Asymmetric synthesis of the polyol subunit of the macrolide antibiotic, ossamycin: A unique approach utilizing stereochemical specificity

Article abstract of DOI:10.1246/bcsj.79.468

An asymmetric synthesis of the C1-C16 polyol subunit 2 of the macrolide antibiotic ossamycin (1) has been achieved through stepwise carbon-chain elongation reaction from D-glucose, based on a chiral pool approach. An outstanding point of this strategy is

Full text of DOI:10.1246/bcsj.79.468

468 Bull. Chem. Soc. Jpn. Vol. 79, No. 3, 468–478 (2006)
ꢀ 2006 The Chemical Society of Japan
Asymmetric Synthesis of the Polyol Subunit of the Macrolide Antibiotic,
Ossamycin: A Unique Approach Utilizing Stereochemical Specificity
ꢀ
Noriki Kutsumura and Shigeru Nishiyama
Department of Chemistry, Faculty of Science and Technology, Keio University,
3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522
Received September 21, 2005; E-mail: nisiyama@chem.keio.ac.jp
An asymmetric synthesis of the C1–C16 polyol subunit 2 of the macrolide antibiotic ossamycin (1) has been
achieved through stepwise carbon-chain elongation reaction from D-glucose, based on a chiral pool approach. An out-
standing point of this strategy is asymmetric induction by utilizing steric hindrance of neighboring groups. The stereo-
genic centers at the C4 and C5 positions of 2 were constructed by mCPBA epoxidation, and the C6 and C7 positions of 2
were produced by catalytic OsO4 dihydroxylation under highly stereoselective conditions.
In 1965, ossamycin (1) was reported as a second metabo-
lite of Streptomyces hygroscopicus var. ossamyceticus strain
C8158 isolated in South America.1 Its structure was deter-
mined2 by single crystal X-ray diffraction studies to be a mem-
ber of such macrolide antibiotics as cytovaricin,3 oligomy-
cins,4 A82548A,5 and rutamycins.6 The aglycone of 1 possess-
es a 24-membered macrolide ring system onto which is incor-
porated both a 6,6-spiroketal and a 5-membered hemiketal ring
system. This macrolide series inhibits the mitochondrial Hþ-
ATPase by interacting with the F0-sector to block proton trans-
location, and has potential as a lead for new anticancer drugs
from recent biological investigation.7 A synthesis of 1 was
planned to develop an efficient synthetic methodology, which
would be useful to elaborate more biologically effective deriv-
atives, and we finally accomplished the asymmetric synthesis
of the C1–C16 polyol subunit 2 of 1.8 Our synthetic approach
is a unique methodology of asymmetric induction by using the
steric hindrance of neighboring group. We describe herein our
efficient synthetic process of 2.
Results and Discussion
Our synthetic plan for the polyol subunit 2 of ossamycin (1)
was based on stepwise carbon-chain elongation reaction by the
chiral pool approach employing methyl ꢀ-D-glucopyranoside
(8) as a starting material (Scheme 1). The synthetic strategy
to assemble the carbon framework and to build stereogenic
centers of 2 employed the Wittig olefination and the following
asymmetric dihydroxylation/epoxidation by utilizing steric ef-
fects. The combination of chiral pool and flexible diastereose-
lective reactions affected the efficient synthetic pathway to the
target molecule.
Along this line, the known sugar 7,9 prepared in seven steps
from commercially available 8, was converted into the iodide
9 via tosylation. Reduction of 9 by zinc powder, followed by
OH
O
OH
OH
1
O
O
HO
O
O
1
O
6
OMe
OH
O
H
23
O
OBn
OTES
O
O
8
21
OBn
OH
O
MeO2C
OTBDPS
BnO
O
H
OH
OBn
O
10
O
19
HO
NMe2
HO
Me2N
3
OTBDPS
H
16
15
ossamycin (1)
polyol subunit (2)
OBn
OBn
OTES
OTES
6
9
HO
4
8
OTBDPS
MeO2C
OTBDPS
5
7
stereoselective
stereoselective
mCPBA epoxidation
OBn
OBn
PMBO
OsO4 dihydroxylation
without ligand
4
5
HO
HO
HO
HO
O
OBn
O
TBDPSO
O
OH
OBn
8
OMe
OMe
OH
9
OMe
OBn
OBn
methyl α-D-glucopyranoside (8)
6
7
TBDPS: t-butyldiphenylsilyl PMB: p-methoxybenzyl
Scheme 1. Retrosynthetic analysis.
Published on the web March 8, 2006; DOI 10.1246/bcsj.79.468

N. Kutsumura et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
469
HO
HO
HO
HO
I
O
ref. 9
O
O
c, d
O
a, b
OBn
OBn
10
OH
OBn
OBn
OMe
OMe
OH
OMe
OMe
OBn
HO
OBn
methyl α-D-glucopyranoside (8)
7
9
PPh3
I
O
OBn
TBDPSO
e, f, g, h
TBDPSO
OMe
OBn
6
11
OBn
OBn
OH
OTES
l, m
i, j, k
HO
OTBDPS
OHC
OTBDPS
OBn
OBn
12
13
Scheme 2. Reagents and conditions: (a) TsCl, pyr (99%). (b) NaI, DMF (92%). (c) Zn powder, EtOH. (d) Amberlyst 15E, MeOH
(71% in two steps). (e) 9-BBN, THF, then H2O2, NaOH. (f) (COCl)2, DMSO, Et3N, CH2Cl2. (g) 11, nBuLi, THF. (h) H2, 10%
Pd–C, EtOH (92% in four steps). (i) Et2O BF3, Ac2O. (j) K2CO3, MeOH. (k) NaBH4, MeOH (93% in three steps). (l) TESOTf,
ꢁ
2,6-lutidine, CH2Cl2 (100%). (m) (COCl)2, DMSO, Et3N, CH2Cl2 (95%).
B
)
OBn
OBn
OTES
OTES
2
9
8
OTBDPS
(29%, ca.1:1)
OHC
OTBDPS
THF-ether
then, aq.NaOH, aq.H2O2
OH OBn
OBn
14
13
X
O
O
1) (PhO)2P(O)CH2CO2Et
NaH / THF
N
O
Bu2BOTf, Et3N
CH2Cl2
OBn
OTES
2) DIBAL-H / CH2Cl2
XN
Bn
OTBDPS
X
O
OH OBn
89% in 2 steps
15
Ti(O-iPr)4, D-(-)-DET
TBHP, MS4A
OBn
OBn
OTES
OTES
HO
HO
OTBDPS
OTBDPS
CH2Cl2
O
OBn
OBn
(20%)
16
17
OTES
17'
X
TBHP: t-butylhydroperoxide
OBn
OBn
6
7
HO
mCPBA
HO
OTBDPS
O
OBn
CH2Cl2
O
OBn
Me
(84%, ca.1:1)
X
Scheme 3. Attempt to establish the stereogenic centers at the C6–C7 positions.
recyclization10 and methylation provided the 5-membered sug-
ar 10. The carbon chain of 10 was extended by successive
manipulation involving hydroboration, oxidation of the result-
ing primary alcohol, the Wittig reaction with the phosphonium
salt 11, and then hydrogenation of the resulting double bond.
The furanoside 6 obtained was transformed into the acyclic
diol 12 in three steps. Conversion to the di-TES ether (TES:
triethylsilyl), followed by the chemoselective Swern oxidation
involving a selective deprotection gave the aldehyde 13,11
which might be an important synthetic intermediate of 2
(Scheme 2).
Our first plan for construction of the stereogenic centers at
the C6 and C7 positions of 2 was the Brown crotyl-boration12
or the Evans aldol reaction13 using the aldehyde 13 as a sub-
strate. However, the former protocol furnished the homoallylic
alcohol 14 in poor yield and low selectivity, and the latter
provided no reaction. Also, conversion of 13 to the (Z)-allyl
alcohol 16 in two steps,14 followed by the Sharpless asymmet-
ric epoxidation15 or mCPBA epoxidation was unsuccessful,
because of poor yield or low selectivity. Assembly of the
asymmetric carbon centers at the C6–C7 positions was exacer-
bated by severe steric hindrance of the adjacent benzyl group
at the C8 position. The difficulty of reagent control against
such bulky substrates prompted us to explore an adverse alter-
native strategy by utilizing this stereochemical specificity
(Scheme 3).
A new approach to produce the stereogenic centers at the
C6–C7 positions was an unprecedented pathway that utilizes
steric hindrance; thus, the carbon chain of the aldehyde 13
was lengthened by the Wittig reaction to give 5 (Scheme 4).
In the next step, asymmetric dihydroxylation of 5 was attempt-
ed with catalytic OsO4 (Table 1). As expected, the approach of

470 Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Synthetic Study on Ossamycin
OBn
OBn
OTES
OTES
Ph3P
CO2Me
OHC
OTBDPS
MeO2C
OTBDPS
PhH 100 °C
100%
OBn
OBn
13
5
Scheme 4.
Table 1. Asymmetric Dihydroxylation of 5
OH OBn
OTES
MeO2C
MeO2C
OTBDPS
OTBDPS
OH OBn
18 (desired)
OBn
OTES
Os catalyst
+
MeO2C
OTBDPS
0 °C to rt
OBn
5
OH OBn
OTES
OH OBn
18' (undesired)
Selectivity
(desired 18:undesired 180)a)
Entry
Reagents
OsO4, NMO
AD mix ꢀ, MeSO2NH2
AD mix ꢁ, MeSO2NH2
OsO4, NMO
Solvent
Yields
1
2
3
4
tBuOH–H2O (1/1)
tBuOH–H2O (1/1)
tBuOH–H2O (1/1)
acetone–H2O (10/1)
58%
57%
28%
100%
>15:1
1:3
15:1
>19:1
1
a) Ratio was determined by H NMR spectra.
