A–D, Gloer et al. determined the trans-relative
stereochemistry between the C3 and C5-substituents of
communiol C by observing several clear diagnostic
NOESY correlations, and assigned the absolute config-
uration at the C6 chiral center to be S by analogy with
the S-absolute configuration of communiol A (1), which
in turn was established unambiguously by the modified
Mosher method.1,3) On the other hand, the threo-relative
stereochemistry between C5 and C6 was proposed based
only on Born’s empirical rule, which has been employed
to determine the relative stereochemistry between the
C2 and C10 stereogenic centers of 2-(10-hydroxyalkyl)-
tetrahydrofurans including those bearing an additional
C5-alkyl substituent (Fig. 2).20–22) According to the rule,
the 10-C signal is observed at ca. 74 ppm in 13C-NMR
and 5,6-erythro. Comparison of the specific rotation of
22
(3S,5S,6R)-3 (½ꢀꢀ
+3.6 (c 0.24, CH2Cl2)) with that of
D
natural communiol C (½ꢀꢀD ꢂ3:4 (c 0.142, CH2Cl2)) as
well as the newly established relative stereochemistry
of communiol C led us to conclude that the genuine
structure of communiol C should be revised to
(3R,5R,6S)-3, the enantiomer of (3S,5S,6R)-3 depicted
in Scheme 4.
Based on our new proposal for the stereochemistry
of communiol C, we embarked on the synthesis of
(3R,5R,6S)-3 (Scheme 5). By following the same two-
DEAD
Ph3P
O
TBAF
(66%)
H
13
CO2H
OH
14
O2N
(59%)
R1
R1
5
O
O
H
H
1) RuCl3
NaIO4
R2
R2
O
O
H
1'
H
4
2
HO2C
2) aq K2CO3
(36%,
R
OH
OH
OPNB
15: R = allyl
OH
C2/C1'-threo
C for 1'-C = ca. 74 ppm
C2/C1'-erythro
C for 1'-C = ca. 72 ppm
2 steps)
(3S,5S,6R)-3
[α]22D +3.6
δ
δ
R1 = H or alkyl
R1 = H or alkyl
(lit.1) [α]D –3.4)
R2 = alkyl
R2 = alkyl
Fig. 2. Born’s Rule for the Assignment of Relative Stereochemistry.
Scheme 4. Synthesis of (3S,5S,6R)-3.

1924
M. ENOMOTO and S. KUWAHARA
O
O
H
O3, MeOH
1) Ph3P=CHCO2Et
EtO2C
1) AD-mix-β
O
H
20
then Me2S
(85%)
2) aq. LiOH, THF
(78%, 2 steps)
2) TsOH
(89%,
OPNB
OHC
21
OH
4
16
2 steps)
(96% ee)
O
H2, Pd/C
(96%)
H
O
HO2C
O
H
LDA, allyl bromide
TBDPSCl
OH
(5S,7R,8S)-2
then
recryst.
(75%)
then
purification
(85%)
O
H
OTBDPS
(100% ee)
17
HO2C
OH
(5S,7R,8S)-1
O
1) DIBAL
2) Et3SiH
BF3·OEt2
(84%,
2 steps)
O
O
H
H
Scheme 6. Synthesis of (5S,7R,8S)-1 and (5S,7R,8S)-2.
R
OTBDPS
OTBDPS
19: R = allyl
18
(½ꢀꢀD ꢂ3:4 (c 0.142, CH2Cl2)). Based on these results,
we concluded that the genuine structure of communiol C
is (3R,5R,6S)-3 as depicted in Scheme 5. The same
conclusion was reported by Murga and coworkers
based on their synthesis of (3S,5S,6R)-3 just after our
preliminary communication.25)
O
1) TBAF
H
2) DEAD, Ph3P
R
CO2H
OPNB
20: R = allyl
1) RuCl3, NaIO4
2) aq K2CO3
(60%, 2 steps)
O2N
Assuming that the structurally-related tetrahydrofuran
derivatives (communiols A and B) of the same microbial
origin should have the same stereochemical arrangement
as communiol C, we supposed that the correct structures
of communiols A and B would be (5S,7R,8S)-1 and
(5S,7R,8S)-2, respectively, and set about their synthesis
from 20, the synthetic intermediate for (3R,5R,6S)-3
(Scheme 6). Exposure of 20 to ozonolysis conditions
gave aldehyde intermediate 21, the chain elongation of
which by the Wittig reaction afforded (5S,7R,8S)-2 after
hydrolysis of the PNB ester group. Finally, catalytic
hydrogenation of (5S,7R,8S)-2 afforded (5S,7R,8S)-1.
