Total synthesis of xestodecalactone c from L-malic acid

Article abstract of DOI:10.1055/s-0029-1216938

An efficient total synthesis of the ten-membered macrolide, xestodecalactone C is described. The synthetic sequence uses Barbier-allylation, LiAlH4/LiI-mediated syn-stereoselective 1,3-asymmetric reduction, and intramolecular Friedel-Crafts acylation as k

Full text of DOI:10.1055/s-0029-1216938

PAPER
3157
Total Synthesis of Xestodecalactone C from L-Malic Acid
Total
S
ynt
.
hesis of
XesStodecalactone
.C
Yadav,* Y. Gopala Rao, K. Ravindar, B. V. Subba Reddy, A. V. Narsaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 19 December 2008; revised 15 May 2009
with 2-iodoxybenzoic acid in dimethyl sulfoxide–dichlo-
romethane to give aldehyde 10, which on further treat-
ment with allyl bromide and activated zinc in
tetrahydrofuran–aqueous ammonium chloride solution
under Barbier reaction conditions,8 gave the homoallyl al-
cohol 11 as a diastereomeric mixture (Scheme 2). Oxida-
tion of secondary alcohol 11 with 2-iodoxybenzoic acid in
dimethyl sulfoxide–dichloromethane afforded the ketone
12. A highly syn-stereoselective 1,3-asymmetric reduc-
tion was carried out using lithium aluminum hydride–lith-
ium iodide in diethyl ether at –100 °C to provide the
desired syn-diol 13 in good yield (syn/anti 95:5).9 The sec-
ondary hydroxy group was protected as its benzyl ether to
give 14, which was subjected to acid-catalyzed hydrolysis
in aqueous methanol to give diol 15a. Chemoselective to-
sylation (TsCl, Et3N, DMAP, CH2Cl2) of 15a gave the
monotosylated compound 15b.
Abstract: An efficient total synthesis of the ten-membered mac-
rolide, xestodecalactone C is described. The synthetic sequence
uses Barbier-allylation, LiAlH4/LiI-mediated syn-stereoselective
1,3-asymmetric reduction, and intramolecular Friedel–Crafts acyla-
tion as key steps.
Key words: xestodecalactone C, Barbier allylation, stereoselective
reduction, intramolecular Friedel–Crafts acylation
Xestodecalactones A, B, and C (1, 2, and 3, respectively)
were isolated from the fungus Penicillium cf. mantanense
obtained from the marine sponge Xestospongia exigua.1
Structurally these natural products constitute ten-mem-
bered macrolides with a fused 1,3-dihydroxybenzene
ring, that are related to a number of compounds isolated
from terrestrial fungi such as sporostatin (4)2 and curvu-
larins 5, 6a, and 6b.3 The absolute stereochemistry of xe-
stodecalactones B and C was determined by Xinfu Pan et
al. by their stereoselective synthesis.4 Xestodecalactone
A–C have been found to exhibit antibacterial and antifun-
gal activities.5 Considering its selective biological profile
and structural features, several syntheses of xestodeca-
lactones A, B, and C have been well reported (Figure 1).6
OH
O
OH
9
OH
O
1
1
7
7
11
11
R
13
13
5
HO
O
HO
O
5
O
O
2: 9S,11R
3: 9R,11R
1
As a part of our interest in the total synthesis of biologi-
cally active natural products, we herein report a total syn-
thesis of xestodecalactone C (3) using a commercially
available and inexpensive starting material, L-malic acid.
This strategy mainly relies on Barbier allylation, syn-ste-
reoselective 1,3-asymmetric reduction, and intramolecu-
lar Friedel–Crafts acylation as the key steps.
Retrosynthetic analysis reveals that target molecule 3
could be easily synthesized from alcohol 8 (Scheme 1),
which in turn could be prepared from commercially avail-
able starting material L-malic acid (9) as outlined in
Scheme 1.
