Synthetic studies on a marine natural product, palmerolide A: Synthesis of C1-C9 and C15-C21 fragments

Article abstract of DOI:10.1055/s-2007-982539

An efficient cross metathesis and Pd-catalyzed allylic rearrangement have been successfully used to construct the northern hemisphere of a cytotoxic marine natural product, palmerolide A. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-982539

LETTER
1537
Synthetic Studies on a Marine Natural Product, Palmerolide A: Synthesis of
C1–C9 and C15–C21 Fragments
Synthetic Studies
o
r
n a Mar
i
ine
N
a
s
P
rodu
h
ct, Palmerol
n
ide
A
a P. Kaliappan,* Parthasarathy Gowrisankar
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Fax +91(22)5723480; E-mail: kpk@chem.iitb.ac.in
Received 13 March 2007
Abstract: An efficient cross metathesis and Pd-catalyzed allylic re-
arrangement have been successfully used to construct the northern
O
northern hemisphere
hemisphere of a cytotoxic marine natural product, palmerolide A.
1
O
21
H
4'
1'
N
Key words: Grubbs’ catalyst, cross metathesis, Pd(II)-catalyzed
allylic rearrangement, marine natural product, Mitsunobu reaction
24
O
26
27
OH
HO
9
15
O
Skin cancer is believed to be the most common type of
cancer in the world and studies revealed that exposure to
southern hemisphere
O
NH2
ultraviolet radiation is the main cause for this cancer. In
the United States alone about 1 million new cases of some
Figure 1 Palmerolide A (1)
form of skin cancers are observed every year. There are
three major types of skin cancers namely basal cell carci-
noma, squamous cell carcinoma and melanoma. While the
first two types are mild and highly unlikely to spread to
other parts of the body, melanoma cancer is known to
spread aggressively to other parts of the body. As far as
treatment is concerned, basal cell carcinoma and squa-
mous cell carcinoma could be treated by surgery and radi-
ation therapy. However, treatment of melanoma requires
chemotherapy as well and found to be a challenging task.
So, discovery of a new drug that selectively kills melano-
ma cells could be of great significance to these patients.
In this connection, isolation1 of a new macrocyclic
polyketide palmerolide A (1, Figure 1) from Antarctic tu-
nicate Synoicum adareanum by B. J. Baker and co-work-
ers, which shows potent and selective cytotoxicity against
melanoma (UACC-62, LC50 = 18 nM), is of potential sig-
nificance. Further biological studies revealed that
palmerolide A has been found to inhibit V-ATPase with
an IC50 of 2 nM.
As per our retrosynthetic analysis (Scheme 1), the north-
ern hemisphere 2 of palmerolide A could be easily ob-
tained by the simple esterification of 4 with alcohol 3. The
alcohol 3 could be traced back to the known alcohol 62 via
the ketone 5 involving asymmetric allylation as key reac-
tion. The diene acid 4 could be synthesized from 7 involv-
ing asymmetric a-hydroxylation and cross metathesis as
key reactions.
Our synthesis of the fragment 3 began with the chelation-
controlled addition of allyltributylstannane in the pres-
ence of stannic chloride to aldehyde 8, following Keck’s
O
O
R1O
1
OR3
2
OR2
The structure of palmerolide A was established using
high-field NMR and stereochemical studies. This struc-
turally challenging natural product is a 20-membered
macrocyclic polyketide bearing a vinyl amide functional-
ity in the side chain and a carbamate moiety, five stereo-
genic centers and a 1,3-diene system in the core of a,b-
unsaturated macrocyclic lactone. In view of its structural
complexity and excellent medicinal properties, we devel-
oped interest in the synthesis of palmerolide A (1), which
is yet to succumb to total synthesis. Herein, we describe
our initial results on the stereoselective synthesis of the
northern hemisphere 2 of palmerolide A.
O
OH
HO
R1O
+
4
3
OR3
OR2
Xc
OR4
O
O
7
R1O
R1O
OH
6
5
SYNLETT 2007, No. 10, pp 1537–1540
1
8
.0
6
.2
0
0
7
Advanced online publication: 07.06.2007
DOI: 10.1055/s-2007-982539; Art ID: G07307ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Retrosynthesis of northern hemisphere of palmerolide A.

