A modular total synthesis of aculeatins A, B, E, F and 6-epi-aculeatins E, F

Article abstract of DOI:10.1016/j.tet.2009.10.058

The total synthesis of aculeatins A, B, E and F confirming the assigned absolute configuration of recently isolated aculeatins E and F is documented. A convergent approach has been designed by the addition of both the terminal units (phenol and side chain) at an advanced stage. The central 1,3,5-triol unit with the requisite stereochemistry was prepared from the commercially available α-d-glucoheptonic-γ-lactone. Selective O-debenzylation during the hydrogenolysis of the diyne intermediate and the one pot phenolic oxidation with concomitant spiroketalization highlight the accomplished total syntheses.

Full text of DOI:10.1016/j.tet.2009.10.058

Tetrahedron 66 (2010) 390–399
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A modular total synthesis of aculeatins A, B, E, F and 6-epi-aculeatins E, F
*
C.V. Ramana , Sunil Kumar Pandey
National Chemical Laboratory, Pune-411008, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 October 2009
Received in revised form 15 October 2009
Accepted 16 October 2009
Available online 21 October 2009
The total synthesis of aculeatins A, B, E and F confirming the assigned absolute configuration of recently
isolated aculeatins E and F is documented. A convergent approach has been designed by the addition of
both the terminal units (phenol and side chain) at an advanced stage. The central 1,3,5-triol unit with the
requisite stereochemistry was prepared from the commercially available a-D-glucoheptonic-g-lactone.
Selective O-debenzylation during the hydrogenolysis of the diyne intermediate and the one pot phenolic
oxidation with concomitant spiroketalization highlight the accomplished total syntheses.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Natural products synthesis
Aculeatins
Alkyne–oxirane coupling
Oxidative spiroketalization
Sonogashira coupling
1. Introduction
also displayed promising activity against the Plasmodium falciparum
strains K1 and NF54.7 With the help of extensive 2D-NMR experi-
Access to a collection of distinctive small molecules is an im-
portant aspect in the realm of chemical genetics and for identifying
new therapeutic candidates.1 Several philosophies addressing the
target molecules ensemble either in a forward or the backward
sense have been put forwarded, with an ultimate aim of providing
flexible and diverse routes with the potential of addressing both the
number and function with an ease.2–4 Concepts funded upon the
designing around, and of the synthesis of natural products and
natural products like small molecules have provided a direct entry
of ‘total synthesis programs’ into medicinal chemistry research.3,4
Development of synthetic methods that are efficient and the design
of strategies that are modular with a flexibility window was a pre-
requisite for the synthesis of natural product derived and inspired
compound collections.5 Herein we describe such a simple tech-
nology that addresses the synthesis of several of naturally occur-
ring aculeatins and also of some of their C(6)-epimers.
Bio-activity guided isolation of herbaceous plants which traces
their origin to folk medicine is one of the reliable approaches in
identifying new drugs of natural origin. In 2000, Heilmann et al.
reported the isolation of three biologically active metabolites acu-
leatins A–C from the petroleum ether extract of the rhizomes of
Amomum aculeatum ROXB, a plant used in the folk medicine of Papua
New Guinea against fever and malaria.6 The aculeatins A–C were
identified as potent inhibitors of the human tumor KB cell line and
ments, the structures of aculeatins A–C were characterized by the
presence of a fascinating 1,7-dioxadispiro[5.1.5.2]-pentadecane spi-
rocyclic architecture. Soon afterward, the same group added acu-
leatin D (4) to this family and reported remarkably high cytotoxicity,
anti-bacterial and anti-protozoal activities.8 In 2007, Kinghorn et al.
reported the isolation of related metabolites aculeatols A–D; the C(9)
hydroxylated aculeatins A or B having either the same or two carbon
truncated side chains.9a Subsequently, the isolation of truncated
aculeatins A and D, named, respectively as aculeatins F (6) and E (5),
were reported by the same group.9b In addition to their promising
biological activities, because of the presence of unprecedented
dioxadispirocyclic architecture, aculeatins A–D aroused substantial
interest culminating in several total syntheses from various
groups.10–13 Wong and co-workers reported the first total synthesis
of racemic aculeatin A (1) and its spiroepimer aculeatin B (2).10a The
construction of the central tricyclic system was accomplished by
using phenol oxidative spirocyclization. In 2005, Bulger and co-
workers reported the first total synthesis of racemic aculeatin D
confirming the structure and relative stereochemistry.12a The abso-
lute configuration of aculeatins A, B and D were established by
Falomir’s group by employing repetitive asymmetric allylations13a
and revealed the interchange in the assigned structures of aculeatins
A and B. This has been further corroborated by the total synthesis of 1
and 2 by several other groups.10,13
The structural similarity present in aculeatins A, B and D–F and
their promising biological activities provide an opportunity to ex-
plore a modular assembly of aculeatins and related derivatives. In
this context, we have recently documented a concise total synthesis
* Corresponding author. Tel.: þ91 20 25902577; fax: þ91 20 25902629.
E-mail address: vr.chepuri@ncl.res.in (C.V. Ramana).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.058

C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
391
of the aculeatin D and its C(6)-epimer.12b Herein we document the
complete details of our work including the synthesis of aculeatins
A, B and the first total synthesis of E and F confirming their absolute
configurations and also report the synthesis of 6-epi-aculeatins E–F.
The synthesis of oxiranes 9 and 10 were planned from the
alkynol 14, which can be accessed from the lactone 15. As part of
our program for 1,3-polyol natural products synthesis, we have
developed a simple six-step protocol for the preparation of 15 from
commercially available
D
-glucoheptonolactone.14 Following the
Yamaguchi protocol,15 the alkyl side chain can be incorporated at
the oxirane end. A Sonogashira coupling16 was opted for the ad-
dition of the phenol unit at the alkyne end. In keeping with our
previous observation, we hypothesized a selective propargylic
–OBn cleavage during the Raney Ni hydrogenolysis of the alkyne
units.17 Oxidation of the released free C(6)–OH should provide the
advanced keto 3,5-diol unit (Scheme 1).
2. Results and discussion
Our retrosynthetic disconnections are outlined in Figure 1. The
constructionof thecentraltricycliccorewasthefinaleventwhichwas
planned through the global deprotection of a differentially protected
keto 3,5-diol unit and subsequent phenol oxidative spiroketalization.
To allow for maximum flexibility, the key disconnection of the acu-
leatins carbon-frame was made at two places resulting in two simple
appending units and an epimeric pair of functionalized building
blocks. Considering the fact that several of the analogs of these two
appending units are commercially available or that one can access
theirfunctionalizedanalogsveryeasily, theadditionswereplannedat
an advanced stage. As given in Figure 2, the diastereomeric alkyne
epoxides 9 and 10 were identified as the central chirons, respectively
for the aculeatins A/B/F (1/2/6) and for the aculeatin D/E (4/5).
The synthesis started with the preparation of the g-lactone 15
following the procedures developed in our laboratory.14 The con-
trolled DIBAL-H reduction of the
g
-lactone 15 in CH2Cl2 at ꢀ78 ꢁC
gave the intermediate lactol in quantitative yields, which upon
alkynylation using the Ohira–Bestmann reagent resulted in the
formation of alkynol 14 in 72% yield.12b,18 To access the oxirane 9
with the central syn,syn-1,3-polyol configuration the configuration
at the C(4) center had to be inverted. The Mitsunobu inverstion of
n-C10H21
n-C7H15
n-C10H21
n-C10H21
HO
n-C12H25
O
O
O
O
HO
O
O
O
OH
O
OH
O
O
O
Aculeatin A (1)
Aculeatin B (2)
Aculeatin D (4)
O
O
OH
n-C10H21
n-C10H21
n-C10H21
n-C10H21
O
O
O
Aculeatin C (3)
HO
O
O
O
HO
O
O
O
OH
OH
O
O
O
O
Aculeatin E (5)
Aculeatin F (6)
6-epi-Aculeatin E (7)
6-epi-Aculeatin F (8)
Figure 1. Natural aculeatins A–F (1–6) and the unnatural 6-epi-aculeatins E (7) and F (8).
alkynol 14 by using DEAD, TPP could be conducted in good yields
by employing the p-nitrobenzoic acid as the nucleophile to afford the
corresponding nitrobenzoate 16.19 Saponification of nitrobenzoate
ester 16 with NaOMe in MeOH secured the required syn,syn-
alkynol 17 having physical data different from that of the starting
alkynol 14 (Scheme 1).
The free hydroxyl group of alkynol 17 was protected as its PMB
ether by employing NaH and PMB-Cl in DMF at ꢀ15 ꢁC. Sub-
sequently, the isopropylidene group of the resulting compound 18
was deprotected by employing PPTS in methanol to afford the diol
19. The primary hydroxyl group of diol 19 was selectively tosylated
by treatment with p-TsCl, catalytic Bu2SnO, DMAP and triethyl-
amine in CH2Cl2 and the resulting tosylate was employed without
any purification for oxirane formation using K2CO3 in methanol to
furnish epoxide 9. The synthesis of the anti,anti-configured oxirane
10 commenced with the PMB protection of free hydroxyl group
present in 14 by using NaH, PMB-Cl in DMF at 0 ꢁC to secure 20. The
isopropylidene group of 20 was hydrolyzed in the presence of PPTS
in methanol and the resulting diol 21 was converted to the corre-
sponding oxirane 10 following the established conditions12b for
selective 1-OH tosylation and the subsequent treatment of the
intermediate tosylate with K2CO3 in methanol (Scheme 1).
We next proceeded for the synthesis of aculeatins A, B and F by
selecting the syn,syn-oxirane 9 as the common starting point
(Scheme 2). The regioselective opening of epoxide 9 with either
Figure 2. Key retrosynthetic disconnections and the modular building blocks.

392
C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
O
OH
i) DIBAl-H
DCM
O
O
O
O
O
OH
DEAD, TPP
NaOMe, MeOH
0 °C, 0.5 h
O
O
O
NO2
O
ii) K2CO3
MeOH, rt, 6 h
O
p-nitrobenzoic acid
THF, 0 °C, 2 h
OBn
O
OBn
14 (72%)
O
O
P
17 (85%)
OMe
OBn
OBn
16 (70%)
OMe
15
N2
OPMB
O
i) TsCl, cat Bu2SnO
Et3N, DMAP, CH2Cl2
OPMB
HO
O
PPTS, MeOH
0 °C - rt, 12 h
NaH, PMB-Cl
HO
9
OBn
0 °C - rt, 1.5 h
DMF, -15 °C, 6 h
OBn
72%
(over 2 steps)
ii) K2CO3, MeOH
0 °C, 0.5 h
18 (93%)
19 (85%)
OPMB
i) TsCl, cat. Bu2SnO
Et3N, DMAP, CH2Cl2
0 °C - rt, 1.5 h
HO
HO
10
OPMB
O
OH
O
O
PPTS, MeOH
0 °C - rt, 12 h
NaH, PMB-Cl
DMF, 0 °C, 4 h
O
82%
OBn
(over 2 steps)
ii) K2CO3, MeOH
0 °C, 0.5 h
OBn
OBn
21 (90%)
14
20 (95%)
Scheme 1. Synthesis of the oxiranes 9 and 10.
TBSO
HO
dodec/dec-1-yne
TBSO
Pd(PPh3)2Cl2
CuI, TPP
TBSO
n-BuLi, BF3-Et2O
n
TBS-Cl, Im, DMF
0 °C - rt, 24 h
n
9
n
THF, -78 °C, 1 h
OBn OPMB
Et3N:DMF (2:1)
rt, 5 h
OBn OPMB
OBn OPMB
22
(n = 9, 90%)
(n = 7, 88%)
24
I
(n = 9, 94%)
(n = 7, 91%)
23
25
26 (n = 9, 85%)
27 (n = 7, 87%)
TBSO
13
H2, Raney-Ni
EtOH, 55 °C, 12 h
rt, 12 h
m
O
m
O
O
+
O
OH
OH
TBSO
TBSO
m
TBSO
TBSO
O
i) DDQ, DCM:H2O
buffer, 0 °C
m
(COCl)2, DMSO
Aculeatin A
Aculeatin B
O
Et3N, DCM,
-78 °C, 30 min
ii) TBAF, THF, 0 °C
iii) PIFA, Acetone:H2O
3 : 1
3 : 1
OH OPMB
O
OPMB
(1, m = 11, 47%)
(2, m = 11, 16%)
28 (m = 11, 83%)
29 (m = 9, 87%)
30 (m = 11, 93%)
31 (m = 9, 95%)
Aculeatin F
6-epi-Aculeatin F
(8, m = 9, 15%)
(6, m = 9, 43%)
Scheme 2. Synthesis of the Aculeatin A (1), B (2), F (6) and 6-epi-F (8).
dodec-1-yne 11 or dec-1-yne 12 was examined under the Yama-
guchi conditions. The successful conditions involved the treatment
of the alkyne (4.5 equiv) with n-BuLi (4.5 equiv) at ꢀ78 ꢁC and then
the addition of BF3$Et2O (4 equiv) followed by the introduction of
the oxirane 9 (1 equiv) after a short interval. Under these condi-
tions, the diynes 22 and 23 were obtained in 90% and 88% yields,
respectively and converted to the corresponding TBS-ethers 24 and
25 by treatment with TBS-Cl/imidazole in DMF. Our next concern
was the extension of the alkyne end in 24 and 25 through the
Sonogashira coupling with a p-iodophenol derivative. Keeping our
experience with the synthesis of aculeatin D in mind, we have
employed the TBS protected p-iodophenol 13, as it gave better
yields in coupling reactions and also as phenol protection is es-
sential for the selective propargylic debenzylation during the
hydrogenolysis of the alkyne units. Thus the Sonogashira coupling
of 24 or 25 with 13 was best effected by a thorough degassing of the
reaction mixture prior to the addition of CuI and gave the coupled
products 26 (85%) and 27 (87%). After this extension at both the
ends, the remaining exercise is the synthesis of advanced keto 3,5-
diols 30 and 31 and their one pot sequential TBS and PMB ethers
deprotection followed by key phenol oxidative spiroketalization, to
complete the synthesis of aculeatins A and F and their spiro-epi-
mers aculeatin B and 6-epi-aculeatin F, the latter being unnatural.