OH
O
7
X
9
OH
1
O
1
9
7
R
11
13
5
HO
5
HO
O
S
O
O
O
4
5: X = H
6a: X = OH; 9R
6b: X = OH; 9S
Accordingly, the precursor 8 was prepared from L-malic
acid.7 Thus, the resulting primary alcohol 8 was treated
Figure 1 Xestodecalactones A, B, and C (1, 2, and 3), sporostatin
(4), curvularins 5, 6a, and 6b
OMe
O
OBn
OH
O
xestodecalactone C
CO2H
O
HO2C
L-malic acid
3
MeO
O
OH
O
7
8
9
Scheme 1 Retrosynthetic analysis of xestodecalactone C
SYNTHESIS 2009, No. 18, pp 3157–3161
x
x.
x
x
.
2
0
0
9
Advanced online publication: 14.08.2009
DOI: 10.1055/s-0029-1216938; Art ID: Z28208SS
© Georg Thieme Verlag Stuttgart · New York

3158
J. S. Yadav et al.
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O
O
O
O
O
c
a
OH
b
O
O
O
O
O
H
OH
8
10
11
12
OH
OBn
OH OBn
O
O
e
f, g
d
O
O
RO
15a R = H
13
14
15b R = Ts
Scheme 2 Reagents and conditions: (a) IBX, DMSO, CH2Cl2, 3 h, 90%; (b) allyl bromide, activated Zn, THF–aq NH4Cl, 0 °C to r.t., 4 h,
90%; (c) IBX, DMSO, CH2Cl2, 3 h, 86%; (d) LiAlH4/LiI (1:1, 3 equiv), Et2O, –100 °C, 92%; (e) BnBr, NaH, THF, r.t., 6 h, 85%; (f) PTSA,
MeOH, r.t., 30 min, 90%; (g) TsCl, Et3N, cat. DMAP, CH2Cl2, r.t., 3 h, 75%.
OMe
OMe
OBn
O
OH OBn
OBn
O
OH
O
MeO
b
a
15b
MeO
c
O
g
17
16
OMe
18
OMe
OBn
OBn
CO2H
CHO
f
O
O
d, e
MeO
MeO
O
O
19
20
OMe
O
OH
O
OH
O
OH
OMe
O
OBn
i
h
MeO
HO
O
MeO
O
O
O
O
7
3
21
Scheme 3 Reagents and conditions: (a) K2CO3, MeOH, r.t., 1 h, 81%; (b) LiAlH4, THF, 0 °C to r.t., 2 h, 90%; (c) DCC, DMAP, CH2Cl2, r.t.,
2 h, 90%; (d) OsO4, NMO, acetone–H2O (8:2), r.t., 2 h, 90%; (e) NaIO4, THF–H2O (2:1), 0 °C to r.t., 1 h, 80%; (f) NaClO2, NaH2PO4·2 H2O,
2-methylbut-2-ene, t-BuOH–H2O (4:1), 0 °C to r.t., 12 h, 85%; (g) TFA, TFAA, r.t., 8 h, 40%; (h) H2, Pd/C, EtOAc, r.t., 90%; (i) AlI3, TBAI,
benzene, 10 °C, 94%.
Monotosylated compound 15b was treated with potassi- 3 in good yield.13 The spectral and analytical data of nat-
um carbonate in methanol to afford the epoxide 16. Ter- ural product 3 were in agreement with the literature
minal epoxide 16 was subjected to regioselective (Scheme 3).1
reductive opening with lithium aluminum hydride in tet-
rahydrofuran to afford the secondary alcohol 17, which
upon treatment with 3,5-dimethoxyphenylacetic acid us-
In conclusion, an efficient total synthesis of xestodecalac-
tone C was accomplished by means of a versatile strategy,
wherein L-malic acid was used as inexpensive starting
material for accessing the natural product.