1538
K. P. Kaliappan, P. Gowrisankar
LETTER
protocol,3 to provide the homoallylic alcohol 9 in 92% de
(Scheme 2). To obtain the syn-relationship between the
methyl and hydroxyl group, Mitsunobu reaction was ef-
fectively carried out on the alcohol 9 with p-nitrobenzoic
acid to afford the ester 10 as a single diastereomer. Using
modified Wacker oxidation conditions,4 10 with its termi-
nal double bond was converted into methyl ketone 11 in
good yield. However, all our attempts like Wittig reaction
and the Horner–Wadsworth–Emmons under different
conditions to successfully introduce the a,b-unsaturated
ester moiety 13 failed and we could obtain only the
elimination product 12.
OPMB
OH
a
b
10
BnO
BnO
14
15
OPMB
O
OPMB
c
d
BnO
BnO
OAc
16
17
OH
OH
e
BnO
OH
OAc
BnO
+
b
a
BnO
BnO
O
BnO
BnO
19
18
8
OAc
9
E/Z = 10:1
OR
O
OR
c
d
Scheme 3 Reagents and conditions: a) K2CO3, MeOH, r.t., 1 h,
96%; b) 4-methoxybenzyltrichloroacetimidate, cat. TfOH, THF,
0 °C, 10 min, 75%; c) PdCl2, O2, Cu(OAc)2·H2O, dimethylacetamide,
r.t., 6 h, 70%; d) i) vinylmagnesium bromide, THF, 0 °C, 2 h, 84%; ii)
Ac2O, pyridine, cat. DMAP, 50 °C, 12 h, 92%; e) i) PdCl2(MeCN)2,
THF, r.t., 2 h, 87%; ii) DDQ, CH2Cl2, pH 7, 0 °C, 30 min, 77%.
10
11
O
OR
BnO
BnO
12
After the successful synthesis of the C15–C21 fragment,
our next task was to synthesize the C1–C9 fragment
(Scheme 4) and for which 6-heptenoic acid was attached
to the Evans chiral auxiliary 20 using mixed anhydride
approach8 to yield compound 22. The key asymmetric a-
hydroxylation9 on 22 using Davis protocol10 offered com-
pound 23 diastereoselectively in 74% yield (37:1 ratio by
HPLC analysis). The chiral auxiliary in compound 23 was
reductively removed11 using NaBH4 to give an insepara-
ble mixture of diol 24 and oxazolidinone 20. However,
formation of oxolane 25 with dimethylacetal anisalde-
hyde in the presence of a catalytic amount of PPTS fol-
lowed by reductive cleavage12 with DIBAL-H paved the
way for the clear separation of alcohol 26. Subsequently,
cross metathesis13 of 26 with methylacrylate using
Grubbs’ second-generation catalyst 21 afforded the a,b-
unsaturated ester 27 in excellent yield (81%) along with a
trace amount of cis-isomer. Our attempts to carry out the
Wittig reaction on the aldehyde, obtained by the oxidation
of the primary alcohol 27 using Dess–Martin periodi-
nane,14 with methyltriphenylphosphoniumbromide using
either n-BuLi or NaHMDS provided the diene ester 28 in
poor yield (15–25%), possibly due to the electrophilic
nature of the enoate moiety.15 However, under ‘forced
conditions’16 with potassium tert-butoxide the Wittig
reaction worked well to provide the desired olefin 28 in
higher yield17 (65% for two steps). Expectedly, saponifi-
cation of the ester 28 proceeded well to provide the
carboxylic acid 29 in 90% yield and this was successfully
coupled with the alcohol 18 using DCC condition to
furnish the northern hemisphere 3018 of palmerolide A in
63% yield.
O
13
CO2Et
R =
NO2
Scheme 2 Reagents and conditions: a) allyltributyltin, SnCl4,
CH2Cl2, –90 °C, 15 min, 89%; b) PPh3, DIAD, THF, 4-nitrobenzoic
acid, r.t., 5 h, 59%; c) PdCl2, O2, Cu(OAc)2·H2O, dimethylacetamide,
r.t., 6 h, 69%; d) condition A: PPh3CHCOOEt, toluene, cat. PhCOOH,
reflux, 12 h, 85%; condition B: NaH, THF, PO(OEt)2CH2COOEt, r.t.,
2 h, 54%.
