Synthesis of (-)-muricatacin from tri- O -acetyl- d -glucal

Article abstract of DOI:10.1055/s-0032-1318113

The total synthesis of (-)-muricatacin is achieved using commercially available tri-O-acetyl-d-glucal as the starting material. The structure of the intermediate chiral butenolide is established unambiguously by X-ray crystallographic analysis, which consequently leads to correction of a previous structural misassignment. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0032-1318113

PAPER
▌625
paper
Synthesis of (–)-Muricatacin from Tri-O-acetyl-D-glucal
Synthesis of (–)-Muricatacin from Tri-O-acetyl-D-glucal
Maria González, Zoila Gándara, Gonzalo Pazos, Generosa Gómez,* Yagamare Fall*
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain
Fax +34(986)812262; E-mail: yagamare@uvigo.es; E-mail: ggomez@uvigo.es
Received: 19.10.2012; Accepted after revision: 28.12.2012
We have previously reported a synthesis of (–)-muricata-
cin using the readily available chiral reagent, D-malic acid
as the starting material.5 Herein, we describe a new syn-
thesis of the title compound that makes use of a chiral
building block derived from tri-O-acetyl-D-glucal, a
cheap and commercially available reagent, that we have
previously used for the synthesis of biologically interest-
ing natural products.6
Abstract: The total synthesis of (–)-muricatacin is achieved using
commercially available tri-O-acetyl-D-glucal as the starting materi-
al. The structure of the intermediate chiral butenolide is established
unambiguously by X-ray crystallographic analysis, which conse-
quently leads to correction of a previous structural misassignment.
Key words: oxygen, natural products, γ-lactones, total synthesis,
oxidation, furans
The synthesis of a number of biologically significant nat-
ural products1 is often accomplished from butenolides or
the corresponding saturated γ-lactones. These structural
moieties can be found in a wide range of biologically ac-
tive natural products.2 (–)-Muricatacin (1) (Figure 1) was
isolated from the seeds of the tropical evergreen, Annona
muricata L. (Annonaceae),3 commonly known as soursop
or guanábana.
O
4
OTBDMS
OTBDPS
O
6
C12H25
OH
O
O
1
OAc
O
O
OAc
OAc
OH
(–)-muricatacin (1)
O
O
O
5
(+)-cognac lactone (2)
Scheme 1 Retrosynthetic analysis of (–)-muricatacin (1)
As outlined in Scheme 1, we anticipated that once the rel-
atively inexpensive and readily available chiral reagent
tri-O-acetyl-D-glucal (5) had been transformed into chiral
butenolide 6, the stage would be set for the synthesis of 1
by hydrogenation of 6, followed by further elaboration to
install the side chain of muricatacin.
HO
OH
OH
HO
O
H25C12
O
H
OH
O
pyranicin (3)
OH
Accordingly, (–)-muricatacin (1) was prepared as shown
in Scheme 2. Furan diol 7 was readily obtained from tri-
O-acetyl-D-glucal (5) using known procedures.7 Selective
protection of the primary hydroxy group of diol 7 as the
tert-butyldimethylsilyl ether was accomplished to afford
alcohol 8 in 92% yield. Next, protection of the secondary
hydroxy group of 8 gave tert-butyldiphenylsilyl ether 9 in
99% yield. Furan 9 was subjected to singlet oxygen oxi-
dation followed by sodium borohydride reduction under
Luche’s conditions to give an intermediate hydroxy acid,
which underwent acid-catalyzed in situ lactonization to
afford butenolides 6 and 10 in 14% and 83% overall
yields, respectively (3 steps). Catalytic hydrogenation of
10 gave the corresponding alcohol 11 in 98% yield. Bu-
tenolide 6 was also converted into alcohol 11 by catalytic
hydrogenation (96%), followed by selective deprotection
of the primary hydroxy group (80%). Oxidation of prima-
O
OH
O
OH
vitamin C (4)
Figure 1 Examples of natural products containing butenolide or γ-
lactone moieties
Both enantiomers of muricatacin are found in Nature, and
exhibit the same potent cytotoxicity toward several hu-
man tumour cell lines.3 Due to this biological activity,
several syntheses of muricatacin have been developed in
recent years.4
SYNTHESIS 2013, 45, 0625–0632
Advanced online publication: 05.02.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318113; Art ID: SS-2012-Z0830-OP
© Georg Thieme Verlag Stuttgart · New York

626
M. González et al.
PAPER
OAc
OAc
iii
i
ii
OTBDMS
OH
O
O
OAc
73%
OH
99%
OH
O
92%
O
7
8
5
OTBDMS
O
4
v
OTBDPS
77%
iv
(14%)
+
6
OH
OTBDPS
OTBDMS
OTBDPS
O
O
O
4
9
vi
11
OH
OTBDPS
98%
O
4
O
10
(83%)
H
C10H21
O
4
viii
vii
O
O
O
4
O
OTBDPS
20%
99%
13
OTBDPS
12
O
4
C10H21
ix
99%
O
x
O
4
O
OH
(–)-muricatacin (1)
OTBDPS
93%
14
Scheme 2 Reagents and conditions: (i) see ref. 7; (ii) TBDMSCl, imidazole, DMAP, DMF, r.t.; (iii) TBDPSCl, imidazole, DMAP, DMF, r.t.;
(iv) (a) O2, MeOH, Rose Bengal, Hünig’s base, hν; (b) NaBH4, CeCl3·7H2O, MeOH; (v) (a) H2, 10% Pd/C, MeOH, r.t.; (b) AcOH–THF–H2O
(3:1:1); (vi) H2, 10% Pd/C, MeOH, r.t.; (vii) 4-hydroxy-TEMPO, BAIB, CH2Cl2, r.t.; (viii) C11H23IPPh3, n-BuLi, THF, 0 °C; (ix) H2, 10% Pd/C,
MeOH, r.t.; (x) TBAF, THF, r.t.
ry alcohol 11 using 4-hydroxy-2,2,6,6-tetramethylpiperi-
dine
1-oxyl–bis(acetoxy)iodobenzene
(4-hydroxy
O
4
O
TEMPO–BAIB) resulted in a 99% yield of aldehyde 12.
This underwent a Wittig reaction with undecyltriphe-
nylphosphonium iodide to give alkene 13, which on cata-
lytic hydrogenation gave lactone 14 in 99% yield. Finally,
deprotection of 14 with tetrabutylammonium fluoride af-
forded the target compound 1.