O
O
OH OBn
OTES
O
OBn
OTES
a, b
c, d
MeO2C
OTBDPS
OTBDPS
OTBDPS
OH OBn
OH OBn
18
19
OBn
OBn
OTES
OTES
e
f, g
HO
HO
OTBDPS
O
OH OBn
OBn
17
20
OBn
OBn
OTES
OTES
OTBDPS
22
h, i
HO
OTBDPS
MeO2C
PMBO
OBn
PMBO
OBn
21
Scheme 5. Reagents and conditions: (a) LiBH4, THF (100%). (b) CO(Im)2, PhH (81%). (c) MsCl, DMAP (4-(dimethylamino)pyri-
dine), pyr. (d) NaOMe, MeOH (95% in two steps). (e) Li2CuMe2(CN), Et2O (87%). (f) p-Anisaldehyde dimethyl acetal, PPTS
(pyridinium p-toluenesulfonate), CH2Cl2 (100%). (g) DIBAL-H, PhMe (64%). (h) Dess–Martin periodinane, NaHCO3, CH2Cl2.
(i) Ph3P=C(Me)CO2Me, PhH (94% in two steps).
the oxidant took place from the least hindered side to give 18
as the predominant product (Entries 1–3). The drawback of the
yields has dramatically improved through solvent selection:
upon using acetone–H2O (10/1), 18 was obtained in 100%
yield (>90% d.e., the minor product could be entirely removed
during the following steps. A detailed inspection of 20 indicat-
ed that no minor product was observed in the spectroscopic
analysis.) (Entry 4).
After LiBH4 reduction, the triol generated was subjected to
selective protection to afford 19 (Scheme 5). After mesylation
and removal of the cyclic carbonate, the resulting diol was
treated under basic conditions to give the epoxy alcohol 17,
the spectroscopic data of which showed the same signal
pattern as that of the product of the Sharpless asymmetric
epoxidation (Scheme 3). Reaction of 17 with Li2CuMe2(CN)
effected the predominant introduction of a methyl group to the
C2 position, leading to the 1,3-diol 20.16 After conversion of
20 to 21 by selective protection of a secondary alcohol, the
remaining primary alcohol was subjected to Dess–Martin oxi-
dation, followed by the Wittig reaction to afford 22. In addi-
tion, the stereochemistry of the asymmetric centers at the C6
and C7 positions was unambiguously established by its con-
version to the 5-membered 24. Thus, 20 was transformed to
the tetrol 23 by the following three-step sequence: (1) trityl

N. Kutsumura et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
471
OBn
OH
OTES
OH
a, b, c
HO
HO
OTBDPS
OTBDPS
OH OBn
OMe OH
20
23
H
6%
O
O
CH3
H
9%
H
OAc
d, e
OTBDPS
3%
9% 5%
H
CH3
H
OCH3
24
OH
OAc
CH3O
H
R
24
Scheme 6. Reagents and conditions: (a) TrCl, pyr, DMAP (86%). (b) MeI, NaH, DMF (74%). (c) H2, Pd(OH)2–C, MeOH–THF
(2/1) (53%). (d) TsCl, pyr. (e) Ac2O, pyr (67% in two steps).
OBn
OBn
OTES
OH
5
OTES
4
MeO2C
OTBDPS
MeO2C
OTBDPS
PMBO
OBn
OP
OBn
22
2
polyol subunit
OPMB
P : protecting group
route A via asymmetric dihydroxylation
OH OH
route B via asymmetric epoxidation
OH
O
R
R
R
R
OH OPMB
inversion
OH OPMB
OPMB
oxygen source
OH OPMB
Scheme 7. Asymmetric induction at the C4–C5 positions.
Table 2. Asymmetric Dihydroxylation of 22
OBn
OH
OTES
MeO2C
OTBDPS
OH
OBn
OPMB
25 (desired)
OBn
OTES
Os catalyst
+
MeO2C
OTBDPS
0 °C to rt
PMBO
OBn
OBn
22
OH
OTES
1 day
MeO2C
OTBDPS
OH
OBn
OPMB
25' (undesired)
Selectivity
(desired 25:undesired 250)a)
Entry
Reagents
Solvent
Yields
1
2
3
4
OsO4, NMO
OsO4, Me3NO
AD mix ꢁ, MeSO2NH2
acetone–H2O (10/1)
acetone–H2O (10/1)
tBuOH–H2O (1/1)
tBuOH–H2O (1/1)
33%
40%
No Reaction
No Reaction
4:1
4:1
AD mix ꢁ, DABCO
1
a) Ratio was determined by H NMR spectra.
protection of the primary alcohol; (2) methyl protection of the
secondary alcohol; and (3) deprotection of trityl, benzyl, and
TES groups. After tosylation of the primary alcohol, the result-
ing triol was treated under basic conditions, followed by ace-
tylation to give the 5-membered 24, the NOE experiments of
which indicated the configuration of the newly introduced ster-
eochemistry as depicted in Scheme 6.
In the next stage, we attempted construction of the stereo-
genic centers at the C4–C5 positions of 22 coinstantaneously
to afford the polyol subunit 2 (Scheme 7). Thus, we considered
two possible pathways to transform 22 into the polyol subunit
2: (1) route A: asymmetric dihydroxylation of 22, followed by
inversion of the secondary alcohol generated and (2) route B:
asymmetric epoxidation of 22, followed by regioselective
induction of an oxygen source.
At first, asymmetric dihydroxylation of 22 (Table 2) provid-
ed 25 and 250 with insufficient yields and selectivity (Entry 2).
Furthermore, the AD mix (reagent for Sharpless asymmetric
dihydroxylation) to improve the selectivity provided no reac-
tion (Entries 3 and 4).
Accordingly, after conversion of 22 to the allyl alcohol 4,
the epoxy alcohol 26 was produced by mCPBA (Scheme 8).
We disclosed that a p-methoxybenzyl group effectively func-
tioned as an anchoring group in the Miyashita epoxidation,

472 Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Synthetic Study on Ossamycin
OBn
OTES
MeO2C
OTBDPS
Ti(O-iPr)4, D-(-)-DET
TBHP, MS4A
PMBO
PMBO
OBn
22
12%
CH2Cl2
X
a
Ac2O
pyr.
26, R = H
27, R = Ac
OBn
OBn
OTES
OTES
4
O
b
RO
HO
RO
OTBDPS
OTBDPS
OTBDPS
PMBO
OBn
OBn
Ti
O
OH
OBn
OTES
O
Table 3
OPMB
oxygen source
OR
OBn
OPMB
Scheme 8. Asymmetric epoxidation of 4 (route B); Reagents and conditions: (a) LiBH4, THF (100%). (b) mCPBA, NaHCO3,
CH2Cl2 (75%).
Table 3. Asymmetric Induction by Oxygen Source
Entry
Substrate
Oxygen source
Additive
Solvent
Conditions
Result
1
2
3
4
26
26
26
26
PivOH
PivOH
PivONa
PivONa
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4,
15-crown-5
Ti(OiPr)4
Ti(OiPr)4,
15-crown-5
Ti(OiPr)4
Ti(OiPr)4
benzene
benzene
DMF
rt, 3d.
No Reaction
No Reaction
No Reaction
No Reaction
70 ꢂC, 1d.
70 ꢂC, 1d.
reflux, 1d.
benzene
5
6
26
26
Bu4NOAc
BzONa
benzene
benzene
70 ꢂC, 2d.
70 ꢂC, 2d.
No Reaction
No Reaction
7
8
9
10
11
12
26
26
27
27
27
27
PhCOOH
AcOCs
PivONa
AcONa
BzONa
CH2Cl2
CH2Cl2
DMF
DMF
DMF
benzene
rt, 1d.
rt, 3d.
115 ꢂC, 3d.
70 ꢂC, 3d.
100 ꢂC, 1d.
reflux, 1d.
No Reaction
No Reaction
No Reaction
No Reaction
No Reaction
No Reaction
15-crown-5
Bu4NOAc
OBn
OBn
OTES
OTES
O
O
a, b
c, d
HO
OTBDPS
MeO2C
OTBDPS
PMBO
OBn
PMBO
OBn
26
28
OH
OBn
OBn
OH
OTES
O
e
MeO2C
OTBDPS
polyol subunit (2)
MeO2C
OTBDPS
O
O
O
OBn
O
OBn
3
Me2N
O
Scheme 9. Reagents and conditions: (a) TPAP, NMO (N-methylmorpholine N-oxide), CH2Cl2. (b) Ph3P=CHCO2Me, benzene
(76% in two steps). (c) DDQ, CH2Cl2–H2O (20/1) (95%). (d) Me2NCOCl, NaH, DMF (64%). (e) Et2O BF3, CH2Cl2 (36%).
ꢁ
while only that of TES groups was reported.17 Interestingly,
exclusive formation of the diastereomeric epoxide 26 as the
sole product was observed from the trisubstituted allylic alco-
hol 4, although the Sharpless asymmetric epoxidation provid-
ed 26 in poor yield. In addition, as shown in Table 3, we
examined introduction of such oxygen sources as tBuCOOH,
tBuCOONa, nBu4NOAc, NaOBz, BzOH, and CsOAc to 26
by expecting a chelation effect by a titanium ion or 27 under
basic conditions. Unfortunately, no desired results were ob-
tained under any of the reaction conditions attempted, because
the severe steric hindrance of the neighboring p-methoxyben-
zyl group interfered with the approach of an oxygen function
to the reactive site. Consequently, we selected removal of
the p-methoxybenzyl group and intramolecular reaction path-
way. After TPAP (tetrapropylammonium perruthenate) oxida-
tion of the epoxy alcohol 26, the carbon-chain elongation af-
forded 28 (Scheme 9). The p-methoxybenzyl group of 28
was removed with DDQ, followed by dimethylcarbamation
to afford 3. At the final stage, exposure of the dimethylcar-
bamyl epoxide 3 to Et2O BF3 at ambient temperature18 gave
the desired polyol subunit cyclic carbonate 2, which possessed
the same carbon framework (C1–C16) as 1. The newly intro-
ꢁ

N. Kutsumura et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
473
dd, J ¼ 1:5, 10.7 Hz), 4.59 (1H, d, J ¼ 3:9 Hz), 4.60–5.05 (4H,
complex), 7.29–7.40 (10H, complex); 13C NMR ꢂ 2.8, 14.9, 55.9,
73.2, 74.4, 74.5, 75.5, 78.9, 82.8, 98.0, 127.7, 127.8, 127.9, 128.0,
128.4, 128.6, 137.8, 138.7; Calcd for C22H27IO5: C, 53.02; H,
5.46%. Found: C, 53.06; H, 5.53%.
