First total synthesis of 6-tuliposide B

Article abstract of DOI:10.1016/j.tetasy.2008.05.019

Labile (+)-6-tuliposide B, an antimicrobial compound produced by tulip, was synthesized in nine steps from d-glucose via the Baylis-Hillman reaction of 2-(tert-butyldimethylsilyloxy)-acetaldehyde with 6-O-acryloyl-1-O-(2-trimethylsilylethyl)-β-d-glucopyranoside, followed by a mild deprotection procedure using TFA in CH₂Cl₂.

Full text of DOI:10.1016/j.tetasy.2008.05.019

Tetrahedron: Asymmetry 19 (2008) 1444–1449
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
First total synthesis of 6-tuliposide B
a
a
b
a,*
Kengo Shigetomi , Takao Kishimoto , Kazuaki Shoji , Makoto Ubukata
a
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan
Agricultural Experiment Station, Toyama Agricultural Research Center, Toyama 939-8153, Japan
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 April 2008
Accepted 12 May 2008
Labile (+)-6-tuliposide B, an antimicrobial compound produced by tulip, was synthesized in nine steps
from -glucose via the Baylis–Hillman reaction of 2-(tert-butyldimethylsilyloxy)-acetaldehyde with 6-
O-acryloyl-1-O-(2-trimethylsilylethyl)-b-
using TFA in CH Cl
D
D
-glucopyranoside, followed by a mild deprotection procedure
2
2
.
Ó 2008 Elsevier Ltd. All rights reserved.
1
. Introduction
Collectively, plants produce a diverse array of low molecular
OH
O
OH
O
HO
weight natural products numbering over 100,000. This rich diver-
sity is the result of an evolutionary process driven by selection
for improved defense against microbial, insect, or animal attack.
O
1
O
O
The simplest definition of such biologically active substances rec-
ognizes phytoalexins, which are synthesized de novo, and phyto-
anticipins as pre-formed infection inhibitors.
Tulip cultivars accumulate phytoanticipins, named 6-tuliposide
B 1 and 6-tuliposide A 3, in flowers, stems, leaves, and bulbs. The
non-sugar groups released by enzymatic or spontaneous hydroly-
HO
HO
OH
2
OH
1
2
O
sis of tuliposides are easily converted to the corresponding
a-
HO
methylene- -butyrolactones, tulipalin B 2 and tulipalin A 4, under
c
O
3
non-alkaline conditions (Fig. 1). Although 3 and 4 are known to
cause allergic contact dermatitis, 1 is non-allergenic.4
O
O
O
Recently, we found compound 1 to have potent antimicrobial
activity against Gram-positive, Gram-negative, and certain fungi-
cide-tolerant strains of bacteria, but it was not active against yeast.
Both compounds 1 and 3 were detected in tulip tissues such as
petal, pistil, leaf, stem, bulb scale, and root. In the anther, 1 was
detected, however 3, which is a precursor of the insecticidal
HO
HO
OH
OH
3
4
Figure 1. Structures of tuliposides B 1 and A 3, and tulipalins B 2 and A 4.
5
compound 4, was not detected under the cultivation conditions
9
our effort. These failures probably stem from the extremely labile
nature of these tuliposides. Herein, we report the first total synthe-
used in the agricultural field. These observations suggest that the
anther-specific production of 1 is a novel defense mechanism
evolved in tulips to protect pollens from bacterial infection that
could be introduced during the reproductive process.6 To verify
this hypothesis and survey the potential of 1 as an antimicrobial
agent against multidrug-resistant microorganisms, we undertook
the total synthesis of 1.
sis of labile tuliposide B 1.
2
2
. Results and discussion
.1. Preparation of 6-O-acryloyl glucosides 8a–8f
Several synthetic methods to produce 2 have already appeared,7
Sugar acrylates 8a and 8b depicted in Table 1 were prepared as
previously described. The synthesis of 2-trimethylsilylethyl
however, the total synthesis of 1 or 3 has not been reported,
9
although there have been three unsuccessful attempts,8 including
(
TMSET) glucoside derivative 8c began with 2,3,4,6-tetra-O-acet-
yl-1-O-(2-triethylsilylethyl)-b- -glucopyranoside 5, which was
prepared from -glucose in three steps according to the reported
procedure, shown in Scheme 1. Methanolysis of the acetate gave
D
D
*
Corresponding author. Tel./fax: +81 11 706 3638.
1
0
E-mail address: m-ub@for.agr.hokudai.ac.jp (M. Ubukata).
0
957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.05.019

K. Shigetomi et al. / Tetrahedron: Asymmetry 19 (2008) 1444–1449
1445
Table 1
a
Baylis–Hillman reaction of tert-butyldimethylsilyloxy-acetaldehyde and sugar acrylates
OH
O
O
TBDMSO
O
O
O
TBDMSO
+
3
-HQD (1eq.)
r.t.
H
O
O
R O
3
R O
OR2
1
R O
3
OR2
R O
1
OR3
OR1
8a-f
12a-f
Entry
Acrylate
R
1
R
2
Product
12a (R
12b (R
Solvent
Time
Yield (%)
1
2
3
4
5
6
7
8a
8b
8c
8c
8d
8e
TMS
TES
H
Me
Me
TMSET
TMSET
TMSET
TCE
3
= H)
= TES)
3
= H)
DMSO
DMSO
MeCN
DMSO
DMSO
DMSO
DMSO
8 days
15 days
44 h
29
47
27
40
3
12c (R
12c (R
12d (R
H
3
= H)
40 h
b
TES
TES
TES
3
= TES)
= TES)
= TES)
23 days
15 days
30 days
0
12e (R
12f (R
3
3
50
6
c
c
8f
TES
a
Reaction was run with 3 equiv of acetaldehyde.
Starting material 8c was recovered in 51% yield.
Diastereomeric mixture (1:1) at the anomeric center of the sugar.
b
c
tetraol 6 and trimethylsilylation of 6 was followed by selective
deprotection of the TMS group at C-6 to produce free alcohol 7.
Acylation of 7 with acryloyl chloride followed by HF treatment
led to the formation of 6-O-acryloyl-1-O-(2-trimethylsilylethyl)-
1
1
b-
D-glucopyranoside 8c.