To this end, the hydrogenolysis of both the alkyne groups and se-
lective debenzylation of compounds 26 and 27 was carried out by
using Raney Ni/H2 (20 psi) at 55 ꢁC in good yields.17 The free C(6)–
OH of the resulting products 28 and 29 was oxidized under Swern
conditions (oxalyl chloride, DMSO and Et3N in DCM at ꢀ78 ꢁC) to
afford the protected keto 3,5-diols 30 and 31.
After having the well functionalized 30 and 31 in hand, our next
concern was their global deprotection and subsequent oxidative
phenol cyclization to complete the total synthesis of aculeatins A, B
and F. Our optimized conditions involving a sequential depro-
tection of PMB ether by employing DDQ (CH2Cl2, pH 7.0 phosphate

C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
393
buffer, 0 ꢁC) followed by TBS-ether deprotection using TBAF (THF at
3. Conclusion
0 ꢁC) produced the completely deprotected keto 3,5-diol which,
upon the oxidative spiroketalization using PIFA (10:1, v/v aceto-
ne:water, rt, under dark) afforded the corresponding epimeric
aculeatins mixture. Thus, following this protocol, aculeatins A and B
(3:1) were prepared in 63% overall yield from the keto 3,5-diol 30.
Our scale-up syntheses involve proceeding with the alcohol via
oxidation, two sequential deprotections and oxidative cyclization
without the purification of any of the intermediates and isolation of
the corresponding natural products without any compromise on
the final yields. The spectral and the analytical data of 1 and 2 were
in good agreement with data reported for natural aculeatins A and
B (Tables 1 and 2, Electronic Supplementary data). Similarly, the
keto 3,5-diol 31, upon one pot sequential deprotections and oxi-
dative phenol cyclization, afforded a 3:1 mixture of aculeatin F (6)
and its C(6)-epimer 8. The spectral data of 6 was in agreement with
A flexible approach for the total synthesis of aculeatins has
been documented. Central to the success of our approach is a dual-
end disconnection of the aculeatins core leading to three segments
in which the two terminal segments are easily available and are
amicable toward alterations for the synthesis of aculeatin like
small molecule libraries. The middle fragment that forms the key
bicyclic spirocyclic core present in the aculeatins has been sim-
plified to differentially protected syn,syn or anti,anti-1,3,5-triol
units having an oxirane and an alkyne as the terminal functional
units to couple the remaining two fragments at an advanced stage.
The key 1,3,5-anti,anti-triol lactone 15 was derived from com-
mercially available
D-glucoheptono-g-lactone which was trans-
formed to the two key diastereomeric coupling units 9 and 10 by
simple synthetic transformations. We hypothesized a selective
propargylic –OBn cleavage during the Raney Ni hydrogenolysis of
the alkyne units which could be executed by protecting the phenol
oxygen as its TBS-ether. After verifying the viability of this con-
vergent strategy taking the total synthesis of the aculeatin D,
in this paper we documented the flexibility of our approach to
synthesize the natural aculeatins A, B, E, and F along with the
unnatural 6-epi-aculeatins E and F.
the data reported for the natural aculeatin F (Table 1, Supplemen-
25
tary data) and the specific rotation measured ([
a
]
D
¼ꢀ4.7 (c 2.0,
23
CHCl3), natural aculeatin F lit.9b
[
a
]
D
¼ꢀ5.3 (c 0.9, CHCl3)) con-
firmed its assigned absolute configuration. The stereochemical
outcome of these oxidative cyclizations is in accordance with the
observations of Wong and co-workers.13b In general shorter re-
action times allowed the isolation of reasonable amounts of less
stable b-anomer (aculeatin B/6-epi-aculeatin F). Earlier, Marco co-
workers have reported the isolation of a 5.5:1 ratio of aculeatins
A:B, when the reaction was prolonged for 24 h.13a Even it has been
noticed that on standing, aculeatin B slowly converts to more stable
aculeatin A.10b
4. Experimental
4.1. General methods
Next, we focused on the synthesis of truncated analog aculeatin
Air and/or moisture sensitive reactions were carried out in an-
hydrous solvents under an atmosphere of argon in oven-dried
E (5) from the oxirane 10 (Scheme 3).12b The opening of the oxirane
HO
dec-1-yne, n-BuLi
TBSO
TBSO
Pd(PPh3)2Cl2
CuI, TPP
BF3-Et2O, THF
TBSO
7
TBS-Cl, Im, DMF
0 °C - rt, 24 h
7
10
-78 °C, 1 h
7
Et3N:DMF (2:1)
rt, 5 h
OBn OPMB
OBn OPMB
33,
OBn OPMB
32
, 91%
I
92%
34, 90%
TBSO
13
H2, Raney-Ni
EtOH, 55 °C 12 h
rt, 12 h
9
9
O
O
HO
HO
O
+
TBSO
(COCl)2, DMSO
TBSO
TBSO
TBSO
i) DDQ, DCM:H2O,
buffer, 0 °C
O
9
9
O
Et3N, DCM,
-78 °C, 95%
ii) TBAF, THF, 0 °C
iii) PIFA, Acetone:H2O
1 : 1
OH OPMB
O
OPMB
36, 93%
Scheme 3. Synthesis of the E (5) and 6-epi-E (7).
Aculeatin E
6-epi-Aculeatin E
(7, 30%)
O
(5, 30%)
35
, 84%
10 with dec-1-yne, gave 32. The free C(5)-OH in 32 was protected as
TBS-ether and then subjected to the Sonogashira coupling with 13
to afford the diynes 34. Subsequently, the diynes 34 was advanced
to the key ketone 1,5-diols 36, by hydrogenolysis with Raney Ni/H2
proceeding via a Swern oxidation. The final stage of the synthesis
are sequential deprotection of the TBS and PMB ethers of 36 and
oxidative phenol cyclization of the intermediate ketodiols, pro-
viding the aculeatin E (5), along with its spiroepimer 7. The natural
product and its epimer were obtained in almost equal ratio, which
is similar to the Wong and co-workers observation with related
aculeatin D synthesis.13b The comparison of the 1H and 13C NMR
spectra with the natural aculeatines D and E (Table 3, Supple-
mentary data) established their structure and the observed similar
glassware. All anhydrous solvents were distilled prior to use: THF
from Na and benzophenone; CH2Cl2 from CaH2; MeOH from Mg
cake. Commercial reagents were used without purification. Column
chromatography was carried out by using Spectrochem silica gel
(100–200 mesh). Optical rotations were determined on a Jasco DIP-
370 digital polarimeter. Specific optical rotations [a] are given in
D
10ꢀ1ꢂdegꢂcm2ꢂgꢀ1. 1H and 13C NMR spectroscopy measurements
were carried out on Bruker AC 200 MHz or Bruker DRX 400 MHz
spectrometers, and TMS was used as internal standard. 1H and 13
C
NMR chemical shifts are reported in ppm downfield from tetra-
methylsilane and coupling constants (J) are reported in Hertz (Hz).
The following abbreviations are used to designate signal multi-
plicity: s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet,
br¼broad. The Multiplicity of 13C NMR signals was assigned with
the help of DEPT spectra and the abbreviations used: s¼singlet
d¼doublet t¼triplet q¼quartet, represent C (quaternary), CH, CH2
specific rotation of the synthetic aculeatin E values confirmed its
25
assigned absolute configuration ([
a
]
¼þ47.7 (c 1, CHCl3); lit.9b
D
23
[
a]
¼þ46.5 (c 1, CHCl3)).
D

394
C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
and CH3, respectively. Mass spectroscopy was carried out on an API
QStar Pulsar (Hybrid Quadrupole-TOF LC/MS/MS) spectrometer.
Elemental analysis data were obtained on a Thermo Finnigan Flash
EA 1112 Series CHNS Analyzer.
reaction mixture was quenched by adding satd Na2SO4, poured into
water and extracted with ethyl acetate. The combined organic
phases were washed with water, brine, dried (Na2SO4) and con-
centrated. Purification of the crude by column chromatography
(15% ethyl acetate in petroleum ether) gave the PMB-derivative 18
4.2. (2S,4S,6R)-1,2-O-isopropylidene-4-O-(4-nitrobenzoyl)-6-
O-benzyl-oct-7-yne-1,2,4,6-tetraol (16)
(634 mg, 93%) as colorless oil. Rf¼0.4 (Petether/EtOAc 7:3),
25
[a
]
¼þ30.4 (c 1.0, CHCl3). IR (CHCl3):
n 3305, 3012, 2932, 2870,
D
2115,1720, 1612,1586,1513,1455,1380,1370,1302,1248,1216,1173,
1158, 1086, 1059, 823, 756, 699, 667 cmꢀ1 1H NMR (400 MHz,
CDCl3):
To a solution of alcohol 1412b (500 mg, 1.64 mmol) in dry THF
(5 mL), TPP (517 mg, 1.97 mmol) and DEAD (343 mg, 1.97 mmol)
were added at 0 ꢁC and stirred for 15 min, followed by p-nitro-
benzoic acid (330 mg,1.97 mmol). After stirring for additional 2 h at
0 ꢁC, the reaction mixture was quenched by adding satd NaHCO3,
poured into water and extracted with ethyl acetate. The combined
organic phases were washed with water, brine, dried over (Na2SO4)
and concentrated. Purification of the crude by column chromatog-
.
d
7.34–7.27 (m, 5H), 7.19 (d, J¼8.5 Hz, 2H), 6.84 (d, J¼8.5 Hz,
2H), 4.79 (d, J¼11.5 Hz, 1H), 4.47 (d, J¼11.5 Hz, 1H), 4.41 (br s, 2H),
4.31 (dt, J¼7.3, 1.8 Hz, 1H), 4.18 (q, J¼7.0 Hz, 1H), 3.91 (dd, J¼7.8,
5.9 Hz, 1H), 3.79 (s, 3H), 3.76 (m, 1H), 3.43 (t, J¼7.8 Hz, 1H), 2.50 (d,
J¼1.9 Hz, 1H), 2.18 (dt, J¼13.9, 7.2 Hz, 1H), 1.98–1.90 (m, 2H), 1.73
(dt, J¼13.4, 6.0 Hz, 1H), 1.38 (s, 3H), 1.32 (s, 3H). 13C NMR (100 MHz,
CDCl3):
d 25.7 (q), 26.9 (q), 37.5 (t), 40.1 (t), 55.2 (q), 66.0 (d), 69.6
raphy (13% ethyl acetate in petroleum ether) gave the 16 (520 mg,
(t), 70.7 (t, 2C), 72.8 (d), 73.0 (d), 74.5 (d), 82.5 (s), 108.5 (s), 113.7 (d,
2C), 127.7 (d), 128.1 (d, 2C), 128.4 (d, 2C), 129.4 (d, 2C), 130.4 (s),
137.6 (s), 137.6 (s), 159.2 (s) ppm. ESI-MS: m/z 463.2 (21%, [MþK]þ),
447.3 (100%, [MþNa]þ), 425.3 (8%, [MþH]þ). Anal. Calcd for
C26H32O5: C, 73.56; H, 7.60. Found: C, 73.45; H, 7.55.
