Thieme chemistry journal awardees - where are they now? synthesis of the marine glycolipid dioctadecanoyl discoside

Article abstract of DOI:10.1055/s-0029-1218301

The first synthesis of the inositol-containing marine glycolipid dioctadecanoyl discoside is reported. The key glycosylation reaction proceeds with β-selectivity at reduced temperature. The separable anomers could be readily progressed to afford discoside

Full text of DOI:10.1055/s-0029-1218301

LETTER
3099
Thieme Chemistry Journal Awardees – Where are They Now?
Synthesis of the Marine Glycolipid Dioctadecanoyl Discoside
Synthesisof
D
isco
o
side rdon J. Florence,*a Tashfeen Aslam,a Gavin J. Miller,a Gavin D. S. Milne,a Stuart J. Conway*b
a
Centre for Biomolecular Sciences, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK
Fax +44(1334)463808; E-mail: gjf1@st-andrews.ac.uk
b
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
Fax +44(1865)285002; E-mail: stuart.conway@chem.ox.ac.uk
Received 1 August 2009
Abstract: The first synthesis of the inositol-containing marine gly-
colipid dioctadecanoyl discoside is reported. The key glycosylation
reaction proceeds with b-selectivity at reduced temperature. The
separable anomers could be readily progressed to afford discoside,
its peracetate and the unnatural b-derivatives.
Key words: marine sponge, glycolipid, mannose, glycosylation,
inositol
The mannose-myo-inositol linkage is a ubiquitous struc-
tural feature of glycosylphosphatidylinositol (GPI) an-
chored cell surface proteins essential for cell–cell
recognition processes in animals and bacteria.1 The phos-
phatidylinositol mannosides (PIMs) and their multiglyco-
sylated lipomannan (LM) forms present in the cell walls
of pathogenic Mycobacterium are implicated in initial in-
fection and subsequent modulation of the immune re-
sponse.2 The resurgence of Mycobacterium tuberculosis
and the onset of multidrug resistance3 has prompted sig-
nificant interest in the evaluation of smaller natural PIMs4
and synthetic analogues5 as biological probes and poten-
tial new therapeutic agents that act via activation of cyto-
kine production, thus promoting a pro-inflammatory
response. Studies by Dunne and co-workers have also
shown that carbohydrate fatty acid ester derivatives dis-
play inhibitory activity against Gram-positive Straphylo-
coccus aureus.6
Dr. Gordon J. Florence was born in Manchester, UK. He gained a
BA degree in Natural Sciences from Cambridge University in 1997.
He received his PhD from Cambridge University in 2001, under the
supervision of Professor Ian Paterson FRS, working on the total syn-
thesis of discodermolide. From 2001 to 2002, he undertook postdoc-
toral research with Professor Craig J. Forsyth at the University of
Minnesota. In 2002, he returned to the group of Professor Paterson in
Cambridge to take up a Research Fellowship at Emmanuel College
focussing on the synthesis of cytotoxic marine macrolides. In 2005,
he was elected to a Royal Society University Research Fellowship
and moved to the University of St Andrews, where his research is di-
rected towards the synthesis and structure determination of bioactive
natural products and the development of new synthetic methodology.
He was awarded the Thieme Chemistry Journal Award in 2006.
terrestrial Propionibacterium,8 which suggests that 1 is
produced by a symbiotic cyanobacteria associated with
the marine sponge. The unknown biological function and
unusual structure of discoside, coupled with our ongoing
interest in the synthesis of myo-inositol-containing com-
pounds and their value as biological probes,9 prompted
this synthetic venture. Herein, we report the total synthe-
sis of dioctadecanoyl discoside (3) and its corresponding
peracetate derivative.