OH
(–)-muricatacin (1)
[α]D –19.9 (c 1.0 in CHCl3)
O
4
O
The reaction sequence described above was initially de-
signed for the synthesis of (+)-epi-muricatacin (Figure 2)
based on previous results from our laboratory.8
OH
(+)-epi-muricatacin (15)
[α]D +27 (c 1.9 in CHCl3)
However, the optical rotation of the final compound we
obtained did not match that in the literature for (+)-epi-
Figure 2 Structures of (–)-muricatacin and (+)-epi-muricatacin
OTBDMS
OTBDMS
OH
OH
i
O
O
ii
4
4
O
O
4
O
O
OH
80%
56%
OTBDPS
17
11
16
H
iii
iv
96%
O
OH
OTBDMS
O
4
O
4
O
O
73%
OTBDMS
19
18
Scheme 3 Reagents and conditions: (i) TBAF, THF, r.t.; (ii) TBDMSCl, imidazole, DMAP, DMF, r.t.; (iii) HF–py, THF; (iv) 4-hydroxy-
TEMPO, BAIB, CH2Cl2, r.t.
Synthesis 2013, 45, 625–632
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of (–)-Muricatacin from Tri-O-acetyl-D-glucal
627
25
muricatacin,9 but instead was [α]D –23.1 (c 0.45, In view of these results, we are obliged to correct the
CHCl3), being similar to the reported values for (–)-muri- structural misassignment of chiral butenolide 218
catacin.4e,5
(Scheme 4).
Hence, we had synthesized (–)-muricatacin instead of (+)- Indeed, in our earlier communication,8 we assigned the
epi-muricatacin, as planned. In order to establish the abso- depicted structure to butenolide 21 on the basis of the
lute configuration of C-4, the intermediate lactone 11 was NOE correlation values of the derived lactones 22 and 23.
converted into the known aldehyde 1910 as shown in However, we recently found out that small NOE values in
Scheme 3.
five-membered rings could sometimes be misleading,12
hence we had to confirm unambiguously that the stereo-
chemistry at C-4 was that shown in compound 24. Ac-
cordingly, butenolide 24 was easily converted into
aldehyde 19, the structure of which was unambiguously
confirmed by X-ray crystallographic analysis, and was
found to be identical to that shown in Figure 3.
The structure of aldehyde 19 was confirmed unambigu-
ously as that shown in Figure 3, by X-ray crystallographic
analysis of the crystals obtained by recrystallization from
hexane.11
In conclusion, we have carried out an enantioselective to-
tal synthesis of (–)-muricatacin from cheap and commer-
cially available tri-O-acetyl-D-glucal, using a method
developed by our research group for oxacyclic systems.
We also demonstrated, by X-ray crystallographic analy-
sis, the stereochemical course of the formation of a chiral
butenolide and have corrected a previously published8
structural misassignment. Work is now in progress on the
synthesis of novel analogues of muricatacin with a view to
evaluate their biological activity.
Solvents were purified and dried by standard procedures. Undecyl-
triphenylphosphonium iodide (C11H23IPPh3) was obtained from 1-
iodoundecane (Aldrich) and triphenylphosphine according to a
standard protocol.13 Flash chromatography was performed on silica
gel (Merck 60, 230–400 mesh). Analytical TLC was performed on
plates precoated with silica gel (Merck 60 F254, 0.25 mm). Melting
points were obtained using a Gallenkamp apparatus and are uncor-
rected. Optical rotations were obtained using a Jasco P-2000 polar-
Figure 3 X-ray crystal structure (ORTEP) of aldehyde 19
i
OTBDPS
OTBDPS
OTBDPS
O
O
4
O
OTBDPS
20
21
incorrect stereochemistry at C-4
Tetrahedron Lett. 2005, 46, 5889
i
2.6%
1.3%
H
H
H
1.2%
O
3.5%
O
1.1%
H
OTBDPS
OTBDPS
O
O
O
OTBDPS
1.8%
H
H
H
1.9%
1.5%
2.4%
22
23
NOE correlations for 23
OTBDPS
OTBDPS
O
4
NOE correlations for 22
O
24
correct stereochemistry at C-4
this work
Scheme 4 Reagents and conditions: (i) (a) O2, MeOH, Rose Bengal, Hünig’s base, hν; (b) NaBH4, CeCl3·7H2O, MeOH.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 625–632

628
M. González et al.
PAPER
imeter. IR spectra were obtained using a Jasco FT/IR-6100 Type A
spectrometer. 1H NMR (400 MHz) and 13C NMR (100 MHz) spec-
tra were recorded on a Bruker ARX-400 spectrometer using TMS
as the internal standard; chemical shifts (δ) are quoted in ppm and
coupling constants (J) in Hz. Mass spectrometry (MS and HRMS)
was carried out a Hewlett-Packard 5988A spectrometer. Elemental
analyses were recorded using a Carlo Erba 1108/combustion chro-
matography fundamental analyser.
with H2O (3 × 10 mL). The organic phase was dried, filtered and
concentrated in vacuo to yield compound 9.
Yield: 3.1 g (99%); yellow oil; Rf = 0.81 (30% EtOAc–hexane);
[α]D24 +39.0 (c 1, CHCl3).
IR (NaCl): 3071, 3049, 2857, 1468 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.57 (m, 10 H, Ph), 7.30 (dd,
J = 4.4 Hz, J = 11.2 Hz, 1 H, H-5), 6.26 (m, 2 H, H-4, H-3), 4.78 (m,
1 H, H-1′), 3.86 (m, 2 H, H-2′), 0.98 (m, 18 H, CH3-t-Bu), 0.02 (m,
6 H, CH3-Si).
13C NMR (100 MHz, CDCl3): δ = 154.5 (C-2), 141.3 (CH-5), 135.7
(CH-Ph), 133.6 (C-Ph), 129.4 (CH-Ph), 127.5 (CH-Ph), 110.0 (CH-
3), 107.6 (CH-4), 70.1 (CH-1′), 66.6 (CH2-2′), 26.7 (CH3-t-Bu),
25.8 (CH3-t-Bu), 19.2 (C-t-Bu), 18.3 (C-t-Bu), –5.5 (CH3-Si).
(1R)-1-(Furan-2-yl)ethane-1,2-diol (7)
To a soln of tri-O-acetyl-D-glucal (5) (10 g, 36.7 mmol) in MeOH
(50 mL) was added K2CO3 (101 mg, 0.7 mmol) and the resulting
mixture stirred at r.t. for 5 h. The solvent was removed and the res-
idue was dissolved in EtOAc (300 mL). After rapid filtration
through silica gel and evaporation of the solvent, D-glucal was ob-
tained (5.1 g, 95%) as a white solid {mp 58–60 °C; Rf = 0.20
(EtOAc); [α]D21 –8 (c 1.9, H2O)}.
MS (ESI): m/z (%) = 505 (18), 504 (48) [M + Na + 1]+, 503 (100)
[M + Na]+, 201 (25).
HRMS (ESI): m/z [M + Na]+ calcd for C28H40NaO3Si2: 503.2408;
found: 503.2401.