OPv
OAc
PvCl, pyridine
O
HO
HO
6
OTMSET
O
(70%)
AcO
AcO
NaOMe, MeOH
89%)
OTMSET
OTMSET
OH
(
OAc
9
5
OPv
OH
TESOTf, lutidine,
CH Cl
1
2
. TMSCl, py
2
2
O
O
TESO
TESO
HO
HO
OTMSET
(quant.)
. K CO , MeOH
2
3
(
89%)
OTES
OH
6
10
OH
OH
1
.acryloyl chloride,
Et N, CH Cl
DIBAL, CH Cl , -78ºC
O
2
2
O
TESO
TESO
TMSO
TMSO
3
2
2
OTMSET
OTMSET
(99%)
2. Aq. HF (3 eq)
(70%)
OTES
OTMS
11
7
O
O
acryloyl chloride,
Et N, CH Cl
O
O
3
2
2
(
85%)
O
O
HO
HO
TESO
TESO
OTMSET
OTMSET
OTES
OH
8c
8d
Scheme 1. Synthesis of TMSET glucoside 8c.
Scheme 2. Synthesis of TMSET glucoside 8d.

1
446
K. Shigetomi et al. / Tetrahedron: Asymmetry 19 (2008) 1444–1449
Scheme 2 shows the synthesis of 6-O-acryloyl-2,3,4-tri-O-tri-
ethylsilyl-1-O-(2-trimethylsilylethyl)-b- -glucopyranoside 8d.
the methyl glucoside 8a was observed to give 12a in 29% yield,
D
whereas the TES derivative 8b produced the desired Baylis–Hill-
man product 12b in moderate yield without loss of the protective
groups. The yield of the Baylis–Hillman reaction for the TES-pro-
tected methyl glucoside 8b was 47% and better than the yield in
the case of TMS-protected methyl glucoside 8a as shown in entries
1 and 2. However, the Baylis–Hillman reaction of 8d did not give
the desired products even after 23 days and only 51% of starting
material 8d was recovered (entry 5). The Baylis–Hillman reaction
of 2,2,2-trichloroethyl glucoside acrylate 8e, derived from 2,2,2-tri-
Protection of 6 with pivaloyl chloride provided monopivaloyl
derivative 9 in 70% yield which was converted in quantitative yield
to the TES derivative 10 using TESOTf. Removal of the pivaloyl
group was achieved by DIBAL reduction to give the free alcohol
in 11 in 99% yield and acylation of 11 with acryloyl chloride pro-
duced compound 8d in 85% yield.
2
,2,2-Trichloroethyl (TCE) glucoside 8e and triethylsilyl gluco-
side 8f as depicted in Table 1 were synthesized by procedures sim-
ilar to those used for the synthesis of TMSET glucoside 8d, shown
in Scheme 2.
1
4
chloroethyl b-D-glucoside, gave 12e in 50% yield after 15 days
(entry 6), whereas another acrylate 8f produced 12f in 6% yield
after 30 days (entry 7). The reaction of the polar and less bulky su-
gar acrylate 8c with 2-(tert-butyldimethylsilyloxy)-acetaldehyde
in the presence of 3-HQD formed the desired product 12c in 40%
yield after 40 h (entry 4). Although an aprotic polar solvent, such
as DMSO or DMF, accelerated the Baylis–Hillman reaction between
methyl acrylate with 2-(tert-butyldimethylsilyloxy)-acetaldehyde,
the use of MeCN instead of DMSO as the reaction solvent resulted
in a convenient separation step for the products. However, the
yield of 12c when MeCN was used was lower than when DMSO
was used (entry 3).
2
.2. Baylis–Hillman reaction of sugar acrylates 8a–f with 2-
(tert-butyldimethylsilyloxy)-acetaldehyde
The results of the Baylis–Hillman reaction of sugar acrylates
8
a–f with 2-(tert-butyldimethylsilyloxy)-acetaldehyde, easily
1
2
prepared from 1,4-di-(tert-butyldimethylsilyloxy)-2-butene, are
summarized in Table 1. During the Baylis–Hillman reaction using
3
-HQD (3-hydroxyquinuclidine),13 the loss of the TMS groups from
OH
O
TBDMSO
O
OH
O
TBDMSO
O
O
HO
HO
OTMSET
®
CHIRALPAK IA column
(
S)-12c
OH
O
HO
HO
OTMSET
+
EtOH : Hexane = 8:92
OH
O
OH
TBDMSO
O
12c
O
HO
HO
OTMSET
(
R)-12c
OH
OH
OH
O
HO
TFA : CH Cl = 2 : 1
O
2
2
TFA : CH Cl = 2 : 1
2
2
O
(
S)-12c
1
day (quant.)
1.5 h (96%)
O
O
HO
HO
(-)-tulipalin B 2
OH
[
α] = - 79.1
D
OH
(c 0.25, MeOH)
lit.) [α]D = - 80 (MeOH)
(
+)-6-tuliposide B 1
OH
OH
O
HO
TFA : CH Cl = 2 : 1
O
2
2
TFA : CH Cl = 2 : 1
2
2
(
R)-12c
O
1
day (quant)
1.5 h (93%)
O
O
HO
HO
(+)-tulipalin B 14
OH
[
α] = + 79.4
D
OH
(c 0.25, MeOH)
1
3
0
Scheme 3. Synthesis of natural 6-tuliposide B (1) and its 3 R-epimer (13).

K. Shigetomi et al. / Tetrahedron: Asymmetry 19 (2008) 1444–1449
1447
2
.3. Synthesis of 6-tuliposide B 1
ylsilane as the internal standard. Coupling constants (J) are given in
Hertz. Mass spectra were acquired using FD and FAB techniques
using a JMS-SX102A. All of the NMR and mass spectra were mea-
sured at the GC–MS and NMR Laboratory, Faculty of Agriculture,
Hokkaido University. Optical rotations were determined on a JAS-
CO DIP-370 polarimeter in £ 3.4 mm ꢁ 5.0 cm cells at 25 °C.
Dichloromethane and acetonitrile were distilled from phosphorous
oxide, and pyridine was distilled from calcium hydride.