The 1H- and 13C-NMR spectra of (5S,7R,8S)-1 and
(5S,7R,8S)-2 were exactly the same as those of natural
communiols A and B, respectively, which confirmed the
5,7-trans-7,8-erythro stereochemistry of natural com-
muniols A and B, as expected. To confirm the absolute
stereochemistry of communiols A and B, we next
compared the specific rotations of synthetic and natural
(68%, 2 steps)
O
H
HO2C
OH
(3R,5R,6S)-3
Scheme 5. Synthesis of (3R,5R,6S)-3.
step sequence of reactions as employed for the prepa-
ration of 6 except that AD-mix-ꢃ, instead of AD-mix-ꢀ,
was used in the asymmetric dihydroxylation step,9,10)
olefinic ester 4 was converted into hydroxy lactone 16,
whose enantiomeric excess was determined to be 96%
by the same MTPA method as used for 6. Protection of
its hydroxyl group as a TBDPS ether gave rise to 17 as a
white crystalline solid. Fortunately, and expectedly as
well, a single recrystallization of the solid from hexane/
EtOAc yielded enantiomerically pure 17 as colorless
prisms (mp 62.5–63.0 ꢁC), whose optical integrity was
checked by deprotecting the TBDPS group with TBAF
into the corresponding alcohol (i.e., 16) and analyzing
the alcoholic product by the MTPA method.7) Lactone
17 was transformed in 3 steps, via allylated intermediate
18, into tetrahydrofuran derivative 19, the TBDPS
protecting group of which was then removed with
TBAF to give an alcoholic intermediate. The inversion
of the absolute configuration of the hydroxyl-bearing
chiral center of the alcohol by the Mitsunobu reaction
afforded 20, which was then converted into (3R,5R,6S)-3
communiols A and B. Curiously, the specific rotations of
22
(5S,7R,8S)-1 (½ꢀꢀ
+1.4 (c 1.17, CH2Cl2)) and
+4.7 (c 1.00, CH2Cl2)) were
D
22
(5S,7R,8S)-2 (½ꢀꢀ
D
inconsistent with reported data for communiols A and
B, ½ꢀꢀD ꢂ1:6 (c 0.25, CH2Cl2) and ½ꢀꢀD ꢂ95 (c 0.075,
CH2Cl2), respectively. Similar discrepancies were also
reported by Murga et al.;25) they attributed the discrep-
ancies to concentration-dependency in specific rotation
of chiral carboxylic acids. We believe that such big
differences in optical rotation might be brought about
also by the presence of small quantities of impurities in
the synthetic and/or natural samples of communiols A
and B; a recent report on the synthesis of communiol A
by Trost and Zhang mentioned concentration- and
impurity-dependency in the specific rotation of commu-
niol A.26) Despite this ambiguity, the complete agree-
1
via oxidative cleavage followed by hydrolysis. The H-
and 13C-NMR spectra of the synthetic product were
identical with those of natural communiol C, and its
22
specific rotation (½ꢀꢀ
ꢂ2:7 (c 1.16, CH2Cl2)) was in
D
1
fairly good agreement with that of natural communiol C
ment in H- and 13C-NMR data between (5S,7R,8S)-1

Synthesis of Communiols A–C
1925
spectrometer. Optical rotation values were measured
with a Horiba Septa-300 polarimeter, and mass spectra
were obtained with a Jeol JMS-700 spectrometer. Merck
silica gel 60 (70–230 mesh) was used for silica gel
column chromatography.
O
H
HO2C
HO2C
OH
O
H
communiol A
(5S,7R,8S)-1
HO2C
OH
(2S,4R,5R)-2-Allyl-5-(tert-butyldiphenylsilyloxy)-4-
heptanolide (18). To a stirred solution of LDA, prepared
by treating a solution of diisopropylamine (1.26 ml,
9.02 mmol) and hexamethylphosphoramide (1.50 ml,
8.63 mmol) in THF (30 ml) with butyllithium (1.6 M in
hexane, 5.39 ml, 8.63 mmol) at ꢂ15 ꢁC, was added
dropwise a solution of 17 (3.00 g, 7.84 mmol) in THF
(30 ml) at ꢂ78 ꢁC. After 25 min, a solution of allyl
bromide (0.747 ml, 8.63 mmol) in THF (10 ml) was
added, and the resulting mixture was stirred for 15 min
at ꢂ78 ꢁC. After the addition of sat. NH4Cl aq. (ca.
20 ml), the mixture was extracted with ether. The extract
was successively washed with water and brine, dried
(MgSO4), and concentrated in vacuo. The residue was
repeatedly chromatographed over SiO2 (hexane/EtOAc,
O
H
communiol C
(3R,5R,6S)-3
OH
communiol B
(5S,7R,8S)-2
Fig. 3. Revised Stereochemistries for Communiols A–C.
and natural communiol A, and between (5S,7R,8S)-2
and natural communiol B, together with the unambig-
uous determination of the absolute configuration of the
C8 hydroxy-bearing stereogenic center as S by the well-
established modified Mosher’s MTPA method3) strongly
supported that the genuine structures of communiols A
and B should be (5S,7R,8S)-1 and (5S,7R,8S)-2, respec-
tively.