To a soln of D-glucal (5.5 g, 37.9 mmol) in MeCN (50 mL) was add-
ed InCl3·4H2O (1.1 g, 3.8 mmol) and the mixture stirred at r.t. for 24
h. Aq sat. Na2CO3 soln (150 mL) was added and the resulting mix-
ture extracted with EtOAc (10 × 75 mL). The combined organic
phase was dried, filtered and concentrated under vacuum to afford
the title compound 7.
Yield: 3.7 g (77%); colorless oil; Rf = 0.63 (EtOAc); [α]D23 +30.4 (c
3.4, CHCl3).
IR (NaCl): 3369, 2933, 2882, 1505, 1418 cm–1.
1H NMR (400 MHz, CD3OD): δ = 7.46 (dd, J = 1.8 Hz, J = 0.8 Hz,
1 H, H-5′), 6.38 (dd, J = 3.2 Hz, J = 1.8 Hz, 1 H, H-4′), 6.34 (d,
J = 3.2 Hz, 1 H, H-3′), 4.70 (dd, J = 6.9 Hz, J = 5.4 Hz, 1 H, H-1),
3.78 (m, 2 H, H-2).
13C NMR (100 MHz, CD3OD): δ = 154.7 (C-2′), 141.8 (CH-5′),
109.8 (CH-4′), 106.3 (CH-3′), 68.1 (CH-1), 64.3 (CH2-2).
MS (ESI): m/z (%) = 152 (7) [M + Na + 1]+, 151 (100) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C6H8NaO3: 151.0365; found:
(1′R,5R)-5-{1′-[(tert-Butyldiphenylsilyl)oxy]-2′-[(tert-butyldi-
methylsilyl)oxy]ethyl}-5H-furan-2-one (6) and (1′R,5R)-5-{1′-
[(tert-Butyldiphenylsilyl)oxy]-2′-(hydroxy)ethyl}-5H-furan-2-
one (10)
To a soln of compound 9 (8.7 g, 18.2 mmol) in MeOH (280 mL)
was added Rose Bengal (437 mg), and the resulting pink soln was
purged with O2 and cooled to –78 °C. DIPEA (13.3 mL, 4.2 mmol)
was added and the mixture irradiated with a 200 W lamp under an
O2 atm for 29 h. The mixture was allowed to reach r.t. and the sol-
vent was evaporated in vacuo. The residue was dissolved in CH2Cl2
(700 mL), and to the resulting pink soln was added a soln of oxalic
acid (800 mL, 0.127 M) to afford an orange mixture, which was
stirred at r.t. for 2 h. After separation of the two phases, the aq layer
was extracted with CH2Cl2 (3 × 300 mL), and the combined organic
phase was dried, filtered and concentrated in vacuo to yield the cor-
responding hydroxybutenolide as a pink oil [Rf = 0.13 (30%
EtOAc–hexane)].
151.0363.
The crude hydroxybutenolide was dissolved in MeOH (200 mL)
and cooled to 0 °C. CeCl3·7H2O (339 mg, 0.91 mmol) and NaBH4
(2.7 g, 72.8 mmol) were added, and the mixture was stirred under
the same conditions for 1 h, after which concd HCl was added drop-
wise until pH 2. The mixture was allowed to stir for 6 h and then the
solvent was evaporated in vacuo. The residue was purified by col-
umn chromatography on silica gel (10% EtOAc–hexane → 40%
EtOAc–hexane) to initially afford butenolide 6, followed by alcohol
10.
(1R)-2-[(tert-Butyldimethylsilyl)oxy]-1-(furan-2-yl)ethanol (8)
To a soln of diol 7 (3.2 g, 25.02 mmol) in DMF (30 mL) were added
imidazole (1.8 g, 27.5 mmol), a catalytic amount of DMAP and
TBDMSCl (3.7 g, 27.5 mmol), and the mixture was stirred at r.t. for
3 h. EtOAc (20 mL) was added and the resulting soln was washed
with H2O (3 × 20 mL). The organic phase was dried, filtered and
concentrated in vacuo to yield compound 8.
Yield: 5.6 g (92%); colorless oil; Rf = 0.82 (EtOAc); [α]D22 +20.8 (c
0.6, CHCl3).
Data for 6
24
IR (NaCl): 3432, 2857, 1467 cm–1.
Yield: 1.5 g (14%); pink oil; Rf = 0.58 (30% EtOAc–hexane); [α]D
+21.2 (c 0.55, CHCl3).
IR (NaCl): 3071, 2857, 1759, 1468 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.30 (dd, J = 4.4 Hz, J = 11.2 Hz,
1 H, H-5′), 6.26 (m, 2 H, H-4′, H-3′), 4.78 (m, 1 H, H-1), 3.86 (m, 2
H, H-2), 0.98 (m, 9 H, CH3-t-Bu), 0.02 (m, 6 H, CH3-Si).
13C NMR (100 MHz, CDCl3): δ = 153.5 (C-2′), 141.5 (CH-5′),
110.0 (CH-3′), 108.2 (CH-4′), 68.6 (CH-1), 66.6 (CH2-2), 26.7
(CH3-t-Bu), 18.3 (C-t-Bu), –5.5 (CH3-Si).
MS (ESI): m/z (%) = 266 (20) [M + Na + 1]+, 265 (100) [M + Na]+,
201 (10).
HRMS (ESI): m/z [M + Na]+ calcd for C12H22NaO3Si: 265.1230;
found: 265.1222.
1H NMR (400 MHz, CDCl3): δ = 7.70 (m, 4 H, Ph), 7.45 (m, 6 H,
Ph), 7.14 (dd, J = 1.6 Hz, J = 5.7 Hz, 1 H, H-4), 6.15 (dd, J = 2.1
Hz, J = 5.7 Hz, 1 H, H-3), 5.35 (m, 1 H, H-5), 3.93 (m, 1 H, H-1′),
3.83 (m, 2 H, H-2′), 0.98 (m, 18 H, CH3-t-Bu), –0.07 (m, 6 H, CH3-
Si).
13C NMR (100 MHz, CDCl3): δ = 173.1 (C=O), 154.2 (CH-4),
135.5 (CH-Ph), 133.2 (C-Ph), 132.0 (CH-Ph), 129.4 (CH-Ph), 122.1
(CH-3), 83.9 (CH-5), 72.5 (CH-1′), 64.5 (CH2-2′), 26.7 (CH3-t-Bu),
25.8 (CH3-t-Bu), 19.3 (C-t-Bu), –5.1 (CH3-Si).