One of the most critical points for the total synthesis of 1 was
the avoidance of the lactonization of 1 and its derivatives. Depro-
tection of the TES glucoside derivative 12f was successful in giving
a 1:1 mixture of 1 and 13 without lactonization. However, because
of the poor yield (6%) for 12f, suitable deprotection conditions for
methyl glucoside 12b, TMSET glucoside 12c, and TCE glucoside 12e
were examined. Demethylation of 12b was unsuccessful under the
various conditions described previously.9 TBDMS and TES groups
of 12e were removed by treating with 46% aqueous HF in MeCN
for 2 h to give 6-O-(3,4-dihydroxy-2-methylene-butanoyl)-1-O-
4.1.1. 1-O-(2-Trimethylsilylethyl)-b-D-glucopyranoside 6
Sodium methoxide (504 l, 28% in MeOH) was added to a solu-
l
tion of 5 (5.65 g, 12.6 mmol) in 90 ml of MeOH at room tempera-
ture. Stirring was continued for 1 h, whereupon the reaction
mixture was neutralized by adding Amberlyst R-150 and filtered.
After evaporation of the filtrate, the crude product was purified
(
2,2,2-trichloroethyl)-b-D-glucopyranoside in quantitative yield.
However, deprotection of the TCE group with Zn in AcOH only pro-
duced (±)-tulipalin. We succeeded in the removal of the TMSET
group from 12c by treating with TFA in CH
2
Cl
2
for 1.5 h. Scheme
by short silica gel column chromatography (MeOH/CHCl
3
, 1:4) to
0
ꢀ1
3
shows the synthetic route for 6-tuliposide B 1 and its (3 R) epi-
give 3.13 g of 6 (89%) as a white solid. IR (
mmax, cm ) 3539,
1
mer 13. The diastereomeric mixture of the Baylis–Hillman adduct
2c was separated using a chiral HPLC column (CHIRALPAKÒ IA.
DAICEL Co. Ltd, Japan) to give (S)-12c and (R)-12c. Deprotection
3351, 1441, 1405, 1250, 1188, 1078, 1031, 868, and 836. H NMR
1
(500 MHz, CD
CH CH TMS), 3.15 (1H, dd, J = 9.1, 7.9 Hz, H-2), 3.26–3.34 (3H, m,
H-3, 4, 5), 3.59–3.67 (2H, m, H-6a and CH CH TMS), 3.86 (1H, dd,
J = 11.9, 1.9 Hz, H-6b), 4.01 (1H, ddd, J = 11.7, 9.6, 5.6 Hz,
3 2 2
OD), 0.02 (9H, s, CH CH TMS), 1.00 (2H, m,
2
2
1
13
of (S)-12c produced 1 whose H NMR data and C NMR data were
2
2
comparable to the reported NMR data of natural 6-tuliposide B. In
0
13
contrast, the NMR data of (3 R)-epimer 13 derived from (R)-12c
CH
2
CH
2
TMS), 4.26, (1H, d, J = 7.9 Hz, H-1), C NMR (125 MHz,
CH TMS), 19.1 (CH CH TMS), 62.8 (C-6), 68.1
were distinguishable from those of natural 1. In order to confirm
the structure of synthetic 6-tuliposide B, we converted both diaste-
reomers 1 and 13 into 2 and 14, respectively. The synthetic com-
CD
3
OD) ꢀ1.4 (CH
2
2
2
2
(CH
2
CH
2
TMS), 71.7 (C-4), 75.1 (C-2), 77.9 (C-5), 78.2 (C-3), 103.9
ꢀ
(C-1), HR-FAB-MS m/z [MꢀH] , calcd for C11
H
23
O
6
Si, 279.1264;
pound
2
showed
a
negative sign for the specific rotation
found, 279.1250.
{
[
a
]
D
1
= ꢀ79.1 (c 0.25, MeOH); [
a
]
D
= ꢀ80 (MeOH) in the litera-
2
ture } that unambiguously indicates the synthetic compounds 1
and 2 to be 6-tuliposide B and tulipalin B, respectively. In contrast,
4.1.2. 6-O-Pivaloyl-1-O-(2-trimethylsilylethyl)-b-
D-
glucopyranoside 9
compound 14 showed a positive specific rotation {[
a
]
D
= +79.4 (c
Pivaloyl chloride solution (1.35 ml, 1.10 mmol/30 ml of pyri-
dine) was added dropwise to a solution of 6 (3.01 g, 10.7 mmol)
in 20 ml of pyridine for 15 min. The reaction was allowed to stir
at room temperature for 20 h and then at 40 °C for 4 h. Pyridine
was azeotropically removed with the repeated addition of toluene,
followed by evaporation which was repeated several times. The
residual mixture was purified by silica gel column chromatography
0
.25, MeOH)}, which indicates 14 to be the antipode of tulipalin
0
B and compound 13 to be (3 R)-epimer of 6-tuliposide B.
3
. Conclusion
We have succeeded in the total synthesis of 6-tuliposide B 1.
with 10% MeOH in CHCl
obtained as a white solid. IR (
3
. After evaporation, 2.74 g of 9 (70%) was
The key point in the synthesis of 1 was to find deprotection condi-
tions for a suitable Baylis–Hillman adduct. The Baylis–Hillman
reaction of 8d or 8f with 2-(tert-butyldimethylsilyloxy)-acetalde-
hyde failed, probably because of the poor accessibility of 3-HQD
to the bulky and less polar compound 8d or 8f. The reaction of
the more polar and less bulky acrylates, 8b, 8c, and 8e, proceeded
to give the corresponding Baylis–Hillman adducts 12b, 12c, and
ꢀ1
m
max, cm ) 3400, 1734, 1457, 1420,
1
1
364, 1287, 1250, 1166, 1077, 862, 836. H NMR (500 MHz, CDCl
3
),
0
.01 (9H, s, CH CH TMS), 1.01 (2H, m, CH CH TMS), 1.21 (9H, s, t-
2
2
2
2
Bu), 3.36 (1H, d, J = 7.8 Hz, H-2), 3.50 (1H, ddd, J = 9.3, 6.8, 2.3 Hz,
H-5), 3.54–3.62 (3H, m, H-3, H-4 and CH CH TMS), 3.93–3.98
1H, m, CH CH TMS), 4.28 (1H, d, J = 7.8 Hz, H-1), 4.27–4.31 (1H,
m, H-6a), 4.39, (1H, dd, J = 11.8, 2.1 Hz, H-6b),
2
2
(
2
2
13
C
NMR
TMS), 27.1
TMS), 70.5 (C-4),
3.6 (C-2), 73.9 (C-5), 76.2 (C-3), 101.9 (C-1), 179.0 (carbonyl).
