Stereoselective synthesis of a protected form of (6R,7E,9S,10R,12Z)-6,9,10- trihydroxy-7,12-hexadecadienoic acid

Article abstract of DOI:10.1271/bbb.110829

The protected stereoisomer of a trihydroxy unsaturated fatty acid, which could be employed as a potential nigricanoside α-chain building block, was synthesized by using Evans asymmetric alkylation, Sharpless kinetic resolution, and diastereoselective reduction as the key steps.

Full text of DOI:10.1271/bbb.110829

Biosci. Biotechnol. Biochem., 76 (3), 605–607, 2012
Note
Stereoselective Synthesis of a Protected Form
of (6R,7E,9S,10R,12Z)-6,9,10-Trihydroxy-7,12-hexadecadienoic Acid
y
Yusuke KURASHINA and Shigefumi KUWAHARA
Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University,
Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
Received October 31, 2011; Accepted November 24, 2011; Online Publication, March 7, 2012
[doi:10.1271/bbb.110829]
The protected stereoisomer of a trihydroxy unsat-
urated fatty acid, which could be employed as a
potential nigricanoside ꢀ-chain building block, was
synthesized by using Evans asymmetric alkylation,
Sharpless kinetic resolution, and diastereoselective re-
duction as the key steps.
connected, for example, to an 110,120-epoxy ꢁ-chain
derivative by an acid-promoted ring-opening substitu-
tion reaction between the C10-OH and C110 allylic
position.4) We describe in this note the stereoselective
synthesis of a stereoisomer of 5 by a strategy previously
developed in our laboratory.
The key reactions for the synthesis of 5, which were
also employed in our recent enantioselective synthesis of
analogous trihydroxy fatty acids,5) are shown at the
bottom of Fig. 1. This strategy would be applicable to
the synthesis of any stereoisomers of 5 by changing the
absolute configuration of the chiral sources in the Evans
asymmetric alkylation (L- or D-Phe) and Sharpless
kinetic resolution (L-DIPT or D-DIPT) as well as by
choosing either syn- or anti-selective reduction to install
the C9 stereochemistry; however, we set compound 50
(Scheme 1) as our present synthetic target mainly by
considering the cheaper prices of L-Phe and L-DIPT than
the corresponding D-enantiomers. Consistent with our
previous synthesis of malyngic acid,5) L-Phe-derived
chiral oxazolidinone 6 was alkylated with (Z)-1-iodo-2-
hexene to give 7. The product was converted into
phosphonate 10 by a three-step sequence (hydrolysis,
Weinreb’s amide formation, and substitution) via 8 and
9. The coupling partner (13) of 10 in the HWE reaction
was prepared from racemic alcohol 116) via acetate 12
with >98% enantiomeric excess according to our
previous protocol comprising Sharpless kinetic resolu-
tion, acetylation, and ozonolysis.5,7) E-Selective HWE
olefination between 10 and 13 proceeded smoothly to
give 14, whose exposure to chelation-controlled reduc-
tion conditions afforded 15 (anti/syn = 7.5:1).8) Acety-
lation of 15 gave acetate 16 which, after chromato-
graphic purification to remove the corresponding syn
isomer, was subjected to DDQ oxidation to afford 50.
In conclusion, we prepared suitably protected fatty
acid stereoisomer 50, which could potentially be em-
ployed as a nigricanoside ꢀ-chain building block, by
using our stereochemically flexible synthetic strategy.
Key words: nigricanoside; fatty acid; glycolipid; anti-
mitotic; cytotoxic
In the course of their screening for antimitotic natural
products, Andersen and co-workers isolated nigricano-
sides A (1) and B (2) as their respective dimethyl ester
derivatives 3 (0.8 mg) and 4 (0.4 mg) from the marine-
derived green alga, Avrainvillea nigricans (28 kg,
collected over an 8-year period) (Fig. 1).1) The paucity
of the isolated materials was probably responsible for
the stereochemistry of 1, 2 and 4 not being assigned,
except for the relative configuration of the galactose
moiety and no biological activity being reported.