MS (ESI): m/z (%) = 521 (17), 520 (40) [M + Na +1]+, 519 (100) [M
(1′R)-2-{1′-[(tert-Butyldiphenylsilyl)oxy]-2′-[(tert-butyldimeth-
ylsilyl)oxy]ethyl}furan (9)
To a soln of alcohol 8 (1.5 g, 6.5 mmol) in DMF (5 mL) were added
imidazole (1.4 g, 21.4 mmol), a catalytic amount of DMAP and
TBDPSCl (1.9 mL, 7.1 mmol), and the mixture was stirred at r.t. for
2 h. EtOAc (10 mL) was added and the resulting soln was washed
+ Na]+, 419 (11).
HRMS (ESI): m/z [M + Na]+ calcd for C28H40NaO4Si2: 519.2357;
found: 519.2370.
Anal. Calcd for C28H40O4Si2: C, 67.70; H, 8.12. Found: C, 67.38; H,
8.35.
Synthesis 2013, 45, 625–632
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of (–)-Muricatacin from Tri-O-acetyl-D-glucal
629
Data for 10
IR (NaCl): 3442, 2857, 1775, 1428 cm–1.
Yield: 5.8 g (83%); pink solid; mp 94–97 °C; Rf = 0.13 (30%
EtOAc–hexane); [α]D23 +67.4 (c 1, CHCl3).
IR (NaCl): 3630, 2848, 1749, 1463 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.72 (m, 4 H, Ph), 7.43 (m, 6 H,
Ph), 4.69 (m, 1 H, H-5), 3.79 (td, J = 4.4 Hz, J = 5.8 Hz, 1 H, H-1′),
3.62 (m, 2 H, H-2′), 2.50 (m, 2 H, H-3), 2.16 (m, 2 H, H-4), 1.09 (s,
9 H, CH3-t-Bu).
13C NMR (100 MHz, CDCl3): δ = 177.5 (C=O), 135.9 (CH-Ph),
133.0 (C-Ph), 130.0 (CH-Ph), 127.8 (CH-Ph), 80.0 (CH-5), 75.0
(CH-1′), 62.9 (CH2-2′), 28.4 (CH2-3), 27.0 (CH3-t-Bu), 23.3 (CH2-
4), 19.5 (C-t-Bu).
MS (ESI): m/z (%) = 408 (33) [M + Na + 1]+, 407 (100) [M + Na]+,
404 (25), 201 (18).
HRMS (ESI): m/z [M + Na]+ calcd for C22H28NaO4Si: 407.1649;
1H NMR (400 MHz, CDCl3): δ = 7.67 (m, 4 H, Ph), 7.44 (m, 6 H,
Ph), 7.25 (dd, J = 1.6 Hz, J = 5.7 Hz, 1 H, H-4), 6.07 (dd, J = 2.1
Hz, J = 5.7 Hz, 1 H, H-3), 5.13 (m, 1 H, H-5), 4.03 (m, 1 H, H-1′),
3.65 (m, 2 H, H-2′), 1.07 (s, 9 H, CH3-t-Bu).
13C NMR (100 MHz, CDCl3): δ = 173.2 (C=O), 154.4 (CH-4),
135.7 (CH-Ph), 132.5 (C-Ph), 130.2 (CH-Ph), 127.8 (CH-Ph), 122.2
(CH-3), 83.4 (CH-5), 72.7 (CH-1′), 62.7 (CH2-2′), 26.8 (CH3-t-Bu),
19.4 (C-t-Bu).
found: 407.1661.
MS (ESI): m/z (%) = 406 (32) [M + Na + 1]+, 405 (100) [M + Na]+,
383 (3) [M + 1]+.
Anal. Calcd for C22H28O4Si: C, 68.71; H, 7.34. Found: C, 68.51; H,
7.35.
HRMS (ESI): m/z [M + Na]+ calcd for C22H26NaO4Si: 405.1492;
found: 405.1492.
(1′S,5R)-5-{1′-[(tert-Butyldiphenylsilyl)oxy]-2′-oxoethyl}-
3H,5H-furan-2-one (12)
Anal. Calcd for C22H26O4Si: C, 69.08; H, 6.85. Found: C, 69.12; H,
6.86.
To a soln of alcohol 11 (456 mg, 1.19 mmol) in CH2Cl2 (50 mL)
were added bis(acetoxy)iodobenzene (BAIB) (439 mg, 1.36 mmol)
and a catalytic amount of 4-hydroxy-2,2,6,6-tetramethylpiperidine
1-oxyl (4-hydroxyTEMPO). The resulting mixture was stirred at r.t.
for 6 h. After this time, the solvent was removed and the residue was
dissolved in MTBE (50 mL). The resulting soln was washed with
15% aq Na2S2O3 soln (3 × 30 mL) and sat. aq NaHCO3 soln (3 × 30
mL). The organic phase was dried and the solvent evaporated under
reduced pressure to afford aldehyde 12.
(1′R,5R)-5-{1′-[(tert-butyldiphenylsilyl)oxy]-2′-(hydroxy)eth-
yl}-3H,5H-furan-2-one (11)
From Butenolide 6
To a soln of butenolide 6 (344 mg, 0.69 mmol) in MeOH (10 mL)
was added 10% Pd/C (40 mg). The resulting suspension was al-
lowed to stir under an atm of H2 for 6 h at r.t. After removing the
catalyst by filtration, the filtrate was concentrated to dryness to give
the corresponding lactone.
Yield: 451 mg (99%); brown oil; Rf = 0.27 (30% EtOAc–hexane);
[α]D24 –42 (c 1, CHCl3).
IR (NaCl): 2929, 1694 cm–1.
Yield: 330 mg (96%); yellow oil; Rf = 0.55 (30% EtOAc–hexane);
[α]D23 –29.3 (c 0.6, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 9.60 (s, 1 H, H-2′), 7.70 (m, 4 H,
Ph), 7.49 (m, 6 H, Ph), 4.80 (t, J = 5.5 Hz, 1 H, H-5), 4.15 (m, 1 H,
H-1′), 2.58 (m, 2 H, H-3), 2.20 (m, 2 H, H-4), 1.19 (s, 9 H, CH3-t-
Bu).
13C NMR (100 MHz, CDCl3): δ = 201.9 (C=O), 176.6 (C-2), 135.8
(CH-Ph), 132.1 (C-Ph), 130.7 (CH-Ph), 128.2 (CH-Ph), 80.3 (CH-
1′), 79.6 (CH-5), 28.0 (CH2-3), 27.0 (CH3-t-Bu), 23.3 (CH2-4), 19.6
(C-t-Bu).
IR (NaCl): 2852, 1772, 1460 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.73 (m, 4 H, Ph), 7.44 (m, 6 H,
Ph), 4.80 (dt, J = 2.3 Hz, J = 7.1 Hz, 1 H, H-5), 3.75 (m, 1 H, H-1′),
3.60 (dd, J = 4.7 Hz, J = 9.7 Hz, 1 H, H-2′), 3.44 (dd, J = 4.4 Hz,
J = 9.7 Hz, 1 H, H-2′), 2.56 (m, 4 H, H-3, H-4), 1.11 (s, 18 H, CH3-
t-Bu), –0.13 (s, 6 H, CH3-Si).