1
1
2e, respectively. After the separation of the diastereomers, (S)-
2c yielded 6-tuliposide B 1. Thus, both stereoisomers of 6-tulipo-
(
125 MHz, CDCl
3
) ꢀ1.5 (CH
2
CH
2
TMS), 18.2 (CH
2 2
CH
(
CMe ), 38.9 (CMe
3
3
), 63.7 (C-6), 67.4 (CH
2
CH
2
side B 1 and 13 and the enantiomers of tulipalin B 2 and 14 are in
hand. These compounds may contribute to the clarification of the
defense mechanism of the tulip and the systematic structure–
activity relationship of tuliposide and tulipalin.
7
+
33 7
HR-FD-MS m/z [M+H] calcd for C16H O Si, 365.1996: found,
3
65.1987.
4
.1.3. 6-O-Pivaloyl-2,3,4-tri-O-triethylsilyl-1-O-(2-
-glucopyranoside 10
Compound 9 (2.02 g, 5.55 mmol) was dissolved in 25 ml of dry
4
4
. Experimental
trimethylsilylethyl)-b-
D
.1. General
CH Cl and cooled to 0 °C. 2,6-Lutidine (3.0 ml, 25.9 mmol) and tri-
2
2
ethylsilyl trifluoromethanesulfonate (4.3 ml, 19.2 mmol) were
added and the mixture was stirred for 5.5 h. The reaction mixture
was diluted with 100 ml of diethyl ether and washed with 1 M HCl
aqueous solution (100 ml). After washing with satd NaHCO3
(100 ml) and brine (100 ml), the organic layer was dried over anhy-
drous Na SO . Evaporation and silica gel column chromatography
Unless otherwise stated, chemicals of the highest commercial
purity were used without further purification. Thin-layer and silica
gel column chromatographies were performed using Merck Silica
Gel 60 F254 and Kanto Chemicals Co. Silica Gel 60 N (spherical, neu-
tral), respectively. Chiral HPLC was performed using a DAICEL
2
4
Ò
CHIRALPAK IA column (£ 20 mm ꢁ 20 cm) and a HITACHI L-
(EtOAc/hexane, 1:4) produced 4.05 g of 10 (quant.) as a colorless
ꢀ1
7
455 photodiode array detector at 30 °C. IR spectra were recorded
syrup. IR (mmax, cm ) 1737, 1460, 1415, 1284, 1249, 1149, 1117,
1
13
1
on a Digilab FTS-50A. H, C, HH-COSY, HMBC, and HMQC NMR
spectra were measured in CDCl or methanol-d , with a Bruker
AMX-500. Chemical shifts are reported in d ppm using tetrameth-
1090, 1006, 860, 838, and 741. H NMR (500 MHz, CDCl ), 0.01
3
3
4
(9H, s, CH CH TMS), 0.62–0.69 (18H, m, SiCH CH ), 0.93–1.04
2
2
2
3
(29H, m, CH CH TMS and SiCH CH ), 1.21 (9H, s, t-Bu), 3.42–3.47
2
2
2
3

1
448
K. Shigetomi et al. / Tetrahedron: Asymmetry 19 (2008) 1444–1449
(
3
2H, m, H-2 and CH
.64 (2H, m, H-3 and H-5), 3.94 (1H, ddd, J = 11.7, 9.4, 6.2 Hz,
CH CH TMS), 4.05 (1H, dd, J = 11.3, 8.0, H-6a), 4.36 (1H, d,
J = 7.0 Hz, H-1), 4.36–4.40, (1H, m, H-6b), C NMR (125 MHz,
CDCl CH TMS), 5.1, 5.1, 5.2 (SiCH CH ), 6.9, 6.9, 7.0
), 18.1 (CH CH TMS), 27.2 (CMe ), 38.7 (CMe ), 64.8 (C-
), 66.3 (CH CH TMS), 72.2 (C-4), 76.1 (C-5), 77.0 (C-2, overlapping
2
CH
2
TMS), 3.53 (1H, t, J = 6.3 Hz, H-4), 3.58–
at 0 °C. After 2 h, toluene was added to the reaction mixture
and evaporated. The addition and evaporation of toluene were
repeated twice. The resulting mixture was dissolved into petro-
leum ether and the insoluble part was filtered off. The filtrate
was evaporated and the resulting crude product was dissolved
2
2
13
3
) ꢀ1.6 (CH
2
2
2
3
(
6
SiCH
2
CH
3
2
2
3
3
2 3
in dry MeOH and then methanolic K CO (2.7 ml, 4.48 mg/ml)
2
2
was added to the solution at 0 °C. After 2 h, the solution was
neutralized by adding AcOH (4.0 ml, 2.78 mg/ml) and evaporated
yielding a white solid. The white solid obtained was purified by
with solvent peak), 76.2 (C-3), 102.1 (C-1), 178.2 (carbonyl). HR-
FD-MS m/z [M+H] , calcd for
+
34 75 7 4
C H O Si , 707.4590; found,
7
07.4600.
silica gel column chromatography (EtOAc/CHCl
3
, 1:29). Evapora-
tion of the eluant produced 4.33 g of 7 (73%) as a syrup. IR (
m
max
,
ꢀ1
4
.1.4. 2,3,4-Tri-O-triethylsilyl-1-O-(2-trimethylsilylethyl)-b-D-
cm ) 3452, 1446, 1250, 1143, 1124, 1080, 869, 841. 1H NMR
(500 MHz, CDCl ) 0.02 (9H, s, CH CH TMS), 0.16, 0.16, 0.18 (9H,
s, OSiMe ), 1.01 (2H, dd, J = 9.7, 8.0 Hz, CH CH TMS), 3.28 (2H,
m, H-2 and H-5), 3.44 (2H, overlapped t, H-3 and H-4), 3.54
(1H, dd, J = 9.5, 7.8 Hz, CH CH TMS), 3.66 (1H, ddd, J = 11.9, 6.5,
5.6 Hz, H-6a), 3.81 (1H, ddd, J = 11.7, 6.5, 2.8 Hz, H-6b), 3.92
(1H, dd, J = 9.7, 8.2 Hz, CH CH TMS), 4.24 (1H, d, J = 7.6 Hz, H-
1), C NMR (125 MHz, CDCl CH TMS), 0.9, 1.2, 1.3
) ꢀ1.5 (CH
(OSiMe ), 18.3 (CH CH TMS), 62.3 (C-6), 67.2 (CH CH TMS),
71.7 (C-4), 75.9, 76.0 (C-2 and C-5), 78.2 (C-3), 103.0 (C-1),
glucopyranoside 11
Pivaloyl ester 10 (4.45 g, 5.73 mmol) was dissolved in 80 ml of
Cl
3
2
2
3
2
2
CH
2
2
and cooled to ꢀ78 °C. DIBAL (12 mmol) was added drop-
wise and left for 3 h under an argon atmosphere at ꢀ78 °C. The
reaction was monitored by TLC, and when it was completed, the
solution was quenched by MeOH and then diluted with diethyl
ether (100 ml). After warming to room temperature, the mixture
2
2
2
2
1
3
3
2
2
was washed with 1 M HCl (100 ml), satd NaHCO
brine (100 ml). The organic layer was dried over Na
3
(100 ml), and
SO and evap-
3
2
2
2
2
2
4
+
orated to give a crude product, which was purified by silica gel col-
umn chromatography (EtOAc/hexane, 1:9). Evaporation yielded
48 6 4
HR-FD-MS m/z [M] calcd for C20H O Si , 496.2528; found,
496.2538.