Isolated in 2005 by Fattorusso and co-workers, discoside
(1; Figure 1) is a unique marine glycolipid, obtained from
the Caribbean deep-sea sponge Discodermia dissoluta,7
which has proven to be a rich source of novel bioactive
secondary metabolites. Structurally, discoside is the first
example to be isolated from either marine or terrestrial
sources of a 4,6-O-diacylated mannoside a-linked to the
2-hydroxyl of a myo-inositol unit; the 4,6-O-fatty acyl
chains in discoside are present as a mixture of octade-
canoate (33% by lipid composition), 10- (51%) and 12-
methyloctadecanoate (16%) homologues, which were not
separated. The only closely related analogue to 1 is 1-O-
pentadecanoyl-2-O-(6-O-heptadecanoyl-a-D-mannopyra-
nosyl)-myo-inositol (2), isolated in 1968 from strains of
As outlined in Scheme 1, our synthetic strategy relied on
a challenging glycosylation of the axial C2 alcohol in ben-
zyl-protected inositol 4 with the D-mannose-derived
thioglycoside 5. In order to increase overall convergency,
we chose to incorporate the C18 lipid sidechains directly
in 5, thereby minimizing the number of post-coupling
transformations and allowing direct access to 3 by global
benzyl deprotection, in preference to employing anchi-
meric assistance and the necessity for further protecting
group manipulations.
SYNLETT 2009, No. 19, pp 3099–3102
x
x
.x
x
.2
0
0
9
Advanced online publication: 21.10.2009
DOI: 10.1055/s-0029-1218301; Art ID: S09409ST
© Georg Thieme Verlag Stuttgart · New York

3100
G. J. Florence et al.
LETTER
OBn
O
O
O
O
1'''
BnO
BnO
OBn
OBn
O
R*
O
O
R2
O
b–d
O
R2O
OH
O
1''
OH
O
72% over
3 steps
R1O
R*
R1
HO
HO
OR
1'
HO
6 R1 = R2 = H
8 R = CH
4 R = H
O
a
e
2CH=CH2
O
7 R1 = Bn, R2 = H
43%
66%
O
OH
O
R1
discoside (1)
2
2
OH
OH
OH
OH
HO
HO
OH
O
SPh
OH
O
SPh
OH
OH
HO
HO
O
f
2 R1 = C14H29, R2 = C16H33
61%
3"/3"'
3"/3"'
PMP
O
33%
18"/18"'
OH
OH
R* = 51%
16%
9
18"/18"'
18"/18"'
10
57% over
2 steps
3"/3"'
g, h
O
O
O
SPh
OBn
O
SPh
OBn
*undefined distribution at 4' and 6'
HO
i
R
O
Figure 1 Structure of discoside (1) and structurally related 1-O-
pentadecanoyl-2-O-(6-O-heptadecanoyl-a-D-mannopyranosyl)-myo-
inositol (2)
HO
O
98%
OBn
OBn
R
11
5 R = (CH2)16Me
O
1'''
O
1'
O
SPh
OBn
Scheme 2 Reagents and conditions: (a) NaH, BnBr, DMF,
0 °C→r.t., 18 h; (b) AllBr, NaH, imidazole, DMF, 0 °C→r.t., 22 h; (c)
HCl, MeOH, 20 min, reflux; (d) NaH, BnBr, DMF, 0 °C→r.t., 5 h; (e)
(i) (Ph3P)3RhCl, n-BuLi, THF, reflux, 5 h; (ii) HCl, MeOH, CH2Cl2,
r.t., 3 h; (f) p-MeOC6H4CH(OMe)2, p-TsOH·H2O (15 mol%), DMF,
50 °C, 130 mmHg, 3 h; (g) NaH, BnBr, TBAI, DMF, 0 °C→r.t., 3 h;
(h) CSA (20 mol%), MeOH–CH2Cl2 (3:1), 75 °C, 1 h; (i) octadecan-
oic acid, DCC, DMAP, CH2Cl2, 16 h.
1'''
R
O
R
O
O
1'' O
OH
O
1''
O
OBn
R
O
glycosylation
R
1'
HO
5 R = (CH2)16Me
O
OBn
BnO
OH
2
OH
OH
OH
OBn
OBn
HO
11 in 57% yield over two steps. The required introduction
of the two octadecanoate ester sidechains proceeded
smoothly under Steglich conditions (DCC, DMAP,
CH2Cl2) to provide the a-thiomannoside donor 5 in excel-
lent yield.15
2
BnO
3 R = (CH2)16Me
OH
4
Scheme 1 Retrosynthetic strategy for dioctadecanoyl discoside (3)
With key subunits 4 and 5 in hand, we then focused on the
key glycosylation reaction (Scheme 3). Thus, activation
of 5 [NIS (2.5 equiv), TESOTf (1.9 equiv), CH2Cl2, –40
to –20 °C] and reaction with 6 afforded a mixture of ano-
mers 12 and 13 in 63% yield with an a:b ratio of 1:4,16,17
which were separable by column chromatography. In an
effort to improve the a-selectivity of the process, we
found that performing the reaction at 0 °C led to a com-
bined 43% yield of 12 and 13 with an a:b ratio of 1:1.5.