However, the dimethyl ester (3) of nigricanoside A
was shown to arrest MCF-7 human breast cancer cells in
mitosis with a remarkably low IC50 value of 3 nM and to
inhibit the proliferation of both MCF-7 and HCT-116
human colon cancer cells (IC50 of ca. 3 nM). The
nigricanosides consist of the same components from a
structural viewpoint (two fatty acids, galactose, and
glycerol) as ordinary monogalactosyldiacylglycerols,
but it is unprecedented that the ꢀ- and ꢁ-fatty acid
chains and the galactose residue are connected to one
another with ether linkages. To our knowledge, no study
directed toward the total synthesis of the nigricanosides
has been reported to date, although the development of a
new NMR method with the objective of elucidating their
relative stereochemistry2) and a general synthetic ap-
proach to the 2-buten-1,4-diol system contained in the
fatty acid segments have appeared in the literature.3) The
unique structural features of the nigricanosides, the
potent biological activity of 3, and the anticipated
difficulty in re-isolating the natural products prompted
us to undertake the stereochemical determination of the
nigricanosides by synthetic studies. Among the many
tasks to be achieved for this was the preparation of
appropriately protected ꢀ-chain segment 5 bearing two
protected hydroxyls at the C6 and C9 positions and an
unprotected one at the C10 position; this could be
Experimental
NMR spectra were recorded with TMS as an internal standard in
CDCl3 by a Varian MR-400 spectrometer (400 MHz for 1H and
100 MHz for 13C). Optical rotation values were measured with a
Horiba Septa-300 polarimeter, and the mass spectra were obtained with
a Jeol JMS-700 spectrometer operated in the EI or FAB mode. Column
chromatography was conducted with Merck silica gel 60 (7–230
y
To whom correspondence should be addressed. Fax: +81-22-717-8783; E-mail: skuwahar@biochem.tohoku.ac.jp
Abbreviations: DCC, dicyclohexylcarbodiimide; DDQ, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; DIPT, diisopropyl tartrate; DMAP, 4-
(dimethylamino)pyridine; HWE, Horner–Wadsworth–Emmons; NaHMDS, sodium hexamethyldisilazide; Phe, phenylalanine; PMB, p-methoxyben-
zyl; TBHP, tert-butyl hydroperoxide

606
Y. KURASHINA and S. KUWAHARA
OH
9
O
O
O
O
-chain
17'
10
O
6
a
b
n-Pr
(CH2)4CO2R
n-Pr
N
O
N
O
OH
PMBO
PMBO
Bn
Bn
12'
(CH2)3CO2R
7
6
11'
-chain
O
O
OH
O
18'
Et
d
HO
n-Pr
n-Pr
OH
OH
X
O
O
HO
PMBO
8: X = OH
9: X = N(OMe)Me
PMBO
P(OMe)2
O
OH
10
c
nigricanoside A (1): R = H, 17',18'-saturated
nigricanodise B (2): R = H, 17',18'-unsaturated
3: R = Me, 17',18'-saturated
e, f
g
(CH2)4CO2Me
(CH2)4CO2Me
OAc
4: R = Me, 17',18'-unsaturated
OH
diastereoselective
11
12
reduction
HWE olefination
OR1
9
OHC
(CH2)4CO2Me
10
6
(CH2)4CO2Me
n-Pr
h
OAc
O
OH
OR2
13
5
n-Pr
(CH2)4CO2Me
Evans asymmetirc
alkylation
Sharpless
kinetic resolution
PMBO
i
OAc
14
Fig. 1. Nigricanosides A (1) and B (2), Their Dimethyl Esters (3 and
4), and Key Reactions for the Synthesis of Protected ꢀ-Chain
Segment 5.
OR
10
9
n-Pr
(CH2)4CO2Me
OAc
PMBO
15: R = H
16: R = Ac
j
mesh). The solvents for the reactions were distilled prior to use: THF
and Et2O from Na/benzophenone, and CH2Cl2 and MeCN from CaH2.
(Z)-1-Iodo-2-hexene. The title compound (2.33 g, 94% yield) was
prepared from (Z)-2-hexen-1-ol (1.18 g, 11.8 mmol) which was treated
k
OAc
n-Pr
(CH2)4CO2Me
1
.
OH
OAc
with NaI and BF3 OEt2 in MeCN according to Ref. 5. H-NMR ꢂ: 0.94
5'
(3H, t, J ¼ 7:4 Hz), 1.45 (2H, sex, J ¼ 7:4 Hz), 2.08 (2H, dq, J ¼ 1:5,
7.4 Hz), 3.92 (2H, d, J ¼ 8:5 Hz), 5.48 (1H, dt, J ¼ 10:6, 7.4 Hz),
5.72–5.81 (1H, m); 13C-NMR ꢂ: 0.7, 13.8, 21.9, 28.7, 126.7, 134.6;
HRMS (EI) m=z: calcd. for C6H11I, 209.9906; found, 209.9906 (Mþ).