25
70%) as colorless oil. Rf¼0.50 (Petether/EtOAc 7:3), [
CHCl3). IR (CHCl3):
1274,1102, 872, 839, 752, 699, 666 cmꢀ1.1H NMR (400 MHz, CDCl3):
a
]
¼þ23.9 (c 1,
D
n
3291, 2931, 2852, 2110, 1724, 1528, 1455, 1350,
d
8.22 (dt, J¼8.8, 2.0 Hz, 2H), 8.09 (dt, J¼8.8, 2.0 Hz, 2H), 7.30–7.26
(m, 5H), 5.57–5.51 (m,1H), 4.80 (d, J¼11.6 Hz,1H), 4.42 (d, J¼11.6 Hz,
1H), 4.26 (ddd, J¼8.5, 6.5, 2.0 Hz, 1H), 4.19 (ddd, J¼12.8, 6.5, 5.8 Hz,
1H), 4.05 (dd, J¼8.1, 5.8 Hz, 1H), 3.53 (t, J¼7.7 Hz, 1H), 2.50 (d,
J¼2.0 Hz, 1H), 2.36 (ddd, J¼14.4, 8.1, 7.0 Hz, 1H), 2.17 (ddd, J¼14.4,
6.3, 4.6 Hz, 1H), 2.06 (dt, J¼14.5, 7.3 Hz, 1H), 1.92 (dt, J¼14.5, 5.8 Hz,
4.5. (2S,4S,6R)-4-O-benzyl-6-O-(4-methoxybenzyl)-oct-7-yne-
1,2,4,6-tetraol (19)
A solution of PMB-derivative 18 (500 mg, 1.17 mmol) in meth-
anol (20 mL) was cooled to 0 ꢁC, PPTS (44 mg, 0.17 mmol) was
added in portions, and the reaction mixture was warmed to rt,
stirred for 12 h. After completion of the reaction as indicated by
TLC, the reaction mixture was concentrated under reduced pres-
sure, dissolved in ethyl acetate, washed with water, brine, dried
(Na2SO4) and concentrated. The residue obtained was purified by
column chromatography (60% ethyl acetate in petroleum ether) to
1H), 1.34 (s, 3H), 1.27 (s, 3H). 13C NMR (100 MHz, CDCl3):
d 25.5 (q),
26.8 (q), 37.9 (t), 39.8 (t), 65.6 (d), 69.3 (t), 70.6 (t), 70.9 (d), 72.7 (d),
74.9 (d), 81.5 (s),109.0 (s), 123.3 (d, 2C),127.7 (d),128.0 (d, 2C),128.2
(d, 2C), 130.6 (d, 2C), 135.7 (s), 137.2 (s), 150.3 (s), 164.0 (s) ppm. ESI-
MS: m/z 476.1 (100%, [MþNa]þ), 492.1(28%, [MþK]þ), 454.2 (14%,
[Mþ1]þ). Anal. Calcd for C25H27NO7: C, 66.21; H, 6.00, N; 3.09.
Found: C, 65.81; H, 5.94, N; 3.2.
afford the diol 19 (380 mg, 85%) as colorless oil. Rf¼0.30 (Petether/
25
4.3. (2S,4S,6R)-1,2-O-isopropylidene-6-O-benzyl-oct-7-yne-
1,2,4,6-tetraol (17)
EtOAc 2:3), [
a]
¼–16.0 (c 1, CHCl3). IR (CHCl3):
n 3423, 3291, 2919,
D
2850, 2112, 1717, 1612, 1514, 1463, 1451, 1305, 1249, 1069, 1028, 822,
752, 699, 665 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
7.36–7.28 (m, 5H),
A solution of benzoate 16 (300 mg, 0.66 mmol) and NaOMe
(35 mg, 0.66 mmol) in MeOH (5 mL) was stirred at 0 ꢁC for 0.5 h.
Several drops of CH3COOH were added to the reaction mixture to
adjust the pH to 7. The solution was diluted with water (20 mL) and
extracted with ethyl acetate. The organic layer was dried over
Na2SO4, filtered and evaporated. Purification of the crude by col-
umn chromatography (20% ethyl acetate in petroleum ether) yiel-
7.20 (d, J¼8.5 Hz, 2H), 6.85 (d, J¼8.5 Hz, 2H), 4.80 (d, J¼11.7 Hz, 1H),
4.53 (d, J¼10.9 Hz, 1H), 4.47 (d, J¼11.7 Hz, 1H), 4.39 (d, J¼10.9 Hz,
1H), 4.21 (dt, J¼7.4, 1.8 Hz, 1H), 3.91 (br s, 1H), 3.78–3.77 (m, 4H),
3.55 (br s, 1H), 3.49 (dd, J¼11.0, 2.5 Hz, 1H), 3.35 (dd, J¼11.0, 6.4 Hz,
1H), 2.53 (s, 1H), 2.40 (br s, 1H), 2.24 (ddd, J¼14.0, 7.4, 5.4 Hz, 1H),
1.92 (dd, J¼14.0, 6.1 Hz, 1H), 1.68 (dt, J¼14.6, 8.9 Hz, 1H), 1.55 (dt,
J¼14.5, 3.0 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d 37.3 (t), 39.9 (t),
ded the alcohol 17 (171 mg, 85%) as colorless oil. Rf¼0.50 (Petether/
55.2 (q), 65.3 (d), 66.7 (t), 70.6 (t, 2C), 71.0 (d), 74.5 (d), 75.5 (d), 82.3
(s), 113.9 (d, 2C), 127.9 (d), 128.2 (d, 2C), 128.4 (d, 2C), 129.6 (d, 2C),
129.7 (s), 137.3 (s), 159.3 (s) ppm. ESI-MS: m/z 423.4 (28%, [MþK]þ),
407.4 (100%, [MþNa]þ), 402.5 (14%, [Mþ18]þ) 385.4 (7%, [Mþ1]þ).
Anal. Calcd for C23H28O5: C, 71.85; H, 7.34. Found: C, 71.96; H, 7.26.
25
EtOAc 1:1), [
a
]
D
¼–8.7 (c 2, CHCl3). IR (CHCl3):
n 3486, 3308, 2923,
2852, 2110,1730,1463,1378,1215,1157,1071, 760, 698, 666 cmꢀ1. 1H
NMR (400 MHz, CDCl3):
d
7.35–7.28 (m, 5H), 4.83 (d, J¼11.6 Hz, 1H),
4.51 (d, J¼11.6 Hz, 1H), 4.36 (dt, J¼7.1, 1.9 Hz, 1H), 4.30–4.24 (m, 1H),
4.08 (dd, J¼8.1, 6.0 Hz, 2H), 3.54 (t, J¼7.7 Hz, 1H), 3.42 (s, 1H), 2.53
(d, J¼2.0 Hz, 1H), 2.05 (ddd, J¼13.8, 9.0, 7.3 Hz, 1H), 1.86 (ddd,
J¼13.8, 6.5, 3.2 Hz, 1H), 1.77–1.65 (m, 2H), 1.41 (s, 3H), 1.36 (s, 3H).
4.6. (S)-2-((2S,4R)-4-(Benzyloxy)-2-(4-methoxy-benzyloxy)-
hex-5-ynyl)oxirane (9)
13C NMR (100 MHz, CDCl3):
d 25.7 (q), 26.8 (q), 40.4 (t), 42.7 (t), 67.1
(d), 68.4 (d), 69.6 (t), 70.8 (t), 74.5 (d), 75.0 (d), 82.1 (s), 109.2 (s),
127.9 (d), 128.1 (d, 2C), 128.5 (d, 2C), 137.3 (s) ppm. ESI-MS: m/z
327.1 (100%, [MþNa]þ), 343.1(19%, [MþK]þ), 305.2 (4%, [Mþ1]þ),
277.1 (15%, [Mþ1–H2O]þ). Anal. Calcd for C18H24O4: C, 71.03; H,
7.95. Found: C, 70.85; H, 7.94.
To a solution of diol 19 (600 mg, 1.56 mmol) in dry CH2Cl2
(15 mL) were added Bu2SnO (7 mg) and p-TsCl (327 mg, 1.71 mmol)
followed by triethylamine (435 mL, 3.12 mmol) and DMAP (20 mg)
at 0 ꢁC. The reaction mixture was slowly warmed to rt and stirred
for 1.5 h. The reaction mixture was diluted with CH2Cl2 and
extracted. The combined organic phases were washed with water
and brine, dried over (Na2SO4), and concentrated. The crude tosy-
late (840 mg) was dissolved in methanol (20 mL) and stirred with
anhydrous K2CO3 (270 mg) for 30 min at 0 ꢁC and concentrated. The
crude was dissolved in ethyl acetate, washed with water, brine,
dried (Na2SO4), and concentrated. Purification of the crude by
column chromatography (18% ethyl acetate in petroleum ether)
gave the epoxide 9 (410 mg, 72% for two steps) as a colorless oil.
4.4. (2S,4S,6R)-1,2-O-isopropylidene-4-O-benzyl-6-O-(4-
methoxybenzyl)-oct-7-yne-1,2,4,6-tetraol (18)
To a solution of alcohol 17 (500 mg, 1.64 mmol) in dry DMF
(2 mL), NaH (78 mg, 1.97 mmol) was added portion-wise at ꢀ15 ꢁC
and stirred for 15 min, followed by p-methoxybenzyl chloride
(0.28 mL, 1.97 mmol). After stirring for additional 6 h at ꢀ15 ꢁC, the

C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
395
25
Rf¼0.50 (Petether/EtOAc 1:1), [
3304, 3010, 2923, 2110, 1720, 1612, 1586, 1514, 1248, 1070, 822, 757,
698, 667 cmꢀ1. 1H NMR (400 MHz, CDCl3):
7.35–7.28 (m, 5H), 7.21
a
]
¼–13.2 (c 1, CHCl3). IR (CHCl3):
n
2.12 (tt, J¼7.2, 2.3 Hz, 2H), 1.96 (dt, J¼14.0, 6.2 Hz, 1H), 1.81 (ddd,
J¼14.5, 4.7, 3.2 Hz, 1H), 1.73 (dt, J¼14.5, 8.8 Hz, 1H), 1.46 (br dt,
Jz14.5, 6.9 Hz, 2H), 1.37–1.31 (m, 3H), 1.26 (br s, 7H), 0.88 (t,
D
d
(d, J¼8.5 Hz, 2H), 6.85 (d, J¼8.5 Hz, 2H), 4.80 (d, J¼11.5 Hz, 1H), 4.48
(d, J¼10.9 Hz, 1H), 4.47 (d, J¼10.8 Hz, 1H), 4.42 (d, J¼10.9 Hz, 1H),
4.33 (ddd, J¼8.3, 6.5, 2.0 Hz, 1H), 3.87 (ddd, J¼10.5, 8.3, 5.5 Hz, 1H),
3.80 (s, 3H), 3.03–2.99 (m, 1H), 2.72 (br t, Jz4.7 Hz, 1H), 2.50 (d,
J¼1.8 Hz, 1H), 2.42 (dd, J¼4.9, 2.5 Hz, 1H), 2.22 (ddd, J¼14.2, 8.3,
6.3 Hz, 1H), 1.98 (ddd, J¼13.2, 8.2, 4.7 Hz, 1H), 1.77 (t, J¼5.5 Hz, 2H).
J¼6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d 14.1 (q),18.8 (t), 22.6 (t),
27.8 (t), 28.9 (t), 29.0 (t), 29.1 (t), 29.2 (t), 31.8 (t), 40.1 (t), 40.2 (t),
55.2 (q), 65.7 (d), 69.4 (d), 70.7 (t), 70.7 (t), 74.4 (d), 75.5 (d), 76.1 (s),
82.4 (s), 82.8 (s), 113.9 (d, 2C), 127.8 (d), 128.1 (d, 2C), 128.4 (d, 2C),
129.6 (d, 2C), 129.9 (s), 137.5 (s), 159.3 (s) ppm. ESI-MS: m/z 527.6
(100%, [MþNa]þ), 543.6 (37%, [MþK]þ), 505.7(8%, [Mþ1]þ). Anal.
Calcd for C33H44O4: C, 78.53; H, 8.79. Found: C, 78.80; H, 9.04.
13C NMR (100 MHz, CDCl3):
d 36.9 (t), 40.4 (t), 46.8 (t), 49.2 (d), 55.3
(q), 66.1 (d), 70.7 (t), 70.9 (t), 73.7 (d), 74.5 (d), 82.5 (s), 113.8 (d, 2C),
127.8 (d), 128.1 (d, 2C),128.4 (d, 2C),129.4 (d, 2C), 130.4 (s), 137.6 (s),
159.2 (s) ppm. ESI-MS: m/z 405.3 (28%, [MþK]þ), 389.3 (100%,
[MþNa]þ), 384.3 (14%þ). Anal. Calcd for C23H26O4: C, 75.38; H, 7.15.
Found: C, 75.30; H, 7.28.