(2R,3S,4S,5SR)-3,4-Bis(benzyloxy)tetrahydro-5-methoxy-2-
methyl-2-vinylfuran (10). A mixture of 9 (11.7 g, 23.5 mmol)
and zinc powder (15 g) in EtOH (400 mL) was refluxed for 15 h,
and filtered through a Celite pad. The filtrate was evaporated,
and chromatographically purified (hexane/EtOAc 2/1) to give a
colorless oil (7.3 g).
H5
5
11%
H7
O
CH3
4
O
O
OH
CO2Me
H
R
5%
CH3
Cyclic carbonate part of 2
Fig. 1. The NOE correlation of 2.
A solution of the hemiacetal (7.3 g) in MeOH (110 mL) in the
presence of excess amounts of Amberlyst 15E was refluxed for
17 h, and filtered. The filtrate was evaporated, and chromatograph-
ically purified (EtOAc) to give 10 (5.9 g, 71% in 2 steps): IR (film)
3064, 923 cmꢄ1; 1H NMR ꢂ 1.37 (5.1H, s), 1.40 (3H, s), 3.40 (3H,
s), 3.43 (5.1H, s), 3.81 (1.7H, d, J ¼ 6:4 Hz), 4.00 (2.7H, com-
plex), 4.12 (1H, d, J ¼ 7:3 Hz), 4.51–4.74 (11.8H, complex),
4.89 (1.7H, d, J ¼ 3:4 Hz), 5.16 (2.7H, complex), 5.28 (1H, dd,
J ¼ 1:5, 17.1 Hz), 5.42 (1.7H, dd, J ¼ 1:5, 17.1 Hz), 5.98 (1H, dd,
J ¼ 10:8, 17.6 Hz), 6.15 (1.7H, dd, J ¼ 10:7, 17.1 Hz), 7.24–7.36
(27H, complex); 13C NMR ꢂ 27.6, 54.8, 72.6, 72.8, 81.0, 83.1,
87.5, 99.5, 113.1, 127.5, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2,
128.3, 137.8, 138.2, 139.9; Calcd for C22H26O4: C, 74.55; H,
7.39%. Found: C, 74.43; H, 7.23%.
duced stereochemistry at the C4–C5 positions of 2 was deter-
mined by its reaction process from 3 and the NOE experiments
(Fig. 1).
In conclusion, this unique approach of the asymmetric syn-
thesis of polyol subunit 2 was accomplished by utilizing the
steric hindrance of neighboring groups. This C1–C16 skeleton
could be a useful synthetic intermediate for the total synthesis
of ossamycin (1).
Experimental
General. IR spectra were recorded on a JASCO Model A-202
1
spectrophotometer. H NMR and 13C NMR spectra were obtained
on JEOL JNM EX-270 and JEOL JNM GX-400 spectrometers in a
deuteriochloroform (CDCl3) solution using tetramethylsilane as
an internal standard. High-resolution mass spectra were obtained
on a Hitachi M-80 B GC-MS spectrometer operating at the ioni-
zation energy of 70 eV or on a JEOL JMS-700 (FAB) spectrome-
ter. Optical rotations were recorded at the sodium D line and at
ambient temperatures with a JASCO DIP-360 digital polarimeter.
Preparative and analytical TLC were carried out on silica-gel
plates (Kieselgel 60 F254, E. Merck AG, Germany) using UV
light and/or 5% phosphomolybdic acid in ethanol for detection.
Kanto Chemical silica 60N (spherical, neutral, 63–210 mm) was
used for column chromatography. Silica-gel column chromatogra-
phy was used for purification of crude products, unless otherwise
stated. Work-up procedure: A reaction mixture was partitioned be-
tween EtOAc or CHCl3 and H2O. The organic layer was washed
with brine, dried (Na2SO4), and then evaporated.
{6-[(2R,3S,4S,5SR)-3,4-Bis(benzyloxy)tetrahydro-5-methoxy-
2-methylfuran-2-yl]hexyloxy}(t-butyl)diphenylsilane (6).
A
mixture of 10 (3.42 g, 9.7 mmol) and 9-BBN (0.5 M solution in
THF, 40 mL, 20.3 mmol) in THF (12 mL) was stirred at ambient
temperature for 16 h; the reaction was quenched by the addition
of 3 M aq NaOH (10 mL) and 35% aq H2O2 (10 mL) at 0 ꢂC.
The reaction mixture was stirred at ambient temperature for
5 h. After work-up, the residue was chromatographically purified
(hexane/EtOAc 3/1) to give a colorless oil (3.49 g, 97%): IR
1
(film) 3457, 2927, 1496 cmꢄ1; H NMR ꢂ 1.36 (3H, s), 1.37 (3H,
s), 1.68–2.10 (4H, complex), 2.59 (1H, br), 3.02 (1H, br), 3.37
(3H, s), 3.40 (3H, s), 3.75–4.15 (8H, complex), 4.52–4.87 (10H,
complex), 7.32–7.38 (20H, complex); Calcd for C22H28O5: C,
70.94; H, 7.58%. Found: C, 70.65; H, 7.66%.
To a solution of (COCl)2 (0.67 mL, 7.5 mmol) in CH2Cl2 (13
mL) was added DMSO (0.67 mL, 9.4 mmol) in CH2Cl2 (9 mL)
at ꢄ78 ꢂC. The mixture was stirred for 5 min, and the alcohol
(1.40 g, 3.8 mmol) in CH2Cl2 (13 mL) was added slowly. After be-
ing stirred at ꢄ78 ꢂC for 10 min, Et3N (2.6 mL, 18.9 mmol) was
added and the mixture was allowed to warm to ambient tempera-
ture. After work-up, the residue was chromatographically purified
(hexane/EtOAc 4/1) to give a colorless oil (1.40 g).
Methyl 2,3-Di-O-benzyl-6-iodo-4-C-methyl-ꢀ-D-glucopyran-
oside (9). A mixture of 7 (589 mg, 1.5 mmol) and TsCl (640
mg, 3.4 mmol) in pyridine (10 mL) was stirred at ambient temper-
ature for 16 h. After work-up, the residue was chromatographical-
ly purified (hexane/EtOAc 3/2) to give a colorless oil (811 mg,
22
99%): ½ꢀꢃD þ17:3 (c 1.00, CHCl3); IR (film) 3585, 1361, 1176
1
cmꢄ1; H NMR ꢂ 1.07 (3H, s), 1.83 (1H, br), 2.43 (3H, s), 3.33
(3H, s), 3.40 (1H, dd, J ¼ 3:9, 10.3 Hz), 3.68 (1H, d, J ¼ 10:0
Hz), 3.79 (1H, dd, J ¼ 1:5, 8.8 Hz), 4.04 (1H, dd, J ¼ 8:8, 10.7
Hz), 4.28 (1H, dd, J ¼ 1:5, 10.7 Hz), 4.55 (1H, d, J ¼ 3:9 Hz),
4.59–5.02 (4H, complex), 7.23–7.38 (12H, complex), 7.76 (2H,
d, J ¼ 8:4 Hz); 13C NMR ꢂ 15.9, 21.7, 55.1, 68.6, 71.0, 72.9,
73.2, 75.6, 78.7, 83.1, 97.6, 127.6, 127.8, 127.9, 128.4, 128.5,
129.7, 132.9, 137.8, 138.6, 144.6; Calcd for C29H34O8S: C,
64.19; H, 6.32; S, 5.91%. Found: C, 64.44; H, 6.40; S, 6.24%.
A mixture of the tosylate (13.8 g, 25.4 mmol) and NaI (38 g) in
DMF (150 mL) was stirred at 95 ꢂC for 14 h. After the addition of
sat. aq Na2SO3 and the following work-up, the crude was chroma-
tographically purified (hexane/EtOAc 3/1) to give 9 (11.7 g,
To a suspension of 11 (6.8 g, 9.7 mmol) in THF (20 mL) was
added n-BuLi (1.58 M solution in hexane, 3.60 mL, 5.7 mmol) at
ꢄ25 ꢂC for 1.5 h. A solution of the aldehyde (1.4 g, 3.8 mmol)
in THF (10 mL) was added at ꢄ20 ꢂC. The mixture was stirred
at ambient temperature for 13 h, and work-up was performed.
The residue was chromatographically purified (hexane/EtOAc
20/1) to give a colorless oil (2.37 g), which was stirred in EtOH
(60 mL) in the presence of catalytic 10% Pd–C for 4 h under
hydrogen pressure. After filtration through a Celite pad, the sol-
vent was removed. The residue was chromatographically purified
(hexane/EtOAc 10/1) to give 6 (2.38 g, 95% in 3 steps): IR (film)
2929, 2360, 2341, 1106 cmꢄ1 1H NMR ꢂ 1.04 (18H, s), 1.26
;
24
92%): ½ꢀꢃD þ9:0 (c 1.00, CHCl3); IR (film) 3540 cmꢄ1; 1H NMR
(3H, s), 1.26–1.66 (20H, complex), 1.30 (3H, s), 3.36 (6H, s),
3.61–3.66 (4H, complex), 3.75–4.10 (4H, complex), 4.50–4.82
(10H, complex), 7.26–7.41 (32H, complex), 7.66 (8H, complex);
ꢂ 1.11 (3H, s), 1.90 (1H, s), 3.07 (1H, t, J ¼ 10:7 Hz), 3.42–3.49
(2H, complex), 3.52 (3H, s), 3.70 (1H, d, J ¼ 9:8 Hz), 3.81 (1H,

474 Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Synthetic Study on Ossamycin
13C NMR ꢂ 19.3, 23.4, 23.7, 24.9, 25.9, 27.0, 28.2, 28.6, 30.1,
30.4, 32.7, 35.6, 37.7, 53.2, 55.4, 55.9, 64.0, 72.3, 72.48, 72.51,
73.0, 77.2, 81.9, 84.0, 84.3, 88.1, 89.3, 89.4, 89.7, 99.4, 99.7,
100.5, 107.2, 111.4, 119.5, 127.4, 127.5, 127.7, 127.9, 128.2,
128.28, 128.33, 129.4, 130.4, 134.1, 135.5, 137.7, 138.2, 142.3,
166.1; Calcd for C42H54O5Si: C, 75.63; H, 8.16%. Found: C,
75.55; H, 8.06%.