In conclusion, the enantioselective synthesis of
the originally proposed structure of communiol C,
(3S,5S,6S)-3, was accomplished in 8 steps from known
olefinic ester 4 using the Sharpless asymmetric dihy-
droxylation as the source of chirality. Clear differences
22
30:1) to give 2.82 g (85%) of 18 as a colorless oil: ½ꢀꢀD
ꢂ10:9 (c 1.00, CHCl3); IR ꢄmax cmꢂ1: 3080 (w), 3050
1
(w), 1770 (s), 1110 (s), 705 (s); H-NMR (300 MHz) ꢂ
0.70 (3H, t, J ¼ 7:5 Hz), 1.04 (9H, s), 1.39 (1H, ddq,
J ¼ 13:8, 5.4, 7.5 Hz), 1.59–1.74 (1H, m), 1.94 (1H, dt,
J ¼ 13:2, 8.1 Hz), 2.16–2.33 (2H, m), 2.51–2.61 (1H,
m), 2.78–2.89 (1H, m), 3.63 (1H, ddd, J ¼ 7:8, 5.1,
3.3 Hz), 4.48 (1H, ddd, J ¼ 8:1, 3.9, 3.3 Hz), 5.10 (1H,
br d, J ¼ 11:1 Hz), 5.11 (1H, dm, J ¼ 15:9 Hz), 5.67–
5.81 (1H, m), 7.35–7.48 (6H, m), 7.65–7.72 (4H, m);
13C-NMR (150 MHz) ꢂ 9.6, 19.5, 25.7, 27.0, 28.9, 35.5,
39.1, 76.6, 78.4, 117.7, 127.5 (2C), 127.7 (2C), 129.7,
129.9, 133.1, 133.9, 134.5, 135.81 (2C), 135.83 (2C),
179.1; HRMS (FAB) m=z calcd for C26H35O3Si
([M + H]þ) 423.2355, found 423.2358.
1
in H-NMR between (3S,5S,6S)-3 and natural commu-
niol C as well as good agreement of natural commu-
niol C with the synthetic C6-epimer of (3S,5S,6S)-3 in
every respect except for the sign of specific rotation
led us to propose that the genuine stereochemistry of
communiol C should be 3R, 5R, and 6S. The synthesis
of (3R,5R,6S)-3 and its good accordance with natural
communiol C in every respect confirmed the new
proposal for the stereochemistry of communiol C
(Fig. 3). Based on this stereochemical revision for
communiol C, (5S,7R,8S)-1 and (5S,7R,8S)-2 were also
synthesized as the most probable candidates for the
genuine structures of communiols A and B, respectively.
(2R,4S)-4-Allyl-2-[(R)-1-(tert-butyldiphenylsilyloxy)-
propyl]tetrahydrofuran (19). To a stirred solution of 18
(0.603 g, 1.43 mmol) in CH2Cl2 (6 ml) was added
dropwise DIBAL (0.94 M in hexane, 1.67 ml, 1.57 mmol)
at ꢂ75 ꢁC. After 20 min, the reaction was quenched with
a saturated aqueous solution of Rochelle’s salt, and the
mixture was gradually warmed to room temperature
over 1 h. The mixture was extracted with EtOAc, and
the extract was washed with brine, dried (MgSO4),
and concentrated in vacuo to give 0.627 g of an oil
containing (2R/S,3S,5R)-3-allyl-5-[(R)-1-(tert-butyldi-
phenylsilyloxy)propyl]tetrahydrofuran-2-ol, which was
then dissolved in CH2Cl2 (6.0 ml). To the solution was
The H- and 13C-NMR of the synthetic products were
1
identical with those of the corresponding natural
products, which, coupled with the unambiguous deter-
mination of the (8S)-absolute stereochemistry by Gloer
et al., strongly supported the genuine structures of
communiols A and B should be (5S,7R,8S)-1 and
(5S,7R,8S)-2, respectively (Fig. 3), although some am-
biguities in their optical rotations have yet to be settled.
Experimental
added dropwise Et3SiH (0.251 ml, 1.57 mmol) at
ꢁ
.
ꢂ78 C, and the mixture was stirred for 5 min. BF3 OEt2
IR spectra were recorded as films by a Jasco IR
1
(0.198 ml, 1.57 mmol) was then added, and the mixture
was gradually warmed to ꢂ5 ꢁC while being stirred
overnight. The reaction was quenched with a suspension
of NaHCO3 in MeOH, and the mixture was diluted
with water and extracted with EtOAc. The extract was
washed with brine, dried (MgSO4), and concentrated in
Report-100 spectrometer. H NMR spectra (300, 500 or
600 MHz) and 13C NMR spectra (125 or 150 MHz) were
recorded with TMS as an internal standard in CDCl3 by
a Varian Gemini 2000 spectrometer, a Varian UNITY
plus-500 spectrometer or a Varian UNITY plus-600

1926
M. ENOMOTO and S. KUWAHARA
vacuo. The residue was chromatographed over SiO2
(hexane/EtOAc, 10:1) to give 0.490 g (84%) of 19 as a
colorless oil: ½ꢀꢀD +18.0 (c 1.00, CHCl3); IR ꢄmax
(1H, dm, J ¼ 17:1 Hz), 5.19 (1H, ddd, J ¼ 7:8, 5.1,
4.8 Hz), 5.76 (1H, ddt, J ¼ 17:1, 10.2, 7.0 Hz), 8.20–
8.25 (2H, m), 8.28–8.33 (2H, m); 13C-NMR (150 MHz)
ꢂ 9.8, 23.8, 33.1, 37.1, 38.4, 73.4, 78.1, 79.0, 116.2,
123.5, 130.7, 135.8, 136.4, 150.5, 164.3; HRMS (FAB)
m=z calcd for C17H22O5N ([M + H]þ) 320.1498, found
320.1498.