ing N,N¢-dicyclohexylcarbodiimide and 4-(dimethylami-
no)pyridine gave the ester 18,10 which was further
converted into aldehyde 19 by dihydroxylation followed
Melting points were recorded on Buchi R-535 apparatus and are un-
by sodium periodate mediated cleavage. Then aldehyde
corrected. IR spectra were recorded on a Perkin-Elmer FT-IR
19 was oxidized to carboxylic acid 20 under Pinnicks re-
action conditions.11 The desired macrolide 7 was obtained
in 40% yield by intramolecular Friedel–Crafts reaction of
the carboxylic acid 20 with a mixture of trifluoroacetic
acid and trifluoroacetic anhydride.12 The benzyl group of
macrolide 7 was cleaved by hydrogenation using palladi-
um-on-carbon in ethyl acetate to furnish compound 21.
Finally, demethylation of 21 was performed using freshly
prepared aluminum(III) iodide to give the target molecule
240-c spectrophotometer using KBr optics. 1H and 13C NMR spec-
tra were recorded on Gemini-200 and Varian Bruker-300 spectrom-
eter in CDCl3 using TMS as internal standard. Mass spectra were
recorded on a Finnigan MAT 1020 mass spectrometer operating at
70 eV. Room temperature = 25 °C.
1-[(2S)-1,4-Dioxaspiro[4.5]decan-2-yl]pent-4-en-2-ol (11)
To a stirred soln of IBX (11.3 g, 40.32 mmol) in anhyd DMSO (40
mL), was added a soln of 8 (5.0 g, 26.8 mmol) in CH2Cl2 (50 mL)
at r.t. The resulting mixture was stirred at this temperature for 3 h.
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Total Synthesis of Xestodecalactone C
3159
Then the mixture was filtered and diluted with H2O (50 mL) and ex-
tracted with CH2Cl2 (2 × 50 mL). The combined organic layers were
washed with brine (20 mL), dried (Na2SO4), and evaporated to give
10 (4.45 g, 90%) as a colorless liquid, which was as used for the
next reaction without purification.
was added NaH (1.0 g, 25.42 mmol, 60% w/w in paraffin oil) at 0
°C. After 30 min, BnBr (1.66 mL, 13.98 mmol) was added at 0 °C
and the mixture was stirred for 6 h. Then the mixture was quenched
with sat. aq NH4Cl (20 mL) at 0 °C and extracted with EtOAc (2 ×
50 mL). The combined organic extracts were washed with brine (20
mL), dried (Na2SO4), and evaporated under reduced pressure and
the resulting crude product was purified by column chromatography
(60–120 silica gel, EtOAc–hexanes, 1:40) to afford 14 (3.41 g,
85%) as a pale yellow liquid.
[a]D20 +4.28 (c 1.2, CHCl3).
IR (neat): 750, 1100, 1250, 1700, 2950, 3050 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.30–1.40 (m, 2 H), 1.48–1.68 (m,
9 H), 1.88–2.00 (m, 1 H), 2.26 (m, 2 H), 3.39–3.62 (m, 2 H), 3.85–
3.94 (m, 1 H), 4.10–4.35 (m, 1 H), 4.50 (q, J = 11.2, 23.0 Hz, 2 H),
5.08 (dd, J = 6.6, 17.0 Hz, 2 H), 5.71–5.92 (m, 1 H), 7.28 (m, 5 H).
To a stirred soln of 10 (4.45 g, 24.1 mmol) in THF (40 mL) was add-
ed Zn (3.14 g, 48.3 mmol) and allyl bromide (4.1 mL, 48.3 mmol)
at 0 °C. Then a soln of sat. NH4Cl (80 mL) was added and the re-
sulting mixture was allowed to stir at this temperature for 4 h. After
completion, the mixture was quenched with H2O (30 mL) and ex-
tracted with EtOAc (2 × 50 mL). The combined organic layers were
washed with brine (50 mL), dried (Na2SO4), and concentrated in
vacuo. The crude residue was purified by column chromatography
(silica gel, 60–120 mesh, EtOAc–hexane, 1:4) to afford 11 (5.13 g,
90%) as a colorless liquid.
[a]D20 +2.8 (c 0.5, CHCl3).