13C NMR ꢂ 6.8, 7.2, 7.5, 19.3, 25.9, 26.9, 32.7, 36.7, 38.9, 64.0,
75.1, 77.2, 84.6, 100.5, 127.5, 127.6, 127.9, 128.1, 128.16, 128.24,
128.3, 129.4, 134.1, 135.5, 202.3; Calcd for C47H66O5Si2
0.6H2O: C, 72.56; H, 8.71%. Found: C, 72.55; H, 9.05%.
(E,4S,5R,6R)-Methyl 4,5-Bis(benzyloxy)-12-t-butyldiphenyl-
siloxy-6-triethylsiloxy-6-methyldodec-2-enoate (5). To a stir-
red solution of 13 (726 mg, 0.95 mmol) in PhH (10 mL) was added
Ph3P=CHCO2Me (949 mg, 2.8 mmol) at 100 ꢂC for 13 h. The re-
action mixture was concentrated in vacuo and chromatographical-
ꢁ
(2S,3R,4R)-2,3-Bis(benzyloxy)-10-t-butyldiphenylsiloxy-4-
methyldecane-1,4-diol (12). To a solution of 6 (2.86 g, 4.3
28
mmol) in Ac2O (40 mL) was added Et2O BF3 (55 mL, 0.43 mmol)
ly purified (hexane/EtOAc 5/1) to give 5 (779 mg, 100%): ½ꢀꢃD
ꢁ
at ꢄ25 ꢂC. After being stirred at the same temperature for 30 min
and the following work-up, the residue was chromatographically
purified (hexane/EtOAc 6/1) to give a crude oil, which was dis-
solved in MeOH (24 mL), and then K2CO3 (62.6 mg, 0.45 mmol)
was added. After being stirred at ambient temperature for 3.5 h,
the solution was evaporated. The residue was chromatographically
purified (hexane/EtOAc 4/1) to give a colorless oil.
þ10:5 (c 1.00, CHCl3); IR (film) 3068, 3029, 2933, 1725, 1654
cmꢄ1; H NMR ꢂ 0.54–0.60 (6H, complex), 0.90–0.94 (9H, com-
1
plex), 1.05 (9H, s), 1.14–1.55 (10H, complex), 1.31 (3H, s), 3.32
(1H, d, J ¼ 4:9 Hz), 3.63 (2H, complex), 3.75 (3H, s), 4.23 (1H,
m), 4.37 (1H, d, J ¼ 11:7 Hz), 4.60 (2H, complex), 4.79 (1H, d,
J ¼ 11:7 Hz), 6.02 (1H, dd, J ¼ 1:0, 15.6 Hz), 7.01 (1H, dd, J ¼
6:3, 15.6 Hz), 7.23–7.43 (16H, complex), 7.66–7.68 (4H, com-
plex); 13C NMR ꢂ 6.7, 6.8, 6.9, 7.3, 19.2, 23.8, 25.7, 25.8, 26.9,
30.1, 32.6, 38.9, 51.4, 63.9, 71.6, 75.7, 77.3, 78.2, 79.0, 87.9,
120.6, 127.2, 127.4, 127.5, 127.7, 127.9, 128.02, 128.1, 128.2,
129.4, 134.0, 135.4, 137.6, 138.5, 147.4, 166.5; Calcd for C50H70-
O6Si2: C, 72.95; H, 8.57%. Found: C, 72.89; H, 8.47%.
A mixture of the hemiacetal and NaBH4 (1.59 g, 42.1 mmol) in
MeOH (42 mL) was stirred at ambient temperature for 2 h. After
work-up, the residue was chromatographically purified (hexane/
22
EtOAc 3/1) to give 12 (2.61 g, 93% in 3 steps): ½ꢀꢃD ꢄ6:6 (c
1.00, CHCl3); IR (film) 3585, 3397, 3068, 2931 cmꢄ1 1H NMR
;
ꢂ 1.04 (9H, s), 1.22–1.65 (10H, complex), 1.25 (3H, s), 2.55 (2H,
br), 2.69 (1H, br), 3.39 (1H, d, J ¼ 4:9 Hz), 3.64 (2H, t, J ¼ 6:3
Hz), 3.74–3.82 (3H, complex), 4.54 (1H, d, J ¼ 11:2 Hz), 4.66
(2H, s), 4.77 (1H, d, J ¼ 11:2 Hz), 7.23–7.41 (16H, complex),
7.65–7.68 (4H, complex); 13C NMR ꢂ 19.3, 22.9, 23.8, 25.9,
26.9, 30.1, 32.6, 39.5, 62.1, 63.9, 72.7, 74.7, 75.0, 79.2, 82.8,
127.5, 127.7, 127.8, 127.9, 128.0, 134.0, 135.4, 138.0; Calcd for
C41H54O5Si: C, 75.19; H, 8.31%. Found: C, 74.87; H, 8.30%.
(2R,3R,4R)-2,3-Bis(benzyloxy)-10-t-butyldiphenylsiloxy-4-
triethylsiloxy-4-methyldecanal (13). A mixture of 12 (2.61 g,
4.0 mmol) and TESOTf (2.7 mL, 12 mmol) in CH2Cl2 (20 mL) in
the presence of 2,6-lutidine (4.6 mL, 40 mmol) was stirred at 0 ꢂC
for 30 min. After work-up, the residue was chromatographically
purified (hexane/EtOAc 5/1) to give a colorless oil (3.52 g,
(2S,3S,4S,5R,6R)-Methyl 4,5-Bis(benzyloxy)-12-t-butyldi-
phenylsiloxy-6-triethylsiloxy-2,3-dihydroxy-6-methyldodecano-
ate (18).
To a solution of 5 (1.08 g, 1.3 mmol) in acetone
(12 mL)–H2O (1.2 mL) was added OsO4 (39.3 mM solution in
tBuOH, 3.3 mL, 0.13 mmol) and N-methylmorpholine N-oxide
(NMO) (461 mg, 3.9 mmol) at 0 ꢂC. The reaction mixture was stir-
red at the same temperature for 10 h, and then at ambient temper-
ature for 30 h. After the addition of sat. aq Na2SO3 and the follow-
ing work-up, the residue was chromatographically purified
25
(hexane/EtOAc 5/1) to give 18 (1.22 g, 100%): ½ꢀꢃD þ1:9 (c
1.00, CHCl3); IR (film) 3444, 3068, 3029, 2933, 2875 cmꢄ1
;
1H NMR ꢂ 0.60–0.66 (6H, complex), 0.92–0.98 (9H, complex),
1.06 (9H, s), 1.06–1.55 (10H, complex), 1.90 (1H, m), 3.09 (1H,
d, J ¼ 8:4 Hz), 3.44 (1H, d, J ¼ 4:8 Hz), 3.64 (2H, complex), 3.78
(3H, s), 3.89 (1H, m), 3.96 (1H, m), 4.28 (1H, m), 4.42 (1H, d, J ¼
11:2 Hz), 4.54 (1H, d, J ¼ 8:4 Hz), 4.69 (2H, m), 4.80 (1H, d, J ¼
11:6 Hz), 7.22–7.43 (16H, complex), 7.66–7.69 (4H, complex);
13C NMR ꢂ 6.8, 6.9, 7.0, 7.2, 19.3, 24.8, 25.4, 25.9, 26.9, 30.1,
32.6, 40.0, 52.3, 63.9, 71.0, 73.1, 73.8, 73.9, 79.5, 83.8, 127.4,
127.5, 127.56, 127.60, 128.0, 128.16, 128.21, 128.3, 129.4, 134.0,
135.4, 138.2, 138.2, 174.3; Calcd for C50H72O8Si2: C, 70.05; H,
8.47%. Found: C, 69.88; H, 8.39%.
28
100%): ½ꢀꢃD ꢄ1:0 (c 1.00, CHCl3); IR (film) 2952, 1456, 1110
cmꢄ1 1H NMR ꢂ 0.54–0.63 (12H, complex), 0.91–0.97 (18H,
;
complex), 1.05 (9H, s), 1.31 (3H, s), 1.16–1.55 (10H, complex),
3.42 (1H, d, J ¼ 2:9 Hz), 3.62–3.75 (5H, complex), 4.61–4.76
(4H, complex), 7.21–7.41 (16H, complex), 7.66–7.68 (4H, com-
plex); 13C NMR ꢂ 4.5, 6.9, 7.1, 7.4, 18.2, 19.3, 19.6, 23.8, 25.87,
25.90, 25.94, 26.88, 26.92, 30.3, 32.7, 34.5, 39.5, 63.7, 63.9, 64.0,
73.4, 75.4, 76.7, 77.3, 78.67, 78.68, 79.9, 84.3, 122.8, 127.1,
127.3, 127.5, 127.7, 128.02, 128.03, 128.1, 129.4, 134.1, 135.5,
138.9, 139.2, 181.0; Calcd for C53H82O5Si3: C, 72.05; H, 9.36%.