22
cmꢂ1: 3080 (w), 3050 (w), 1430 (m), 1110 (s), 700 (s);
1H-NMR (300 MHz) ꢂ 0.75 (3H, t, J ¼ 7:5 Hz), 1.04
(9H, s), 1.28–1.42 (1H, m), 1.47–1.63 (2H, m), 1.97 (1H,
ddd, J ¼ 12:3, 7.8, 6.3 Hz), 2.07 (2H, t, J ¼ 7:2 Hz),
2.14–2.30 (1H, m), 3.33 (1H, dd, J ¼ 8:4, 6.3 Hz), 3.59
(1H, dt, J ¼ 5:5, 5.1 Hz), 3.83 (1H, dd, J ¼ 6:3, 8.4 Hz),
4.00 (1H, ddd, J ¼ 7:8, 6.6, 5.1 Hz), 4.98 (1H, dm,
J ¼ 10:2 Hz), 5.01 (1H, dm, J ¼ 17:1 Hz), 7.33–7.46
(6H, m), 7.68–7.75 (4H, m); 13C-NMR (150 MHz) ꢂ
10.0, 19.5, 25.5, 27.1, 32.7, 37.5, 38.8, 73.0, 76.6, 79.9,
115.7, 127.32 (2C), 127.35 (2C), 129.3, 129.4, 134.2,
134.7, 135.96, 135.98, 137.0; HRMS (FAB) m=z calcd
for C26H36O2SiNa ([M + Na]þ) 431.2382, found
431.2390.
{(3R,5R)-5-[(S)-1-Hydroxypropyl]tetrahydrofuran-3-
yl}acetic acid [(3R,5R,6S)-3]. To a stirred solution of 20
(70.0 mg, 0.219 mmol) in H2O/CH3CN/CCl4 (3:2:2,
2.8 ml) was successively added NaIO4 (0.192 mg,
0.899 mmol) and a catalytic amount of RuCl3(H2O)n at
0 ꢁC. After 2.5 h, the reaction was quenched with 2-
propanol, and the mixture was extracted with CH2Cl2.
The extract was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatograph-
ed over SiO2 (CHCl3/MeOH, 75:1) to give 52.0 mg
(70%) of {(3R,5R)-5-[(S)-1-(p-nitrobenzoyloxy)propyl]-
tetrahydrofuran-3-yl}acetic acid as a colorless crystal-
(S)-1-[(2R,4S)-4-Allyltetrahydrofuran-2-yl]propyl p-
nitrobenzoate (20). To
a stirred solution of 19
line solid (mp 100.0–100.2 ꢁC): ½ꢀꢀD ꢂ5:14 (c 2.60,
22
(0.941 g, 2.30 mmol) in THF (2 ml) was added TBAF
(1 M in THF, 11.5 ml, 11.5 mmol) at room temperature.
After 3 d, the reaction was quenched with water, and the
mixture was extracted with EtOAc. The extract was
successively washed with water and brine, dried
(MgSO4), and concentrated in vacuo. The residue was
chromatographed over SiO2 (hexane/ethyl acetate, 10:1)
to give 0.386 g (99%) of (S)-1-[(2R,4S)-4-allyltetrahy-
CHCl3); IR ꢄmax cmꢂ1: ꢃ3000 (br m), 1720 (vs), 1600
(w), 1510 (s), 1275 (s), 1100 (s); 1H-NMR (300 MHz) ꢂ
0.98 (3H, s, J ¼ 7:5 Hz), 1.68–1.86 (3H, m), 2.18 (1H,
ddd, J ¼ 12:9, 7.8, 6.3 Hz), 2.47 (2H, d, J ¼ 7:5 Hz),
2.61–2.76 (1H, m), 3.46 (1H, dd, J ¼ 8:7, 6.6 Hz), 4.04
(1H, dd, J ¼ 8:7, 6.6 Hz), 4.21 (1H, ddd, J ¼ 7:8, 6.3,
5.1 Hz), 5.22 (1H, dt, J ¼ 7:8, 4.8 Hz), 8.21–8.26 (2H,
m), 8.28–8.33 (2H, m); 13C-NMR (150 MHz) ꢂ 9.8,
23.9, 33.0, 35.1, 36.9, 73.2, 77.8, 78.9, 123.5, 130.7,
135.6, 150.5, 164.3, 178.1; HRMS (FAB) m=z calcd for
C16H20O7N ([M + H]þ) 338.1240, found 338.1243. To
a stirred solution of the carboxylic acid (48.3 mg,
0.143 mmol) in THF (1 ml) was added 1 M K2CO3 aq.
(1 ml) at room temperature. After 3 d, the mixture was
acidified with 2 M HCl aq., and extracted with EtOAc.