13C NMR (100 MHz, CDCl3): δ = 177.7 (C=O), 135.5 (CH-Ph),
133.1 (C-Ph), 129.8 (CH-Ph), 127.8 (CH-Ph), 79.4 (CH-5), 75.2
(CH-1′), 62.9 (CH2-2′), 28.6 (CH2-3), 26.6 (CH3-t-Bu), 25.7 (CH3-
t-Bu), 23.4 (CH2-4), 19.4 (C-t-Bu), 18.1 (C-t-Bu), –5.7 (CH3-Si).
MS (ESI): m/z (%) = 406 (30), 405 (100) [M – Na]+, 305 (7) [M –
Ph]+, 201 (47).
HRMS (ESI): m/z [M + Na]+ calcd for C22H26NaO4Si: 405.1492;
found: 405.1485.
MS (ESI): m/z (%) = 521 (67) [M + Na]+, 408 (33), 407 (100), 283
(42).
HRMS (ESI): m/z [M + Na]+ calcd for C28H42NaO4Si2: 521.2513;
found: 521.2511.
(1′R,5R,2E/Z)-5-{1′-[(tert-Butyldiphenylsilyl)oxy]tridec-2′-
enyl}-3H,5H-furan-2-one (13)
To a soln of undecyltriphenylphosphonium iodide (361 mg, 0.68
mmol) in THF (3 mL) at 0 °C was added dropwise a soln of n-BuLi
(275 μL, 0.68 mmol, 1.6 M in hexanes). After the addition was com-
plete, the mixture was stirred for 30 min under the same conditions.
A soln of aldehyde 12 (187 mg, 0.5 mmol) in THF (3 mL) was add-
ed and stirring was continued for 1.5 h at 0 °C. Aq sat. NaHCO3 soln
(5 mL) was added and the mixture extracted with EtOAc (3 ×
10mL). The combined organic phase was washed with brine (3 × 10
mL), dried, filtered and concentrated in vacuo. The residue was pu-
rified by column chromatography on silica gel (2% EtOAc–hexane)
to afford alkene 13.
A soln of the above lactone (310 mg, 0.62 mmol) in a mixture of
AcOH–THF–H2O (3:1:1, 20 mL) was stirred at r.t. for 16 h. Next,
sat. aq K2CO3 soln (50 mL) was added, followed by solid K2CO3
until pH 7 was attained. The aq layer was extracted with EtOAc (5
× 30 mL). The combined organic layer was dried, filtered and the
solvent removed in vacuo. The residue was purified by column
chromatography on silica gel (10% → 50% EtOAc–hexane) to af-
ford alcohol 11 (190 mg, 80%) as a colorless oil. The physical and
spectroscopic data were virtually identical to those of the same
compound obtained from alcohol 10 (see below).
From Alcohol 10
Yield: 71 mg (20%); colorless oil; Rf = 0.72 (30% EtOAc–hexane);
[α]D24 –1.25 (c 1, CHCl3).
IR (NaCl): 2916, 2842, 1772, 1506 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.67 (m, 4 H, Ph), 7.39 (m, 6 H,
Ph), 5.39 (m, 2 H, H-2′, H-3′), 4.39 (m, 1 H, H-1′), 4.21 (dd, J = 3.6
Hz, J = 5.4 Hz, 1 H, H-5), 2.43 (m, 2 H, H-3), 2.14 (m, 2 H, H-4),
1.55 (m, 2 H, H-4′), 1.26 (m, 9 H, CH3-t-Bu), 1.06 (m, 16 H, CH2),
0.88 (t, J = 6.9 Hz, 3 H, CH3).
To a soln of alcohol 10 (358 mg, 0.9 mmol) in MeOH (10 mL) was
added 10% Pd/C (55 mg). The resulting suspension was allowed to
stir under an atm of H2 for 3 d at r.t. After removing the catalyst by
filtration, the filtrate was concentrated to dryness, resulting in the
desired lactone 11.
Yield: 354 mg (98%); colorless oil; Rf = 0.45 (30% EtOAc–
hexane); [α]D25 –7.2 (c 0.8, CHCl3).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 625–632

630
M. González et al.
PAPER
13C NMR (100 MHz, CDCl3): δ = 177.2 (C=O), 135.9 (CH-Ph),
134.9 (CH-2′), 134.8 (CH-Ph), 133.5 (C-Ph), 129.6 (CH-Ph), 127.7
(CH-Ph), 126.6 (CH-3′), 82.5 (CH-5), 75.4 (CH-1′), 32.2–27.9 (9 ×
CH2), 27.0–26.6 (CH3-t-Bu), 22.7–22.5 (2 × CH2), 19.3 (C-t-Bu),
14.1 (CH3).
MS (ESI): m/z (%) = 543 (5) [M + Na]+, 418 (32), 417 (100), 201
(26).
IR (NaCl): 3425, 3023, 1765, 1322, 1058 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.57 (m, 1 H, H-5), 3.74 (m, 3 H,
H-1′, H-2′), 2.61 (m, 2 H, H-3), 2.27 (m, 2 H, H-4).
13C NMR (100 MHz, CDCl3): δ = 178.0 (C=O), 80.8 (CH-1′), 73.6
(CH-5), 63.3 (CH2-2′), 28.4 (CH2-3), 23.9 (CH2-4).
MS (ESI): m/z (%) = 169 (88) [M + Na]+, 148 (14) [M + 2]+, 147
(100) [M + 1]+.
HRMS (ESI): m/z [M + Na]+ calcd for C33H48NaO3Si: 543.3264;
found: 543.3278.
HRMS (ESI): m/z [M + 1]+ calcd for C6H11O4: 147.0651; found:
147.0657.
(1′R,5R)-5-{1′-[(tert-Butyldiphenylsilyl)oxy]tridecanyl}-3H,5H-
furan-2-one (14)
Anal. Calcd for C6H10O4: C, 49.31; H, 6.90. Found: C, 49.38; H,
6.83.
To a soln of alkene 13 (26 mg, 0.05 mmol) in MeOH (4 mL) was
added 10% Pd/C (4 mg). The resulting suspension was allowed to
stir under an atm of H2 for 5 h. After removing the catalyst by filtra-
tion, the filtrate was concentrated to dryness resulting in the desired
lactone 14.
(1′R,5R)-5-{1′-[(tert-Butyldimethylsilyl)oxy]-2′-[(tert-butyldi-
methylsilyl)oxy]ethyl}-3H,5H-furan-2-one (17)
To a soln of diol 16 (126 mg, 0.861 mmol) in DMF (5 mL) were
added imidazole (469 mg, 6.88 mmol), a catalytic amount of DMAP
and TBDMSCl (470 mg, 3.44 mmol). The mixture was stirred at r.t.
for 2 d. EtOAc (10 mL) was added and the resulting soln was
washed with H2O (3 × 10 mL). The organic phase was dried, filtered
and concentrated in vacuo. The residue was chromatographed on
silica gel (5% EtOAc–hexane) to afford compound 17.