IR (neat): 3448, 3059, 2918, 1580, 1050 cm–1.
MS (EI): m/z = 317 [M + H]+.
1H NMR (300 MHz, CDCl3): d = 5.90–5.73 (m, 1 H), 5.13–5.04 (m,
1 H), 4.29–4.18 (m, 1 H), 4.15–3.98 (m, 1 H), 3.96–3.80 (m, 1 H),
3.50 (t, J = 6.7 Hz, 1 H), 3.10–3.02 (m, 1 H), 2.32–2.14 (m, 2 H),
1.74–1.51 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 134.2, 118.1, 75.5, 70.4, 69.1, 42.0,
40.1, 36.5, 35.1, 25.4, 23.9.
(2S,4S)-4-(Benzyloxy)hept-6-ene-1,2-diol (15a)
To a stirred soln of 14 (2.0 g, 6.32 mmol) in MeOH was added a cat-
alytic amount of PTSA (0.107 g, 0.632 mmol) and the mixture was
stirred at r.t. for 30 min. The mixture was neutralized with Et3N (3
mL) and the solvent was evaporated. The crude residue was purified
by column chromatography (60–120 silica gel, EtOAc–hexanes,
1:1) to afford 15 (1.33 g, 90%) as a syrup.
1 H NMR (200 MHz, CDCl3): d = 1.58–1.78 (m, 2 H), 2.36–2.46 (m,
2 H), 3.28–3.85 (m, 4 H), 4.60 (ABq, J = 11.1 Hz, 2 H), 5.03–5.22
(m, 2 H), 5.64–5.84 (m, 1 H), 7.26–7.40 (m, 5 H).
MS (ESI): m/z = 227 [M + H]+.
Anal. Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 68.95; H,
9.70.
MS (EI): m/z = 237 [M + H]+.
(2S)-1-[(2S)-1,4-Dioxaspiro[4.5]decan-2-yl]pent-4-en-2-ol (13)
A soln of IBX (7.11 g, 25.42 mmol) in anhyd DMSO (30 mL) at r.t.
was stirred for 30 min, then a soln of 11 (4 g, 16.94 mmol) in
CH2Cl2 (50 mL) was added. The resulting mixture was allowed to
stir at r.t. for 3 h. Then the mixture was filtered and diluted with H2O
(50 mL) and extracted with CH2Cl2 (2 × 50 mL).The combined or-
ganic layers were washed with brine (20 mL), dried (anhyd Na2SO4)
and evaporated to give 12 (3.41 g, 86%) as a colorless liquid, which
was used for the next reaction.
(2S,4S)-4-(Benzyloxy)-1-tosylhept-6-en-2-ol (15b)
To a soln of 15 (1.3 g, 5.55 mmol) in anhyd CH2Cl2 (15.0 mL) was
added Et3N (1.55 mL, 11.11 mmol) at 0 °C. Then TsCl (1.16 g, 6.11
mmol) and was added over 2 h and then DMAP (cat.) was added.
The resulting mixture was allowed to warm to r.t. and stirred for 3
h. Then the mixture was treated with aq 1 M HCl (10 mL) and ex-
tracted with CH2Cl2 (3 × 30 mL). The organic layers were washed
with sat. NaHCO3 (15 mL) and H2O (15 mL), dried (anhyd
Na2SO4), and concentrated under reduced pressure. Flash chroma-
tography of the crude product afforded 15b (1.57 g, 75%) as a gum-
my liquid; Rf = 0.5 (silica gel, 80% EtOAc–hexane).
To a stirred soln of 12 (3.41 g, 14.5 mmol) in anhyd Et2O (10 mL)
was added a soln of LiI (5.85 g, 43.7 mmol) in Et2O at 0 °C and the
mixture was stirred for 10 min. Then LiAlH4 (1.66 g, 43.7 mmol)
was added at –78 °C and the resulting mixture was stirred for 10 min
after which the temperature was decreased to –100 °C and stirred
for 30 min. Upon completion, the mixture was quenched with sat.
aq KOH (10 mL) and extracted with Et2O (2 × 50 mL). The com-
bined organic layers were washed with brine (20 mL), dried (anhyd
Na2SO4), and concentrated in vacuo. The crude residue was purified
by column chromatography (silica gel, 60–120 mesh, EtOAc–hex-
ane, 1:9) to afford 13 (3.16 g, 92%) as a colorless syrup.