The extract was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatograph-
ed over SiO2 [CHCl3/MeOH (50:1) containing a trace
amount of AcOH] to give 23.0 mg (86%) of [(3R,5R,6S)-
22
drofuran-2-yl]-1-propanol as a colorless oil: ½ꢀꢀD
ꢂ1:59 (c 1.00, CHCl3) ; IR ꢄmax cmꢂ1: 3460 (m),
1
3070 (w), 1640 (m); H-NMR (300 MHz) ꢂ 1.00 (3H, t,
J ¼ 7:4 Hz), 1.34–1.57 (2H, m), 1.66 (1H, ddd, J ¼
12:9, 7.5, 5.7 Hz), 2.13 (2H, t, J ¼ 6:5 Hz), 2.25–2.38
(1H, m), 2.38 (1H, d, J ¼ 4:2 Hz, OH), 3.27–3.36 (1H,
m), 3.45 (1H, dd, J ¼ 8:4, 6.3 Hz), 3.82 (1H, q,
J ¼ 6:9 Hz), 3.95 (1H, dd, J ¼ 8:4, 6.3 Hz), 5.02 (1H,
dm, J ¼ 10:2 Hz), 5.05 (1H, dm, J ¼ 17:1 Hz), 5.77
(1H, ddd, J ¼ 17:1, 10.2, 6.5 Hz); 13C-NMR (150 MHz)
ꢂ 10.1, 26.5, 33.8, 37.4, 38.9, 72.9, 75.4, 81.4, 116.0,
136.6; HRMS (EI) m=z calcd for C10H18O2 (Mþ)
170.1306, found 170.1313. To a stirred solution of the
alcohol (0.117 g, 0.684 mmol) in THF (4 ml) was
successively added Ph3P (0.718 g, 2.74 mmol), p-nitro-
benzoic acid (0.457 g, 2.74 mmol), and DEAD
(0.499 ml, 2.74 mmol) at 0 ꢁC, and the mixture was
stirred for 2 d at room temperature. The reaction was
quenched with sat. NaHCO3 aq., and the mixture was
extracted with EtOAc. The extract was washed with
brine, dried (MgSO4), and concentrated in vacuo. The
residue was chromatographed over SiO2 (hexane/
EtOAc/CHCl3, 20:1:2) to give 0.150 g (69%) of 20 as
22
3 as a colorless oil: ½ꢀꢀD ꢂ2:7 (c 1.16, CH2Cl2); IR
ꢄmax cmꢂ1: 3350 (m), ꢃ3000 (m), 1710 (s), 1460 (w),
1410 (m), 1235 (m), 1080 (m), 975 (m), 760 (m);
1H-NMR (300 MHz) ꢂ 0.99 (3H, t, J ¼ 7:4 Hz), 1.38–
1.50 (2H, m), 1.56 (1H, ddd, J ¼ 12:6, 7.7, 6.0 Hz), 2.15
(1H, ddd, J ¼ 12:6, 8.5, 7.4 Hz), 2.42 (1H, dd, J ¼ 16:1,
8.0 Hz), 2.48 (1H, dd, J ¼ 16:1, 6.9 Hz), 2.58–2.73 (1H,
m), 3.44 (1H, dd, J ¼ 8:8, 6.6 Hz), 3.72 (1H, ddd,
J ¼ 8:0, 5.2, 3.6 Hz), 3.95 (1H, dt, J ¼ 3:6, 7.5 Hz), 4.12
(1H, dd, J ¼ 8:5, 6.6 Hz); 13C-NMR (125 MHz) ꢂ 10.3,
25.6, 30.7, 35.5, 37.3, 73.3, 73.7, 81.3, 177.4; HRMS
(FAB) m=z calcd for C9H17O4 ([M + H]þ) 189.1127,
found 189.1128.
22
a colorless oil: ½ꢀꢀD ꢂ1:88 (c 1.00, CHCl3); IR ꢄmax
1
cmꢂ1: 3070 (w), 1720 (s), 1515 (s), 1270 (s); H-NMR
(300 MHz) ꢂ 0.98 (3H, t, J ¼ 7:4 Hz), 1.66–1.84 (3H,
m), 2.00 (1H, ddd, J ¼ 12:6, 7.8, 6.3 Hz), 2.14 (2H, t,
J ¼ 7:0 Hz), 2.26–2.40 (1H, m), 3.43 (1H, dd, J ¼ 8:4,
6.6 Hz), 3.95 (1H, dd, J ¼ 8:4, 6.6 Hz), 4.16 (1H, ddd,
J ¼ 7:5, 6.3, 5.1 Hz), 5.02 (1H, dm, J ¼ 10:2 Hz), 5.05
1H- and 13C-NMR data for (3S,5S,6S)-3, the origi-
nally proposed structure for communiol C. 1H-NMR
(500 MHz) ꢂ 1.00 (3H, t, J ¼ 7:6 Hz), 1.37–1.54 (2H,
m), 1.70 (1H, ddd, J ¼ 12:7, 7.3, 5.9 Hz), 1.94 (1H, ddd,

Synthesis of Communiols A–C
1927
J ¼ 12:7, 7.8, 7.3 Hz), 2.46 (2H, d, J ¼ 7:3 Hz), 2.68
(1H, sep, J ¼ 6:8 Hz), 3.32–3.37 (1H, m), 3.49 (1H, dd,
J ¼ 8:3, 6.3 Hz), 3.85 (1H, q, J ¼ 6:8 Hz), 4.06 (1H, dd,
J ¼ 8:3, 6.8 Hz); 13C-NMR (125 MHz) ꢂ 10.1, 26.5,
33.9, 35.6, 37.2, 72.8, 75.2, 81.3, 177.1.