Yield: 25 mg (99%); colorless oil; Rf = 0.62 (30% EtOAc–hexane);
[α]D23 –15.6 (c 0.78, CHCl3).
IR (NaCl): 2923, 2852, 1742, 1456 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.73 (m, 4 H, Ph), 7.43 (m, 6 H,
Ph), 4.54 (dt, J = 3.7 Hz, J = 7.0 Hz, 1 H, H-5), 3.74 (m, 1 H, H-1′),
2.60 (m, 2 H, H-3), 2.48 (m, 2 H, H-4), 2.16 (m, 2 H, H-2′), 1.28 (m,
9 H, CH3-t-Bu), 1.06 (m, 20 H, CH2), 0.91 (t, J = 6.8 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 177.4 (C=O), 135.2 (CH-Ph),
134.8 (CH-Ph), 133.3 (C-Ph), 129.7 (CH-Ph), 127.7 (CH-Ph), 81.1
(CH-5), 74.9 (CH-1′), 32.6–28.6 (9 × CH2), 27.0 (CH3-t-Bu), 26.6–
22.7 (4 × CH2), 19.5 (C-t-Bu), 14.2 (CH3).
Yield: 216 mg (56%); yellow oil; Rf = 0.71 (30% EtOAc–hexane);
[α]D27 –23.30 (c 0.53, CHCl3).
IR (NaCl): 2932, 1780, 1255, 1090 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.76 (m, 1 H, H-5), 3.64 (m, 3 H,
H-1′, H-2′), 2.54 (m, 2 H, H-3), 2.22 (m, 2 H, H-4), 0.90 (s, 18 H,
CH3-t-Bu), 0.10 (s, 6 H, CH3-Si), 0.07 (s, 6 H, CH3-Si).
13C NMR (100 MHz, CDCl3): δ = 177.7 (C=O), 79.3 (CH-1′), 75.0
(CH-5), 63.5 (CH2-2′), 28.4 (CH2-3), 25.9 (CH3-t-Bu), 25.7 (CH3-t-
Bu), 23.6 (CH2-4), 18.3 (C-t-Bu), 18.0 (C-t-Bu), –4.4 (CH3-Si),
–4.8 (CH3-Si), –5.4 (CH3-Si), –5.5 (CH3-Si).
MS (ESI): m/z (%) = 545 (100) [M + Na]+, 521 (9) [M – 1]+, 510
(64), 279 (63), 445 (60).
HRMS (ESI): m/z [M + Na]+ calcd for C33H50NaO3Si: 545.3421;
found: 545.3437.
MS (ESI): m/z (%) = 397 (11) [M + Na]+, 376 (30) [M + 2]+, 375
(1′R,5R)-5-(1′-Hydroxytridecanyl)-3H,5H-furan-2-one
[(–)-muricatacin] (1)
(100) [M + 1]+, 261 (4).
HRMS (ESI): m/z [M + 1]+ calcd for C18H39O4Si2: 375.2381; found:
375.2394.
To a soln of lactone 14 (25 mg, 0.04 mmol) in THF (1 mL) was add-
ed a soln of TBAF (50 μL, 0.04 mmol, 1 M in THF), and the mixture
was stirred at r.t. for 24 h. The residue obtained after evaporation of
the solvent was purified by column chromatography on silica gel
(40% EtOAc–hexane) to give (–)-muricatacin (1).
Anal. Calcd for C18H38O4Si2: C, 57.70; H, 10.22. Found: C, 57.77;
H, 10.31.
(1′R,5R)-5-{1′-[(tert-Butyldimethylsilyl)oxy]-2′-(hydroxy)eth-
yl}-3H,5H-furan-2-one (18)
Yield: 13 mg (93%); white solid; mp 70-72 °C; Rf = 0.17 (30%
EtOAc–hexane); [α]D25 –23.1 (c 0.45, CHCl3).
IR (NaCl): 3445, 2916, 2845, 1746, 1463 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.40 (dd, J = 7.3 Hz, J = 12.1 Hz,
1 H, H-5), 3.65 (dd, J = 4.9 Hz, J = 10.1 Hz, 1 H, H-1′), 2.57 (m, 2
H, H-3), 2.18 (m, 2 H, H-4), 1.51 (m, 2 H, H-2′), 1.25 (m, 20 H,
CH2), 0.87 (t, J = 6.6 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 177.1 (C=O), 82.9 (CH-5), 73.7
(CH-1′), 33.0–21.1 (13 × CH2), 14.1 (CH3).
To a soln of lactone 17 (426 mg, 1.13 mmol) in THF (10 mL) at 0
°C was added py (767 μL) and a soln of 30% HF–py (378 μL). The
resulting mixture was stirred for 22 h at r.t.. EtOAc (14 mL) and aq
sat. NaHCO3 soln (14 mL) were added and the mixture stirred for
10 min, and then extracted with EtOAc (3 × 10 mL). The combined
organic phase was dried, filtered and concentrated in vacuo to give
a residue, which was chromatographed on silica gel (10% EtOAc–
hexane) to afford primary alcohol 18.
Yield: 215 mg (73%); colorless oil; Rf = 0.14 (30% EtOAc–
hexane); [α]D27 –10.97 (c 1, CHCl3).
IR (NaCl): 3409, 2940, 1763, 1192 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.64 (m, 1 H, H-5), 3.58 (m, 3 H,
H-1′, H-2′), 3.21 (s, 1 H, OH), 2.47 (m, 2 H, H-3), 2.24 (m, 1 H, H-
4), 2.00 (m, 1 H, H-4), 0.82 (s, 9 H, CH3-t-Bu), 0.04 (s, 3 H, CH3-
Si), 0.03 (s, 3 H, CH3-Si).
MS (ESI): m/z (%) = 308 (18), 307 (100) [M + Na]+, 285 (20) [M +
1]+, 201 (16).
HRMS (ESI): m/z [M]+ calcd for C17H33O3: 285.2424; found:
285.2426.
Anal. Calcd for C17H32O3: C, 71.79; H, 11.34. Found: C, 71.89; H,
11.95.
13C NMR (100 MHz, CDCl3): δ = 177.7 (C=O), 80.0 (CH-5), 74.3
(CH-1′), 62.7 (CH2-2′), 28.3 (CH2-3), 25.6 (CH3-t-Bu), 23.5 (CH2-
4), 17.8 (C-t-Bu), –4.7 (CH3-Si), –4.9 (CH3-Si).
