Stereoselective total syntheses of leiocarpin A and (-)-galantinic acid starting from D-mannitol

Article abstract of DOI:10.1055/s-0028-1087993

Stereoselective total syntheses of leiocarpin A and (-)-galantinic acid, starting from D-mannitol as a chiral synthon, are described. The key steps involve stereoselective allylations, a Grignard reaction to control the required stereogenic centers, and r

Full text of DOI:10.1055/s-0028-1087993

1386
PAPER
Stereoselective Total Syntheses of Leiocarpin A and (–)-Galantinic Acid
Starting from D-Mannitol
Total
S
ynthesesof
o
L
eiocarpinA
m
and(–)-Galantinic
m
A
cid u Nagaiah,* Domalapally Sreenu, Kamaraju V. Purnima, Ramisetti Srinivasa Rao, Jhillu S. Yadav
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: nagaiah@iict.res.in
Received 3 December 2008; revised 22 December 2008
O
O
OH
Abstract: Stereoselective total syntheses of leiocarpin A and
(–)-galantinic acid, starting from D-mannitol as a chiral synthon, are
described. The key steps involve stereoselective allylations, a Grig-
nard reaction to control the required stereogenic centers, and ring-
closing metathesis followed by intramolecular Michael addition.
H
O
O
H
O
O
O
7
O
6
HO
H
Key words: D-mannitol, allylation, Grignard reaction, ring-closing
metathesis, Michael addition
OH
leiocarpin A (1)
leiocarpin B (2)
O
H
O
OH
Trees of the genus Goniothalamus of the plant family An-
nonaceae, which grow in South East Asia, have long been
known for their proven use in folk medicine. So far, more
than twenty bioactive styryl lactones have been isolated
from these plants.1 These styryl lactones exhibit pesticid-
al, teratogenic, embryotoxic, antifungal, antibacterial, and
antimalarial activities, and significant-to-marginal cyto-
toxicity against a broad array of human tumor cell lines,
including breast, colon, kidney, and pancreatic carcinoma
cells.2 Because of their unique and intriguing structures
and broad spectra of activities, these styryl lactones have
attracted the attention of several research groups in recent
H
O
O
OH
O
7
O
6
OH
leiocarpin C (3)
HO
H
9-deoxygoniopypyrone (4)
OH OH
HO
OH
H2N
O
O
NH2
HO
OH
revised structure of (–)-galantinic acid (5)
proposed structure of (–)-galantinic acid (6)
years.3 The leiocarpins are a newly discovered series of Figure 1 Structures of leiocarpins, 9-deoxygoniopypyrone, and
(–)-galantinic acid
styryl lactones. Leiocarpin A (1), leiocarpin B (2), and
leiocarpin C (3) (Figure 1) were recently isolated from the
ethanolic extract of the stem bark of Goniothalamus leio-
sis of galantinic acid starting from protected L-serine and
capus (Annonaceae) from the south of the Yunnan prov-
involving a Claisen condensation and an Evans diastereo-
ince in China; these leiocarpins posses cytotoxic activities
selective reduction as key steps.
against several human tumor cell lines.4a,b Leiocarpin A is
As a continuation of our efforts toward the total syntheses
of biologically active natural products,15 we describe
a stereoselective total synthesis of leiocarpin A (1) and
(–)-galantinic acid (5), starting from D-mannitol-derived
structurally related to 9-deoxygoniopypyrone 4 (Figure 1)
in regard of the configuration at C-6.3 Despite the impor-
tance of leiocarpin A with respect to its cytotoxic activity,
only one synthesis of this compound has been reported.4c
(R)-2,3-O-isopropylidineglyceraldehyde
[(4R)-2,2-di-
Galantinic acid (5) is a constituent of the peptide antibiot-
ic galantin I, isolated from a culture broth of Bacillus pul-
vifaciens.5 The originally proposed pyranoid structure 6
for (–)-galantinic acid was later revised to that of 5 by Sa-
kai and Ohfune (Figure 1).6 Galantinic acid, which is an
unusual amino acid, is an attractive target for synthetic
chemists because of its unique structure with dense func-
tionalisation, and also because of its excellent antibacteri-
al activity. A number of synthetic routes to galantinic acid
have been reported.7–14 Recently, Bethuel and
Gademann13 reported an efficient stereoselective synthe-
methyl-1,3-dioxolane-4-carbaldehyde] as a chiral synthon.
For the synthesis of leiocarpin A (1), the key steps involve
diastereoselective allylation and phenyl Grignard reac-
tions to control the required stereogenic centers, and ring-
closing metathesis followed by the formation of the py-
rone ring through intramolecular Michael addition reac-
tions, whereas for the synthesis of (–)-galantinic acid (5),
we used diastereoselective allylic additions as a promi-
nent part of the strategy (Scheme 1).
In our initial attempted synthesis, we performed a zinc-
mediated16 stereoselective allylation of (R)-2,3-O-isopro-
pylidineglyceraldehyde (10)17 to give the corresponding
homoallylic alcohol as a mixture of diastereomers 9a and
9b (anti/syn = 95:5) in 92% overall yield. The required
stereoisomer 9a was protected by treatment with 4-meth-