To circumvent this difficulty, we examined the possibility
of introducing a,b-unsaturated ester moiety in a stereose-
lective manner by employing the Pd(II)-catalyzed allylic
rearrangement.5 Thus, the ester 10 was hydrolyzed to af-
ford the alcohol 14 in quantitative yield and subsequently,
the hydroxyl group was protected as PMB ether 15 using
Yonemitsu procedure6 from 4-methoxybenzyltrichloro-
acetimidate in the presence of a catalytic amount of triflic
acid (Scheme 3). Then, Wacker oxidation4 of 15 proceed-
ed smoothly to furnish the ketone 16, which upon addition
of vinyl Grignard reagent provided an inseparable mixture
of allylic alcohols, and it was not possible to separate the
diastereomeric mixture even after acetylating to 17. This
really did not matter much as when we executed the ste-
reoselective Pd(II)-catalyzed allylic acetate rearrange-
ment, using PdCl2(MeCN)2 followed by the removal of
PMB group,7 provided a readily separable mixture of
alcohol 18 (70%) and its Z-isomer 19 (7%) in a ratio of
10:1. The stereochemical assignment of 18 was confirmed
by NOE experiment where irradiation of the C16 olefinic
proton enhanced the C26 methyl proton signal to only 7%,
whereas 16% enhancement was observed for 19.
Synlett 2007, No. 10, 1537–1540 © Thieme Stuttgart · New York

LETTER
Synthetic Studies on a Marine Natural Product, Palmerolide A
1539
O
References and Notes
O
OH
b
a
(1) Diyabalange, T.; Amsler, C. D.; McClintock, J. B.; Baker, B.
J. J. Am. Chem. Soc. 2006, 128, 5630.
(2) (a) White, J. D.; Kawasaki, M. J. Org. Chem. 1992, 57,
5292. (b) Roush, W. R.; Palkowitz, A. D.; Ando, K. J. Am.
Chem. Soc. 1990, 112, 6348.
(3) (a) Harried, S. S.; Lee, C. P.; Yang, G.; Lee, T. I. H.; Myles,
D. C. J. Org. Chem. 2003, 68, 6646. (b) White, J. D.;
Blakemore, P. R.; Green, N. J.; Hauser, E. B.; Holoboski, M.
A.; Keown, L. E.; Kolz, C. S. N.; Phillips, B. W. J. Org.
Chem. 2002, 67, 7750. (c) Keck, G. E.; Abbott, D. E.
Tetrahedron Lett. 1984, 25, 1883.
N
3
3
O
O
22
Bn
O
O
d
c
N
3
HO
3
O
OH
OH
24
Bn
23
f
O
e
HO
26
3
3
O
OPMB
(4) Smith, A. B. III; Cho, Y. S.; Friestad, G. K. Tetrahedron
Lett. 1998, 39, 8765.
25
PMP
(5) Overman, L. E.; Knoll, F. M. Tetrahedron Lett. 1979, 20,
321.
(6) Nakajima, N.; Horita, K.; Abe, R.; Yonemitsu, O.
Tetrahedron Lett. 1988, 29, 4139.
g
HO
COOMe
3
COOMe
3
OPMB
OPMB
27
28
(7) Experimental Procedure for Compound 18
To a solution of acetate 17 (230 mg, 0.54 mmol) in anhyd
THF (10 mL) was added PdCl2(MeCN)2 (6 mg, 4 mol%) at
0 °C under nitrogen. After being stirred at 0 °C for 30 min,
the mixture was further stirred at r.t. for another 1 h. The
solvent was evaporated and the residue was further purified
by flash chromatography (silica gel, 5–10% EtOAc–
hexanes) to afford the E/Z mixture of acetate (200 mg, 0.47
mmol, 87%). To a solution of the above acetate (160 mg,
0.37 mmol) in CH2Cl2 (3.4 mL) and buffer (pH 7, 390 mL)
was added DDQ (102 mg, 0.45 mmol) at 0 °C. After being
stirred at the same temperature for 1 h, the reaction mixture
was quenched with sat. NaHCO3 (8 mL) and the aqueous
layer was extracted with CH2Cl2 (4 × 10 mL). The combined
organic layers were washed with brine, dried over Na2SO4,
and concentrated in vacuo. The residue was purified by flash
column chromatography (silica gel, 10–20% EtOAc–
hexanes) to give the Z-isomer 19, (8 mg, 0.026 mmol, 7%)
as a colorless oil and the E-isomer 18 (80 mg, 0.26 mmol,
70%) as a pale yellow oil in a ratio of 1:10.