(S)-4-Benzyl-3-[(2R,4Z)-2-(4-methoxybenzyloxy)-4-octenoyl]-2-ox-
Scheme 1. Synthesis of Protected Trihydroxy Fatty Acid 50.
Reagents and conditions: a) NaHMDS, (Z)-1-iodo-2-hexene,
THF, ꢁ78 ꢂC (83%); b) LiOH, H2O2, aq. THF, 0 ꢂC to rt; c)
ꢂ
.
MeNH(OMe) HCl, DCC, DMAP, CH2Cl2, 0 C to rt (64% from 7);
d) MePO(OMe)2, n-BuLi, THF, ꢁ78 ꢂC (97%); e) L-DIPT, Ti(Oi-
azolidinone (7). Compound 7 (1.43 g, 83% yield) was prepared from 6
24
ꢂ
˚
(1.40 mg, 3.94 mmol) according to Ref. 5. ½ꢀꢀ
þ77:7 (c 1.22,
Pr)4, TBHP, MS 4 A, CH2Cl2, ꢁ20 C; f) Ac2O, Py, rt (59% from
11); g) O3, CH2Cl2, ꢁ78 ꢂC, then Me2S, ꢁ78 ꢂC to rt (88%); h) 10,
LiBr, Et3N, THF, rt (85%); i) Zn(BH4)2, Et2O, ꢁ15 to ꢁ10 ꢂC
(81%); j) Ac2O, Py, DMAP, rt (85%); k) DDQ, CH2Cl2/H2O, 0 ꢂC
to rt (79%).
D
CHCl3); 1H-NMR ꢂ: 0.89 (3H, t, J ¼ 7:4 Hz), 1.37 (2H, sex,
J ¼ 7:4 Hz), 2.00–2.07 (2H, m), 2.50–2.64 (2H, m), 2.70 (1H, dd,
J ¼ 13:4, 9.7 Hz), 3.23 (1H, dd, J ¼ 13:4, 3.3 Hz), 3.78 (3H, s), 4.12–
4.17 (2H, m), 4.48 (1H, d, J ¼ 11:2 Hz), 4.53 (1H, d, J ¼ 11:2 Hz),
4.55–4.62 (1H, m), 5.12 (1H, dd, J ¼ 7:2, 5.0 Hz), 5.47–5.57 (2H, m),
6.86 (2H, d, J ¼ 8:4 Hz), 7.19 (2H, d, J ¼ 6:9 Hz), 7.25–7.36 (5H, m);
13C-NMR ꢂ: 13.8, 22.6, 29.4, 30.9, 37.8, 54.9, 55.2, 66.6, 72.4, 76.5,
113.6 (2C), 122.5, 127.4, 128.9 (2C), 129.4 (2C), 129.7, 130.0 (2C),
133.0, 135.0, 152.9, 159.3, 172.7; HRMS (FAB) m=z: calcd. for
Methyl (R)-6-acetoxy-7-octenoate (12). Compound 12 (607 mg,
59% yield) was prepared in two steps from racemic alcohol 11 (1.65 g,
9.59 mmol) according to Refs. 5 and 7, except that L-DIPT, instead of
25
D-DIPT, was used as the catalyst in the kinetic resolution step. ½ꢀꢀ
D
C
26H31NO5Na, 460.2100; found, 460.2099 (½M þ Naꢀþ).
þ7:95 (c 1.27, CHCl3); 1H-NMR ꢂ: 1.29–1.43 (2H, m), 1.55–1.71 (4H,
m), 2.06 (3H, s), 2.31 (2H, t, J ¼ 7:4 Hz), 3.67 (3H, s), 5.17 (1H, d,
J ¼ 10:6 Hz), 5.20–5.26 (2H, m), 5.76 (1H, ddd, J ¼ 17:4, 10.6,
6.2 Hz); 13C-NMR ꢂ: 21.2, 24.59, 24.63, 33.8, 33.9, 51.5, 74.5, 116.8,
(2R,4Z)-N-Methoxy-2-(4-methoxybenzyloxy)-N-methyl-4-octenamide
(9). Compound 9 (218 mg, 64% yield) was prepared from 7 (470 mg,
26
1.07 mmol) via 8 according to Ref. 5. ½ꢀꢀ
þ63:5 (c 1.20, CHCl3);
D
1H-NMR ꢂ: 0.88 (3H, t, J ¼ 7:4 Hz), 1.35 (2H, sex, J ¼ 7:4 Hz), 1.97–
2.04 (2H, m), 2.42–2.55 (2H, m), 3.20 (3H, s), 3.58 (3H, s), 3.80 (3H,
s), 4.28 (1H, br t, J ¼ 5:7 Hz), 4.35 (1H, d, J ¼ 12:5 Hz), 4.62 (1H, d,
J ¼ 12:5 Hz), 5.41–5.53 (2H, m), 6.84–6.88 (2H, m), 7.26–7.30 (2H,
m); 13C-NMR ꢂ: 13.7, 22.6, 29.3, 30.3, 32.3, 55.2, 61.2, 71.0, 75.0,
113.6 (2C), 124.4, 129.5 (2C), 129.9, 132.4, 159.2, 173.0; HRMS
(FAB) m=z: calcd. for C18H28NO4, 322.2018; found, 322.2020
(½M þ Hꢀþ).