The observed b-selectivity can be rationalised by the for-
mation of a low-temperature stable a-triflate intermediate
following the activation of 5,14a,17 which, in combination
with the preferential equatorial addition of the axial 2-hy-
droxyl of the inositol acceptor, leads to the b-linkage.4a,18
Completion of the total synthesis by global debenzylation
via hydrogenolysis of 12 with catalytic Pd black at atmo-
spheric pressure provided 4,6-octadecanoyl discoside 3 in
excellent yield, as an amorphous solid.
As shown in Scheme 2, the synthesis of the inositol sub-
unit 4 started with benzylation of the axial hydroxyls of
the orthoformate 6.10–12 Allylation of the remaining hy-
droxyl in 7 was followed by cleavage of the orthoformate
(3M HCl/MeOH, reflux) and benzylation (NaH/BnBr/
DMF) to afford 8 in 72% yield over three steps. Boon’s
modified Rh-mediated isomerisation of allyl ether 8
[(Ph3P)3RhCl, n-BuLi],13 and acidic methanolysis (AcCl/
MeOH), completed the inositol subunit 4 in 66% yield.
With the inositol subunit 4 in hand, attention was then di-
rected towards the preparation of the thiomannoside do-
nor 5, as shown in Scheme 2. Starting from a-D-
phenylthiomannoside 9, which was readily available in
three steps from D-mannose,14 temporary protection of the
4- and 6-position hydroxyl groups was achieved by treat-
ment with p-MeOC6H4CH(OMe)2 and CSA (20 mol%) to
give 10 in 61% yield.14a The remaining two hydroxyl
groups were then benzylated under standard conditions
(BnBr, NaH, TBAI), prior to acidic methanolysis (CSA,
MeOH/CH2Cl2) of the anisylidene acetal to provide diol
Spectroscopic characterization of 3 proved challenging
due to its insolubility across a range of solvents (DMSO-
d6, CD3OD, CDCl3, D2O, CD3OD/CDCl3).19 In order to
Synlett 2009, No. 19, 3099–3102 © Thieme Stuttgart · New York

LETTER
Synthesis of Discoside
3101
O
O
R
O
O
R
O
O
O
O
OBn
O
OR1
O
R
R
BnO
R1O
c 98%
O
O
OBn
OR1
OBn
OBn
OBn
OR1
OR1
BnO
R1O
4
OR1
a or b
3 R = (CH2)16Me, R1 = H
14 R = (CH2)16Me, R1 = Ac
12 R = (CH2)16Me
d
76%
+
+
Conditions Yield 12/13
5
O
O
a
b
63
43
1:4
R
O
R
O
O
O
1:1.5
OBn
O
OAc
O
c 85%
d 56%
R
O
R
O
O
O
BnO
AcO
OBn
OAc
OBn
OBn
OBn
OAc
OAc
OAc
BnO
13 R = (CH2)16Me
AcO
15 R = (CH2)16Me
Scheme 3 Reagents and conditions: (a) TESOTf (1.9 equiv), NIS (2.5 equiv), CH2Cl2, 4 Å MS, –40 to –20 °C, 2 h; (b) TESOTf (1.9 equiv),
NIS (2.5 equiv), CH2Cl2, 4 Å MS, 0 °C, 1.5 h; (c) Pd black, EtOH, H2 (1 atm), r.t., 1 h; (d) Ac2O, pyridine, r.t., 16 h.
research funding. S.J.C. thanks St Hugh’s College, Oxford, for the
provision of research support. We also thank the EPSRC National
Mass Spectrometry Service Centre, Swansea and the University of
St Andrews NMR and Mass Spectrometry Services.
overcome this problem, synthetic 3 was treated with Ac2O
in pyridine to give the peracetate 14 in 76% yield
(Scheme 3), according to the original isolation by Fat-
torusso.7 In this case, the spectroscopic data (1H and 13C
20
NMR, IR, MS) and specific rotation {synthetic [a]D
25
+11.3 (c 0.37, CHCl3) cf. natural [a]D +12 (c 0.5, References and Notes
CHCl3)}7 for the synthetic material were in excellent
(1) (a) Udenfriend, S.; Kodukula, K. Ann. Rev. Biochem. 1995,
agreement with those reported for natural discoside per-
acectate.20 In an analogous manner, the b-anomer 13 was
readily transformed into its respective b-peracetate 15.21
This allowed detailed NOE and HSQC analysis of the
64, 563. (b) McConville, M. J.; Ferguson, M. A. J. Biochem.