4.9. ((3R,5S,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-
oxy)icosa-1,9-diyn-7-yloxy)(tert-butyl)-dimethylsilane (24)
A solution of alcohol 22 (1 g, 1.87 mmol) in dry DMF (4 mL) was
cooled to 0 ꢁC, imidazole (766 mg, 11.26 mmol) followed by TBS-Cl
(848 mg, 5.63 mmol) were added and stirring was continued at rt
for 24 h. The reaction mixture was partitioned between ethyl ace-
tate and water, organic layer was separated and aqueous layer was
extracted with ethyl acetate. Combined organic layer was washed
with brine, dried (Na2SO4), filtered and concentrated under reduced
pressure. Purification of the crude product by column chromatog-
raphy (10% ethyl acetate in petroleum ether) afforded TBS-de-
4.7. (3R,5R,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-oxy)icosa-
1,9-diyn-7-ol (22)
Dodec-1-yne (816 mg, 4.91 mmol) was taken in a flame-dried
two-necked round-bottom flask (50 mL) and dissolved in anhy-
drous THF (15 mL). The reaction mixture was cooled to ꢀ78 ꢁC,
treated with n-BuLi (2.1 mL, 4.91 mmol, 2.34 M in hexane) drop
wise and stirred for 15 min, to this BF3$Et2O (0.55 mL, 4.36 mmol)
was added and stirring was continued for an additional 15 min. A
solution of epoxide 9 (400 g, 1.09 mmol) in anhydrous THF (10 mL)
was added and stirred for 30 min at ꢀ78 ꢁC. The reaction mixture
was quenched at ꢀ78 ꢁC by addition of satd Na2SO4 (20 mL), diluted
with ethyl acetate and water. The aqueous phase was extracted with
ethyl acetate and the combined organic phases were washed with
brine, dried (Na2SO4) and concentrated. Purification of the crude
residue by column chromatography (20% ethyl acetate in petroleum
rivative 24 (1.14 g, 94%) as colorless oil. Rf¼0.45 (Petether/EtOAc
25
4:1), [
a
]
¼þ11.0 (c 2, CHCl3). IR (CHCl3):
n 3308, 2926, 2855, 2110,
D
1614,1514,1463,1249,1095, 836, 776, 697 cmꢀ1. 1H NMR (400 MHz,
CDCl3):
d
7.35–7.28 (m, 5H), 7.19 (d, J¼8.7 Hz, 2H), 6.83 (d, J¼8.7 Hz,
2H), 4.80 (d, J¼11.5 Hz, 1H), 4.49 (d, J¼11.5 Hz, 1H), 4.48 (d,
J¼10.8 Hz, 1H), 4.39 (br ddd, J¼8.7, 5.9, 2.0 Hz, 1H), 4.35 (d,
J¼10.8 Hz,1H), 3.84–3.81 (m, 2H), 3.80 (s, 3H), 2.47 (d, J¼2.0 Hz,1H),
2.29–2.27 (m, 2H), 2.13–2.10 (m, 2H), 2.04 (br s, 1H), 1.58 (br s, 1H),
1.49–1.42 (m, 3H), 1.27–1.25 (m, 15H), 0.89 (s, 9H), 0.87 (t, J¼4.0 Hz,
ether) afforded 22 (512 mg, 90%) as colorless oil. Rf¼0.40 (Petether/
25
EtOAc 3:2), [
a]
¼ꢀ19.8 (c 1.0, CHCl3). IR (CHCl3):
n 3469, 3308,
D
3H), 0.08 (s, 6H).13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (q), ꢀ4.3 (q),14.1
2922, 2851, 2111, 1738, 1612, 1588, 1514, 1463, 1248, 1089, 1031, 823,
(q), 14.2 (q), 18.0 (s), 18.8 (t), 22.7 (t), 25.9 (q, 2C), 28.1 (t), 28.9 (t),
29.0 (t), 29.2 (t), 29.3 (t), 29.5 (t), 29.6 (t), 31.9 (t), 40.8 (t), 41.3 (t),
55.3 (q), 66.5 (d), 68.7 (d), 70.6 (t), 70.7 (t), 73.1 (d), 74.5 (d), 76.9 (s),
82.4 (s), 82.8 (s), 113.7 (d, 2C), 127.7 (d), 128.1 (d, 2C), 128.4 (d, 2C),
129.4 (d, 2C), 130.8 (s), 137.8 (s), 159.1 (s) ppm. ESI-MS: m/z 669.7
(100%, [MþNa]þ), 685 (29%, [MþK]þ), 647.7 (26%, [Mþ1]þ). Anal.
Calcd for C41H62O4Si: C, 76.11; H, 9.66. Found: C, 76.32; H, 9.85.
665 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
7.35–7.28 (m, 5H), 7.20 (d,
J¼8.6 Hz, 2H), 6.84 (d, J¼8.6 Hz, 2H), 4.81 (d, J¼11.6 Hz, 1H), 4.50 (d,
J¼11.6 Hz, 1H), 4.50 (d, J¼10.8 Hz, 1H), 4.41 (d, J¼10.8 Hz, 1H), 4.26
(br ddd, 7.3, 6.3, 1.9 Hz, 1H), 3.94–3.88 (m, 1H), 3.83–3.81 (m, 1H),
3.78 (s, 3H), 3.19 (br s, 1H), 2.51 (d, J¼2.0 Hz, 1H), 2.29–2.26 (m, 2H),
2.22 (ddd, J¼14.1, 7.2, 5.9 Hz,1H), 2.14–2.09 (m, 2H),1.96 (dt, J¼14.0,
6.2 Hz, 1H), 1.82 (ddd, J¼14.4, 4.5, 3.2 Hz, 1H), 1.73 (br dt, J¼14.6,
8.5 Hz,1H),1.46 (br dt, J¼14.6, 7.2 Hz, 2H),1.35–1.25 (br s, 14H), 0.88
(t, J¼7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d 14.1 (q), 18.7 (t), 22.6
(t), 27.8 (t), 28.9 (t), 29.0 (t), 29.1 (t), 29.3 (t), 29.5 (t), 29.6 (t), 31.9 (t),
40.1 (t), 40.2 (t), 55.2 (q), 65.7 (d), 69.3 (d), 70.6 (t), 70.7 (t), 74.4 (d),
75.5 (d), 76.1 (s), 82.4 (s), 82.8 (s), 113.9 (d, 2C), 127.8 (d), 128.0 (d,
2C),128.4 (d, 2C),129.6 (d, 2C),129.9 (s),137.5 (s),159.3 (s) ppm. ESI-
MS: m/z 571.6 (26%, [MþK]þ), 555.6 (100%, [MþNa]þ), 533.6 (7%,
[Mþ1]þ). Anal. Calcd for C35H48O4: C, 78.91; H, 9.08; Found: C,
78.67; H, 9.22.
4.10. ((3R,5S,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-
oxy)octadeca-1,9-diyn-7-yloxy)(tert-butyl)-dimethylsilane (25)
The same procedure as in the preparation of 24 was used with
the alcohol 23 (500 mg, 1.0 mmol) affording TBS-derivative 25
(554 mg, 91%) as colorless oil. Rf¼0.50 (Petether/EtOAc 4:1),
25
[a
]
¼þ53.6 (c 1, CHCl3). IR (CHCl3):
n 3308, 2929, 2856, 2110, 1613,
D
1514, 1463, 1361, 1248, 1091, 1039, 835, 775, 697 cmꢀ1
.
1H NMR
4.8. (3R,5R,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-
oxy)octadeca-1,9-diyn-7-ol (23)
(400 MHz, CDCl3):
d
7.35–7.29 (m, 5H), 7.20 (d, J¼8.5 Hz, 2H), 6.84
(d, J¼8.5 Hz, 2H), 4.80 (d, J¼11.5 Hz,1H), 4.49 (d, J¼11.5 Hz,1H), 4.48
(d, J¼10.9 Hz, 1H), 4.41–4.37 (m, 1H), 4.35 (d, J¼10.9 Hz, 1H), 3.86–
3.82 (m, 1H), 3.80 (s, 3H), 2.46 (d, J¼1.9 Hz, 1H), 2.28 (dd, J¼4.7,
2.2 Hz, 2H), 2.12 (tt, J¼7.0, 2.4 Hz, 2H), 2.06–1.90 (m, 3H), 1.85–1.78
(m, 1H), 1.49–1.42 (m, 2H), 1.37–1.33 (m, 3H), 1.26 (s, 8H), 0.89 (s,
9H), 0.87 (t, J¼4.0 Hz, 3H), 0.08 (s, 6H). 13C NMR (100 MHz, CDCl3):
The similar procedure as in the preparation of 22 was used to
open epoxide 9 (400 mg, 1.09 mmol) with the dec-1-yne (680 mg,
4.91 mmol) affording 23 (484 mg, 88%) as colorless oil. Rf¼0.45
25
(Petether/EtOAc 3:2) [
a]
¼–101.4 (c 1.6, CHCl3). IR (CHCl3):
n 3439,
D
3152, 2917, 2857, 2111, 1613, 1403, 1216, 1085, 1039, 757, 669 cmꢀ1
.
d
ꢀ4.5 (q), ꢀ4.2 (q), 14.1 (q), 18.0 (s), 18.8 (t), 22.6 (t), 25.9 (q, 3C),
1H NMR (400 MHz, CDCl3):
d
7.35–7.28 (m, 5H), 7.20 (d, J¼8.6 Hz,
28.1 (t), 28.9 (t), 29.0 (t), 29.1 (t), 29.2 (t), 29.7 (t), 31.9 (t), 40.8 (t),
41.3 (t), 55.3 (q), 66.5 (d), 68.6 (d), 70.6 (t), 70.8 (t), 73.1 (d), 74.6 (s),
82.4 (s), 82.7 (s), 113.7 (d, 2C), 127.7 (d), 128.1 (d, 2C), 128.4 (d, 2C),
129.4 (d, 2C), 130.7 (s), 137.8 (s), 159.1 (s) ppm. ESI-MS: m/z 641.9
(100%, [MþNa]þ), 657.9(66%, [MþK]þ), 619.9 (25%, [Mþ1]þ). Anal.
Calcd for C39H58O4Si: C, 75.68; H, 9.44. Found: C, 75.52; H, 9.51.
2H), 6.84 (d, J¼8.6 Hz, 2H), 4.82 (d, J¼11.6 Hz, 1H), 4.51 (d,
J¼11.0 Hz, 1H), 4.48 (d, J¼11.6 Hz, 1H), 4.42 (d, J¼10.7 Hz, 1H), 4.26
(dd, J¼6.3, 2.0 Hz 1H), 3.87 (ddd, J¼14.0, 10.8, 5.8 Hz, 1H), 3.85–3.81
(m, 1H), 3.80 (s, 3H), 3.21 (d, J¼2.5 Hz, 1H), 2.52 (d, J¼2.0 Hz, 1H),
2.28 (ddd, J¼8.0, 4.7, 2.0 Hz, 2H), 2.23 (ddd, J¼13.9, 7.2, 5.9 Hz, 1H),

396
C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
4.11. ((3R,5S,7R)-3-(Benzyloxy)-1-(4-(tert-butyl-dimethyl-
silyloxy)phenyl)-5-(4-methoxy-benzyloxy)icosa-1,9-diyn-
7-yloxy)(tert-butyl)dimethylsilane (26)
gas and stirred under hydrogen (20 psi) atmosphere at 55 ꢁC for
12 h and then stirred at rt for 12 h. The reaction mixture was fil-
tered through a plug of filter aid, washed with ethyl acetate thor-
oughly (3ꢂ20 mL), and concentrated. Purification of crude product
by column chromatography (10% ethyl acetate in petroleum ether)
To a solution of alkyne 24 (300 mg, 0.46 mmol), TBS-iodophenol
13 (310 mg, (0.)93 mmol) in Et3N (8 mL) and DMF (4 mL), TPP
(12 mg, 0.046 mmol) and Pd(PPh3)2Cl2 (32 mg, 0.046 mmol), were
added and degassed with argon for 30 min. CuI (9 mg, 0.046 mmol)
was added and degassed with argon for 10 min and stirred at rt for
5 h. The reaction mixture was partitioned between ethyl acetate
and water. Organic layer was separated, washed with brine, dried
(Na2SO4), concentrated and the residue obtained was purified by
column chromatography (5%/10% ethyl acetate in petroleum
yielded hydrogenated product 28 (100 mg, 83%) as a colorless oil.
25
Rf¼0.45 (Petether/EtOAc 8:2), [
a
]
¼ꢀ5.1 (c 1, CHCl3). IR (CHCl3):
n
D
3480, 2855, 1611, 1510, 1252, 1039, 836, 758, 692 cmꢀ1
.