Found: C, 71.70; H, 9.08%.
To a solution of (COCl)2 (0.39 mL, 4.4 mmol) in CH2Cl2 (3
mL) was added DMSO (0.63 mL, 8.9 mmol) in CH2Cl2 (3 mL)
at ꢄ78 ꢂC. The mixture was stirred for 15 min, and then the di-
TES ether (884 mg, 1.0 mmol) in CH2Cl2 (3 mL) was added slow-
ly. After being stirred at ꢄ40 ꢂC for 2 h, Et3N (2.1 mL, 15.1 mmol)
was added at ꢄ78 ꢂC and the mixture allowed to warm to ambient
temperature. After work-up, the residue was chromatographically
(R)-4-[(1S,2S,3R,4R)-2,3-Bis(benzyloxy)-10-t-butyldiphenyl-
siloxy-4-triethylsiloxy-1-hydroxy-4-methyldecyl]-1,3-dioxolan-
2-one (19). A mixture of 18 (55.5 mg, 0.065 mmol) and LiBH4
(16.7 mg, 0.77 mmol) in THF (1 mL) was stirred at 0 ꢂC for 2 h,
and then work-up was performed. The residue was chromato-
graphically purified (hexane/EtOAc 1/1) to give a colorless oil
26
(58.2 mg, 100%): ½ꢀꢃD ꢄ4:6 (c 1.00, CHCl3); IR (film) 3424,
3068, 3029, 2933, 2875 cmꢄ1 1H NMR ꢂ 0.60–0.66 (6H, com-
;
plex), 0.93–0.97 (9H, complex), 0.97–1.55 (9H, complex), 1.05
(9H, s), 1.36 (3H, s), 1.90 (1H, m), 2.73 (1H, d, J ¼ 9:2 Hz),
2.91 (1H, d, J ¼ 8:8 Hz), 3.39 (1H, d, J ¼ 4:8 Hz), 3.64 (2H, com-
plex), 3.75 (1H, m), 3.83 (1H, m), 3.96–4.03 (3H, complex), 4.19
(1H, m), 4.42 (1H, d, J ¼ 11:6 Hz), 4.67 (2H, s), 4.77 (1H, d,
J ¼ 11:6 Hz), 7.24–7.43 (16H, complex), 7.66–7.68 (4H, com-
plex); 13C NMR ꢂ 6.8, 7.0, 7.1, 7.3, 19.3, 24.7, 25.0, 25.4, 25.9,
26.9, 30.2, 32.6, 40.2, 63.9, 66.2, 69.5, 73.8, 74.18, 74.21, 77.9,
79.5, 83.5, 126.8, 127.50, 127.54, 127.6, 127.7, 128.0, 128.1,
128.21, 128.24, 128.3, 128.5, 129.4, 130.6, 130.8, 134.0, 135.5,
26
purified (hexane/EtOAc 5/1) to give 13 (726 mg, 95%): ½ꢀꢃD
þ9:45 (c 0.20, CHCl3); IR (film) 3068, 2929, 2856, 1729, 1456,
1427 cmꢄ1; H NMR ꢂ 0.56–0.62 (6H, complex), 0.91–0.95 (9H,
1
complex), 0.93–1.55 (9H, complex), 1.05 (9H, s), 1.30 (3H, s),
1.66 (1H, m), 3.58 (1H, d, J ¼ 5:9 Hz), 3.63 (2H, t, J ¼ 6:3 Hz),
4.05 (1H, dd, J ¼ 2:4, 5.9 Hz), 4.49–4.55 (2H, complex), 4.68
(1H, d, J ¼ 11:7 Hz), 4.76 (1H, d, J ¼ 11:2 Hz), 7.26–7.41 (16H,
complex), 7.66–7.67 (4H, complex), 9.58 (1H, d, J ¼ 2:8 Hz);

N. Kutsumura et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
475
138.10, 138.15; Calcd for C49H72O7Si2: C, 70.97; H, 8.75%.
Found: C, 70.99; H, 8.69%.
A mixture of the triol (546 mg, 0.66 mmol) and Im2CO
(124 mg, 0.77 mmol) in PhH (7 mL) was stirred at room tempera-
ture for 1.5 h. After work-up, the residue was chromatographically
(2S,3R,4S,5R,6R)-4,5-Bis(benzyloxy)-12-t-butyldiphenylsil-
oxy-6-triethylsiloxy-3-(4-methoxybenzyloxy)-2,6-dimethyldo-
decan-1-ol (21). A mixture of 20 (1.7 g, 2.1 mmol) and p-anisal-
dehyde dimethyl acetal (0.35 mL, 2.1 mmol) in CH2Cl2 in the
presence of catalytic amounts of PPTS was stirred at room tem-
perature for 7 h. After work-up, the residue was chromatographi-
cally purified (hexane/EtOAc 2/1) to give a colorless oil (1.4 g,
23
purified (hexane/EtOAc 4/1) to give 19 (455 mg, 81%): ½ꢀꢃD
ꢄ35:2 (c 1.00, CHCl3); IR (film) 3444, 2935, 1808, 1646 cmꢄ1
;
26
1H NMR ꢂ 0.60–0.66 (6H, complex), 0.91–0.95 (9H, complex),
1.05 (9H, s), 1.09–1.56 (9H, complex), 1.36 (3H, s), 1.93 (1H,
m), 3.43 (1H, d, J ¼ 3:9 Hz), 3.65 (2H, complex), 3.94 (2H, com-
plex), 4.19 (1H, m), 4.43 (2H, complex), 4.52 (1H, m), 4.59 (1H,
d, J ¼ 11:2 Hz), 4.69 (1H, d, J ¼ 11:2 Hz), 4.78 (1H, d, J ¼ 11:2
Hz), 5.04 (1H, m), 7.25–7.43 (16H, complex), 7.66–7.68 (4H,
complex); 13C NMR ꢂ 6.8, 7.0, 19.3, 25.1, 25.4, 26.0, 26.9, 30.2,
32.6, 40.1, 63.9, 65.8, 71.9, 73.9, 74.1, 75.5, 76.7, 77.2, 79.6, 83.2,
127.5, 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 129.4, 134.0,
135.5, 137.7, 155.3; Calcd for C50H70O8Si2: C, 70.22; H, 8.25%.
Found: C, 70.34; H, 8.20%.
100%): ½ꢀꢃD ꢄ20:5 (c 1.00, CHCl3); IR (film) 3068, 3029, 2933,
2875, 2858 cmꢄ1; 1H NMR ꢂ 0.63–0.69 (6H, complex), 1.00 (9H,
complex), 1.06 (9H, s), 1.16–1.62 (11H, complex), 1.22 (3H, d,
J ¼ 6:4 Hz), 1.44 (3H, s), 3.43 (1H, m), 3.65 (2H, complex), 3.77–
3.83 (3H, complex), 3.80 (3H, s), 4.29 (1H, d, J ¼ 8:3 Hz), 4.56
(1H, d, J ¼ 10:8 Hz), 4.63 (1H, d, J ¼ 12:2 Hz), 4.92 (2H, com-
plex), 5.44 (1H, s), 6.85 (2H, complex), 7.17–7.44 (18H, com-
plex), 7.67–7.69 (4H, complex); 13C NMR ꢂ 7.1, 7.4, 12.0, 19.3,
24.0, 26.0, 26.3, 26.9, 30.1, 30.3, 32.7, 40.6, 55.3, 63.9, 73.7, 74.2,
75.0, 77.2, 78.0, 80.1, 82.6, 83.1, 101.9, 113.4, 127.1, 127.2,
127.3, 127.5, 127.7, 127.9, 128.19, 128.21, 129.4, 131.4, 134.1,
135.3, 135.5, 138.8, 139.1, 159.6; Calcd for C58H80O7Si2: C,
73.68; H, 8.53%. Found: C, 73.82; H, 8.42%.
{(2R,3R)-3-[(1S,2R,3R)-1,2-Bis(benzyloxy)-9-t-butyldiphenyl-
siloxy-3-triethylsiloxy-3-methylnonyl]oxiran-2-yl}methanol (17).
A mixture of 19 (455 mg, 0.53 mmol), MsCl (412 mL, 5.3 mmol),
and catalytic amounts of DMAP in pyridine (5.3 mL) was stirred
at ambient temperature for 12 h. After work-up, the residue was
chromatographically purified (PhH/Et2O 30/1) to give a colorless
oil (515 mg).
To a solution of the acetal (1.4 g, 1.5 mmol) in PhMe (15 mL)
was added DIBAL-H (1.01 M solution in PhMe, 1.8 mL, 1.8
mmol) at 0 ꢂC. After being stirred for 8 h, the reaction was
quenched by the addition of sat. aq NH4Cl, and then work-up
was performed. The residue was chromatographically purified
26
A mixture of the mesylate (515 mg) and NaOMe (0.5 M solu-
tion in MeOH, 0.93 mL, 0.47 mmol) in MeOH (6 mL)–THF
(3 mL) was stirred at 0 ꢂC for 4 h and then work-up was per-
formed; the residue was chromatographically purified (hexane/
(hexane/EtOAc 2/1) to give 21 (0.91 g, 64%): ½ꢀꢃD þ10:6 (c
1.00, CHCl3); IR (film) 3585, 3438, 3068, 3029, 2933, 2875
1
cmꢄ1; H NMR ꢂ 0.58–0.64 (6H, complex), 0.94–0.99 (9H, com-
plex), 0.94–0.99 (3H, complex), 1.05 (9H, s), 1.09–1.34 (7H, com-
plex), 1.15 (3H, s), 1.49–1.54 (2H, complex), 1.85 (1H, m), 2.14
(1H, m), 2.36 (1H, br), 3.22 (1H, d, J ¼ 3:9 Hz), 3.49–3.54 (3H,
complex), 3.63 (2H, complex), 3.74 (3H, s), 3.94 (1H, m), 4.50–
4.64 (4H, complex), 4.80–4.85 (2H, complex), 6.80 (2H, com-
plex), 7.17–7.27 (12H, complex), 7.36–7.43 (6H, complex), 7.66–
7.68 (4H, complex); 13C NMR ꢂ 7.0, 7.3, 12.6, 19.3, 24.7, 25.96,
26.00, 26.9, 30.4, 32.8, 35.9, 40.4, 55.2, 64.0, 65.5, 72.4, 73.9,
74.6, 76.2, 78.7, 81.2, 83.3, 113.7, 126.9, 127.2, 127.46, 127.49,
128.1, 129.4, 130.0, 130.3, 134.1, 135.5, 138.4, 139.6, 159.1;
Calcd for C58H82O7Si2: C, 73.53; H, 8.72%. Found: C, 73.53;
H, 8.65%.