136.3, 170.3, 173.9; HRMS (FAB) m=z: calcd. for C11H19O4,
215.1283; found, 215.1287 ð½M þ Hꢀþ). The enantiomeric excess of
(R)-11 obtained by the Sharpless kinetic resolution of 11 was
determined to be >98% by 1H-NMR analyses of the corresponding
(R)- and (S)-MTPA esters according to Ref. 7.
Methyl (R)-6-acetoxy-7-oxoheptanoate (13). Compound 13
(280 mg, 88% yield) was prepared from 12 (317 mg, 1.48 mmol)
24
according to Ref. 5. ½ꢀꢀ
þ33:5 (c 1.07, CHCl3); 1H-NMR ꢂ: 1.41–
D
Dimethyl [(R)-3-(4-methoxybenzyloxy)-2-oxo-5-nonenyl]phospho-
1.51 (2H, m), 1.62–1.72 (2H, m), 1.72–1.80 (1H, m), 1.80–1.91 (1H,
m), 2.19 (3H, s), 2.34 (2H, t, J ¼ 7:4 Hz), 3.68 (3H, s), 4.99 (1H, dd,
J ¼ 8:2, 4.7 Hz), 9.51 (1H, br s); 13C-NMR ꢂ: 20.6, 24.4 (2C), 28.3,
33.6, 51.5, 78.0, 170.6, 173.7, 198.2; HRMS (FAB) m=z: calcd. for
nate (10). Compound 10 (1.52 g, 97% yield) was prepared from 9
25
(1.31 g, 4.09 mmol) according to Ref. 5. ½ꢀꢀ
þ27:8 (c 1.07, CHCl3);
D
1H-NMR ꢂ: 0.89 (3H, t, J ¼ 7:4 Hz), 1.36 (2H, sex, J ¼ 7:4 Hz), 1.95–
2.03 (2H, m), 2.39–2.53 (2H, m), 3.16 (1H, dd, J ¼ 21:9, 14.6 Hz),
3.32 (1H, dd, J ¼ 21:7, 14.6 Hz), 3.76 (3H, d, J ¼ 5:8 Hz), 3.79 (3H, d,
J ¼ 5:8 Hz), 3.81 (3H, s), 3.96 (1H, t, J ¼ 6:2 Hz), 4.46 (1H, d,
J ¼ 11:3 Hz), 4.57 (1H, d, J ¼ 11:3 Hz), 5.34–5.41 (1H, m), 5.47–5.55
(1H, m), 6.86–6.90 (2H, m), 7.26–7.30 (2H, m); 13C-NMR ꢂ: 13.7,
22.6, 29.3, 29.4, 36.2 (d, J ¼ 132:7 Hz), 52.9 (d, J ¼ 5:9 Hz), 53.0 (d,
J ¼ 5:9 Hz), 55.2, 72.2, 84.0 (d, J ¼ 2:4 Hz), 113.8 (2C), 123.3, 129.4,
129.6 (2C), 133.1, 159.4, 203.9 (d, J ¼ 6:9 Hz); HRMS (FAB) m=z:
calcd. for C19H30O6P, 385.1780; found, 385.1786 (½M þ Hꢀþ).
C
10H17O5, 217.1076; found, 217.1075 (½M þ Hꢀþ).