i
h
COOH
3
OPMB
29
O
O
N
N
Mes
Mes
O
NH
Bn
O
Cl
Cl
Ru
Ph
PCy3
BnO
20
21
OPMB
OAc
30
Scheme 4 Reagents and conditions: a) PivCl, Et3N, THF, LiCl,
–10 °C, 2 h, then LiCl, 20, r.t., 12 h, 88%; b) NaHMDS, THF, –78 °C,
( )-trans-2-(phenylsulfonyl)-3-phenyloxaziridine, 2 min then ( )-
CSA, THF, 74%; c) NaBH4, THF, H2O, r.t., 1 h; d) PPTS, CH2Cl2, 4-
anisaldehyde dimethyl acetal, r.t., 1 h; e) DIBAL-H, CH2Cl2, –20 °C,
1 h, 43% for 3 steps; f) 21, methyl acrylate, CH2Cl2, 40 °C, 4 h, 81%;
g) i) Dess–Martin reagent, CH2Cl2, 0 °C, r.t., 2 h; ii) MePPh3Br, to-
luene, KOt-Bu, 0 °C to r.t., 30 min, 65% for 2 steps; h) LiOH, THF,
MeOH, H2O, r.t., 2 h, 90%; i) DCC, 18, DMAP, toluene, r.t., 12 h,
63%.
Data for compound 18: Rf = 0.8 (20% EtOAc–hexanes). 1H
NMR (400 MHz, CDCl3): d = 7.37–7.27 (m, 5 H), 5.43 (tq,
J = 7.0, 1.2 Hz, 1 H), 4.60 (d, J = 7.0 Hz, 2 H), 4.51 (s, 2 H),
3.95 (m, 1 H), 3.53 (d, J = 0.6 Hz, 1 H), 3.52 (s, 1 H), 2.47
(br s, 1 H), 2.23–2.06 (m, 2 H), 2.05 (s, 3 H), 1.89–1.84 (m,
1 H), 1.75 (d, J = 1.2 Hz, 3 H), 0.96 (d, J = 7.0 Hz, 3 H). 13
NMR (100 MHz, CDCl3): d = 171.0, 139.3, 137.9, 128.3,
C
127.6, 127.5, 121.1, 74.4, 73.3, 70.9, 61.1, 44.2, 37.6, 20.9,
16.5, 10.7. IR (neat): 3477 (br), 2966, 2931, 2868, 1733,
1450, 1373, 1239, 1098, 1027, 743 cm–1. HRMS (ESI-TOF):
m/z calcd for [C18H26O4 + Na]+: 329.1729; found: 329.1723.
[a]D20 4.3 (c 1.45, CHCl3).
In conclusion, we have designed and successfully accom-
plished the synthesis of the northern hemisphere of palm-
erolide A. This first synthetic effort toward palmerolide A
involved two key steps namely Pd(II)-catalyzed allylic
rearrangement and cross metathesis to furnish the E and
trans double bonds at C16-C17 and C2-C3, respectively.
Synthesis of the southern hemisphere and total synthesis
of palmerolide A are underway in our laboratory.
(8) Ho, G.-J.; Mathre, D. J. J. Org. Chem. 1995, 60, 2271.
(9) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am. Chem.
Soc. 1985, 107, 4346.
(10) (a) Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. Org.
Synth., Coll. Vol. VIII 1993, 546. (b) Davis, F. A.; Stringer,
O. D. J. Org. Chem. 1982, 47, 1774.
(11) Prashad, M.; Har, D.; Kim, H.-Y.; Repic, O. Tetrahedron
Lett. 1998, 39, 7067.
(12) Takano, S.; Akiyama, M.; Sato, S.; Ogasawara, K. Chem.
Lett. 1983, 1593.
(13) Chatterjee, A. K.; Grubbs, R. H. Angew. Chem. Int. Ed.
2002, 41, 3171.
Acknowledgment
Authors acknowledge DST, New Delhi for financial support and
SAIF, IIT Bombay for providing spectral facilities. P.G. thanks
CSIR, New Delhi for a fellowship.