The residue was chromatographed over SiO2 [CHCl3/
MeOH (70:1) containing a trace amount of AcOH] to
give 0.074 g (95%) of (5S,7R,8S)-2 as a colorless oil:
½ꢀꢀD +4.7 (c 1.00, CH2Cl2); IR ꢄmax cmꢂ1: 3400 (m),
22
ꢃ3000 (m, broad), 1700 (s), 1655 (m), 1250 (m), 1085
1
(w), 980 (m), 885 (w), 760 (m); H-NMR (300 MHz) ꢂ
(S)-1-[(2R,4R)-4-(2-Oxoethyl)tetrahydrofuran-2-yl]-
propyl p-nitrobenzoate (21). Ozone was bubbled into a
stirred solution of 20 (0.200 g, 0.626 mmol) in MeOH
(2 ml) at ꢂ78 ꢁC until the disappearance of 20 was
observed by TLC monitoring. Me2S (0.4 ml) was then
added, and the mixture was gradually warmed to room
temperature and then concentrated in vacuo. The residue
was chromatographed over SiO2 (hexane/EtOAc, 2:1)
0.99 (3H, t, J ¼ 7:4 Hz), 1.38–1.49 (2H, m), 1.52 (1H,
ddd, J ¼ 12:6, 7.4, 5.2 Hz), 2.09 (1H, dt, J ¼ 12:6,
7.8 Hz), 2.32 (2H, br t, J ¼ 7:1 Hz), 2.32–2.46 (1H, m),
3.42 (1H, dd, J ¼ 8:5, 6.6 Hz), 3.71 (1H, ddd, J ¼ 7:7,
5.5, 3.6 Hz), 3.93 (1H, dt, J ¼ 3:6, 7.7 Hz), 4.05 (1H, dd,
J ¼ 8:5, 6.6 Hz), 5.87 (1H, br d, J ¼ 15:7 Hz), 7.01 (1H,
dt, J ¼ 15:7, 7.1 Hz); 13C-NMR (150 MHz) ꢂ 10.3, 25.7,
30.5, 35.7, 38.2, 73.2, 73.6, 81.4, 122.0, 149.3, 170.7;
HRMS (FAB) m=z calcd for C11H19O4 ([M + H]þ)
215.1283, found 215.1286.
22
to give 0.171 g (85%) of 21 as a colorless oil: ½ꢀꢀD
ꢂ3:8 (c 0.510, CHCl3); IR ꢄmax cmꢂ1: 2725 (w), 1720
1
(vs), 1605 (m), 1525 (s), 1275 (s); H-NMR (300 MHz)
ꢂ 0.98 (3H, t, J ¼ 7:5 Hz), 1.63–1.88 (3H, m), 2.18 (1H,
ddd, J ¼ 12:9, 7.8, 6.3 Hz), 2.60 (2H, d, J ¼ 6:8 Hz),
2.65–2.80 (1H, m), 3.39 (1H, dd, J ¼ 8:7, 6.6 Hz), 4.05
(1H, dd, J ¼ 8:7, 6.6 Hz), 4.17 (1H, ddd, J ¼ 7:5, 6.3,
4.8 Hz), 5.22 (1H, dt, J ¼ 7:8, 3.9 Hz), 8.20–8.26 (2H,
m), 8.28–8.34 (2H, m), 9.79 (1H, s); 13C-NMR
(125 MHz) ꢂ 9.8, 23.9, 32.9, 33.2, 47.1, 73.3, 77.9,
78.9, 123.6, 130.7, 135.7, 150.5, 164.3, 200.6; HRMS
(FAB) m=z calcd for C16H20O6N ([M + H]þ) 322.1290,
found 322.1293.
4-{(3S,5R)-5-[(S)-1-Hydroxypropyl]tetrahydrofuran-
3-yl}butanoic acid [(5S,7R,8S)-1].
A mixture of
(5S,7R,8S)-2 (0.025 g, 0.117 mmol) and 10% Pd-C
(2.5 mg) in ethanol (0.25 ml) was stirred at room
temperature for 1.5 h under hydrogen at atmospheric
pressure. The mixture was filtered through a pad of
Celite, and the filter cake was washed with EtOAc. The
combined filtrates were concentrated in vacuo, and the
residue was chromatographed over SiO2 [CHCl3/MeOH
(70:1) containing a trace amount of AcOH] to give
22
0.024 g (96%) of (5S,7R,8S)-1 as a colorless oil: ½ꢀꢀD
4-{(3S,5R)-5-[(S)-1-(p-Nitrobenzoyloxy)propyl]tetra-
hydrofuran-3-yl}-2-butenoic acid [(5S,7R,8S)-2].