(1′R,5R)-5-(1′,2′-Dihydroxyethyl)dihydrofuran-2(3H)-one (16)
To a soln of alcohol 11 (974 mg, 2.53 mmol) in THF (10 mL) was
added a soln of TBAF (2.53 mL, 2.53 mmol, 1 M in THF), and the
mixture was stirred at r.t. for 5 h. The residue obtained after evapo-
ration of the solvent was purified by column chromatography on sil-
ica gel (5% MeOH–CH2Cl2) to give diol 16.
MS (ESI): m/z (%) = 283 (11) [M + Na]+, 278 (14), 262 (20) [M +
2]+, 261 (100) [M + 1]+, 219 (6).
HRMS (ESI): m/z [M + 1]+ calcd for C12H25O4Si: 261.1516; found:
Yield: 294 mg (80%); colorless oil; Rf = 0 (30% EtOAc–hexane);
[α]D27 –22.68 (c 1, CHCl3).
261.1529.
Synthesis 2013, 45, 625–632
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of (–)-Muricatacin from Tri-O-acetyl-D-glucal
631
Anal. Calcd for C12H24O4Si: C, 55.30; H, 9.29. Found: C, 55.63; H,
9.23.
5), 72.8 (CH-1′), 64.1 (CH2-2′), 26.9 (CH3-t-Bu), 19.3 (C-t-Bu),
19.2 (C-t-Bu).
HRMS (FAB): m/z [M – t-Bu]+ calcd for C38H44O4Si2: 564.2200;
found: 563.2065.
(1′S,5R)-5-{1′-[(tert-Butyldimethylsilyl)oxy]-2′-oxoethyl}-
3H,5H-furan-2-one (19)
To a soln of alcohol 18 (215 mg, 0.729 mmol) in CH2Cl2 (10 mL)
were added bis(acetoxy)iodobenzene (BAIB) (270 mg, 0.838
mmol) and a catalytic amount of 4-hydroxy-2,2,6,6-tetramethylpi-
peridine 1-oxyl (4-hydroxyTEMPO). The resulting mixture was
stirred at r.t. for 24 h. After this time, the solvent was removed and
the residue dissolved in MTBE (50 mL). The resulting soln was
washed with 15% aq Na2S2O3 soln (3 × 30 mL) and sat. aq NaHCO3
soln (3 × 30 mL). The organic phase was dried and the solvent evap-
orated under reduced pressure to give a brown residue, which was
chromatographed on silica gel (30% EtOAc–hexane) to afford alde-
hyde 19.
Anal. Calcd for C38H44O4Si2: C, 73.50; H, 7.14. Found: C, 73.54; H,
7.15.
Acknowledgment
This work was supported financially by the Spanish Ministry of
Foreign Affairs and Cooperation (PCI A/030052/10) and the Xunta
de Galicia (INCITE845B-2010/020, INCITE08PXIB314255PR).
The NMR and MS divisions of the research support services of the
University of Vigo (CACTI) are also gratefully acknowledged.
Zoila Gándara thanks the Xunta de Galicia for an Angeles Alvariño
contract, and Maria González, the University of Vigo for a PhD fel-
lowship.
Yield: 182 mg (96%); colorless crystals; mp 60–61 °C; Rf = 0.28
(30% EtOAc–hexane); [α]D25 –90.0 (c 1, CHCl3).
IR (NaCl): 2938, 1703, 1402, 1040 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.66 (s, 1 H, OCH), 4.85 (m, 1 H,
H-1′), 4.01 (m, 1 H, H-5), 2.56 (m, 2 H, H-3), 2.36 (m, 1 H, H-4),
2.18 (m, 1 H, H-4), 0.94 (s, 9 H, CH3-t-Bu), 0.12 (s, 6 H, CH3-Si).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
13C NMR (100 MHz, CDCl3): δ = 202.1 (C=O), 176.5 (C=O), 79.8
(CH-1′), 79.4 (CH-5), 27.8 (CH2-3), 25.7 (CH3-t-Bu), 23.3 (CH2-4),
18.1 (C-t-Bu), –4.6 (CH3-Si), –5.1 (CH3-Si).
References
(1) (a) Yoshimitsu, T.; Makino, T.; Nagaoka, H. J. Org. Chem.
2004, 69, 1993. (b) Ma, S. Acc. Chem. Res. 2003, 36, 701.
(c) de March, P.; Figueredo, M.; Font, J.; Raya, J.; Alvarez-
Larena, A.; Piniella, J. F. J. Org. Chem. 2003, 68, 2437.
(d) Kang, K. H.; Cha, M. Y.; Pae, A. N.; Choi, K. I.; Cho, Y.
S.; Koh, H. Y.; Chung, B. Y. Tetrahedron Lett. 2000, 41,
8137. (e) Ha, J. D.; Cha, J. K. J. Am. Chem. Soc. 1999, 121,
10012. (f) Sinha, S. C.; Keinan, E. J. Org. Chem. 1999, 64,
7067. (g) Kabeya, M.; Hamada, Y.; Shioiri, T. Tetrahedron
1997, 53, 9769. (h) Pearson, W. H.; Hembre, E. J. J. Org.
Chem. 1996, 61, 7217.
(2) (a) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod.
1999, 62, 504. (b) Zafra-Polo, M. C.; Figadere, B.; Gallardo,
T.; Tormo, J. R.; Cortes, D. Phytochemistry 1998, 48, 1087.
(c) Koch, S. S. C.; Chamberlin, A. R. Enantiomerically Pure
γ-Butyrolactones in Natural Products Synthesis, In Studies
in Natural Products Chemistry: Stereoselective Synthesis;
Part J, Vol. 16; Atta-ur-Rahman, Ed.; Elsevier Science:
Amsterdam, 1995, 687–725.
MS (ESI): m/z (%) = 281 (10) [M + Na]+, 260 (6) [M + 2]+, 259 (37)
[M + 1]+, 158 (100).
HRMS (ESI): m/z [M + 1]+ calcd for C12H23O4Si: 259.1360; found:
259.1369.
(1′R,5R)-5-{1′-[(tert-Butyldiphenylsilyl)oxy]-2′-[(tert-butyldi-
phenylsilyl)oxy]ethyl}-5H-furan-2-one (24)
To a soln of compound 20 (2.8 g, 4.63 mmol) in MeOH–CH2Cl2
(2:3, 50 mL) was added Rose Bengal (128 mg), and the resulting
pink soln was purged with O2 and cooled to –78 °C. DIPEA (3.40
mL, 19.48 mmol) was added and the mixture irradiated with a 200
W lamp under an O2 atm for 9 h. The mixture was allowed to reach
r.t. and the solvent was evaporated in vacuo. The residue was dis-
solved in CH2Cl2 (30 mL) and a soln of oxalic acid (40.90 mL,
0.127 M) was added to the resulting pink soln. This gave an orange
mixture which was stirred at r.t. for 2 h. After separation of the two
phases, the aq phase was extracted with CH2Cl2 (3 × 300 mL), and
the combined organic phase dried, filtered and concentrated in vac-
uo to yield the expected intermediate hydroxybutenolide as a pink
oil [Rf = 0.14 (10% EtOAc–hexane)].