ꢀ1
3
1
CDCl
0
.51 g of 11 (99%) as a syrup. IR (
250, 1142, 1086, 1006, 860, 837, 802, 740. H NMR (500 MHz,
), 0.02 (9H, s, CH CH TMS), 0.64–0.70 (18H, m, SiCH CH ),
.94–1.06 (29H, m, CH CH TMS and SiCH CH ), 3.42–3.52 (3H, m,
H-2, H-5 and CH CH TMS), 3.57–3.60 (2H, m, H-3 and H-4), 3.70
1H, m, H-6a), 3.78 (1H, ddd, J = 8.6, 6.2, 2.9 Hz, H-6b), 3.94, (1H,
ddd, J = 11.7, 9.4, 6.2 Hz, CH CH TMS), 4.38 (1H, d, J = 7.0 Hz, H-
), C NMR (125 MHz, CDCl CH TMS), 5.0, 5.1, 5.2
) ꢀ1.5 (CH
SiCH CH ), 6.9, 6.9, 7.0 (SiCH CH ), 18.2 (CH CH TMS), 63.1 (C-
), 66.6 (CH CH TMS), 72.0 (C-4), 76.9 (C-2), 78.6 (C-5), 78.9 (C-
mmax, cm ) 3503, 1459, 1416,
1
4.1.7. 6-O-Acryloyl-1-O-(2-trimethylsilylethyl)-b-D-
glucopyranoside 8c
3
2
2
2
3
2
2
2
3
The same procedure as in the case of the synthesis of 8d was
applied to (3.42 g, 6.89 mmol). Acryloyl chloride (800 ml,
9.8 mmol), 2.0 ml of triethylamine (14.3 mmol), and 55 ml of dry
CH Cl gave 2.66 g of 6-O-acryloyl-2,3,4-tri-O-trimethylsilyl-1-O-
(2-trimethylsilylethyl)-b- -gluco-pyranoside (4.83 mmol, 70%) as
a syrup after purification by silica gel column chromatography
2
2
7
(
2
2
2
2
1
3
1
(
3
2
2
D
2
3
2
3
2
2
ꢀ1
6
3
6
2
2
(EtOAc/hexane, 1:19). IR (
1179, 1159, 1092, 1079, 870, and 841. H NMR (500 MHz, CDCl
0.01 (9H, s, CH CH TMS), 0.16, 0.16, 0.17 (9H, s, OSiMe ), 0.99
2H, m, CH CH TMS), 3.33 (1H, t, J = 8.0, H-2), 3.41–3.54 (4H, m,
H-3, H-4, H-5 and CH CH TMS), 3.89 (1H, m, CH CH TMS), 4.15
mmax, cm ) 1733, 1637, 1408, 1250,
+
1
), 102.6 (C-1), HR-FD-MS m/z [M+H] calcd for C29
H
67
O
6
Si
4
,
3
)
23.4015: found, 623.3997.
2
2
3
(
2
2
4
.1.5. 6-O-Acryloyl-2,3,4-tri-O-triethylsilyl-1-O-(2-
2
2
2
2
trimethylsilylethyl)-b-
Silylated sugar 11 (3.52 g, 5.64 mmol) was dissolved in 100 ml
of dry CH Cl . To the 0 °C-cooled solution, 2.0 ml of triethylamine
14.3 mmol) and 650 l of acryloyl chloride (8.0 mmol) were added
sequentially. After 3 h of stirring at room temperature, the solvent
was evaporated. The mixture was dissolved into petroleum ether
and the insoluble part was filtered off. The filtrate was evaporated
and the residue was purified by silica gel column chromatography
D
-glucopyranoside 8d
(1H, dd, J = 11.8, 6.2 Hz, H-6a), 4.18 (1H, d, J = 7.5 Hz, H-1), 4.47
(1H, dd, J = 11.7, 2.3 Hz, H-6b), 5.84 (1H, dd, J = 10.4, 1.4 Hz, H-b),
2
2
6.15 (1H, dd, J = 17.4, 10.4 Hz, H-
a
), 6.42 (1H, dd, J = 17.4, 1.4 Hz,
) ꢀ1.5 (CH CH TMS), 0.9, 1.2, 1.3
TMS), 64.0 (C-6), 66.8 (CH CH TMS), 72.2
(C-4), 73.7 (C-2), 76.0 (C-5), 78.7 (C-3), 102.7 (C-1), 128.3 (C-b),
1
3
(
l
H-b), C NMR (125 MHz, CDCl
(OSiMe ), 18.3 (CH CH
3
2
2
3
2
2
2
2
+
130.9 (C-
Si
The above trimethylsilyl derivative (2.36 g, 4.29 mmol) was
dissolved in MeCN (60 ml) and cooled to 0 °C. To the reaction
mixture, stoichiometric amount of aqueous HF aqueous
(800 l, 13.3 mmol) was slowly added and stirring was contin-
ued for 70 min. Evaporation of solvent and subsequent short sil-
ica gel column chromatography (MeOH/CHCl , 1:9) produced
1.44 g of 8c (quant.) as a colorless syrup. IR (
1730, 1636, 1618, 1409, 1250, 1195, 1083, 861, and 836.