[a]D20 +14.2 (c 0.8, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.56–1.6 (m, 3 H), 2.24–2.40 (m,
2 H), 2.42 (s, 3 H), 3.71–4.11 (m, 4 H), 4.52 (ABq, J = 11.3 Hz, 2
H), 5.04–5.12 (m, 2 H), 5.66–5.84 (m, 1 H), 7.26–7.27 (m, 7 H),
7.69–7.9 (m, 2 H).
MS (EI): m/z = 390 [M]+.
[a]D20 +12.2 (c 1.0, CHCl3).
IR (neat): 3440, 3050, 2920, 1590, 1054 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.90–5.73 (m, 1 H), 5.13–5.04 (m,
1 H), 4.29–4.18 (m, 1 H), 4.05 (q, J = 8.3, 6.0 Hz, 1 H), 3.90–3.80
(m, 1 H), 3.52 (t, J = 6.7 Hz, 1 H), 3.10 (br s, 1 H), 2.32–2.14 (m, 2
H), 1.74–1.51 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 134.2, 118.1, 75.5, 70.4, 69.1, 42.0,
40.1, 36.5, 35.1, 25.4, 23.9.
MS (ESI): m/z = 227 [M + H]+.
(S)-2-[(S)-2-(Benzyloxy)pent-4-enyl]oxirane (16)
To a stirred soln of 15b (1.5 g, 3.96 mmol) in anhyd MeOH (20
mL), was added K2CO3 (1.64 g, 11.9 mmol) and the mixture was
stirred at r.t. for 1 h. Then the solvent was evaporated and the resi-
due was dissolved in CH2Cl2 (10 mL), washed with H2O, dried (an-
hyd Na2SO4), and concentrated under reduced pressure. The
resulting crude residue was purified by column chromatography to
give 16 (0.701 g, 81%) as a pale yellow liquid.
[a]D20 24.23 (c 0.2, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.42–1.55 (m, 1 H), 1.76–1.86 (m,
1 H), 2.34–2.40 (m, 2 H), 2.44 (q, J = 3.0 Hz, 1 H), 2.75 (q, J = 3.7
Hz, 1 H), 3.65–3.73 (m, 2 H), 4.58 (ABq, J = 11.3 Hz, 2 H), 5.03–
5.12 (m, 2 H), 5.72–5.88 (m, 1 H), 7.2–7.32 (m, 5 H).
Anal. Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 68.90; H,
9.78.
MS (EI): m/z = 219 (M + H)+.
(2S)-2-(Benzyloxy)-1-[(2S)-1,4-dioxaspiro[4.5]decan-2-yl]pent-
4-ene (14)
To a stirred soln of 13 (3.0 g, 12.7 mmol) in anhyd THF (40 mL)
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(2R,4S)-4-(Benzyloxy)hept-6-en-2-ol (17)
mL). The organic phase was separated and the aqueous phase was
extracted with Et2O. The combined organic phases were washed
with brine, dried (Na2SO4), and concentrated in vacuo and purified
by flash chromatography to afford 20 (511 mg, 85%).
To a stirred soln of LiAlH4 (366 mg, 9.63 mmol) in anhyd THF (10
mL) at 0 °C, was added slowly a soln of 16 (700 mg, 3.21 mmol) in
anhyd THF (5 mL) and the mixture was stirred at r.t. for 2 h. After
completion, the mixture was quenched with sat. aq NH4Cl (20 mL)
at 0 °C and stirred for 1 h and then extracted with EtOAc (2 × 20
mL). The combined organic extracts were washed with brine (20
mL), dried (anhyd Na2SO4), and concentrated under reduced pres-
sure. The resulting residue was purified by column chromatography
(60–120 silica gel, EtOAc–hexane, 1:40) to afford 17 (632 mg,
90%) as a colorless liquid.