J. 1993, 294, 305.
(2) (a) Briken, V.; Porcelli, S. A.; Besra, G. S.; Kremer, L. Mol.
Microbiol. 2004, 53, 391. (b) Gilleron, M.; Nigou, J.;
Cahuzac, B.; Puzo, G. J. Mol. Biol. 1999, 285, 2147.
(3) (a) van den Boogaard, J.; Kibiki, G. S.; Kisanga, E. R.;
Boeree, M. J.; Aarnouste, R. E. Antimicrob. Agents
Chemother. 2009, 53, 849. (b) Sharma, S. K.; Mohan, A.
Chest 2006, 130, 261.
(4) (a) Boonyarattanakalin, S.; Liu, X.; Michieletti, M.;
Lepenies, B.; Seeberger, P. H. J. Am. Chem. Soc. 2008, 130,
16791. (b) Gilleron, M.; Quesniaux, V. F.; Puzo, G. J. Biol.
Chem. 2003, 278, 29880.
(5) (a) Ainge, G. D.; Parlane, N. A.; Denis, M.; Dyer, B. S.;
Härer, A.; Hayman, C. M.; Larsen, D. S.; Painter, G. F.
J. Org. Chem. 2007, 72, 5291. (b) Ainge, G. D.; Hudson, J.;
Larsen, D. S.; Painter, G. F.; Gill, G. S.; Harper, J. L. Bioorg.
Med. Chem. 2006, 14, 5632.
(6) Smith, A.; Nobmann, P.; Henehan, G.; Bourke, P.; Dunne, J.
Carbohydr. Res. 2008, 343, 2557.
1
synthetic a- and b-anomers. Characteristic JC1¢-H1¢ ano-
meric coupling constants of 175 and 162 Hz for 14 and 15
were observed in the respective HSQC experiments, thus
providing unambiguous confirmation of the C1¢-configu-
ration in 1.7
In conclusion, we have completed the first synthesis of di-
octadecanoyl discoside (3) and its peraceatate derivative
via a convergent route that proceeds in eight steps from
myo-inositol. The key glycosylation reaction proceeds
with high levels of b-selectivity at low temperature, and
further studies of 4,6-O-acylated phenylthiomannosides
are underway to examine the utility of this effect for the
synthesis of b-glycosides. With access to both anomers,
deprotection directly afforded both the dioctadecanoyl
discoside (3) and the unnatural b-analogue, and the re-
spective peracetate derivatives enabled direct spectro-
scopic comparison. Assessment of both the natural and
unnatural anomers for biological function and antimicro-
bial activity is currently being undertaken and will be re-
ported in due course.
(7) Barbieri, L.; Costantino, V.; Fattorusso, E.; Mangoni, A.
J. Nat. Prod. 2005, 68, 1527.
(8) Prottey, C.; Ballou, C. E. J. Biol. Chem. 1968, 243, 6196.
(9) (a) Keddie, N. S.; Bultynck, G.; Luyten, T.; Slawin, A. M.
Z.; Conway, S. J. Tetrahedron: Asymmetry 2009, 20, 857.
(b) Bello, D.; Aslam, T.; Bultynck, G.; Slawin, A. M. Z.;
Roderick, H. L.; Bootman, M. D.; Conway, S. J. J. Org.
Chem. 2007, 72, 5647. (c) Conway, S. J.; Thuring, J. W.;
Andreu, S.; Kvinlaug, B. T.; Roderick, H. L.; Bootman,
M. D.; Holmes, A. B. Aust. J. Chem. 2006, 59, 887. (d) For
a review, see: Conway, S. J.; Miller, G. J. Nat. Prod. Rep.
2007, 24, 687.
Acknowledgment
G.D.S.M. and G.J.F. thank the EPSRC/University of St Andrews
for a research internship. G.J.F. thanks the Royal Society for a Uni-
versity Research Fellowship and AstraZeneca for unrestricted re-
search support. T.A., G.J.M. and S.J.C. thank the BBSRC for
(10) (a) Lee, H. W.; Kishi, Y. J. Org. Chem. 1985, 50, 4402.