NMR (500 MHz, CDCl ) 0.02 (9H, s, CH CH TMS), 1.01 (2H, m,
CH CH TMS), 3.38 (1H, t, J = 8.6 Hz, H-2), 3.41 (1H, t, J = 9.3 Hz,
H-4), 3.51 (1H, ddd, J = 9.7, 5.0, 2.2 Hz, H-5), 3.58 (1H, t,
J = 8.9 Hz, H-3), 3.58–3.63 (1H, m, CH CH TMS), 3.98 (1H, ddd,
J = 11.2, 9.9, 6.1 Hz, CH CH TMS), 4.30 (1H, d, J = 7.8 Hz, H-1),
a), 166.0 (carbonyl), HR-FD-MS m/z [M] calcd for
C H
23 50
O
7
4
, 550.2634; found, 550.2654.
(
(
1
CH
2 2
Cl /hexane, 1:1). Evaporation of the eluant gave 3.26 g of 8d
ꢀ1
85%) as a syrup. IR (
190, 1118, 1090, 1006, 860, 838, 808, 740. H NMR (500 MHz,
m
max, cm ) 1734, 1636, 1458, 1407, 1249,
1
a
CDCl
3
) 0.01 (9H, s, CH
2
CH
CH
TMS), 3.60–3.68 (3H, m, H-3, H-4 and H-5), 3.92
1H, ddd, J = 11.7, 9.4, 6.2 Hz, CH CH TMS), 4.25 (1H, dd, J = 11.4,
2
TMS), 0.64–0.69 (18H, m, SiCH
2
CH
3
),
l
0
.93–1.04 (29H, m, SiCH
2
3
and CH CH TMS), 3.43–3.49 (2H, m,
2
2
H-2 and CH CH
(
2
2
3
ꢀ
1
2
2
mmax, cm ) 3391,
1
6
4
.8 Hz, H-6a), 4.39 (1H, d, J = 6.7 Hz, H-1), 4.41 (1H, dd, J = 11.2,
.4 Hz, H-6b), 5.83 (1H, dd, J = 10.5, 1.4 Hz, H-b), 6.14 (1H, dd,
H
3
2
2
1
3
J = 17.3, 10.5 Hz, H-a), 6.42 (1H, dd, J = 17.3, 1.5 Hz, H-b),
C
),
2
2
NMR (125 MHz, CDCl
.9, 6.9, 7.0 (SiCH CH
CH CH TMS), 71.9 (C-4), 76.0 (C-5), 77.0 (C-2, overlapping with
the solvent peak), 79.0 (C-3), 102.1 (C-1), 128.3 (C-b), 130.8 (C-
3
) ꢀ1.5 (CH
2
CH
2
TMS), 5.0, 5.1, 5.2 (SiCH
2
CH
3
6
(
2
3
), 18.1 (CH
2
CH
2
TMS), 64.7 (C-6), 66.4
2
2
2
2
2
2
4.40 (1H, dd, J = 12.1, 2.2 Hz, H-6a), 4.54 (1H, dd, J = 12.1,
5.0 Hz, H-6b), 5.88 (1H, dd, J = 10.5, 1.3 Hz, H-b), 6.17 (1H, dd,
+
a
), 165.9 (carbonyl), HR-FD-MS m/z [M+H] calcd for C32
69 7 4
H O Si ,
6
77.4120: found, 677.4118.
J = 17.3, 10.4 Hz, H-
NMR (125 MHz, CDCl
63.4 (C-6), 67.6 (CH CH
76.0 (C-3), 102.1 (C-1), 127.9 (C-b), 131.8 (C-
a C
), 6.46 (1H, dd, J = 17.3, 1.3 Hz, H-b), 13
3
) ꢀ1.5 (CH
TMS), 70.0 (C-4), 73.6 (C-2), 73.9 (C-5),
), 166.8 (carbonyl),
Si, 335.1526; found,
2 2 2 2
CH TMS), 18.2 (CH CH TMS),
4
.1.6. 2,3,4-Tri-O-trimethylsilyl-1-O-(2-trimethylsilylethyl)-b-
D
-
2
2
glucopyranoside 7
a
+
Trimethylsilyl chloride (6.5 ml, 51.3 mmol) was added drop-
27 7
HR-FD-MS m/z [M+H] calcd for C14H O
wise to a solution of 6 (3.53 g, 12.0 mmol) in 25 ml of pyridine
335.1553.

K. Shigetomi et al. / Tetrahedron: Asymmetry 19 (2008) 1444–1449
1449
0
4
.1.8. 1-O-(2-Trimethylsilylethyl)-6-O-[4 -(tert-
J = 9.4, 5.6, 1.9 Hz, H-5(b)), 3.68 (t, J = 9.3 Hz, H-3(
a
)), 3.73 (1H,
0
0
0
0
butyldimethylsilyloxy)-3 -hydroxy-2 -methylenebutanoyl]-b-
D
-
overlapped dd, J = 11.3, 3.1 Hz, H-4 b(
J = 10.0, 5.1, 2.1 Hz, H-5( )), 4.26 (dd, J = 12.0, 5.6 Hz, H-6a(b)),
4.28 (dd, J = 12.3, 4.8 Hz, H-6a( )), 4.47 (dd, J = 11.9, 2.3 Hz, H-
6b( )), 4.50 (d, J = 7.8 Hz, H-1 (b)), 4.51 (dd, J = 11.9, 2.2 Hz, H-
6b(b)), 4.59 (1H, br q, H-3 ), 5.10 (d, J = 3.8 Hz, H-1 (a)), 6.00 (1H,
a) and H-4 b(b)), 4.01 (ddd,
glucopyranoside 12c
a
To a solution of 8c (54.3 mg, 162
-(tert-butyldimethylsilyloxy)-acetaldehyde (84.9 mg, 487
and 3-hydroxy quinuclidine (20.6 mg, 162 mol) were added at
l
mol) in dry DMSO (1.62 ml),
a
2
l
mol)
a
0
l
1
3
room temperature. After 40 h, the reaction mixture was diluted
with EtOAc (2.0 ml) and extracted with 2.0 ml of brine. The water
layer was then washed with EtOAc (2.0 ml ꢁ 2). The combined or-
s, @CH
65.1 (C-6(
71.8 (C-4(b)), 72.1 (C-4(
3( )), 75.3 (C-5(b)), 76.2 (C-2(b)), 77.9 (C-3(b)), 94.0 (C-1(
2
, Ha), 6.36 (1H, s, @CH
2
, Hb), C NMR (125 MHz, CD
3
OD)
)),
)), 74.8 (C-
0
a
)), 65.2 (C-6(b)), 66.7 and 66.8 (C-4 ), 70.7 (C-5(
a
0
a)), 72.1 (C-3 ), 73.8 (C-2(
a
ganic layer was dried over Na
2
SO
4
and evaporated. Silica gel col-
) yielded
mol, 40%, 3% de) as a colorless syrup. IR (
cm ) 3417, 1717, 1630, 1412, 1362, 1251, 1167, 1080, 860, and
a
a
)),
0
umn chromatography (5% then 10% MeOH in CHCl
2.4 mg of 12c (64
3
98.3 (C-1(b)), 126.7 and 126.8 (@CH
167.4 and 167.5 (C-1 ).