1H NMR
7.29 (d, Jz8.5 Hz, 2H), 7.06 (d, J¼8.3 Hz, 2H),
(400 MHz, CDCl3):
d
6.89 (d, J¼8.5 Hz, 2H), 6.76 (d, J¼8.3 Hz, 2H), 4.59 (d, J¼10.9 Hz, 1H),
4.36 (d, J¼10.9 Hz, 1H), 3.84 (br s, 1H), 3.82 (s, 3H), 3.80–3.76 (m,
1H), 3.72–3.66 (m, 1H), 2.71 (ddd, J¼13.8, 10.2, 5.5 Hz, 1H), 2.60
(ddd, J¼13.8, 10.0, 6.5 Hz, 1H), 1.94 (ddd, J¼13.8, 8.2, 3.5 Hz, 1H),
1.78–1.74 (m, 2H), 1.68–1.63 (m, 5H), 1.51–1.41 (m, 3H), 1.25 (br s,
20H), 0.96 (s, 9H), 0.87 (s, 12H), 0.170 (s, 6H), 0.03 (s, 3H), 0.01 (s,
ether) to afford 26 (340 mg, 85%) as colorless oil. Rf¼0.45 (Petether/
25
EtOAc 4:1), [
a]
¼þ49.2 (c 1, CHCl3). IR (CHCl3):
n 3436, 2928, 2224,
D
1603, 1507, 1251, 1096, 911, 837, 778, 697 cmꢀ1. 1H NMR (400 MHz,
CDCl3):
7.39–7.31 (m, 5H), 7.30 (d, J¼8.5 Hz, 2H), 7.22 (d, J¼8.5 Hz,
3H). 13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (q), ꢀ4.4 (q, 2C), ꢀ4.1 (q),
d
14.1 (q), 18.0 (s), 18.2 (s), 22.7 (t), 25.0 (t), 25.7 (q, 3C), 25.9 (q, 3C)
29.4 (t), 29.7 (t, 6C), 29.8 (t), 30.9 (t), 31.9 (t), 37.9 (t), 39.7 (t), 41.0
(t), 41.3 (t), 55.3 (q), 69.5 (d), 71.1 (t), 71.2 (d), 77.7 (d), 113.9 (d, 2C),
119.8 (d, 2C),129.2 (d, 2C),129.6 (d, 2C),129.9 (s), 135.0 (s), 153.5 (s),
159.3 (s) ppm. ESI-MS: m/z 793.98 (100, [MþNa]þ). Anal. Calcd for
C46H82O5Si2: C, 71.63; H, 10.72. Found: C, 71.79; H, 10.91.
2H), 6.83 (d, J¼8.5 Hz, 2H), 6.77 (d, J¼8.5 Hz, 2H), 4.85 (d, J¼11.6 Hz,
1H), 4.56 (d, J¼11.6 Hz, 1H), 4.50 (d, J¼10.9 Hz, 1H), 4.39 (d,
J¼10.9 Hz, 1H), 3.89–3.82 (m, 2H), 3.78 (s, 3H), 2.29–2.27 (m, 2H),
2.16–2.09 (m, 3H), 2.05 (ddd, J¼13.3, 9.2, 4.2 Hz, 1H), 1.96 (ddd,
J¼14.0, 4.2, 5.0 Hz, 1H), 1.85 (ddd, J¼14.0, 7.4, 4.6 Hz, 1H), 1.45 (dd,
J¼14.8, 7.4 Hz, 2H), 1.36–1.30 (m, 2H), 1.25 (m, 10H), 0.98 (s, 9H),
0.87 (t, J¼6.8 Hz, 3H), 0.83 (s, 9H), 0.20 (s, 6H), 0.06 (s, 6H), 0.03 (s,
4.14. (3S,5S,7R)-5-O-(4-Methoxybenzyl)-7-O-tert-
butyldimethylsilyl-1-(4-tert-butyldimethyl-
silyloxyphenyl)octadecane-3,5,7-triol (29)
3H). 13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (q), ꢀ4.4 (q, 2C), ꢀ4.3 (q),
14.1 (q), 17.9 (s), 18.2 (s), 18.8 (t), 22.7 (t), 25.6 (q, 3C), 25.8 (q, 3C),
28.1 (t), 28.9 (t), 29.0 (t), 29.2 (t), 29.3 (t), 29.5 (t), 29.6 (t), 29.7 (t),
31.9 (t), 41.1 (t), 41.4 (t), 55.2 (q), 67.2 (d), 68.7 (d), 70.6 (t), 70.7 (t),
73.2 (d), 76.7 (s), 82.3 (s), 86.6 (s), 86.7 (s), 113.7 (d, 2C), 115.6 (s)
120.1 (d, 2C),128.1 (d, 2C),128.3 (d, 2C),129.5 (d, 2C),130.8 (s),133.2
(d, 2C), 138.1 (s), 155.9 (s), 159.1 (s) ppm. ESI-MS: m/z 876.3 (100%,
[MþNa]þ). Anal. Calcd for C53H80O5Si2: C, 74.59; H, 9.45. Found: C,
74.82; H, 9.31.
The same procedure as in the preparation of 28 was used with
the di-TBS-derivative 27 (180 mg, 0.22 mmol) to procure 29 as
colorless oil (142 mg, 87% yield). Rf¼0.40 (Petether/EtOAc 8:2),
25
[a
]
¼ꢀ5.1 (c 1, CHCl3). IR (CHCl3):
n 3480, 2928, 2855, 1611, 1509,
D
1470, 1252, 1040, 836, 775, 692 cmꢀ1 1H NMR (500 MHz, CDCl3):
.
d
7.36 (d, J¼8.2 Hz, 2H), 7.15 (d, J¼7.7 Hz, 2H), 6.90 (d, J¼8.2 Hz, 2H),
6.86 (d, J¼7.7 Hz, 2H), 4.69 (d, J¼10.7 Hz, 1H), 4.46 (d, J¼10.7 Hz,
1H), 3.94 (br s, 1H), 3.91(s, 3H), 3.90–3.87 (m, 1H), 3.80 (br s, 1H),
2.80 (ddd, J¼14.4, 9.9, 5.1 Hz, 1H), 2.70 (ddd, J¼14.4, 9.9, 5.8 Hz, 1H),
2.04 (ddd, J¼13.1, 8.3, 3.7 Hz, 1H), 1.85 (d, J¼14.3 Hz, 2H), 1.80–1.62
(m, 4H),1.57 (br s. 2H),1.38 (br s,18H),1.09 (s, 9H),1.00 (s,12H), 0.30
4.12. ((3R,5S,7R)-3-(Benzyloxy)-1-(4-(tert-butyl-dimethyl-
silyloxy)phenyl)-5-(4-methoxy-benzyloxy)octadeca-1,9-diyn-
7-yloxy)(tert-butyl)dimethylsilane (27)
The similar procedure as in the preparation of 26 was used with
the alkyne 25 (400 mg, 0.65 mmol). The crude was purified by
column chromatography (5%/10% ethyl acetate in petroleum
(s, 6H), 0.17 (s, 3H), 0.12 (s, 3H). 13C NMR (125 MHz, CDCl3):
d
ꢀ4.5
(q), ꢀ4.5 (q, 2C), ꢀ4.1 (q), 14.1 (q), 18.0 (s), 18.2 (s), 22.7 (t), 25.0 (t),
25.7 (q, 3C), 25.9 (q, 3C) 29.3 (t), 29.6 (t, 4C), 29.8 (t), 30.9 (t), 31.9
(t), 37.9 (t), 39.6 (t), 40.9 (t), 41.3 (t), 55.2 (q), 69.4 (d), 70.1 (t), 71.2
(d), 77.7 (d), 113.9 (d, 2C), 119.8 (d, 2C), 129.2 (d, 2C), 129.6 (d, 2C),
130.0 (s),135.0 (s),153.5 (s),159.3 (s) ppm. ESI-MS: m/z 766.2 (100%,
[MþNa]þ), 782.4 (35%, [MþK]þ), 744.4 (35%, [Mþ1]þ). Anal. Calcd
for C44H78O5Si2: C, 71.10; H, 10.58. Found: C, 71.06; H, 10.76.
ether) to afford 27 (465 mg, 87% yield) as colorless oil. Rf¼0.40
25
(Petether/EtOAc 4:1), [
a]
¼þ49.2 (c 1, CHCl3). IR (CHCl3):
n 3436,
D
2929, 2857, 2224, 1603, 1507, 1463, 1251, 1096, 911, 837, 777,
665 cmꢀ1. 1H NMR (500 MHz, CDCl3):
d
7.38–7.30 (m, 7H), 7.22 (d,
J7.2 Hz, 2H), 6.83 (d, J¼7.4 Hz, 2H), 6.78 (d, J¼7.2 Hz, 2H), 4.86 (d,
J¼11.6 Hz, 1H), 4.57 (d, J¼11.6 Hz, 1H), 4.51 (d, J¼10.7 Hz, 1H), 4.41
(d, J¼10.7 Hz,1H), 3.89–3.81 (br s, 2H), 3.79 (s, 3H), 2.29 (s, 2H), 2.12
(s, 3H), 2.05 (br s, 1H), 1.98–1.90 (m, 1H), 1.89–1.86 (m, 1H), 1.46 (t,
J¼6.4 Hz, 2H), 1.35 (br s, 2H), 1.30–1.22 (br s, 9H), 0.99 (s, 9H), 0.87
(t, J¼6.85 Hz, 3H), 0.83 (s, 9H), 0.21 (s, 6H), 0.05 (s, 6H). 13C NMR
4.15. (5R,7R)-5-(4-Methoxy-benzyloxy)-7-(tert-
butyldimethylsilyloxy)-1-(4-tert-butyldimethyl-
silyloxyphenyl)icosan-3-one (30)
(125 MHz, CDCl3):
d
ꢀ4.5 (q), ꢀ4.4 (q, 2C), ꢀ4.3 (q), 14.1 (q), 17.9 (s),
In a flame-dried, two-necked, round-bottom flask (25 mL) was
dissolved oxalyl chloride (34 mL, 0.39 mmol) under N2 atmo-
18.2 (s), 18.8 (t), 22.6 (t), 25.6 (q, 3C), 25.8 (q, 3C), 25.9 (s), 28.1 (t),
28.9 (t), 29.0 (t), 29.1 (t), 29.2 (t), 31.9 (t), 41.1 (t), 41.4 (t), 55.2 (q),
67.2 (d), 68.7 (d), 70.6 (t), 70.7 (t), 73.2 (d), 82.3 (s), 86.6 (s), 86.7 (s),
113.7 (d, 2C), 115.6 (s) 120.1 (d, 2C), 127.6 (d), 128.1 (d, 2C), 128.3 (d,
2C), 129.5 (d, 2C), 130.8 (s), 133.2 (d, 2C), 138.1 (s), 155.9 (s), 159.1 (s)
ppm. ESI-MS: m/z 848.3 (100%, [MþNa]þ). Anal. Calcd for
C51H76O5Si2: C, 74.22; H, 9.28. Found: C, 74.38; H, 9.16.
sphere in dry CH2Cl2 (5 mL). After the solution was cooled to
ꢀ78 ꢁC, dry DMSO (50
mL, 0.71 mmol) was added drop wise with
stirring for 15 min. A solution of alcohol 28 (100 mg, 0.12 mmol)
in dry CH2Cl2 (5 mL) was added drop-wise and stirred for 30 min.
To this was added Et3N (108 mL, 0.78 mmol) and stirring contin-
ued for 15 min at ꢀ78 ꢁC. The reaction mixture was partitioned
between CH2Cl2 and water, the organic phase was separated, and
the aqueous phase was extracted with CH2Cl2. Combined organic
phases were washed with brine, dried (Na2SO4), and concen-
trated. Purification of the crude by column chromatography (5%
4.13. (3S,5S,7R)-5-O-(4-Methoxybenzyl)-7-O-tert-
butyldimethylsilyl-1-(4-tert-butyldimethyl-
silyloxyphenyl)icosane-3,5,7-triol (28)
ethyl acetate in petroleum ether) afforded ketone 30 (93 mg, 93%)
25
A suspension of di-TBS-derivative 26 (150 mg, 0.174 mmol) and
Raney-Ni (300 mg) in ethanol (10 mL) was flushed with hydrogen
as a colorless oil. Rf¼0.50 (Petether/EtOAc 8:2), [
a
]
¼–4.5 (c 1,
D
CHCl3). IR (CHCl3): n 3432, 2927, 2955, 2854, 1718, 1611, 1510,

C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
397
1252, 1081, 1040, 836, 775 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
7.19
(m, 2H), 3.37 (d, J¼9.9 Hz, 1H), 2.43–2.33 (m, 1H), 2.24 (dd, J¼10.4,
7.3 Hz, 1H), 2.05–1.98 (m, 3H), 1.96–1.90 (m, 1H), 1.80 (ddd, J¼13.6,
5.4, 2.5 Hz, 1H), 1.50–1.39 (m, 4H), 1.30–1.23 (s, 21H), 0.88 (t,
(d, J¼8.5 Hz, 2H), 6.99 (d, J¼8.3 Hz, 2H), 6.84 (d, J¼8.5, Hz, 2H),
6.72 (d, J¼8.3 Hz, 2H), 4.40 (d, J¼11.0 Hz, 1H), 4.36 (d, J¼11.0 Hz,
1H), 4.05–3.99 (m, 1H), 3.79 (s, 3H), 3.70 (dd, J¼11.2, 5.7 Hz, 1H),
2.80 (t, J¼7.1 Hz, 2H), 2.70 (br d, Jz7.1 Hz, 2H), 2.64 (d, J¼7.8 Hz,
1H), 1.42 (br s, 4H), 1.29 (br s, 5H), 1.26 (s, 18H), 0.97 (s, 9H), 0.88
(s, 12H), 0.17 (s, 6H), 0.03 (s, 6H). 13C NMR (100 MHz, CDCl3):
J¼6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 14.1 (q), 22.7 (t), 25.6 (t),
29.3 (t), 29.6 (t), 29.7 (t, 6C), 31.9 (t), 34.1 (t), 35.9 (t), 37.9 (t), 39.1
(t), 64.8 (d), 65.3 (d), 72.2 (t), 79.7 (s), 109.1 (s), 127.1 (d), 127.3 (d),
148.7 (d), 150.9 (d), 185.3 (s) ppm. ESI-MS: m/z 860 (47%,
[2MþNa]þ), 441 (36%, [MþNa]þ), 419 (48%, [Mþ1]þ), 507.4 (100%).