+1.4 (c 1.17, CH2Cl2); IR ꢄmax cmꢂ1: 3400 (m), ꢃ3000
(m, broad), 1710 (s), 1460 (m), 1260 (m), 1070 (m), 975
(w); 1H-NMR (300 MHz) ꢂ 0.97 (3H, t, J ¼ 7:4 Hz),
1.37–1.51 (5H, m), 1.56–1.73 (2H, m), 2.06 (1H, ddd,
J ¼ 12:4, 8.8, 6.9 Hz), 2.12–2.27 (1H, m), 2.36 (2H, t,
J ¼ 7:4 Hz), 3.35 (1H, dd, J ¼ 8:2, 7.7 Hz), 3.69 (1H,
ddd, J ¼ 7:7, 5.5, 3.3 Hz), 3.91 (1H, ddd, J ¼ 7:7, 6.7,
3.6 Hz), 4.04 (1H, dd, J ¼ 8:2, 6.6 Hz); 13C-NMR
(150 MHz) ꢂ 10.4, 23.5, 25.7, 30.9, 32.5, 34.0, 39.3,
73.69, 73.74, 81.5, 178.7; HRMS (FAB) m=z calcd for
C11H21O4 ([M + H]þ) 271.1440, found 271.1442.
A
mixture of 21 (0.170 g, 0.530 mmol) and Ph3P=CHCO2-
Et (0.203 g, 0.583 mmol) in CH2Cl2 (2.5 ml) was stirred
for 9 h at room temperature. The mixture was diluted
with water and extracted with EtOAc. The extract was
washed with brine, dried (MgSO4), and concentrated in
vacuo. The residue was chromatographed over SiO2
(hexane/EtOAc, 10:1) to give 0.170 g (82%) of ethyl
4-{(3S,5R)-5-[(S)-1-(p-nitrobenzoyloxy)propyl]tetrahy-
22
drofuran-3-yl}-2-butenoate as a colorless oil: ½ꢀꢀD
ꢂ1:9 (c 0.810, CHCl3); IR ꢄmax cmꢂ1: 1720 (vs), 1650
(m), 1605 (w), 1530 (s), 1280 (s); 1H-NMR (300 MHz) ꢂ
0.98 (3H, t, J ¼ 7:4 Hz), 1.29 (3H, t, J ¼ 7:1 Hz), 1.67–
1.86 (3H, m), 2.05 (1H, ddd, J ¼ 12:9, 7.8, 6.3 Hz), 2.29
(1H, br t, J ¼ 7:0 Hz), 2.34–2.46 (1H, m), 3.44 (1H, dd,
J ¼ 8:7, 6.3 Hz), 3.97 (1H, dd, J ¼ 8:7, 6.3 Hz), 4.15–
4.24 (1H, m), 4.18 (2H, q, J ¼ 7:1 Hz), 5.20 (1H, dt,
J ¼ 8:1, 4.8 Hz), 5.85 (1H, dt, J ¼ 15:6, 1.4 Hz), 6.89
(1H, dt, J ¼ 15:6, 7.0 Hz), 8.19–8.25 (2H, m), 8.28–8.34
(2H, m); 13C-NMR (125 MHz) ꢂ 9.8, 14.2, 23.9, 33.1,
35.4, 37.8, 60.4, 73.3, 77.9, 79.0, 122.8, 123.6, 130.7,
135.7, 146.3, 150.5, 164.3, 166.3; HRMS (FAB) m=z
calcd for C20H26O7N ([M + H]þ) 392.1709, found
392.1709. The ethyl ester (0.143 g, 0.364 mmol) was
dissolved in THF (2.5 ml) and mixed with 1 M LiOH aq.
(2 ml), and the mixture was stirred at room temperature
for 20 h. The mixture was acidified with 2 M HCl aq.
and extracted with EtOAc. The extract was washed
with brine, dried (MgSO4), and concentrated in vacuo.
Acknowledgments
We are grateful to Prof. Gloer (University of Iowa)
for providing the copies of the NMR spectra of
communiols A–C. We also thank Ms. Yamada (Tohoku
University) for measuring NMR and MS spectra. This
work was supported, in part, by a Grant-in-Aid for
Scientific Research (B) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan
(no. 19380065).
References
1) Che, Y., Gloer, J. B., Scott, J. A., and Malloch, D.,
Communiols A–D: new mono- and bis-tetrahydrofuran
derivatives from the coprophilous fungus Podospora
communis. Tetrahedron Lett., 45, 6891–6894 (2004).
2) Che, Y., Araujo, A. R., Gloer, J. B., Scott, J. A., and

1928
M. ENOMOTO and S. KUWAHARA
´
precurseurs de synthons chiraux (IV) synthese
diastereoselective d’ꢀ-diols enantiomeriquement purs;
´ ´
preparation de la (+)-exobrevicomine. Bull. Soc. Chim.
`
Malloch, D., Communiols E–H: new polyketide metab-
olites from the coprophilous fungus Podospora commu-
nis. J. Nat. Prod., 68, 435–438 (2005).
´ ´
´
´
´
3) Ohtani, I., Kusumi, T., Kashman, Y., and Kakisawa, H.,
High-field FT NMR application of Mosher’s method.
The absolute configurations of marine terpenoids. J. Am.
Chem. Soc., 113, 4092–4096 (1991).
Fr., 116–122 (1987).
16) Colin-Messager, S., Girard, J.-P., and Rossi, J.-C.,
Convenient method for the preparation of trityl ethers
from secondary alcohols. Tetrahedron Lett., 33, 2689–
2692 (1992).