[a]D20 –33.5 (c 1.05, CHCl3).
IR (neat): 3675, 3468, 2928, 2852, 1731, 1597, 1459, 1431, 1350,
1205, 1066 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34–7.16 (m, 5 H), 6.41 (d,
J = 2.2 Hz, 2 H), 6.31 (t, J = 2.2 Hz, 1 H), 5.78–5.62 (m, 1 H), 4.27
(ABq, J = 11.3, 10.5 Hz, 2 H), 3.78–3.65 (s, 6 H), 3.47 (s, 2 H),
2.64–2.39 (m, 2 H), 1.83–1.74 (m, 1 H), 1.42–1.30 (m, 2 H), 1.27
(d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 175.92, 170.89, 160.85, 137.66,
137.20, 136.24, 128.41, 128.06, 127.83, 107.26, 99.26, 72.41,
72.15, 68.37, 55.28, 42.18, 41.63, 39.48, 20.57.
[a]D20 –33.1 (c 0.61, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.36–7.22 (m, 5 H), 5.85–5.70 (m,
1 H), 5.13–5.03 (m, 2 H), 4.56 (ABq, J = 11.5 Hz, 2 H), 4.11–4.01
(m, 1 H), 3.72–3.68 (m, 1 H), 2.50–2.25 (m, 2 H), 1.65–1.57 (m, 2
H), 1.15 (d, J = 6.2 Hz, 3 H).
HRMS: m/z [M + Na]+ calcd for C23H28NaO7: 439.1732; found:
439.1723.
MS (EI): m/z = 221 [M + H]+.
(2R,4S)-4-(Benzyloxy)hept-6-en-2-yl 2-(3,5-Dimethoxyphe-
nyl)acetate (18)
(4R,6R)-6-(Benzyloxy)-9,11-dimethoxy-4-methyl-4,5,6,7-tetra-
hydro-2H-3-benzoxecine-2,8(1H)-dione (7)12
Reddish oil.
[a]D20 –5.90 (c 1.01, CHCl3).
To a stirred soln of 17 (500 mg, 2.28 mmol) in anhyd CH2Cl2 at 0
°C was added DMAP (557 mg, 4.56 mmol), DCC (940.7 mg, 4.56
mmol), and 3,5-dimethoxyphenylacetic acid (492 mg, 2.51 mmol)
and the resulting mixture was stirred at r.t. for 2 h. The mixture was
filtered, washed with brine, dried (Na2SO4), and concentrated in
vacuo. The residue was purified by column chromatography (hex-
anes–EtOAc, 10:1) to afford the 18 (815 mg, 90%) as a yellow oil.
[a]D20 –77.0 (c 1.15, CHCl3).
IR (KBr): 2934, 2839, 1730, 1597, 1459, 1431, 1350, 1205 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.16 (m, 5 H), 6.38 (d,
J = 2.2 Hz, 2 H), 6.28 (t, J = 2.2 Hz, 1 H), 5.78–5.62 (m, 1 H), 5.08–
4.96 (m, 2 H), 4.22 (ABq, J = 11.3, 10.5 Hz, 2 H), 3.78–3.67 (m, 7
H), 3.42 (s, 2 H), 3.30–3.18 (m, 1 H), 2.32–2.11 (m, 2 H), 1.72–1.51
(m, 2 H), 1.22 (d, J = 6.7 Hz, 3 H).