(14) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(15) Kireev, A. S.; Breithaupt, A. T.; Collins, W.; Nadein, O. N.;
Kornienko, A. J. Org. Chem. 2005, 70, 742.
Synlett 2007, No. 10, 1537–1540 © Thieme Stuttgart · New York

1540
K. P. Kaliappan, P. Gowrisankar
LETTER
(16) (a) Conia, J. M.; Limasset, J. C. Bull. Soc. Chim. Fr. 1967,
1936. (b) Fitjer, L.; Quabeck, U. Synth. Commun. 1985, 15,
855.
1607, 1528, 1411, 1349, 1275, 1169, 1102 cm–1. HRMS
(ESI-TOF): m/z calcd for [C21H23O6N + Na]+: 408.1423;
found: 408.1422. [a]D20 –10.7 (c 0.67, CHCl3).
(17) Procedure for the Synthesis of Compound 28
A solution of methyltriphenylphosphonium bromide (273
mg, 0.76 mmol) in dry toluene (12 mL) was heated to reflux
and about 10 mL of toluene were distilled off azeotropically
to remove moisture. To the above suspension was added
KOt-Bu (86 mg, 0.76 mmol), the mixture was stirred at
105 °C for 1 h, and then cooled to 0 °C. A solution of
aldehyde (180 mg, 0.58 mmol) in dry toluene (0.5 mL) was
added dropwise to the above suspension with stirring, and
the resulting mixture was stirred at 0 °C for 1 h. After
addition of sat. NH4Cl (5 mL), the resulting mixture was
extracted with EtOAc (3 × 10 mL). The combined organic
layers were washed with brine, dried over Na2SO4 and
concentrated in vacuo. The resulting residue was purified by
flash column chromatography (silica gel, 5–15% EtOAc–
hexanes) to give 28 (116 mg, 0.38 mmol, 65% for two steps)
as a colorless oil. Rf = 0.57 (30% EtOAc–hexanes). 1H NMR
(400 MHz, CDCl3): d = 7.25 (dt, J = 8.9, 2.1 Hz, 2 H), 6.94
(dt, J = 15.6, 7.0 Hz, 1 H), 6.87 (dt, J = 8.9, 2.2 Hz, 2 H),
5.79 (dt, J = 15.5, 1.5 Hz, 1 H), 5.71 (ddd, J = 17.1, 10.4, 7.9
Hz, 1 H), 5.26–5.18 (m, 2 H), 4.39 (AB pattern, J = 11.6 Hz,
2 H), 3.80 (s, 3 H), 3.72 (s, 3 H), 3.77–3.67 (m, 1 H), 2.19–
2.14 (m, 2 H), 1.64–1.46 (m, 4 H). 13C NMR (100 MHz,
CDCl3): d = 167.0, 159.0, 149.2, 138.8, 130.6, 129.3, 120.9,
117.2, 113.7, 79.6, 69.6, 55.1, 51.3, 34.8, 31.9, 23.8. IR
(neat): 2948, 2838, 1724, 1657, 1613, 1514, 1463, 1248,
1201, 1172, 1036, 928 cm–1. HRMS (ESI-TOF): m/z calcd
Data for compound 12: Rf = 0.35 (20% EtOAc–hexanes). 1H
NMR (400 MHz, CDCl3): d = 7.37–7.27 (m, 5 H), 6.79 (dd,
J = 16.2, 7.0 Hz, 1 H), 6.11 (dd, J = 16.2, 1.5 Hz, 1 H), 4.52
(s, 2 H), 3.42 (d, J = 6.7 Hz, 2 H), 2.72–2.65 (m, 1 H), 2.25
(s, 3 H), 1.10 (d, J = 6.7 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): d = 198.7, 150.2, 138.1, 130.6, 128.4, 127.6, 127.5,
73.9, 73.1, 36.9, 26.8, 16.0. IR (neat): 2965, 2856, 1676,
1626, 1528, 1454, 1360, 1257, 1099, 982, 739, 699 cm–1.
HRMS (ESI-TOF): m/z calcd for [C14H18O2 + Na]+:
241.1204; found: 241.1214. [a]D20 –15.8 (c 1.13, CHCl3).