2
), 142.2 and 142.3 (C-2 ),
0
3
l
m
max
,
ꢀ1
+
8
5
37. HR-FD-MS m/z [M+H] calcd for C22
H
45
O
9
Si
2
, 509.2602; found,
4.1.9.2. 6-Tuliposide B. Compound 1: [
a
]
D
= +37.7 (c 1.0, MeOH),
1
09.2597.
H NMR (500 MHz, CD OD), 3.14 (dd, J = 8.9, 7.9 Hz, H-2(b)),
3
The obtained mixture of diastereomers was further separated
3.30–3.38 (m, H-2(
lapped dd, J = 11.3, 6.8 Hz, H-4 a(
a
), H-3(b), H-4(
a
a
), and H-4(b)), 3.44 (1H, over-
) and H-4 a(b)), 3.53 (ddd,
by chiral HPLC (EtOH/hexane, 8:92; CHIRALPAKÒ IA column (£
0
0
2
0 mm ꢁ 20 cm)).
J = 9.4, 5.8, 2.2 Hz, H-5(b)), 3.68 (t, J = 9.4 Hz, H-3(
a
)), 3.72 and
0
0
3
.73 (1H, overlapped dd, J = 11.3, 3.7 Hz, H-4 b(a), and H-4 b(b)),
4
.1.8.1. First eluted diastereomer. (R)-12c (rt = 87.1 min),
4.01 (ddd, J = 10.1, 5.4, 2.2 Hz, H-5(
H-6a(b)), 4.30 (dd, J = 11.8, 5.4 Hz, H-6a(a
a
)), 4.28 (dd, J = 12.0, 5.8 Hz,
1
[
CH
(
a
]
D
= ꢀ35.1 (c 1.0, CHCl
CH
2H, m, CH
3
), H NMR (500 MHz, CDCl
3
) 0.02 (9H, s,
)), 4.42 (dd, J = 11.8,
2
2
TMS), 0.06 and 0.07 (3H, s, MeSi), 0.90 (9H, s, t-Bu), 1.01
2.3 Hz, H-6b(a)), 4.48 (dd, J = 11.9, 2.0 Hz, H-6b(b)), 4.50 (d,
0
2
CH
2
TMS), 3.34 (1H, t, J = 8.5 Hz, H-2), 3.41 (1H, t,
J = 7.8 Hz, H-1 (b)), 4.57 (1H, br q, J = 6.8, 3.5 Hz, H-3 ), 5.09 (d,
0
J = 9.3 Hz, H-4), 3.48–3.56 (3H, m, H-3,5 and H-4 a), 3.59 (1H,
ddd, J = 11.2, 9.9, 6.0 Hz, CH
4
4
4
J = 3.7 Hz, H-1 (
a
)), 5.99 (1H, s, @CH
C NMR (125 MHz, CD OD) 65.0 (C-6(
)), 71.7 (C-4(b)), 72.0 (C-4(a)), 72.1 (C-3 ), 73.8 (C-
2
, Ha), 6.35 (1H, s, @CH
2
, Hb),
1
3
2
CH
2
TMS), 3.85 (1H, dd, J = 10.1,
CH TMS),
3
a
)), 65.1 (C-6(b)), 66.6 (C-
0
0
0
.2 Hz, H-4 b), 3.95 (1H, ddd, J = 11.2, 9.9, 6.0 Hz, CH
2
2
4 ), 70.7 (C-5(
a
.28 (1H, d, J = 7.8 Hz, H-1), 4.44–4.45 (2H, m, H-6a and H-6b),
2(a)), 74.7 (C-3(a)), 75.3 (C-5(b)), 76.2 (C-2(b)), 77.9 (C-3(b)),
0
0
.56 (1H, br q, H-3 ), 6.00 (1H, s, @CH
2
, Ha), 6.40 (1H, s, @CH
2
,
94.0 (C-1(
167.3 and 167.4 (C-1 ).
a
)), 98.2 (C-1(b)), 126.8 and 126.9 (@CH
2
), 142.1 (C-2 ),
1
3
0
Hb), C NMR (125 MHz, CDCl
3
) ꢀ5.4 and ꢀ5.3 (Me
CH2TMS), 18.2 (Me C), 25.9 (Me
CH
2
Si), ꢀ1.4
(
CH
2
CH
2
TMS), 18.2 (CH
2
3
3
C), 63.8
0
0
(
C-6), 66.3 (C-4 ), 67.4 (CH
2
2
TMS), 70.2 (C-4), 70.7 (C-3 ), 73.5
Acknowledgments
(
2
2
C-5), 73.7 (C-2), 76.1 (C-3), 102.1 (C-1), 127.4 (@CH ), 139.0 (C-
), and 166.2 (C-1 ).
0
0
This work was supported by the Grant-in-Aid for Scientific Re-
search on Priority Area ‘Creation of Biologically Functional Mole-
cules’ from the Ministry of Education, Culture, Sports, Science
and Technology of Japan and Grant-in-Aid for Scientific Research
(A) from the Japanese Society for the Promotion of Science (JSPS).