Methyl (6R,7E,10R,12Z)-6-acetoxy-10-(4-methoxybenzyloxy)-9-oxo-
7,12-hexadecadienoate (14). Compound 14 (245 mg, 85% yield) was
prepared from 10 (235 mg, 0.61 mmol) and 13 (139 mg, 0.64 mmol)
23
according to Ref. 5. ½ꢀꢀ
þ42:1 (c 1.09, CHCl3); 1H-NMR ꢂ: 0.88
D
(3H, t, J ¼ 7:4 Hz), 1.28–1.41 (4H, m), 1.61–1.72 (4H, m), 1.96 (2H,
br q, J ¼ 7:3 Hz), 2.10 (3H, s), 2.31 (2H, t, J ¼ 7:5 Hz), 2.43 (2H, t,
J ¼ 6:8 Hz), 3.67 (3H, s), 3.81 (3H, s), 3.92 (1H, t, J ¼ 6:6 Hz), 4.36
(1H, d, J ¼ 11:1 Hz), 4.49 (1H, d, J ¼ 11:1 Hz), 5.32–5.52 (3H, m),

Synthesis of a Protected Trihydroxy Fatty Acid
607
6.61 (1H, dd, J ¼ 15:9, 1.2 Hz), 6.83–6.90 (3H, m), 7.25 (2H, d,
J ¼ 8:4 Hz); 13C-NMR ꢂ: 13.7, 21.0, 22.6, 24.5 (2C), 29.4, 30.3, 33.5,
33.7, 51.5, 55.3, 72.0, 72.6, 83.8, 113.8 (2C), 123.4, 124.1, 129.4,
129.7 (2C), 132.9, 144.6, 159.4, 170.0, 173.8, 200.7; HRMS (FAB)
m=z: calcd. for C27H38O7Na, 497.2515; found, 497.2516 (½M þ Naꢀþ).
Methyl (6R,7E,9S,10R,12Z)-6-acetoxy-9-hydroxy-10-(4-methoxy-
(2C), 124.9, 127.2, 129.4 (2C), 130.3, 132.0, 132.6, 159.1, 169.9,
170.1, 173.8; HRMS (FAB) m=z: calcd. for C29H42O8Na, 541.2778;
found, 541.2781 (½M þ Naꢀþ).
Methyl (6R,7E,9S,10R,12Z)-6,9-diacetoxy-10-hydroxy-7,12-hexa-
decadienoate (50). To a stirred mixture of 16 (17.6 mg, 33.9 mmol) in
CH2Cl2/water (10:1, 0.33 mL) was added DDQ (23.1 mg, 102 mmol) at
0 ꢂC, and the mixture was stirred at room temperature for 2 h. The
mixture was diluted with water and extracted with CH2Cl2. The
resulting extract was successively washed with water and brine, dried
(MgSO4) and concentrated in vacuo. The residue was chromato-
benzyloxy)-7,12-hexadecadienoate (15). To
a stirred solution of
anhydrous ZnCl2 (91.9 mg, 0.674 mmol) in Et2O (4.5 mL) was added
NaBH4 (51.1 mg, 1.35 mmol) at 0 ꢂC. The mixture was stirred at room
temperature for 12 h, and then re-cooled to ꢁ15 ꢂC. To the mixture was
added dropwise a solution of 14 (80.0 mg, 0.169 mmol) in Et2O
(3.4 mL), and the mixture was stirred overnight at ꢁ15 ꢂC and then for
an additional 5 h at ꢁ10 ꢂC. The mixture was quenched with satd. aq.
NH4Cl, filtered through a pad of Florisil, and extracted with CH2Cl2.
The resulting extract was washed with brine, dried (MgSO4) and
concentrated in vacuo. The residue was chromatographed over SiO2
graphed over SiO2 (hexane/EtOAc = 6:1) to give 50 (10.7 mg, 79%).
24
½ꢀꢀ
þ31:0 (c 0.525, CHCl3); 1H-NMR ꢂ: 0.91 (3H, t, J ¼ 7:4 Hz),
D
1.25 (1H, s, OH), 1.29–1.43 (4H, m), 1.56–1.69 (4H, m), 2.01 (2H, br
q, J ¼ 7:0 Hz), 2.06 (3H, s), 2.10 (3H, s), 2.21 (2H, br t, J ¼ 7:0 Hz),
2.31 (2H, t, J ¼ 7:5 Hz), 3.67 (3H, s), 3.77 (1H, dt, J ¼ 4:0, 6.6 Hz),
5.21–5.28 (2H, m), 5.36–5.44 (1H, m), 5.52–5.60 (1H, m), 5.68–5.78
(2H, m); 13C-NMR ꢂ: 13.8, 21.20, 21.22, 22.7, 24.5 (2C), 29.4, 30.7,
33.79, 33.84, 51.5, 72.6, 73.5, 76.3, 124.2, 126.3, 133.5, 133.6, 170.0,
170.3, 173.9; HRMS (FAB) m=z: calcd. for C21H34O7Na, 421.2203;
found, 421.2204 (½M þ Naꢀþ).