Data for compound 16: Rf = 0.28 (10% EtOAc–hexanes). 1H
NMR (400 MHz, CDCl3): d = 7.36–7.27 (m, 5 H), 7.19 (dt,
J = 8.8, 2.1 Hz, 2 H), 6.84 (dt, J = 8.8, 2.1 Hz, 2 H), 4.46 (d,
J = 1.5 Hz, 2 H), 4.43 (d, J = 7.3 Hz, 2 H), 4.08 (dt, J = 7.9,
4.3 Hz, 1 H), 3.78 (s, 3 H), 3.49 (dd, J = 8.8, 6.7 Hz, 1 H),
3.33 (dd, J = 9.2, 6.1 Hz, 1 H), 2.74 (dd, J = 16.2, 8.2 Hz, 1
H), 2.52 (dd, J = 16.2, 4.6 Hz, 1 H), 2.13 (s, 3 H), 2.04–1.99
(m, 1 H), 0.96 (d, J = 7.0 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): d = 207.8, 159.1, 138.5, 130.8, 129.5, 129.4, 128.4,
127.7, 127.6, 113.7, 76.0, 73.0, 72.3, 55.3, 46.5, 37.5, 31.1,
12.4. IR (neat): 2917, 2861, 1715, 1611, 1513, 1457, 1361,
1301, 1248, 1173, 1078, 822 cm–1. HRMS (ESI-TOF): m/z
calcd for [C22H28O4 + Na]+: 379.1885; found: 379.1880.
[a]D20 9.7 (c 1.05, CHCl3).
Data for compound 30: Rf = 0.55 (25% EtOAc–hexanes). 1H
NMR (400 MHz, CDCl3): d = 7.34–7.26 (m, 7 H), 6.92–6.84
(m, 3 H), 5.74 (d, J = 15.9 Hz, 1 H), 5.74–5.67 (m, 1 H),
5.37–5.19 (m, 4 H), 4.57–4.43 (m, 5 H), 4.27 (d, J = 11.3 Hz,
1 H), 3.8 (s, 3 H), 3.78–3.68 (m, 1 H), 3.38–3.27 (m, 2 H),
2.37–2.13 (m, 4 H), 2.03–1.96 (m, 1 H), 2.01 (s, 3 H), 1.74
20
for [C18H24O4 + Na]+: 327.1572; found: 327.1588. [a]D
34.3 (c 2.15, CHCl3).
(18) Spectral Data for Selected Compounds
Data for ketone 11: Rf = 0.34 (30% EtOAc–hexanes). 1H
NMR (400 MHz, CDCl3): d = 8.24 (dt, J = 8.8, 2.1 Hz, 2 H),
8.12 (dt, J = 9.2, 2.2 Hz, 2 H), 7.29–7.23 (m, 5 H), 5.72 (dt,
J = 7.7, 5.1 Hz, 1 H), 4.46 (s, 2 H), 3.42 (d, J = 6.2 Hz, 2 H),
2.93 (dd, J = 16.5, 7.7 Hz, 1 H), 2.82 (dd, J = 16.5, 5.5 Hz, 1
H), 2.26–2.19 (m, 1 H), 2.17 (s, 3 H), 1.06 (d, J = 7.0 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 205.1, 163.9, 150.4,
138.0, 135.6, 130.6, 128.2, 127.6, 127.5, 123.4, 73.1, 72.7,
71.9, 45.7, 37.1, 30.1, 12.1. IR (neat): 2933, 2863, 1725,
(s, 3 H), 1.72–1.47 (m, 4 H), 0.97 (d, J = 6.7 Hz, 3 H). 13
C
NMR (100 MHz, CDCl3): d = 170.9, 166.0, 159.0, 148.8,
138.9, 138.4, 138.3, 130.7, 129.3, 128.3, 127.6, 127.5,
121.6, 121.4, 117.2, 113.7, 79.8, 73.1, 72.5, 71.5, 69.7, 61.0,
55.2, 42.2, 36.8, 35.0, 32.0, 23.8, 20.9, 16.4, 11.4. IR (neat):
2961, 2930, 2851, 2361, 1738, 1715, 1513, 1454, 1260,
1245, 1091, 1027, 801 cm–1. HRMS (ESI-TOF): m/z calcd
for [C35H46O7 + Na]+: 601.3141; found: 601.3146. [a]D20 9.8
(c 0.60, CHCl3).
Synlett 2007, No. 10, 1537–1540 © Thieme Stuttgart · New York

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