Anal. Calcd for C26H42O4: C, 74.60; H,10.11. Found: C, 74.47; H,10.34.
d
ꢀ4.5 (q, 3C), ꢀ4.3 (q), 14.1 (q), 18.0 (s), 18.2 (s), 22.7 (t, 2C) 25.2
(t), 25.8 (q, 3C), 25.9 (q, 3C), 28.7 (t), 29.4 (t, 2C), 29.7 (t, 3C), 29.8
(t), 31.9 (t, 2C), 37.2 (t), 41.9 (t), 45.8 (t), 48.3 (t), 55.2 (q), 69.4 (d),
71.1 (t), 72.8 (d), 113.7 (d, 2C), 120.0 (d, 2C), 129.1 (d, 2C), 129.5 (d,
2C), 130.6 (s), 133.7 (s), 153.8 (s), 159.1 (s), 208.9 (s) ppm. ESI-MS:
m/z 792.3 (100, [MþK]þ). Anal. Calcd for C46H80O5Si2: C, 71.82; H,
10.48. Found: C, 71.99; H, 10.76.
26
4.17.2. Aculeatin B (2). Rf¼0.20 (Petether/EtOAc 7:3); [
a
]
¼þ46.8 (c
D
23
1.0, CHCl3); lit.10
2849, 1665, 1621, 1068, 1020, 1005, 854 cmꢀ1
CDCl3)
[a]
¼þ50.0 (c 0.2, CHCl3). IR (neat):
n
3521, 2916,
D
.
1H NMR (400 MHz,
d
6.99 (dd, J¼10.0, 3.0 Hz, 1H), 6.78 (dd, J¼10.0, 3.0 Hz, 1H),
6.14 (dd, J¼10.0, 2.0 Hz, 1H), 6.11 (dd, J¼10.0, 2.0 Hz, 1H), 4.39–4.35
(m, 1H), 3.91–3.82 (m,1H), 2.69 (ddd, J¼13.1, 7.4, 1.6 Hz,1H), 2.31 (dt,
J¼12.3, 7.3 Hz, 1H), 2.11–2.02 (m, 2H), 1.98–1.86 (m, 2H), 1.65–1.53
(m, 2H), 1.49–1.42 (m, 4H), 1.23–1.33 (s, 21H), 0.88 (t, J¼7.0 Hz, 3H).
4.16. (5R,7R)-5-(4-Methoxy-benzyloxy)-7-(tert-
butyldimethylsilyloxy)-1-(4-tert-butyldimethyl-
silyloxyphenyl)octadecan-3-one (31)
13C NMR (100 MHz, CDCl3)
d 14.1 (q), 22.7 (t), 25.9 (t), 29.4 (t, 2C),
The same procedure as in the preparation of 28 was used with
29.6 (t, 3C), 29.7 (t, 3C), 31.9 (t), 35.3 (t), 35.4 (t), 35.7 (t), 37.9 (t), 40.6
(t), 65.2 (d), 69.4 (d), 77.6 (s), 108.5 (s), 127.1 (d), 149.1 (d), 152.2 (d),
185.7 (s). ESI-MS: m/z 441 (100% [MþNa]þ), 419 (44% [Mþ1]þ). Anal.
Calcd for C26H42O4: C, 74.60; H, 10.11. Found: C, 74.52; H, 10.31.
the alcohol 29 (120 mg, 0.49 mmol) affording 31 (114 mg, 95%
25
yield) as colorless oil. Rf¼0.45 (Petether/EtOAc 4:1), [
CHCl3). IR (CHCl3):
916, 836, 775 cmꢀ1. 1H NMR (400 MHz, CDCl3):
a
]
D
¼–4.5 (c 1,
n
3432, 2928, 2855, 1713, 1611, 1510, 1251, 1039,
7.19 (d, J¼8.5 Hz,
d
2H), 6.99 (d, J¼8.3 Hz, 2H), 6.84 (d, J¼8.5, Hz, 2H), 6.73 (d, J¼8.3 Hz,
2H), 4.40 (d, J¼11.0 Hz, 1H), 4.37 (d, J¼11.0 Hz, 1H), 4.01
(ddd, J¼13.7, 6.7, 4.2 Hz, 1H), 3.79 (s, 3H), 3.70 (dd, J¼11.6, 5.8 Hz,
1H), 2.80 (t, Jz7.4 Hz, 2H), 2.70 (t, Jz7.4 Hz, 2H), 2.65 (d,
J¼7.9 Hz, 1H), 2.54 (dd, J¼15.9, 4.4 Hz, 1H), 1.83–1.78 (m, 1H),
1.54–1.49 (m, 1H),1.39 (br s, 2H),1.29 (br s, 3H), 1.26 (s, 15H), 0.97 (s,
9H), 0.88 (s, 12H), 0.17 (s, 6H), 0.03 (s, 6H). 13C NMR (100 MHz,
4.18. Aculeatin F (6) and 6-epi-aculeatin F (8)
The similar procedure as in the preparation of aculeatin A/B was
used with the ketone 31 (100 mg, 0.13 mmol) to afford 6 (21 mg,
43%) and 8 (8 mg, 15%) as colorless oils.
26
4.18.1. Aculeatin F (6). Rf¼0.24 (Petether/EtOAc 7:3). [
a
n
]
¼ꢀ4.7 (c
D
23
CDCl3):
d
ꢀ4.5 (q, 3C), ꢀ4.3 (q),14.1 (q),18.0 (s), 18.2 (s), 22.7 (t) 25.2
2.0, CHCl3); lit.9b
2854, 1677, 1633, 1100, 1046, 998, 852 cmꢀ1
CDCl3)
[
a]
¼ꢀ5.3 (c 0.9, CHCl3). IR (neat):
3494, 2927,
D
(t), 25.7 (q, 3C), 25.9 (q, 3C), 28.7 (t), 29.4 (t), 29.7 (t, 4C), 29.8 (t),
31.9 (t), 37.2 (t), 41.9 (t), 45.8 (t), 48.3 (t), 55.2 (q), 69.4 (d), 71.1 (t),
72.8 (d), 113.7 (d, 2C), 119.9 (d, 2C), 129.1 (d, 2C), 129.5 (d, 2C), 130.6
(s), 133.7 (s), 153.8 (s), 159.1 (s), 208.9 (s) ppm. ESI-MS: m/z 764.4
(100%, [MþNa]þ), 780.6 (56%, [MþK]þ), 759.6 (20%, [MþH2O]þ),
743.6 (15%, [Mþ2]þ), 741.6 (11%, [Mþ1]þ). Anal. Calcd for
C44H76O5Si2: C, 71.30; H, 10.33. Found: C, 71.47; H, 10.35.
.
1H NMR (500 MHz,
d
6.85 (dd, J¼10.0, 2.8 Hz, 1H); 6.76 (dd, J¼10.0, 2.8 Hz, 1H),
6.15 (dd, Jz10.0, 1.8 Hz, 1H), 6.12 (dd, Jz10.0, 1.8 Hz, 1H), 4.17–4.06
(m, 2H), 3.38 (d, J¼10.0 Hz, 1H), 2.42–2.34 (m, 1H), 2.24 (dd, J¼10.3,
8.1 Hz, 1H), 2.05–1.98 (m, 3H), 1.94 (br t, J¼14.0 Hz, 1H), 1.80 (d,
J¼13.5 Hz, 1H), 1.54–1.39 (m, 4H), 1.29 (s, 17H), 0.88 (t, J¼6.9 Hz,
3H). 13C NMR (100 MHz, CDCl3)
d 14.1 (q), 22.7 (t), 25.6 (t), 29.3 (t),
29.6 (t), 29.7 (t, 4C), 31.9 (t), 34.1 (t), 35.9 (t), 37.9 (t), 39.0 (t), 39.1
(t), 64.8 (d), 65.3 (d), 79.7 (s), 109.1 (s), 127.0 (d), 127.3 (d), 148.8 (d),
150.9 (d), 185.3 (s). ESI-MS: m/z 804.0 (47% [2MþNa]þ), 413.5 (36%
[MþNa]þ), 491.5 (48% [Mþ1]þ), 507.4 (100%). Anal. Calcd for
C24H38O4: C, 73.81; H, 9.81. Found: C, 73.69; H, 9.94.
4.17. Aculeatins A (1) and B (2)
To a solution of PMB ether 30 (80 mg, 0.10 mmol) in CH2Cl2
(10 mL) and buffer (2 mL) was added DDQ (26 mg, 0.11 mmol) por-
tion-wise at 0 ꢁC and stirring continued for another 30 min at the
same temperature. The reaction mixture was filtered through a plug
of filter aid. The organic phase was washed with water and brine,
dried (Na2SO4), and concentrated. The crude (72 mg) was dissolved in
4.18.2. 6-epi-Aculeatin
F
(8). Rf¼0.18 (Petether/EtOAc 7:3).
¼þ46.8 (c 1.0, CHCl3), IR (CHCl3): 3520, 2916, 2848, 1664,
1620, 1067, 1020, 1004, 853 cmꢀ1. 1H NMR (400 MHz, CDCl3)
6.99
26
[a
]
n
D
d
dry THF (5 mL) and treated with TBAF (222
m
L of 1 M solution in THF,
(dd, J¼10.0, 3.0 Hz, 1H), 6.78 (dd, J¼10.0, 3.0 Hz, 1H), 6.14 (dd,
J¼10.0, 2.0 Hz, 1H), 6.11 (dd, J¼10.0, 2.0 Hz, 1H), 4.39–4.35 (m, 1H),
3.91–3.83 (m, 1H), 2.69 (br dd, J¼12.3, 7.4, Hz, 1H), 2.31 (dt, J¼12.3,
7.4 Hz, 1H), 2.10–2.01 (m, 2H), 1.97–1.85 (m, 2H), 1.64–1.52 (m, 3H),
1.49–1.39 (m, 3H), 1.29 (s, 17H), 0.88 (t, J¼6.9 Hz, 3H). 13C NMR
0.22 mmol) at 0 ꢁC. After the mixture was stirred for 15 min at the
same temperature, solvent was evaporated under reduced pressure.
The crude ketal (38 mg) wasdissolved in acetone/H2O (2.5 mL,10:1 v/
v solution), and PIFA (50 mg, 0.117 mmol) was added in single portion
at room temperature. After the mixture was stirred for 15 min in
darkness, a saturated aqueous solution of NaHCO3 (4 mL) was added
and the resulting mixtureextracted with ethyl acetate(3ꢂ10 mL). The
combined organic layers were dried (Na2SO4), filtered, and concen-
trated. The crude product was purified by flash column chromatog-
raphy (30% and 35% ethyl acetate in petroleum ether) to afford 1
(23 mg, 47%) and 2 (9 mg, 16%) as colorless oils.
(100 MHz, CDCl3) d 14.1 (q), 22.7 (t), 25.9 (t), 29.3 (t), 29.4 (t), 29.6 (t,
4C), 31.9 (t), 35.3 (t, 2C), 35.7 (t), 37.9 (t), 40.5 (t), 65.2 (d), 69.4 (d),
77.6 (s), 108.5 (s), 127.1 (d, 2C), 149.2 (d), 152.3 (d), 185.7 (s). ESI-MS:
m/z 413.5 (100% [MþNa]þ), 429.5 (22% [MþK]þ), 491 (24% [Mþ1]þ),
373.5 (22%, [Mþ1–H2O]þ). Anal. Calcd for C24H38O4: C, 73.81; H,
9.81. Found: C, 73.97; H, 9.88.
4.19. (3R,5S,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-
oxy)octadeca-1,9-diyn-7-ol 32
25
4.17.1. Aculeatin A (1). Rf¼0.25 (Petether/EtOAc 7:3) [
a
n
]
¼ꢀ4.7 (c
D
23
2.0, CHCl3); lit.10
2855, 1674, 1634, 1100, 1047, 999, 853 cmꢀ1
CDCl3)
6.85 (dd, J¼10.0, 3.0 Hz, 1H), 6.76 (dd, J¼10.0, 3.0 Hz, 1H),
6.15 (dd, J¼10.0, 2.0 Hz, 1H), 6.12 (dd, J¼10.0, 2.0 Hz, 1H) 4.16–4.07
[
a
]
¼ꢀ5.3 (c 0.9, CHCl3). IR (neat):
3495, 2926,
D
.