(E,4S,5R,6S,7R,8R)-Methyl 6,7-Bis(benzyloxy)-14-t-butyldi-
phenylsiloxy-8-triethylsiloxy-5-(4-methoxybenzyloxy)-2,4,8-tri-
methyltetradec-2-enoate (22). A mixture of 21 (100 mg, 0.11
mmol) and Dess–Martin periodinane (135 mg, 0.32 mmol) in
CH2Cl2 (1.1 mL) in the presence of NaHCO3 (89 mg, 1.1 mmol)
was added at room temperature for 4 h. After work-up, the residue
was chromatographically purified (hexane/EtOAc 3/1) to give a
colorless oil (98.1 mg).
24
EtOAc 7/1) to give 17 (424 mg, 95% in 2 steps): ½ꢀꢃD þ19:1
(c 1.00, CHCl3); IR (film) 3455, 2935, 2873, 1457, 1106 cmꢄ1
;
1H NMR ꢂ 0.58–0.65 (6H, complex), 0.92–0.96 (9H, complex),
1.02–1.51 (9H, complex), 1.05 (9H, s), 1.37 (3H, s), 1.65 (1H, m),
2.69 (1H, dd, J ¼ 4:4, 9.3 Hz), 2.91 (1H, m), 3.34–3.45 (4H, com-
plex), 3.62 (2H, complex), 3.71 (1H, m), 4.49 (2H, complex), 4.59
(1H, d, J ¼ 11:7 Hz), 4.83 (1H, d, J ¼ 12:2 Hz), 7.25–7.45 (16H,
complex), 7.66–7.68 (4H, complex); 13C NMR ꢂ 7.0, 7.2, 19.3,
24.6, 25.7, 25.9, 26.9, 30.1, 32.7, 40.7, 54.6, 58.9, 60.8, 64.0, 72.0,
74.0, 78.8, 83.1, 127.5, 127.6, 128.1, 128.2, 128.4, 129.0, 129.4,
134.0, 135.5, 137.1, 138.0; Calcd for C49H70O6Si2: C, 72.55; H,
8.70%. Found: C, 72.33; H, 8.64%.
(2S,3R,4S,5R,6R)-4,5-Bis(benzyloxy)-12-t-butyldiphenylsil-
oxy-6-triethylsiloxy-2,6-dimethyldodecane-1,3-diol (20). To a
suspension of CuCN (711 mg, 7.9 mmol) in Et2O (1 mL) was add-
ed MeLi (1.02 M solution in Et2O, 15 mL, 15.3 mmol) at ꢄ78 ꢂC.
After being stirred at 0 ꢂC for 10 min, 17 (644 mg, 0.79 mmol) in
Et2O (4 mL) was added at ꢄ78 ꢂC, and the mixture was stirred at
0 ꢂC for 8 h. After the addition of 35% aq NH3 and the following
work-up, the residue was chromatographically purified (PhH/
A mixture of the aldehyde (98.1 mg) and Ph3P=C(Me)CO2Me
(181 mg, 0.52 mmol) in PhH (4 mL) was stirred at 100 ꢂC for 18 h.
The reaction mixture was concentrated in vacuo and chromato-
graphically purified (hexane/EtOAc 10/1) to give 22 (101 mg,
25
Et2O 10/1) to give 20 (570 mg, 87%): ½ꢀꢃD ꢄ11:3 (c 1.00,
1
CHCl3); IR (film) 3446, 3068, 3029, 2933, 2875 cmꢄ1; H NMR
ꢂ 0.60–0.65 (6H, complex), 0.94–0.98 (9H, complex), 1.04 (9H,
s), 1.04 (3H, m), 1.23–1.59 (9H, complex), 1.26 (3H, s), 2.00 (2H,
complex), 2.12 (1H, br), 2.84 (1H, d, J ¼ 6:8 Hz), 3.50 (1H, d,
J ¼ 6:4 Hz), 3.62–3.65 (4H, complex), 3.70 (1H, m), 3.89 (1H,
m), 4.48 (1H, d, J ¼ 10:8 Hz), 4.53 (1H, d, J ¼ 11:7 Hz), 4.82
(1H, d, J ¼ 11:7 Hz), 4.94 (1H, d, J ¼ 10:8 Hz), 7.25–7.41 (16H,
complex), 7.66–7.67 (4H, complex); 13C NMR ꢂ 7.0, 7.3, 12.5,
19.3, 24.8, 25.7, 26.0, 26.9, 30.4, 32.7, 39.1, 39.6, 64.0, 66.8, 73.9,
74.6, 75.4, 78.0, 78.5, 84.0, 127.2, 127.5, 127.6, 128.06, 128.09,
25
94% in 2 steps): ½ꢀꢃD ꢄ10:2 (c 1.00, CHCl3); IR (film) 3068,
3030, 2933, 2873, 1716, 1612 cmꢄ1 1H NMR ꢂ 0.57–0.63 (6H,
;
complex), 0.93–0.97 (9H, complex), 0.97–1.38 (7H, complex),
1.04 (9H, s), 1.15–1.18 (3H, complex), 1.18 (3H, s), 1.50–1.54
(2H, complex), 1.81 (3H, s), 1.90 (1H, m), 3.13 (1H, m), 3.30 (1H,
m), 3.37 (1H, m), 3.61–3.64 (2H, complex), 3.70 (3H, s), 3.75
(3H, s), 3.84 (1H, m), 4.36–4.42 (2H, complex), 4.58 (1H, d, J ¼
11:2 Hz), 4.71 (1H, d, J ¼ 11:2 Hz), 4.82–4.87 (2H, complex),
6.77 (1H, d, J ¼ 9:8 Hz), 6.82 (2H, complex), 7.19–7.26 (12H,
complex), 7.35–7.41 (6H, complex), 7.66–7.67 (4H, complex);
128.3, 129.4, 134.1, 135.5, 138.3, 138.9; Calcd for C50H74O6Si2
0.4H2O: C, 71.97; H, 9.04%. Found: C, 71.85; H, 8.90%.
ꢁ

476 Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Synthetic Study on Ossamycin
13C NMR ꢂ 7.0, 7.3, 12.7, 16.2, 19.3, 24.9, 25.9, 26.1, 26.9, 30.4,
32.8, 35.8, 40.1, 51.7, 55.2, 64.0, 74.2, 74.3, 74.4, 77.3, 78.0, 78.4,
83.3, 84.2, 113.7, 126.76, 126.79, 126.9, 127.2, 127.5, 127.7,
127.85, 127.88, 129.4, 129.8, 130.5, 134.1, 135.5, 139.0, 139.5,
144.7, 159.1, 168.4; Calcd for C62H86O8Si2: C, 73.33; H, 8.54%.
Found: C, 73.38; H, 8.45%.
for 13 h. After work-up, the residue was chromatographically
purified (hexane/EtOAc 2/1) to give a colorless oil.
A mixture of the product and Ac2O (0.5 mL, 5.3 mmol) in pyr-
idine (1.5 mL) was stirred at room temperature for 17 h. After
work-up, the residue was chromatographically purified (hexane/
24
EtOAc 2/1) to give 24 (27.4 mg, 67% in 2 steps): ½ꢀꢃD þ9:1
(2S,3R,4R,5R,6R)-12-t-Butyldiphenylsiloxy-3-methoxy-2,6-di-
methyldodecane-1,4,5,6-tetrol (23). A mixture of 20 (329 mg,
0.40 mmol), TrCl (311 mg, 1.1 mmol), and catalytic amounts of
DMAP in pyridine (5 mL) was stirred at 75 ꢂC for 18 h. After
work-up, the residue was chromatographically purified (hexane/
(c 1.00, CHCl3); IR (film) 3498, 3070, 2933, 2857, 1741 cmꢄ1
;
1H NMR ꢂ 1.03–1.07 (3H, complex), 1.05 (9H, s), 1.21–1.44 (8H,
complex), 1.22 (3H, s), 1.54 (2H, complex), 2.09 (3H, s), 2.36
(1H, m), 3.27–3.36 (2H, complex), 3.31 (3H, s), 3.55 (1H, m),
3.63–3.66 (2H, complex), 4.11 (1H, m), 4.33 (1H, m), 5.06 (1H,
m), 7.35–7.41 (6H, complex), 7.64–7.68 (4H, complex); 13C NMR
ꢂ 16.6, 19.3, 21.4, 23.4, 24.2, 25.9, 26.9, 30.1, 32.6, 38.57, 38.60,
57.9, 64.0, 73.0, 74.1, 74.29, 74.31, 77.8, 88.4, 127.5, 129.4,
24
EtOAc 4/1) to give a colorless oil (365 mg, 86%): ½ꢀꢃD ꢄ14:4
(c 1.00, CHCl3); IR (film) 3568, 3066, 3032, 2933, 2873 cmꢄ1
;
1H NMR ꢂ 0.55–0.61 (6H, complex), 0.90–0.96 (9H, complex),
1.05 (9H, s), 1.05–1.52 (9H, complex), 1.16 (3H, d, J ¼ 6:8 Hz),
1.19 (3H, s), 1.80 (1H, m), 2.06 (1H, m), 2.46 (1H, d, J ¼ 8:3 Hz),
2.96 (1H, m), 3.27 (1H, m), 3.45 (1H, d, J ¼ 6:4 Hz), 3.61–3.66
(4H, complex), 4.13 (1H, m), 4.47 (1H, d, J ¼ 11:7 Hz), 4.77 (2H,
complex), 7.10–7.26 (19H, complex), 7.35–7.44 (12H, complex),
7.66–7.68 (4H, complex); 13C NMR ꢂ 7.0, 7.3, 13.9, 19.3, 24.8,
25.6, 26.0, 26.9, 30.3, 32.7, 37.9, 39.5, 64.0, 66.1, 74.0, 74.3, 74.6,
77.2, 78.4, 78.7, 84.6, 86.5, 126.8, 127.0, 127.2, 127.4, 127.5,
127.6, 127.7, 127.96, 128.04, 128.7, 129.4, 134.1, 135.5, 138.7,
139.0, 144.2; Calcd for C69H88O6Si2: C, 77.48; H, 8.29%. Found:
C, 77.59; H, 8.09%.