(hexane/EtOAc = 4:1) to give 15 (64.9 mg, 81%) as a 7.5:1 mixture
25
with its 9R-epimer. ½ꢀꢀ
þ5:96 (c 1.12, CHCl3); 1H-NMR ꢂ: 0.90
D
(3H, t, J ¼ 7:4 Hz), 1.24–1.42 (5H, m), 1.54–1.72 (4H, m), 2.00 (2H, q,
J ¼ 7:0 Hz), 2.04 (3H, s), 2.15–2.23 (1H, m), 2.29 (2H, t, J ¼ 7:5 Hz),
2.28–2.37 (1H, m), 3.46 (1H, ddd, J ¼ 7:1, 5.7, 3.8 Hz), 3.66 (3H, s),
3.81 (3H, s), 4.24 (1H, br q, J ¼ 4:6 Hz), 4.50 (1H, d, J ¼ 11:3 Hz),
4.57 (1H, d, J ¼ 11:3 Hz), 5.26 (1H, br q, J ¼ 6:3 Hz), 5.37–5.50 (2H,
m), 5.68 (1H, dd, J ¼ 15:8, 6.1 Hz), 5.75 (1H, dd, J ¼ 15:8, 5.5 Hz),
6.86–6.90 (2H, m), 7.24–7.28 (2H, m); 13C-NMR ꢂ: 13.7, 21.2, 22.6,
24.57, 24.62, 27.6, 29.4, 33.8, 33.9, 51.4, 55.2, 71.8, 72.6, 73.7, 81.6,
113.7 (2C), 125.3, 129.3 (2C), 130.2, 130.3, 131.2, 131.9, 159.2, 170.2,
173.9; HRMS (FAB) m=z: calcd. for C27H40O7Na, 499.2672; found,
499.2676 (½M þ Naꢀþ).
Acknowledgments
This work was supported, in part, by grant-aid for
scientific research from the Ministry of Education,
Culture, Sports, Science and Technology of Japan
(no. 22380064).
Methyl (6R,7E,9S,10R,12Z)-6,9-diacetoxy-10-(4-methoxybenzyloxy)-
7,12-hexadecadienoate (16). To a stirred solution of 15 (19.9 mg,
42 mmol) in pyridine (0.4 mL) was added Ac2O at 0 ꢂC, and the mixture
was stirred for 8 h at room temperature. DMAP (2.8 mg, 23 mmol) was
then added, and the mixture was stirred for an additional 2 h. The
mixture was quenched with satd. aq. NH4Cl and extracted with Et2O.
The resulting extract was successively washed with cold 1 M aq. HCl,
satd. aq. NaHCO3, water and brine, dried (MgSO4) and concentrated
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in vacuo. The residue was chromatographed over SiO2 (hexane/
24
EtOAc = 4:1) to give 16 (18.6 mg, 85%). ½ꢀꢀ
þ35:5 (c 1.48,
D
CHCl3); 1H-NMR ꢂ: 0.89 (3H, t, J ¼ 7:4 Hz), 1.27–1.41 (4H, m),
1.53–1.70 (4H, m), 1.97 (2H, br q, J ¼ 7:0 Hz), 2.04 (3H, s), 2.07 (3H,
s), 2.17–2.28 (2H, m), 2.29 (2H, t, J ¼ 7:5 Hz), 3.48–3.53 (1H, m),
3.66 (3H, s), 3.80 (3H, s), 4.48 (1H, d, J ¼ 11:1 Hz), 4.58 (1H, d,
J ¼ 11:1 Hz), 5,26 (1H, br q, J ¼ 6:4 Hz), 5.35–5.50 (3H, m), 5.66
(1H, dd, J ¼ 15:6, 6.3 Hz), 5.76 (1H, dd, J ¼ 15:6, 6.3 Hz), 6.85–6.89
(2H, m), 7.24–7.28 (2H, m); 13C-NMR ꢂ: 13.8, 21.2 (2C), 22.6, 24.6
(2C), 28.8, 29.4, 33.8, 33.9, 51.4, 55.2, 72.0, 73.4, 74.7, 79.8, 113.7
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