1H NMR (400 MHz,
The same procedure as in the preparation of 22 was used to
couple the dec-1-yne (12) and oxirane 10 (400 mg, 1.1 mmol) to
procure the diyne 32 (500 mg, 91%) as colorless oil. Rf¼0.30
d

398
C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
25
(Petether/EtOAc 8:2), [
a]
¼þ79.7 (c 2.0, CHCl3). IR (CHCl3):
n
1H), 4.00–3.88 (m, 2H), 3.77 (s, 3H), 2.32 (ddd, J¼5.3, 2.2 Hz, 2H),
D
3469, 3305, 2930, 2857, 2111, 1612, 1586, 1513, 1455, 1249, 1216,
2.17–2.05 (m, 4H), 2.01 (ddd, J¼14.1, 7.7, 3.8 Hz, 1H), 1.68 (ddd,
J¼14.1, 8.0, 4.7 Hz, 1H), 1.64–1.57 (br s, 1H), 1.50–1.43 (m, 2H), 1.38–
1.33 (m, 2H), 1.25 (s, 7H), 0.98 (s, 9H), 0.89 (s, 9H), 0.86 (t, J¼5.0 Hz,
3H), 0.20 (s, 6H), 0.08 (s, 3H), 0.06 (s, 3H). 13C NMR (100 MHz,
1069, 1034, 822, 756, 665 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
7.34
(d, J¼4H), 7.32–7.28 (m, 1H), 7.14 (ddd, J¼8.6, 2.9, 2.0 Hz, 2H), 6.82
(ddd, J¼8.6, 2.9, 2.0 Hz, 2H), 4.79 (d, J¼11.6 Hz, 1H), 4.48 (d,
J¼10.8 Hz, 1H), 4.38 (d, J¼11.6 Hz, 1H), 4.27 (d, J¼10.8 Hz, 1H),
4.27–4.23 (m, 1H), 4.02–3.91 (m, 2H), 3.76 (s, 3H), 2.48 (d,
J¼2.0 Hz, 1H), 2.34–2.30 (m, 2H), 2.17–2.07 (m, 3H), 1.97 (ddd,
J¼14.5, 9.4, 3.9 Hz, 1H), 1.84 (ddd, J¼14.5, 9.7, 3.9 Hz, 1H), 1.72
(ddd, J¼14.5, 6.0, 2.7 Hz, 1H), 1.48 (dt, J¼7.0, 1.2 Hz, 2H), 1.39–1.32
(m, 2H), 1.31–1.21 (br s, 9H), 0.86 (t, J¼6.8 Hz, 3H). 13C NMR
CDCl3):
d
ꢀ4.6 (q), ꢀ4.5 (q, 2C), ꢀ4.1 (q), 14.1 (q), 18.1 (s), 18.2 (s),
18.8 (t), 22.6 (t), 25.6 (q, 3C), 25.9 (q, 3C), 28.3 (t), 28.9 (t), 29.0 (t),
29.2 (t), 29.3 (t), 31.9 (t), 41.9 (t), 42.3 (t), 55.2 (q), 66.1 (d), 68.6 (d),
70.3 (t), 70.6 (t), 72.4 (d), 77.2 (s), 82.4 (s), 85.9 (s), 87.1 (s), 113.7 (d,
2C), 115.6 (s), 120.1 (d, 2C), 127.6 (d), 128.0 (d, 2C), 128.3 (d, 2C),
129.2 (d, 2C), 131.0 (s), 133.2 (d, 2C), 138.1 (s), 155.9 (s), 159.0 (s)
ppm. ESI-MS: m/z 848.3 (100%, [MþNa]þ). Anal. Calcd for
C51H76O5Si2: C, 74.22; H, 9.28. Found: C, 74.09; H, 9.15.
(100 MHz, CDCl3):
d 14.1 (q), 18.7 (t), 22.6 (t), 27.8 (t), 28.9 (t), 29.0
(t), 29.1 (t), 29.2 (t), 31.8 (t), 39.2 (t), 41.1 (t), 55.2 (q), 65.0 (d), 67.4
(d), 70.6 (t), 71.5 (t), 73.1 (d), 74.0 (d), 76.0 (s), 82.8 (s), 83.0 (s),
113.8 (d, 2C), 127.8 (d), 128.2 (d, 2C), 128.4 (d, 2C), 129.7 (d, 2C),
130.1 (s), 137.6 (s), 159.3 (s) ppm. ESI-MS: m/z 527.6 (100%,
[MþNa]þ), 543.6 (36%, [MþK]þ), 505.7(7%, [Mþ1]þ). 407.5 (46%,
[M–97]þ), 383.4 (74%, [M–115]þ). Anal. Calcd for C33H44O4: C,
78.53; H, 8.79. Found: C, 78.88; H, 9.02.
4.22. (3S,5R,7R)-5-O-(4-Methoxybenzyl)-7-O-tert-butyl-
dimethylsilyl-1-(4-tert-butyldimethyl-silyloxyphenyl)-
octadecane-3,5,7-triol (35)
The same procedure as in the preparation of 28 was used with
the di-TBS-derivative 34 (140 mg, 0.17 mmol) affording 35
4.20. ((3R,5R,7R)-3-(Benzyloxy)-5-(4-methoxybenzyl-oxy)-
octadeca-1,9-diyn-7-yloxy)(tert-butyl)-dimethylsilane (33)
(105 mg, 84% yield) as colorless oil. Rf¼0.30 (Petether/EtOAc 7:3),
25
[a
]
¼ꢀ5.1 (c 1, CHCl3). IR (CHCl3):
n 3480, 2855, 1611, 1510, 1252,
D
1039, 836, 758, 692 cmꢀ1 1H NMR (500 MHz, CDCl3):
. d 7.24 (d,
A solution of alcohol 32 (500 g, 0.99 mmol) in anhydrous DMF
(3 mL) was cooled to 0 ꢁC, imidazole (404 mg, 5.94 mmol) followed
by TBS-Cl (447 mg, 2.97 mmol) were added and stirring was con-
tinued at rt for 24 h. The reaction mixture was portioned between
ethyl acetate and water, organic layer was separated and aqueous
layer was extracted with ethyl acetate. Combined organic layers
were washed with brine, dried (Na2SO4), filtered and concentrated
under reduced pressure. Purification of the crude product by col-
umn chromatography (10% ethyl acetate in petroleum ether)
J¼8.5 Hz, 2H), 7.04 (dt, J¼8.3 Hz, 2H), 6.87 (d, J¼8.5 Hz, 2H), 6.73
(d, J¼8.3 Hz, 2H), 4.52 (d, J¼10.9 Hz, 1H), 4.42 (d, J¼10.9 Hz, 1H),
3.94–3.90 (br s, 1H), 3.84–3.81 (m, 2H), 3.80 (s, 3H), 3.13 (br s, 1H),
2.72 (ddd, J¼14.6, 9.7, 5.4 Hz, 1H), 2.54 (ddd, J¼15.8, 9.7, 6.3 Hz,
1H), 1.91–1.81 (m, 2H), 1.79–1.72 (m, 1H), 1.67–1.59 (m, 1H), 1.58–
1.52 (m, 2H), 1.45–1.40 (m, 2H), 1.26 (s, 18H), 0.98 (s, 9H), 0.87 (s,
9H), 0.87 (t, J¼5.0 Hz, 3H), 0.18 (s, 6H), 0.04 (s, 3H), 0.03 (s, 3H). 13C
NMR (125 MHz, CDCl3):
d
ꢀ4.5 (q, 2C), ꢀ4.4 (q), ꢀ4.1 (q), 14.1 (q),
18.1 (s), 18.2 (s), 22.7 (t, 2C), 24.7 (t), 25.7 (q, 3C), 25.9 (q, 3C), 29.3
(t), 31.1 (t, 2C), 31.9 (t), 37.7 (t, 2C), 39.5 (t, 2C), 39.8 (t), 41.5 (t),
55.2 (q), 68.1 (d), 69.7 (d), 70.7 (t, 2C), 74.9 (d), 113.9 (d, 2C), 119.8
(d, 2C), 129.2 (d, 2C), 129.4 (d, 2C), 130.2 (s), 134.9 (s), 153.6 (s),
159.3 (s) ppm. ESI-MS: m/z 766.1 (80%, [MþNa]þ), 779.1 (10%,
[MþK]þ), 565.5 (100%). Anal. Calcd for C44H78O5Si2: C, 71.10; H,
10.58. Found: C, 71.25; H, 10.64.
afforded TBS-derivative 33 (563 mg, 92%) as colorless oil. Rf¼0.40
25
(Petether/EtOAc 7:3) [
a]
¼þ24.2 (c 1.0, CHCl3). IR (CHCl3):
n 3308,
D
2928, 2856, 2110, 1613, 1514, 1463, 1248, 1091, 1039, 835, 775,
697 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
7.37–7.28 (m, 5H), 7.16 (d,
J¼8.5 Hz, 2H), 6.83 (d, J¼8.5 Hz, 2H), 4.79 (d, J¼11.5 Hz, 1H), 4.43 (d,
J¼10.5 Hz, 1H), 4.40 (d, J¼11.5 Hz, 1H), 4.30 (d, J¼10.5 Hz, 1H), 4.27
(dt, J¼6.9, 2.0 Hz, 1H), 3.99–3.92 (m, 1H), 3.90–3.83 (m, 1H), 3.76 (s,
3H), 2.47 (d, J¼2.0 Hz, 1H), 2.33–2.30 (m, 2H), 2.13 (tt, J¼7.0, 2.3 Hz,
2H), 2.05–1.97 (m, 3H), 1.64 (ddd, J¼14.2, 8.0, 4.8 Hz, 1H), 1.50–1.43
(m, 2H), 1.38–1.34 (m, 2H), 1.246 (s, 8H), 0.89 (s, 9H), 0.86 (t,
J¼5.0 Hz, 3H), 0.09 (s, 3H), 0.07 (s, 3H). 13C NMR (100 MHz, CDCl3):
4.23. (5S,7R)-5-(4-Methoxy-benzyloxy)-7-(tert-butyl-
dimethylsilyloxy)-1-(4-tert-butyldimethyl-
silyloxyphenyl)octadecan-3-one (36)
d
ꢀ4.6 (q), ꢀ4.1 (q), 14.1 (q), 18.1 (s), 18.8 (t), 22.7 (t), 25.9 (q, 3C),
28.2 (t), 28.9 (t), 29.0 (t), 29.2 (t), 29.3 (t), 31.9 (t), 41.8 (t), 42.2 (t),
55.2 (q), 65.3 (d), 68.6 (d), 70.4 (t), 70.6 (t), 72.1 (d), 73.8 (d), 76.6 (s),
82.5 (s), 83.0 (s), 113.7 (d, 2C), 127.7 (d), 128.0 (d, 2C), 128.3 (d, 2C),
129.2 (d, 2C), 130.8 (s), 137.8 (s), 159.0 (s) ppm. ESI-MS: m/z 641.8
(23%, [MþNa]þ), 657.9 (14%, [MþK]þ), 429.5 (73%, [M–189]þ), 421.5
(100%, [M–197]þ). Anal. Calcd for C39H58O4Si: C, 75.68; H, 9.44.
Found: C, 75.51; H, 9.67.