134.1, 135.5, 170.3; Calcd for C33H50O6Si 0.1H2O: C, 69.21; H,
8.84%. Found: C, 69.02; H, 8.65%.
ꢁ
(E,4S,5R,6S,7R,8R)-6,7-Bis(benzyloxy)-14-t-butyldiphenyl-
siloxy-8-triethylsiloxy-5-(4-methoxybenzyloxy)-2,4,8-trimethyl-
tetradec-2-en-1-ol (4). A mixture of 22 (114 mg, 0.11 mmol) and
LiBH4 (25 mg, 1.1 mmol) in THF (1.2 mL) was stirred at room
temperature for 3.5 h. After work-up, the residue was chromato-
graphically purified (hexane/EtOAc 3/1) to give 4 (109 mg,
27
100%): ½ꢀꢃD þ4:5 (c 1.00, CHCl3); IR (film) 3585, 3438,
1
3030, 2933, 2873, 1612, 1587, 1513 cmꢄ1; H NMR ꢂ 0.58–0.64
(6H, complex), 0.93–0.97 (9H, complex), 1.01–1.38 (8H, com-
plex), 1.04 (9H, s), 1.12 (3H, d, J ¼ 6:8 Hz), 1.18 (3H, s), 1.50–
1.54 (2H, complex), 1.64 (3H, s), 1.88 (1H, m), 3.01 (1H, m),
3.30 (2H, complex), 3.62 (2H, complex), 3.75 (3H, s), 3.89 (1H,
m), 3.93 (2H, complex), 4.41–4.45 (2H, complex), 4.57 (1H, d,
J ¼ 11:2 Hz), 4.70 (1H, d, J ¼ 11:2 Hz), 4.81–4.86 (2H, com-
plex), 5.38 (1H, d, J ¼ 9:8 Hz), 6.80–6.82 (2H, complex), 7.17–
7.25 (12H, complex), 7.35–7.41 (6H, complex), 7.66–7.68 (4H,
complex); 13C NMR ꢂ 7.1, 7.3, 11.2, 14.0, 17.1, 19.3, 24.0, 24.9,
25.9, 26.1, 26.9, 30.4, 32.8, 34.5, 34.6, 40.2, 55.3, 64.0, 68.9, 74.2,
77.3, 78.5, 84.7, 113.6, 126.7, 126.9, 127.2, 127.5, 127.8, 127.85,
127.91, 129.4, 129.8, 130.8, 134.0, 134.1, 135.5, 139.2, 139.7;
Calcd for C61H86O7Si2: C, 74.19; H, 8.78%. Found: C, 73.90;
H, 8.84%.
A mixture of the trityl compound (365 mg, 0.34 mmol), NaH
(60% dispersion in mineral oil, 34 mg, 0.93 mmol), and MeI
(0.21 mL, 3.4 mmol) in DMF (5 mL) was stirred at ambient tem-
perature for 16 h. After work-up, the residue was chromatograph-
ically purified (hexane/EtOAc 6/1) to give a colorless oil (276
24
mg, 74%): ½ꢀꢃD ꢄ12:2 (c 1.00, CHCl3); IR (film) 3066, 3031,
2933, 2875 cmꢄ1; 1H NMR ꢂ 0.56–0.62 (6H, complex), 0.92–0.96
(9H, complex), 0.99 (3H, d, J ¼ 6:8 Hz), 1.04 (9H, s), 1.10–1.52
(9H, complex), 1.28 (3H, s), 1.71 (1H, m), 2.17 (1H, m), 3.06 (1H,
m), 3.13 (1H, m), 3.30 (3H, s), 3.32 (1H, m), 3.48 (1H, m), 3.61
(2H, complex), 3.72 (1H, m), 4.52 (1H, d, J ¼ 11:2 Hz), 4.64 (2H,
complex), 4.85 (1H, d, J ¼ 11:7 Hz), 7.16–7.26 (19H, complex),
7.34–7.41 (12H, complex), 7.65–7.67 (4H, complex); 13C NMR
ꢂ 7.1, 7.4, 19.3, 24.5, 25.99, 26.09, 26.9, 30.4, 32.7, 36.0, 40.0,
60.8, 64.0, 65.9, 73.9, 75.0, 77.2, 78.4, 78.7, 83.5, 84.4, 86.5,
126.76, 126.79, 126.82, 127.2, 127.5, 127.56, 127.60, 127.9, 128.7,
129.4, 134.1, 135.5, 139.2, 139.4, 144.2; Calcd for C70H90O6Si2:
C, 77.59; H, 8.37%. Found: C, 77.86; H, 8.29%.
{(2R,3R)-3-[(2R,3R,4S,5R,6R)-4,5-Bis(benzyloxy)-12-t-butyl-
diphenylsiloxy-6-triethylsiloxy-3-(4-methoxybenzyloxy)-6-meth-
yldodecan-2-yl]-2-methyloxiran-2-yl}methanol (26). A mix-
ture of 4 (109 mg, 0.11 mmol) and mCPBA (190 mg, 1.1 mmol) in
CH2Cl2 (1.1 mL) in the presence of NaHCO3 (185 mg, 2.2 mmol)
was stirred at ꢄ22 ꢂC for 1 h. After the addition of sat. aq
Na2S2O3 and the following work-up, the residue was chromato-
graphically purified (hexane/EtOAc 3/1) to give 26 (83 mg,
A solution of the methyl ether (193 mg, 0.18 mmol) in MeOH
(4 mL)–THF (2 mL) in the presence of catalytic 20% Pd(OH)2–
C was stirred for 24 h under hydrogen pressure. After filtration
through a Celite pad, the solvent was removed. The residue was
chromatographically purified (EtOAc) to give 23 (51.2 mg, 53%):
27
75%): ½ꢀꢃD þ4:9 (c 0.22, CHCl3); IR (film) 3509, 2931, 1716,
1699, 1605, 1455 cmꢄ1 1H NMR ꢂ 0.59–0.65 (6H, complex),
;
24
½ꢀꢃD ꢄ7:5 (c 1.00, CHCl3); IR (film) 3398, 3070, 3049, 2931,
0.94–0.98 (9H, complex), 1.02 (9H, s), 1.05–1.59 (10H, complex),
1.06 (3H, d, J ¼ 6:8 Hz), 1.24 (3H, s), 1.29 (3H, s), 1.76–1.87
(2H, complex), 2.98 (1H, d, J ¼ 9:8 Hz), 3.27 (1H, d, J ¼ 3:4 Hz),
3.57–3.67 (4H, complex), 3.76 (3H, s), 3.79 (1H, m), 3.98 (1H,
m), 4.57–4.83 (6H, complex), 6.79 (2H, complex), 7.17–7.42
(18H, complex), 7.66–7.68 (4H, complex); 13C NMR ꢂ 7.0, 7.1,
7.3, 7.4, 11.6, 13.4, 14.3, 19.3, 24.6, 25.8, 25.9, 26.0, 30.4, 32.7,
32.8, 35.0, 36.8, 40.0, 55.2, 60.1, 60.9, 61.9, 62.0, 64.0, 65.4,
73.9, 74.0, 74.4, 74.5, 76.3, 77.3, 78.4, 78.5, 78.6, 81.9, 84.7,
113.5, 126.9, 127.1, 127.3, 127.5, 127.8, 127.9, 128.0, 128.06,
128.08, 129.4, 129.7, 130.9, 134.1, 135.5, 139.1, 139.2, 139.5,
2858 cmꢄ1; 1H NMR ꢂ 0.97 (3H, d, J ¼ 6:8 Hz), 1.05 (9H, s), 1.23
(3H, s), 1.23–1.58 (9H, complex), 1.85 (1H, br), 2.12 (1H, m),
2.98 (1H, br), 3.25 (1H, br), 3.41 (2H, complex), 3.50 (3H, s),
3.54 (1H, m), 3.65 (2H, t, J ¼ 6:3 Hz), 3.76 (1H, m), 3.84 (1H,
br), 3.98 (1H, m), 4.10 (1H, m), 7.36–7.42 (6H, complex),
7.65–7.67 (4H, complex); 13C NMR ꢂ 12.1, 19.3, 22.6, 23.9,
25.8, 26.9, 27.4, 30.0, 32.6, 35.8, 39.2, 58.8, 63.2, 63.9, 69.0, 75.0,
75.8, 77.3, 85.5, 127.5, 129.4, 134.0, 135.5; Calcd for C31H50-
O6Si 1.2H2O: C, 65.50; H, 9.30%. Found: C, 65.39; H, 9.58%.
ꢁ
(1R,2R)-1-Acetoxy-8-t-butyldiphenylsiloxy-1-[(2S,3S,4R)-
tetrahydro-3-methoxy-4-methylfuran-2-yl]-2-methyloctan-2-ol
(24). A mixture of 23 (39 mg, 0.071 mmol) and TsCl (27 mg,
0.14 mmol) in pyridine (1.5 mL) was stirred at room temperature
158.9; Calcd for C61H86O8Si2 1.5H2O: C, 71.10; H, 8.71%.