IR (KBr): 2925, 1730, 1638, 1603, 1456, 1336, 1239, 1157, 1092
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36–7.17 (m, 5 H), 6.37 (d,
J = 1.5 Hz, 1 H), 6.21 (d, J = 1.5 Hz, 1 H), 4.91–4.81 (m, 1 H), 4.56
(ABq, J = 12.8, 11.3 Hz, 2 H), 4.27–4.17 (m, 1 H), 4.01–3.89 (m, 1
H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.38–3.28 (m, 1 H), 3.15–3.06 (m, 2
H), 2.10–2.01 (m, 1 H), 1.80–1.74 (m, 1 H), 1.20 (d, J = 6.0 Hz, 3
H).
13C NMR (75 MHz, CDCl3): d = 204.59, 168.75, 161.33, 159.02,
138.24, 134.40, 128.36, 127.65, 124.19, 107.75, 96.94, 71.70,
70.72, 55.65, 55.36, 52.35, 43.66, 40.31, 29.62, 20.84.
13C NMR (75 MHz, CDCl3): d = 170.71, 160.73, 138.39, 136.41,
134.20, 128.30, 127.89, 127.48, 117.39, 107.23, 99.09, 74.77,
71.39, 68.57, 55.19, 42.21, 41.17, 38.29, 20.57.
HRMS: m/z [M + Na]+ calcd for C23H26NaO6: 421.1627; found:
421.1620.
HRMS: m/z [M + Na]+ calcd for C24H30NaO5: 421.1990; found:
421.2004.
(4R,6R)-6-Hydroxy-9,11-dimethoxy-4-methyl-4,5,6,7-tetra-
hydro-2H-3-benzoxecine-2,8(1H)-dione (21)
To a stirred soln of 7 (0.150 mg, 0.37 mmol) in EtOAc (4 mL), was
added 10% Pd/C (catalytic) under a H2 atmosphere and stirred for 6
h. Then the mixture was filtered through a pad of Celite and concen-
trated in vacuo. The crude residue thus obtained was purified by col-
umn chromatography (silica gel, 60–120 mesh, EtOAc–hexane,
1:4) to afford 21 (104 mg, 90%) as colorless syrup.
(3R,5R)-3-(Benzyloxy)-5-[2-(3,5-dimethoxyphenyl)acet-
oxy]hexanoic Acid (20)
To a stirred soln of 18 (800 mg, 2.01 mmol) in acetone–H2O (8:2)
at r.t. was added OsO4 (cat.). After 15 min, NMO (258 mg, 2.21
mmol) was added and stirring was continued for 2 h. Acetone was
removed under reduced pressure and the mixture was quenched
with NaHSO3 soln at 0 °C and extracted with EtOAc (2 × 30 mL).
The combined organic extracts were washed with brine (20 mL),
dried (Na2SO4), and concentrated in vacuo. The resulting crude diol
(780 mg, 90%) was used in next reaction without further purifica-
tion.
[a]D20 +13.5 (c 0.3, CHCl3).
IR (KBr): 3350, 2925, 1730, 1638, 1603, 1456, 1239, 1157, 1092
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.39 (s, 1 H), 6.27 (s, 1 H), 5.38–
5.09 (m, 1 H,), 4.29–4.11 (m, 1 H), 3.82 (s, 3 H), 3.81 (s, 3 H), 3.51–
3.40 (d, J = 13.5 Hz, 1 H), 3.09 (s, 2 H), 2.39–2.21 (m, 1 H), 2.19–
1.91 (m, 1 H), 1.82–1.4 (m, 1 H), 1.19 (d, J = 6.4 Hz, 3 H).
To a stirred soln of diol in a mixture of THF–H2O (2:1) at 0 °C was
added NaIO4 (774 mg, 3.61 mmol) and stirring was continued at r.t.
for 1 h. Then the mixture was extracted with EtOAc (2 × 30 mL) and
the combined organic extracts were washed with brine (20 mL) and
dried (Na2SO4). Removal of solvent followed by purification gave
the crude aldehyde 19 (577 mg, 80%) which was used in next reac-
tion without further purification.
HRMS: m/z [M + Na]+ calcd for C16H20NaO6: 331.1157; found:
331.1155.