`
4) Bermejo, A., Figadere, B., Zafra-Polo, M.-C.,
Barrachina, I., Estornell, E., and Cortes, D., Acetogenins
from Annonaceae: recent progress in isolation, synthesis
and mechanisms of action. Nat. Prod. Rep., 22, 269–303
(2005).
17) Kraus, G. A., Frazier, K. A., Roth, B. D., Taschner,
M. J., and Neuenschwander, K., Conversion of lactones
into ethers. J. Org. Chem., 46, 2417–2419 (1981).
18) Bruckner, C., Holzinger, H., and Reissig, H.-U., Dia-
¨
5) Wierenga, W., The total synthesis of ionophores. In
‘‘The Total Synthesis of Natural Products’’ Vol. 4, ed.
ApSimon, J., Wiley, New York, pp. 263–351 (1981).
6) Kuwahara, S., and Enomoto, M., Enantioselective syn-
thesis and stereochemical revision of communiols A–C.
Tetrahedron Lett., 46, 6297–6300 (2005).
7) Enomoto, M., Nakahata, T., and Kuwahara, S., Stereo-
chemical revision of communiols D and H through
synthesis. Tetrahedron, 62, 1102–1109 (2006).
8) Enomoto, M., and Kuwahara, S., Enantioselective total
synthesis and stereochemical revision of communiols E
and F. J. Org. Chem., 71, 6287–6290 (2006).
9) Kolb, H. C., VanNieuwenhze, M. S., and Sharpless,
K. B., Catalytic asymmetric dihydroxylation. Chem.
Rev., 94, 2483–2547 (1994).
10) Avedissian, H., Sinha, S. C., Yazbak, A., Sinha, A.,
Neogi, P., Sinha, S., and Keinan, E., Total synthesis of
asimicin and bullatacin. J. Org. Chem., 65, 6035–6051
(2000).
stereoselective syntheses of highly substituted methyl
tetrahydrofuran-3-carboxylates by reactions of ꢁ-lactols
with silylated nucleophiles. J. Org. Chem., 53, 2450–
2456 (1988).
19) Carlsen, P. H. J., Katsuki, T., Martin, V. S., and
Sharpless, K. B., A greatly improved procedure for
ruthenium tetraoxide catalyzed oxidations of organic
compounds. J. Org. Chem., 46, 3936–3938 (1981).
20) Born, L., Lieb, F., Lorentzen, J. P., Moeschler, H.,
Nonfon, M., Sollner, R., and Wendisch, D., The relative
¨
configuration of acetogenins isolated from Annona
squamosa; annonin I (squamocin) and annonin VI.
Planta Med., 56, 312–316 (1990).
´
21) Chavez, D., Acevedo, L. A., and Mata, R., Jimenezin, a
novel annonaceous acetogenin from the seeds of Rollinia
mucosa containing adjacent tetrahydrofuran–tetrahydro-
pyran ring systems. J. Nat. Prod., 61, 419–421 (1998).
22) Fujimoto, Y., Murasaki, C., Shimada, H., Nishioka, S.,
Kakinuma, K., Singh, S., Singh, M., Gupta, Y. K., and
Sahai, M., Annonaceous acetogenins from the seeds of
Annona squamosa. Non-adjacent bis-tetrahydrofuranic
acetogenins. Chem. Pharm. Bull., 42, 1175–1184 (1994).
23) Mitsunobu, O., The use of diethyl azodicarboxylate and
triphenylphosphine in synthesis and transformation of
natural products. Synthesis, 1–28 (1981).
11) Sells, T. B., and Nair, V., Synthetic approaches to novel
cis and trans dideoxynucleosides of the apiose family.
Tetrahedron, 50, 117–138 (1994).
´
12) Bouchard, H., Soulie, J., and Lallemand, J. Y., Towards
the total synthesis of clerodin. Part II. Tetrahedron Lett.,
32, 5957–5958 (1991).
13) Odinokov, V. N., Vakhidov, R. R., Shakhmaev, R. N.,
and Zorin, V. V., Insect pheromones and their analogs.
LIV. Synthesis of (E)-dodec-9-en-1-ol and its acetate,
components of the sex pheromone of Sparganothis
pilleriana. Khim. Prir. Soedin., 936–939 (1996).
24) Martin, S. F., and Dodge, J. A., Efficacious modification
of the Mitsunobu reaction for inversions of sterically
hindered secondary alcohols. Tetrahedron Lett., 32,
3017–3020 (1991).
25) Murga, J., Falomir, E., Carda, M., and Marco, J. A.,
Stereoselective synthesis of ent-communiols A–C.
Tetrahedron Lett., 46, 8199–8202 (2005).
26) Trost, B. M., and Zhang, T., Asymmetric synthesis
of ꢀ-substituted aldehydes by Pd-catalyzed asymmetric
allylic alkylation–alkene isomerization–Claisen rear-
rangement. Org. Lett., 8, 6007–6010 (2006).
`
14) Bruyere, D., Bouyssi, D., and Balme, G., A study on
the regio-and stereoselectivity in palladium-catalyzed
cyclizations of alkenes and alkynes bearing bromoaryl
and nucleophilic groups. Tetrahedron, 60, 4007–4017
(2004).
ˆ
15) Larcheveque, M., and Lalande, J., Les aminoacides