(b) For a review, see: Sureshan, K. M.; Shashidhar, M. S.;
Praveen, T.; Das, T. Chem. Rev. 2003, 103, 4477.
Synlett 2009, No. 19, 3099–3102 © Thieme Stuttgart · New York

3102
G. J. Florence et al.
LETTER
(11) Billington, D. C.; Baker, R.; Kulagowski, J. J.; Mawer, I. M.;
Vacca, J. P.; Desolms, S. J.; Huff, J. R. J. Chem. Soc., Perkin
Trans. 1 1989, 1423.
(12) Painter, G. F.; Grove, S. J. A.; Gilbert, I. H.; Holmes, A. B.;
Raithby, P. R.; Hill, M. L.; Hawkins, P. T.; Stephens, L. R.
J. Chem. Soc., Perkin Trans. 1 1999, 1423.
(13) Boons, G. J.; Burton, A.; Isles, S. Chem. Commun. 1996,
141.
(14) (a) Crich, D.; Sun, S. Tetrahedron 1998, 54, 8321.
(b) Kartha, K. P. R.; Field, R. A. Tetrahedron 1997, 53,
11753.
(t, J = 9.6 Hz, 1 H, H-5), 5.09 (dd, J = 10.4, 2.4 Hz, 1 H, H-
3), 5.00 (dd, J = 10.8, 2.8 Hz, 1 H, H-1), 4.95 (d, J = 1.6 Hz,
1 H, H-1¢), 4.30 (t, J = 2.8 Hz, 1 H, H-2), 4.26 (dd, J = 12.3,
4.2 Hz, 1 H, H-6¢a), 4.20–4.15 (m, 1 H, H-5¢), 4.09 (dd,
J = 12.3, 2.4 Hz, 1 H, H-6¢b), 2.36–2.27 (m, 4 H, H-2¢¢ and
H-2¢¢¢), 2.14 (s, 3 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.03 (s,
3 H), 2.02 (s, 3 H), 2.01 (s, 3 H), 2.00 (s, 3 H), 1.65–1.56 (m,
4 H, H-3¢¢ and H-3¢¢¢), 1.33–1.22 (m, 56 H, 28 × CH2-lipid),
0.89–0.83 (m, 6 H, H-18¢¢ and H-18¢¢¢); 13C NMR (101 MHz,
CDCl3): d = 173.4, 172.5, 169.84, 169.78, 169.76, 169.6,
169.5, 169.4, 169.3, 99.5, 76.4, 70.6, 70.4, 69.6 (3 × C), 69.5,
69.3, 68.7, 65.2, 61.7, 34.1, 34.0, 31.9, 29.7, 29.7, 29.6, 29.5,
29.5, 29.4, 29.3, 29.3, 29.2, 29.1, 24.9, 24.7, 22.7, 20.8, 20.7,
20.7, 20.6 (2 × C), 20.5, 20.5, 14.1; LRMS (ES+): m/z (%) =
1191.7 (100) [M + Na]+; HRMS (ES+): m/z [M + Na]+ calcd
for C62H104O20Na: 1191.7019; found: 1191.7043.
(15) Nieses, B.; Steglich, W. Angew. Chem. Int. Ed. Engl. 1978,
17, 522.
(16) (a) Zuurmond, H. M.; van der Laan, S. C.; van der Marel,
G. A.; van Boom, J. H. Carbohydr. Res. 1991, 215, C1.
(b) Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H.
Tetrahedron Lett. 1990, 31, 1331. (c) Binder, W. H.;
Kahlig, H.; Schmidt, W. Tetrahedron 1994, 50, 10407.
(17) (a) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.
(b) Marsh, S. J.; Ravindranathan, K. P.; Field, R. A. Synlett
2003, 1376.
(18) (a) Ainge, G. D.; Parlane, N. A.; Denis, M.; Hayman, C. M.;
Larsen, D. S.; Painter, G. F. Bioorg. Med. Chem. 2006, 14,
7615. (b) Uriel, C.; G ómez, A. M.; López, J. C.; Fraser-
Reid, B. Eur. J. Org. Chem. 2009, 403.