4
.1.8.2. Second eluted diastereomer. (S)-12c (rt = 94.5 min),
1
[
CH
(
a
]
D
= ꢀ24.0 (c 1.0, CHCl
CH TMS), 0.06 and 0.07 (3H, s, MeSi), 0.90 (9H, s, t-Bu), 1.01
2H, m, CH
3 3
), H NMR (500 MHz, CDCl ), 0.02 (9H, s,
2
2
2
CH
2
TMS), 3.35 (1H, t, J = 8.6 Hz, H-2), 3.42 (1H, t,
0
J = 9.3 Hz, H-4), 3.49–3.53 (3H, m, H-3,5 and H-4 a), 3.60 (1H,
References
ddd, J = 11.3, 9.8, 6.0 Hz, CH
2
CH
2
TMS), 3.86 (1H, dd, J = 10.0 Hz,
CH TMS),
0
1. Dixon, R. A. Nature 2001, 411, 843–847.
4
4
4
.1 Hz, H-4 b), 3.96 (1H, ddd, J = 11.3, 9.8, 6.0 Hz, CH
.28 (1H, d, J = 7.6 Hz, H-1), 4.40 (2H, dd, J = 12.0, 5.5 Hz, H-6a),
.47 (2H, dd, J = 12.0, 2.2 Hz, H-6b), 4.56 (1H, br q, H-3 ), 5.99
2
2
2.
VanEtten, H.; Mansfield, J. W.; Bailey, J. A.; Farmer, E. E. Plant Cell 1994, 6, 1191–
192.
1
0
3. (a) Tschesche, R.; Kämmerer, F. J.; Wulff, G.; Schönbeck, F. Tetrahedron Lett.
1968, 6, 701–706; (b) Tschesche, R.; Kämmerer, F. J.; Wulff, G. Chem. Ber. 1969,
, Hb), 1 C NMR (125 MHz,
3
(
1H, s, @CH
2
, Ha), 6.39 (1H, s, @CH
ꢀ5.4 and ꢀ5.3 (Me
TMS), 18.3 (Me C), 25.9 (Me
7.5 (CH CH
6.2 (C-3), 102.0 (C-1), 127.4 (@CH
2
1
02, 2057–2071; (c) Christensen, L. P. Phytochemistry 1999, 51, 969–974.
CDCl
3
)
2
Si), ꢀ1.4 (CH
2
CH
2
TMS), 18.2
4.
(a) Solb, A. Phytochemistry 1973, 12, 811–815; (b) Solb, A. Phytochemistry 1975,
14, 1997–2005; (c) Hausen, B. M.; Prater, E.; Schubert, H. Contact Dermatitis
1983, 9, 46–54; (d) Santucci, B.; Picardo, M.; Iavarone, C.; Trogolo, C. Contact
Dermatitis 1985, 12, 215–219.
0
(
CH
2
CH
2
3
3
C), 63.9 (C-6), 66.3 (C-4 ),
0
6
7
2
2
TMS), 70.3 (C-4), 70.8 (C-3 ), 73.5 (C-5), 73.6 (C-2),
0
0
2
), 139.0 (C-2 ), and 166.2 (C-1 ).
5.
(a) Kim, C.-S.; Hara, T.; Probal, K. D.; Itoh, E.; Horiike, M. Biosci., Biotechnol.,
Biochem. 1998, 62, 1546–1594; (b) Probal, K. D.; Kim, C.-S.; Hara, T.; Itoh, E.
Biosci., Biotechnol., Biochem. 1999, 63, 760–761.
4
.1.9. Deprotection of Baylis–Hillman adducts
BH adduct (S)-12c (17.2 mg, 33.9 mol) was dissolved in 172
of deprotection reagent (trifluoroacetic acid/CH Cl , 2:1, v/v) and
6
.
.
Shoji, K.; Ubukata, M.; Momonoi, K.; Tsuji, T.; Morimatsu, T. J. Jpn. Soc. Hort. Sci.
l
ll
2005, 74, 469–475.
2
2
7
(a) Tanaka, A. Agric. Biol. Chem. 1980, 44, 199–203; (b) Papagerorgiou, C.;
Benezra, C. J. Org. Chem. 1985, 50, 1144–1145; (c) Ohgiya, T.; Nishiyama, S.
Heterocycles 2004, 63, 2349–2354.
left for 1.5 h at room temperature. Dilution of the reaction mixture
with toluene followed by evaporation was repeated until the TFA
was completely removed. The resulting mixture was then purified
8.
(a) Hutchinson, C. R. J. Org. Chem. 1974, 39, 1854–1858; (b) Corbet, J. P.;
Benezra, C. J. Org. Chem. 1981, 46, 1141–1147.
via silica gel column chromatography (H
2
O/MeCN, 1:5). Subse-
9. Preliminary accounts for the synthesis of 1-O-methyl 6-tuliposide B:
Shigetomi, K.; Kishimoto, T.; Shoji, K.; Ubukata, M. Heterocycles 2006, 69, 63–
quent evaporation of the solvent provided 9.6 mg of 1 (96%) as a
67.
0
colorless syrup. (3 R)-Diastereomer 13 was obtained from (R)-12c
10. Jansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J.; Magnusson, G. J. Org. Chem. 1988,
by the same procedure as for 1 and provided a 93% yield. IR (
cm ) 3326, 1718, 1653, 1277, and 1020. HR-FD-MS m/z [M+Na]
m
max
,
53, 5629–5647.
ꢀ1
+
11. (a) Richard, F. H.; John, R.; Ronald, D. H. Carbohydr. Res. 1992, 229, 183–194;
Preparation of methyl 2,3,4-tris-O-trimethylsilyl- -glucoside: (b) Hurst, D.
T.; McInnes, A. G. Can. J. Chem. 1965, 43, 2004–2011.
a-D
calcd for C11 Na, 317.0849; found, 317.0840.
18 9
H O
12. (a) Enders, D.; Schübeler, T. Synthesis 2002, 15, 2280–2288; (b) Lafontaine, J. A.;
Provencal, D. P.; Gardelli, C.; Leahy, J. W. J. Org. Chem. 2003, 68, 4215–4234.
4
.1.9.1. epi-6-Tuliposide B. Compound 13: [
a
]
D
= +30.9 (c 1.0,
1
13. (a) Drewes, S. E.; Freese, S. D.; Emslie, N. D.; Roos, G. H. P. Synth. Commun. 1988,
8, 1565–1572; (b) Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. Synth.
MeOH), H NMR (500 MHz, CD
.30-3.39 (m, H-2( ), H-3(b), H-4(
lapped dd, J = 11.3, 6.7 Hz, H-4 a(
3
OD), 3.15 (d, J = 8.4 Hz, H-2(b)),
1
3
a
a
a
) and H-4(b)), 3.45 (1H, over-
) and H-4 a(b)), 3.53 (ddd,
Commun. 1988, 18, 495–500.
0
0
14. Lemiux, R. U.; Driguez, H. J. Am. Chem. Soc. 1975, 97, 4069–4075.