(3) Rieser, M. J.; Kozlowski, J. F.; Wood, K. V.; McLaughlin,
J. L. Tetrahedron Lett. 1991, 32, 1137.
The crude hydroxybutenolide was dissolved in MeOH (40 mL) and
cooled to 0 °C before adding CeCl3·7H2O (86.3 mg, 0.232 mmol)
and NaBH4 (702 mg, 18.55 mmol). The mixture was stirred at 0 °C
for 3 h, after which concd HCl was added dropwise until pH 2. The
mixture was stirred for 18 h and then the solvent was evaporated in
vacuo. The residue was chromatographed on silica gel (5% EtOAc–
hexane) to afford compound 24.
(4) For recent syntheses of muricatacin, see: (a) Kumaraswamy,
G.; Ramakrishna, D.; Santhakumar, K. Tetrahedron:
Asymmetry 2010, 21, 544. (b) Ghosal, P.; Kumar, V.; Shaw,
A. K. Carbohydr. Res. 2010, 345, 41. (c) Barros, M. T.;
Charmier, M. A. J.; Maycock, C. D.; Michaud, T.
Tetrahedron 2009, 65, 396. (d) Prasad, K. R.; Gandi, V.
Tetrahedron: Asymmetry 2008, 19, 2616. (e) Ferrié, L.;
Reymond, S.; Capdevielle, P.; Cossy, J. Synlett 2007, 2891.
(f) Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry
2006, 17, 2465. (g) Ahmed, Md. M.; Cui, H.; O’Doherty, G.
A. J. Org. Chem. 2006, 71, 6686. (h) Popsavin, V.; Krstić, I.;
Popsavin, M.; Srećo, B.; Benedeković, G.; Kojić, V.;
Bogdanović, G. Tetrahedron 2006, 62, 11044. (i) Quinn, K.
J.; Isaacs, A. K.; Arvary, R. A. Org. Lett. 2004, 6, 4143. For
a recent review on the synthesis of muricatacin and related
compounds, see: (j) Csákÿ, A. G.; Moreno, A.; Navarro, C.;
Murcia, M. C. Curr. Org. Chem. 2010, 14, 15.
Yield: 1.73 g (60%); white solid; mp 83–85 °C; Rf = 0.33 (20%
EtOAc–hexane); [α]D24 +16.70 (c 1, CHCl3).
IR (NaCl): 3063, 2938, 2860, 1760, 1105 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.48 (m, 20 H, Ph), 7.02 (dd,
J = 1.5 Hz, J = 5.7 Hz, 1 H, H-4), 6.05 (dd, J = 2.1 Hz, J = 5.7 Hz,
1 H, H-3), 5.34 (m, 1 H, H-5), 3.97 (m, 1 H, H-2′), 3.89 (dd, J = 8.3
Hz, J = 9.8 Hz, 1 H, H-1′), 3.71 (dd, J = 4.3 Hz, J = 9.9 Hz, 1 H, H-
2′), 1.04 (s, 9 H, CH3-t-Bu), 1.00 (s, 9 H, CH3-t-Bu).
13C NMR (100 MHz, CDCl3): δ = 173.3 (C=O), 154.3 (CH-4),
136.0 (CH-Ph), 135.8 (CH-Ph), 135.5 (CH-Ph), 135.4 (CH-Ph),
133.12 (C-Ph), 133.06 (C-Ph), 132.8 (C-Ph), 132.7 (C-Ph), 130.1
(CH-Ph), 129.92 (CH-Ph), 129.86 (CH-Ph), 129.8 (CH-Ph), 127.82
(CH-Ph), 127.80 (CH-Ph), 127.6 (CH-Ph), 122.4 (CH-3), 83.1 (CH-
(5) González, M.; Gándara, Z.; Covelo, B.; Gómez, G.; Fall, Y.
Tetrahedron Lett. 2011, 52, 5983.
(6) (a) Pazos, G.; Pérez, M.; Gándara, Z.; Gómez, G.; Fall, Y.
Tetrahedron Lett. 2009, 50, 5285. (b) Zúñiga, A.; Pérez, M.;
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 625–632

632
M. González et al.
PAPER
Pazos, G.; Gómez, G.; Fall, Y. Synthesis 2010, 2446.
(c) Zúñiga, A.; Pérez, M.; González, M.; Gómez, G.; Fall, Y.
Synthesis 2011, 3301.
Bruker SAINT software package and the data were corrected
for absorption using the program SADABS. The structures
were solved by direct methods using the program
(7) (a) Mori, Y.; Hayashi, H. J. Org. Chem. 2001, 66, 8666.
(b) Sobhana Babu, B.; Balasubramanian, K. K. J. Org.
Chem. 2000, 65, 4198. (c) Teijeira, M.; Fall, Y.; Francisco,
S.; Tojo, E. Tetrahedron Lett. 2007, 48, 7926.
(8) Teijeira, M.; Suárez, P.-L.; Gómez, G.; Terán, C.; Fall, Y.
Tetrahedron Lett. 2005, 46, 5889.
(9) Couladouros, E. A.; Mihou, A. P. Tetrahedron Lett. 1999,
40, 4861.
(10) Rassu, G.; Pinna, L.; Spanu, P.; Zanardi, F.; Battistini, L.;
Casiraghi, G. J. Org. Chem. 1997, 62, 4513.
(11) Crystallographic data were collected on a Bruker Smart
1000 CCD diffractometer (at CACTI, Universidade de
Vigo) at 20 °C using graphite monochromated MoKα
radiation (λ = 0.71073 Å), and were corrected for Lorentz
and polarization effects. The frames were integrated with the
SHELXS97. All non-hydrogen atoms were refined with
anisotropic thermal parameters by full-matrix least-squares
calculations on F2 using the program SHELXL97. Hydrogen
atoms were inserted at calculated positions and constrained
with isotropic thermal parameters. The structural data have
been deposited with the Cambridge Crystallographic Data
Centre (CCDC) with reference number, CCDC 877793.
Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ
[fax: +44(1223)336033, e-mail: deposit@ccdc.cam.ac.uk].
(12) Canoa, P.; Gándara, Z.; Pérez, M.; Gago, R.; Gómez, G.;
Fall, Y. Synthesis 2010, 431.
(13) Roberts, D. W.; Williams, D. L.; Bethell, D. J. Chem. Soc.,
Perkin Trans. II 1985, 3, 389.
Synthesis 2013, 45, 625–632
© Georg Thieme Verlag Stuttgart · New York