(4R,6R)-6,9,11-Trihydroxy-4-methyl-4,5,6,7-tetrahydro-2H-3-
benzoxecine-2,8(1H)-dione (3)13
White solid; mp 166–168 °C.
[a]D20 +22.5 (c 0.8, MeOH).
IR (KBr): 3345, 2923, 1739, 1630, 1461, 1370 cm–1.
1H NMR (400 MHz, DMSO): d = 9.92 (s, 1 H), 9.71 (s, 1 H), 6.27
(d, J = 1.6 Hz, 1 H), 6.10 (s, 1 H), 4.75 (d, J = 4.0 Hz, 1 H), 4.72
To a stirred soln of crude 19 in t-BuOH (3 mL) was added 2-meth-
ylbut-2-ene (1.2 mL) in t-BuOH (2 mL). The mixture was cooled to
0 °C and then treated with a soln of NaClO2 (196 mg, 2.16 mmol)
and NaH2PO4 (338 mg, 2.17 mmol) in H2O (1 mL). After 12 h, the
mixture was diluted with brine (5 mL) and extracted with Et2O (5
Synthesis 2009, No. 18, 3157–3161 © Thieme Stuttgart · New York

PAPER
Total Synthesis of Xestodecalactone C
3161
(dd, J = 11.2, 5.6 Hz, 1 H), 3.96 (br s, 1 H), 3.80 (d, J = 19.0 Hz, 1
H), 3.48 (d, J = 19.0 Hz, 1 H), 3.08 (dd, J = 14.8, 10.4 Hz, 1 H), 2.81
(d, J = 14.5 Hz, 1 H), 1.83 (d, J = 13.0 Hz, 1 H), 1.63 (dd, J = 14.8,
11.2 Hz, 1 H), 1.08 (d, J = 6.5 Hz, 3 H).
Prod. 1985, 48, 139. (d) Ghisalberti, E. L.; Rowland, C. Y.
J. Nat. Prod. 1993, 56, 2175.
(4) Liang, Q.; Zhang, J.; Quan, W.; Sun, Y.; She, X.; Pan, X.
J. Org. Chem. 2007, 72, 2694.
(5) Bringmann, G.; Proksch, P.; Edrada, R. A.; Heubes, M.;
Sudarsono; Gunther, E. US 2003,216,354, 2003.
(6) (a) Bringmann, G.; Lang, G.; Michel, M.; Heubes, M.
Tetrahedron Lett. 2004, 45, 2829. (b) Yoshino, T.; Ng, F.;
Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 14185.
(c) Yadav, J. S.; Thrimurtulu, N.; Uma Gayathri, K.;
Subba Reddy, B. V.; Prasad, A. R. Tetrahedron Lett. 2008,
49, 6617.
13C NMR (75 MHz, DMSO): d = 204.51, 167.75, 159.15, 157.02,
134.44, 121.80, 110.0, 101.25, 70.64, 67.78, 55.17, 45.99, 20.73.
HRMS: m/z [M + Na]+ calcd for C14H16NaO6: 303.0844; found:
303.0844.
Acknowledgment
(7) Hanessian, S.; Ugolini, A.; Dube, D.; Glamyan, A. Can. J.
Chem. 1984, 62, 2146.
(8) (a) Petrier, C.; Luche, J.-L. J. Org. Chem. 1985, 50, 910.
(b) Luche, J.-L.; Einhorn, C. J. Organomet. Chem. 1987,
322, 177.
(9) (a) Ghosh, A. K.; Lei, H. J. Org. Chem. 2002, 67, 8783.
(b) Sabitha, G.; Sudhakar, K.; Mallikarjun Reddy, N.;
Rajkumar, M.; Yadav, J. S. Tetrahedron Lett. 2005, 46,
6567.
(10) Baker, P. M.; Bycroft, B. W.; Roberts, J. C. J. Chem. Soc. C
1967, 1913.
Y.G.R and K.R thank the CSIR, New Delhi, for the award of fel-
lowships.
References
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Synthesis 2009, No. 18, 3157–3161 © Thieme Stuttgart · New York