ꢁ
Found: C, 71.15; H, 8.90%.
(E)-Methyl 3-{(2R,3R)-3-[(2R,3R,4S,5R,6R)-4,5-Bis(benzyl-

N. Kutsumura et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
477
oxy)-12-t-butyldiphenylsiloxy-6-triethylsiloxy-3-(4-methoxyben-
zyloxy)-6-methyldodecan-2-yl]-2-methyloxiran-2-yl}acrylate
(28). To a solution of 26 (313 mg, 0.31 mmol) in CH2Cl2 (5 mL)
was added catalytic amounts of TPAP and NMO (37 mg, 0.31
mmol) at room temperature. After being stirred for 1.5 h, the reac-
tion mixture was chromatographically purified (hexane/EtOAc
3/1) to give a colorless oil (237 mg).
J ¼ 5:9 Hz), 3.62 (2H, t, J ¼ 6:3 Hz), 3.75 (3H, s), 4.22 (1H, d,
J ¼ 11:2 Hz), 4.32 (1H, m), 4.51 (1H, d, J ¼ 10:7 Hz), 4.85 (1H,
d, J ¼ 8:8 Hz), 4.95 (1H, d, J ¼ 10:7 Hz), 5.01 (1H, d, J ¼ 11:2
Hz), 6.02 (1H, d, J ¼ 15:6 Hz), 6.78 (1H, d, J ¼ 15:6 Hz), 7.22–
7.26 (10H, complex), 7.35–7.41 (6H, complex), 7.66–7.67 (4H,
complex); 13C NMR ꢂ 7.0, 7.3, 13.1, 15.4, 19.3, 25.0, 25.7, 25.9,
26.9, 30.4, 32.7, 35.4, 36.0, 36.7, 39.9, 51.7, 57.7, 64.0, 67.4, 73.5,
73.9, 76.5, 77.9, 79.6, 82.7, 120.8, 126.8, 126.9, 127.4, 127.5,
127.8, 127.9, 129.4, 134.1, 135.5, 139.4, 139.8, 150.0, 156.6,
166.5; Calcd for C59H85NO9Si2: C, 70.27; H, 8.50; N, 1.39%.
Found: C, 70.13; H, 8.61; N, 1.46%.
A mixture of the aldehyde (237 mg, 0.24 mmol) and Ph3P=
CHCO2Me (240 mg, 0.72 mmol) in PhH (3 mL) was stirred at
100 ꢂC for 12 h. The reaction mixture was concentrated in vacuo
and chromatographically purified (hexane/EtOAc 5/1) to give 28
28
(250 mg, 76% in 2 steps): ½ꢀꢃD ꢄ9:8 (c 1.00, CHCl3); IR (film)
(R,E)-Methyl 4-{(4S,5R,6R)-6-[(1S,2R,3R)-1,2-Bis(benzyl-
oxy)-9-t-butyldiphenylsiloxy-3-hydroxy-3-methylnonyl]-5-meth-
1
2931, 1725, 1654, 1612, 1513, 1247 cmꢄ1; H NMR ꢂ 0.61–0.66
(6H, complex), 0.96–1.00 (9H, complex), 1.02–1.57 (9H, com-
plex), 1.06 (9H, s), 1.10 (3H, d, J ¼ 6:8 Hz), 1.29 (3H, s), 1.44
(3H, s), 1.81 (1H, m), 1.89 (1H, m), 2.80 (1H, d, J ¼ 9:3 Hz), 3.29
(1H, m), 3.63 (2H, complex), 3.75 (1H, m), 3.77 (3H, s), 3.78 (3H,
s), 3.99 (1H, m), 4.57 (1H, d, J ¼ 11:7 Hz), 4.66 (2H, complex),
4.76 (2H, complex), 4.83 (1H, d, J ¼ 11:7 Hz), 5.99 (1H, d, J ¼
15:6 Hz), 6.77 (1H, d, J ¼ 16:1 Hz), 6.81 (2H, complex), 7.19–
7.44 (18H, complex), 7.67–7.69 (4H, complex); 13C NMR ꢂ 7.1,
7.4, 11.7, 15.3, 19.3, 24.7, 26.0, 26.9, 32.7, 34.7, 39.9, 55.2,
58.5, 64.0, 68.2, 74.0, 74.5, 75.1, 76.6, 76.7, 77.27, 77.31, 78.4,
78.6, 82.1, 84.6, 113.6, 120.8, 126.9, 127.3, 127.49, 127.51, 127.8,
127.90, 127.95, 129.4, 129.6, 130.8, 134.1, 135.46, 135.48, 139.5,
159.0, 166.5, 182.2; Calcd for C64H88O9Si2: C, 72.69; H, 8.39%.
Found: C, 72.44; H, 8.40%.
yl-2-oxo-1,3-dioxan-4-yl}-4-hydroxypent-2-enoate (2).
To a
solution of 3 (17.5 mg, 0.017 mmol) in CH2Cl2 (1.7 mL) was add-
ed Et2O BF3 (2.2 mL, 0.017 mmol) at room temperature. After be-
ꢁ
ing stirred for 23 h, the reaction was quenched by the addition of
sat. aq NaHCO3. The resulting mixture was extracted with EtOAc,
washed with brine, dried (Na2SO4), and then evaporated. The res-
idue was chromatographically purified (hexane/EtOAc 3/1) to
25
give 2 (5.4 mg, 36%): ½ꢀꢃD ꢄ9:5 (c 0.20, CHCl3); IR (film)
1
3585, 2929, 2856, 1806, 1725 cmꢄ1; H NMR ꢂ 1.00 (3H, d, J ¼
6:8 Hz), 1.07 (3H, s), 1.22 (3H, s), 1.22–1.59 (10H, complex), 1.64
(3H, s), 1.90 (1H, m), 2.30 (1H, s), 3.36 (1H, d, J ¼ 6:8 Hz), 3.43
(1H, d, J ¼ 5:4 Hz), 3.66–3.69 (3H, complex), 3.81 (3H, s), 4.03
(1H, m), 4.40 (1H, d, J ¼ 10:7 Hz), 4.50 (1H, d, J ¼ 11:2 Hz),
4.54 (1H, d, J ¼ 11:2 Hz), 4.73 (1H, d, J ¼ 11:2 Hz), 4.82 (1H,
d, J ¼ 10:8 Hz), 6.23 (1H, d, J ¼ 15:6 Hz), 6.93 (1H, d, J ¼
15:6 Hz), 7.28–7.44 (16H, complex), 7.69–7.70 (4H, complex);
13C NMR ꢂ 9.7, 19.3, 22.5, 24.0, 24.8, 25.9, 26.9, 30.1, 32.6,
38.0, 40.1, 52.1, 64.0, 69.9, 73.5, 74.5, 74.8, 77.2, 79.2, 81.8,
84.0, 87.2, 123.3, 127.5, 127.86, 127.92, 128.0, 128.1, 128.4,
129.4, 134.1, 135.5, 137.6, 137.7, 142.1, 152.5, 165.6; HRMS
Calcd for C49H64O8Si (Mþ þ H ꢄ COOMe): 808.4367. Found
(FAB): 808.4375.
(2R,3R,4S,5R,6R)-2-{(2R,3R)-3-[(E)-2-(Methoxycarbonyl)-
vinyl]-3-methyloxiran-2-yl}-4,5-bis(benzyloxy)-12-t-butyldi-
phenylsiloxy-6-triethylsiloxy-6-methyldodecan-3-yl Dimethyl-
carbamate (3).
A mixture of 28 (166 mg, 0.16 mmol) and
DDQ (43 mg, 0.19 mmol) in CH2Cl2 (1.5 mL)–H2O (75 mL) was
stirred at 0 ꢂC for 50 min. After work-up, the residue was chro-
matographically purified (benzene and then hexane/EtOAc 5/1) to
26
give a colorless oil (139 mg, 95%): ½ꢀꢃD ꢄ47:2 (c 1.00, CHCl3);
IR (film) 3552, 2933, 2874, 1727, 1652, 1454, 1428, 1267 cmꢄ1
;
1H NMR ꢂ 0.60–0.66 (6H, complex), 0.94–0.96 (9H, complex),
1.07 (3H, d, J ¼ 7:3 Hz), 1.24–1.55 (9H, complex), 1.28 (3H,
s), 1.31 (3H, s), 1.74 (1H, m), 1.87 (1H, m), 2.62 (1H, br), 2.62
(1H, d, J ¼ 9:8 Hz), 3.50 (1H, d, J ¼ 6:8 Hz), 3.61–3.66 (3H,
complex), 3.73 (3H, s), 4.16 (1H, d, J ¼ 6:8 Hz), 4.50 (1H, d, J ¼
11:7 Hz), 4.61 (1H, d, J ¼ 10:3 Hz), 4.83 (1H, d, J ¼ 11:2 Hz),
4.88 (1H, d, J ¼ 10:3 Hz), 6.02 (1H, d, J ¼ 15:6 Hz), 6.78 (1H, d,
J ¼ 15:6 Hz), 7.22–7.41 (16H, complex), 7.66–7.69 (4H, com-
plex); 13C NMR ꢂ 7.0, 7.3, 13.3, 15.4, 19.3, 24.7, 25.8, 26.0, 26.9,
30.4, 32.7, 37.3, 39.3, 51.7, 57.9, 64.0, 67.9, 73.9, 74.5, 76.1, 77.2,
78.2, 78.4, 84.1, 120.8, 127.1, 127.3, 127.47, 127.51, 128.0, 128.1,
128.2, 129.4, 134.1, 135.5, 139.0, 150.0, 166.4; Calcd for C56H80-
This work was supported by Grant-in-Aid for the 21st
Century COE program ‘‘Keio Life Conjugate Chemistry,’’ as
well as Scientific Research C from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
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