The Swern oxidation of the alcohol 35 (100 mg, 0.14 mmol) was
carried out as described for the preparation of 30 and the ketone 36
(93 mg, 93%) was obtained as a colorless syrup after usual workup
and purification by column chromatography (5% ethyl acetate in
25
petroleum ether). Rf¼0.50 (Petether/EtOAc 8:2), [
CHCl3). IR (CHCl3):
759, 686 cmꢀ1 1H NMR (500 MHz, CDCl3): 1H NMR (500 MHz,
CDCl3):
7.19 (br.d, J¼8.7 Hz, 2H), 6.99 (br.d, J¼8.3 Hz, 2H), 6.85
a
]
¼–4.5 (c 1,
D
n
3415, 2927, 1715, 1612, 1511, 1252, 1040, 836,
.
d
4.21. ((3R,5R,7R)-3-(Benzyloxy)-1-(4-(tert-butyl-dimethyl-
silyloxy)phenyl)-5-(4-methoxy-benzyloxy)octadeca-1,9-diyn-
7-yloxy)(tert-butyl)dimethylsilane (34)
(br.d, J¼8.7 Hz, 2H), 6.73 (br.d, J¼8.3 Hz, 2H), 4.43 (d, J¼11.0 Hz, 1H),
4.39 (d, J¼11.0 Hz,1H), 4.08–4.02 (m,1H), 3.84–3.73 (m,1H), 3.79 (s,
3H), 2.80 (t, J¼7.3 Hz, 2H), 2.71 (dd, J¼15.5, 7.0 Hz, 1H), 2.69 (t,
J¼7.3 Hz, 2H), 2.49 (dd, J¼15.6, 5.1 Hz, 1H), 1.76–1.69 (m, 1H),
1.52–1.41 (m, 3H), 1.25 (br s, 18H), 0.97 (s, 9H), 0.88 (s, 9H), 0.87 (t,
J¼7.2 Hz, 3H), 0.17 (s, 6H), 0.03 (s, 6H). 13C NMR (100 MHz, CDCl3):
The coupling of alkyne 33 (200 mg, 0.32 mmol) and the iodo
derivative 13 was carried out according to the procedure used for
the preparation of 26. Purification of the crude by column chro-
matography (5% ethyl acetate in petroleum ether) gave 34 (180 mg,
d
ꢀ4.5 (q, 3C), ꢀ4.0 (q),14.1 (q),18.1 (s),18.2 (s), 22.7 (t) 24.7 (t), 25.3
(t), 25.7 (q, 3C), 25.8 (q, 3C), 28.7 (t), 29.3 (t), 29.6 (t, 2C), 29.8 (t),
31.9 (t), 37.3 (t), 40.4 (t), 41.7 (t), 45.6 (t), 48.8 (t), 55.2 (q), 69.4 (d),
71.1 (t), 73.1 (d), 113.9 (d, 2C), 120.0 (d, 2C), 129.2 (d, 2C), 129.5
(d, 2C),130.6 (s), 133.6 (s),153.8 (s), 159.1 (s), 208.6 (s) ppm. ESI-MS:
m/z 764.5 (100%, [MþNa]þ), 777.5 (56%, [MþK]þ), 742.5 (11%,
[Mþ1]þ). Anal. Calcd for C44H76O5Si2: C, 71.30; H, 10.33. Found: C,
71.16; H, 10.52.
90%) as
a
colorless syrup. Rf¼0.60 (Petether/EtOAc 7:3),
¼þ26.1 (c 1.5, CHCl3). IR (CHCl3): 3351, 2929, 2224, 1603,
1H NMR (400 MHz, CDCl3):
25
[
a]
n
D
1507, 1217, 1094, 838, 759, 697 cmꢀ1
.
d
7.39–7.27 (m, 7H), 7.18 (d, J¼8.6 Hz, 2H), 6.82 (d, J¼8.6 Hz, 2H),
6.77 (d, J¼8.6 Hz, 2H), 4.84 (d, J¼11.6 Hz, 1H), 4.48 (d, J¼11.6 Hz,
1H), 4.49–4.46 (m, 1H), 4.44 (d, J¼10.8 Hz, 1H), 4.35 (d, J¼10.8 Hz,

C.V. Ramana, S.K. Pandey / Tetrahedron 66 (2010) 390–399
399
4.24. Aculeatin E (4) and 6-epi-Aculeatin E (7)
and F. Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2009.10.058.
The same sequence of procedures as in the preparation of acu-
leatin A/B were used with the ketone 36 (90 mg, 0.122 mmol)
affording an easily separable mixture of (flash column chroma-
tography, 30–35% ethyl acetate in petroleum ether) aculeatin E (5)
(16 mg, 30%) and 6-epi-aculeatin E 7 (15 mg, 30%) as colorless oils.
References and notes
1. (a) Haustedt, L. O.; Mang, C.; Siems, K.; Schiewe, H. Curr. Opin. Drug Discov. Dev.
2006, 9, 445–462; (b) Shuker, G.; D. E.. Phys. Chem. Chem. Phys. 2007, 9, 165–
173; (c) Triggle, D. J. Biochem. Pharmacol. 2009, 78, 217–223.
2. (a) Wessjohann, L. A.; Ruijter, E. Top. Curr. Chem. 2005, 243, 137–184; (b)
Nielsen, T. E.; Schreiber, S. L. Angew. Chem., Int. Ed. 2008, 47, 48–56; (c)
Schreiber, S. L. Nature 2009, 457, 153–154.
3. (a) Hu¨ bel, K.; Leßmann, T.; Waldmann, H. Chem. Soc. Rev. 2008, 37, 1361–1374;
(b) Kumar, K.; Waldmann, H. Angew. Chem., Int. Ed. 2009, 48, 3224–3242;
Angew. Chem. 2009, 121, 3272–3290.
4. (a) Wilson, R. M.; Danishefsky, S. J. J. Org. Chem. 2006, 71, 8329–8351; (b)
Wilson, R. M.; Danishefsky, S. J. J. Org. Chem. 2007, 72, 4293–4305.
5. For selected examples see: (a) Harris, C. R.; Kuduk, S. D.; Danishefsky, S. J.
Chemistry for the 21st Century; Wiley VCH: Weinheim, 2001; p 8; (b) Cho, Y. S.;
Wu, K. D.; Moore, M. A. S.; Chou, T. C.; Danishefsky, S. J. Drugs Future 2005,
30, 737–745; (c) Fu¨rstner, A.; Kirk, D.; Fenster, M. D. B.; Aı¨ssa, C.; De Souza,
D.; Mu¨ller, O. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 8103–8108; (d) Fu¨rstner,
A.; Nagano, T.; Mu¨ller, C.; Seidel, G.; Mu¨ller, O. Chem.d Eur. J. 2007, 13,
1452–1462.
6. Heilmann, J.; Mayr, S.; Brun, R.; Rali, T.; Sticher, O. Helv. Chim. Acta 2000, 83,
2939–2945.
7. Holdsworth, D. K.; Mahana, P. Int. J. Crude Drug Res. 1983, 21, 121–133.
8. Heilmann, J.; Brun, R.; Mayr, S.; Rali, T.; Sticher, O. Phytochemistry 2001, 57,
1281–1285.
25
4.24.1. Aculeatin E (5). Rf¼0.20 (Petether/EtOAc 7:3), [
a
]
¼þ47.7
D
23
(c 1, CHCl3); lit.9b
2849, 1665, 1628, 1057, 1009 cmꢀ1
6.99 (dd, J¼10.3, 3.0 Hz, 1H), 6.78 (dd, J¼10.3, 3.0 Hz, 1H), 6.14 (dd,
[
a
]
¼þ46.5 (c 1, CHCl3). IR (neat):
n
3410, 2916,
D
.
1H NMR (500 MHz, CDCl3):
d
J¼10.0, 1.7 Hz, 1H), 6.12 (dd, J¼10.0, 1.7 Hz, 1H), 3.85 (tt, J¼11.2,
4.4 Hz, 1H), 3.40–3.34 (m, 1H), 2.39 (ddd, J¼12.7, 7.5, 2.0 Hz, 1H),
2.27 (br ddd, J¼12.5, 11.2, 7.5 Hz, 1H), 2.13 (ddd, J¼12.3, 4.3, 1.8 Hz,
1H), 2.07 (ddd, J¼12.5, 8.2, 1.9 Hz, 1H), 1.96 (br ddd, J¼12.3, 4.4,
2.0 Hz,1H),1.84 (dt, J¼12.5, 8.5 Hz, 2H),1.67–1.57 (m, 3H),1.50–1.48
(m, 2H), 1.26 (s, 17H), 0.88 (t, J¼6.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3): d 14.1 (q), 22.7 (t), 25.9 (t), 29.3 (t), 29.4 (t), 29.6 (t, 4C), 31.9
(t), 33.4 (t), 34.9 (t), 35.7 (t), 40.8 (t), 43.6 (t), 66.8 (d), 71.6 (d), 78.1
(s), 109.2 (s), 127.2 (d), 127.4 (d), 148.8 (d), 151.6 (d), 185.5 (s) ppm.
ESI-MS: m/z 413.5 (100%, [MþNa]þ), 429.5 (33%, [MþK]þ), 391.5
(26%, [Mþ1]þ), 373.5 (18%, [Mþ1-H2O]þ). Anal. Calcd for C24H38O4:
C, 73.81; H, 9.81. Found: C, 74.08; H, 10.02.
9. (a) Salim, A. A.; Su, B. N.; Chai, H. B.; Riswan, S.; Kardono, L. B. S.; Ruskandi, A.;
Farnsworth, N. R.; Swanson, S. M.; Douglas Kinghorn, A. Tetrahedron Lett. 2007,
48, 1849–1853; (b) Chin, Y. W.; Salim, A. A.; Su, B. N.; Mi, Q.; Chai, H. B.; Riswan,
S.; Kardono, L. B. S.; Ruskandi, A.; Farnsworth, N. R.; Swanson, S. M.; Kinghorn,
A. D. J. Nat. Prod. 2008, 71, 390–395.
4.24.2. 6-epi-Aculeatin
E
(7). Rf¼0.25 (Petether/EtOAc 7:3),
¼þ14.6 (c 0.2, CHCl3). IR (neat): 3412, 2915, 2848, 1662, 1627,
1H NMR (500 MHz, CDCl3):
6.82 (dd, J¼10.2,
25
[
a]
n
D
1052, 1004 cmꢀ1
.
d
´
10. (a) Wong, Y. S. Chem. Commun. 2002, 686–687; (b) Falomir, E.; Alvarez-Bercedo, P.;
Carda, M.; Marco, J. A. Tetrahedron Lett. 2005, 46, 8407–8410; (c) Chandrasekhar, S.;
Rambabu, C.; Shyamsunder, T. Tetrahedron Lett. 2007, 48, 4683–4685; (d) Suresh,
V.; Jon Paul Selvam, J.; Rajesh, K.; Venkateswarlu, Y. Tetrahedron: Asymmetry 2008,
19, 1508–1512.
3.0 Hz,1H), 6.76 (dd, J¼10.2, 3.0 Hz,1H), 6.12 (dd, J¼10.1,1.9 Hz,1H),
6.10 (dd, J¼10.1, 1.9 Hz, 1H), 4.10 (tt, J¼12.2, 4.8 Hz, 1H), 3.83–3.77
(m, 1H), 2.43–2.35 (m, 1H), 2.25 (dd, Jz10.9, 7.8 Hz, 1H), 2.10 (ddd,
J¼12.4, 4.8, 1.8 Hz, 1H), 2.06–2.00 (m, 2H), 1.97 (ddd, J¼12.3, 4.4,
1.9 Hz, 1H), 1.65 (t, J¼11.8 Hz, 1H), 1.57–1.51 (m, 1H), 1.49–1.41 (m,
2H),1.32–1.22 (m,18H),1.18 (q, J¼11.8 Hz,1H), 0.88 (t, J¼6.6 Hz, 3H).
11. Peuchmaur, M.; Wong, Y. S. Synlett 2007, 2902–2906.
12. (a) Baldwin, J. E.; Adlington, R. M.; Sham, V. W. W.; Marquez, R.; Bulger, P. G.
Tetrahedron 2005, 61, 2353–2363; (b) Ramana, C. V.; Srinivas, B. J. Org. Chem.
2008, 73, 3915–3918; (c) Zhen, Z. B.; Gao, J.; Wu, Y. J. Org. Chem. 2008, 73, 7310–
7316.
13C NMR (100 MHz, CDCl3):
d 14.1 (q), 22.7 (t), 25.7 (t), 29.3 (t), 29.6
´
13. (a) Alvarez-Bercedo, P.; Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2006, 62,
(t, 5C), 31.9 (t), 34.6 (t), 35.9 (t), 38.8 (t), 40.6 (t), 43.0 (t), 65.3 (d),
69.1 (d), 79.0 (s), 109.0 (s), 127.0 (d), 127.1 (d), 149.2 (d), 151.4 (d),
185.4 (s) ppm. ESI-MS: m/z 413.5 (100%, [MþNa]þ), 429.5 (22%,
[MþK]þ), 391.5 (24%, [Mþ1]þ), 373.5 (22%, [Mþ1-H2O]þ). Anal.
Calcd for C24H38O4: C, 73.81; H, 9.81. Found: C, 73.77; H, 10.09.
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Acknowledgements
We thank the Department of Science and Technology (SR/S5/
GC-20/2007) for funding and CSIR (New Delhi) for the research
fellowship to S.K.P.
Supplementary data
Tables of the spectral data of natural and synthetic aculeatins,
NMR and MS Spectra of aculeatins A, B, E, F and 6-epi-aculeatins E
19. (a) Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40, 2380–2382; (b)
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