(21) Data for b-peracetate 15: Oil; Rf = 0.67 (PE–EtOAc, 6:4);
[a]D20 –20.0 (c 0.73, CHCl3); IR (neat): 2923.1, 2853.6,
1753.3, 1369.4, 1225.5, 1043.8 cm–1; 1H NMR (400 MHz,
CDCl3): d = 5.58 (dd, J = 3.2, 0.8 Hz, 1 H, H-2¢), 5.41 (t,
J = 10.4 Hz, 1 H, H-4), 5.39 (t, J = 10.0 Hz, 1 H, H-6), 5.23
(t, J = 10.0 Hz, 1 H, H-4¢), 5.11 (t, J = 9.6 Hz, 1 H, H-5),
5.10–5.05 (m, 2 H, H-3 and H-3¢), 4.70 (dd, J = 10.4, 2.4 Hz,
1 H, H-1), 4.67 (d, J = 0.8 Hz, 1 H, H-1¢), 4.51 (t, J = 2.8 Hz,
1 H, H-2), 4.23 (dd, J = 12.4, 6.0 Hz, 1 H, H-6¢a), 4.05 (dd,
J = 12.4, 2.4 Hz, 1 H, H-6¢b), 3.57 (ddd, J = 10.0, 6.4, 1.6
Hz, 1 H, H-5¢), 2.40–2.30 (m, 2 H, H-2¢¢), 2.29–2.23 (m,
2 H, H-2¢¢¢), 2.27 (s, 3 H), 2.09 (s, 3 H), 2.03 (s, 3 H), 2.01
(s, 3 H), 2.00 (s, 3 H), 2.00 (s, 3 H), 1.97 (s, 3 H), 1.63–1.54
(m, 4 H, H-3¢¢ and H-3¢¢¢), 1.33–1.22 (m, 56 H), 0.88 (t,
J = 6.8 Hz, 6 H, H-18¢¢ and H-18¢¢¢); 13C NMR (101 MHz,
CDCl3): d = 173.4, 172.5, 169.84, 169.78, 169.76, 169.6,
169.5, 169.4, 169.3, 99.5, 76.4, 70.6, 70.4, 69.6 (3 × C), 69.5,
69.3, 68.7, 65.2, 61.7, 34.1, 34.0, 31.9, 29.7, 29.7, 29.6, 29.5,
29.5, 29.4, 29.3, 29.3, 29.2, 29.1, 24.9, 24.7, 22.7, 20.8, 20.7,
20.7, 20.6 (2 × C), 20.5, 20.5, 14.1; LRMS (ES+): m/z (%) =
1191.7 (100) [M + Na]+; HRMS (ES+): m/z [M + Na]+ calcd
for C62H104O20Na: 1191.7019; found: 1191.7015.
(19) The 1H NMR of 3 in 1% CD3OD/CDCl3 gave a broad,
unresolved spectrum. Selected data for 3: Amorphous
colourless solid; mp 110–115 °C; 1H NMR (400 MHz, 1%
CD3OD/CDCl3): d = 5.40–4.90 (m, 4 H), 4.50–3.30 (m,
8 H), 2.40–2.10 (m, 4 H, H-2¢¢ and H-2¢¢¢), 1.65–1.40 (m,
4 H, H-3¢¢ and H-3¢¢¢), 1.20 (s, 56 H, 28 × CH2-lipid), 0.85–
0.75 (m, 6 H, H-18¢¢ and H-18¢¢¢); LRMS (MALDI-TOF):
m/z (%) = 897.9 (20) [M + Na]+, 453.5 (100).
(20) Data for a-peracetate 14: Oil; Rf = 0.46 (PE–EtOAc, 6:4);
[a]D20 +11.3 (c 0.73 CHCl3) (Lit.3 +12.0, c 0.5 CHCl3); IR
(neat): 2918.2, 2850.3, 1753.2, 1369.3, 1225.2, 1043.9 cm–1;
13C NMR (400 MHz, CDCl3): d = 5.53 (dd, J = 10.3, 10.2
Hz, 1 H, H-4), 5.50 (dd, J = 10.4, 9.6 Hz, 1 H, H-6), 5.43–
5.40 (m, 2 H, H-3¢ and H-4¢), 5.38–5.36 (m, 1 H, H-2¢), 5.19
Synlett 2009, No. 19, 3099–3102 © Thieme Stuttgart · New York