SYNTHESIS 2009, No. 8, pp 1386–1392
x
x
.
x
x
.2
0
0
9
Advanced online publication: 06.03.2009
DOI: 10.1055/s-0028-1087993; Art ID: Z26508SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Total Syntheses of Leiocarpin A and (–)-Galantinic Acid
1387
n
O
H
H
OH OPMB
SETO
O
H
O
O
O
OTES
OTES
HO
1
7
8a
O
O
O
O
D-mannitol
CHO
OH
10
9
OBn
OBn
OH
OH
OH
BnO
COOH
BnO
Cbz
HO
NBn
NBn
12
NH2
Cbz
6
11
Scheme 1 Retrosynthetic strategy for leiocarpin A and (–)-galantinic acid
oxybenzyl bromide and sodium hydride at 0 °C to give the dominant stereoisomer 9a was protected as its benzyl de-
ether 13. Hydrolysis of the 2,3-O-isopropylidine moiety rivative 19; subsequent hydrolysis of the 2,3-O-
of 13 with 1 M hydrochloric acid in tetrahydrofuran at isopropylidine moiety with 2 M hydrochloric acid in tet-
room temperature gave the diol 14, which on subsequent rahydrofuran at room temperature afforded the diol 20,
protection with triethylsilyl chloride and imidazole in which was subjected to selective protection of the primary
dichloromethane gave the bistriethylsilyl derivative 15. alcohol group by treatment with benzyl bromide in the
Selective oxidation of this derivative under Swern presence of dibutyltin oxide19–20 in refluxing benzene to
conditions18 gave the corresponding aldehyde through produce the dibenzyl derivative 21. This was treated with
domino deprotection of the primary O-triethylsilyl group methanesulfonyl chloride to afford the corresponding me-
and subsequent oxidation of the primary alcohol. The al- syl ester 22, which was subsequently heated with excess
dehyde, without further purification, underwent Grignard benzylamine21 at 120 °C under solvent-free conditions to
reaction with phenylmagnesium bromide, generated in afford the desired amino compound 23 in 85% yield. The
situ from bromobenzene and magnesium in THF at 0 °C, SN2 substitution occurred smoothly, even though the me-
to give the benzylic alcohol 8 as a mixture of diastereo- sylate group is flanked by bulky benzylic groups
mers 8a and 8b (anti/syn = 9:1) in 76% overall yield for (Scheme 3).
the two steps. The required anti-diastereomer 8a was pro-
tected with triethylsilyl chloride, and subsequent 2,3-
dichloro-5,6-dicyanobenzo-1,4-quinone (DDQ)-mediat-
ed deprotection of the 4-methoxybenzyl ether 16 gave the
alcohol 17. The alcohol 17 was acryloylated with acryloyl
chloride to give the Grubbs precursor 18, which was then
treated with Grubbs’ first-generation catalyst
[(PCy3)2Cl2Ru=CHPh (Ru-I)] to give the desired bis(tri-
ethylsilyl)-protected 6-epi-goniodiol 7. Finally, the pro-
tected 6-epi-goniodiol 7 was deprotected by treatment
with tetrabutylammonium fluoride in dichloromethane; a
subsequent intramolecular Michael addition reaction in
the same pot gave the target leiocarpin A (1) in 86% yield;
the spectral and analytical data for this compound were
consistent with those reported in the literature
(Scheme 2).4b
We next focused on stereoselective hydroxylation at the
C-3 position. To achieve this, the amine 23 was first pro-
tected as its carbamate derivative 11, and subsequent di-
hydroxylation with osmium tetroxide gave a diol that was
cleaved with sodium periodate to give the aldehyde in a
pure form in one pot; this sets the stage for chelation-con-
trolled diastereoselective allylation. Thus, the aldehyde
was treated with allyl(tributyl)stannane in the presence of
magnesium bromide22 at 0 °C to give the corresponding
homoallylic alcohol as a mixture of isomers 12a and 12b
in 72% overall yield. The desired major 1,3-anti-addition
product 12a was easily separated by column chromatog-
raphy from the undesired isomer (Scheme 4).
After assembling the three key internal groups with appro-
priate stereochemistry, our final task was to generate the
terminal carboxylic acid. Accordingly, the homoallylic al-
cohol 12a was treated with a catalytic amount of osmium
tetroxide to give the 1,2-diol, which was oxidatively
cleaved with NaIO4 in THF–H2O (5:1) to afford the alde-
hyde in one pot. The crude aldehyde was oxidized to the
Our attempted at a stereoselective synthesis of (–)-galan-
tinic acid (5) revolved around the generation of the left-
hand fragment of galantinic acid containing the 6-amino
and the 5- and 7-hydroxy groups. Accordingly, the pre-
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York

1388
K. Nagaiah et al.
PAPER
.
OH
OPMB
OPMB
OPMB
CHO
c
e
b
d
O
O
TESO
TESO
O
HO
a
O
O
O
HO
10
dr = 95:5 (anti/syn)
13
15
14
9a:9b
O
OH
OPMB
OTES
OPMB
OTES
OH
OTES
O
f
g
h
i
Ph
Ph
Ph
Ph
TESO
TESO
16
TESO
17
TESO
18
dr = 9:1 (anti/syn)
8a:8b
O
H
H
O
j
OTES
TESO
O
H
Ph
O
Ph
O
HO
leiocarpin A (1)
7
Scheme 2 Reagents and conditions: (a) Zn, allyl bromide, THF, sat. aq NH4Cl, 0 °C to r.t., 4 h, 92%; (b) PMBBr, NaH, THF, 0 °C to r.t., 4
h, 86%; (c) 1 M HCl, THF, r.t., 95%; (d) TESCl, imidazole, CH2Cl2, 0 °C to r.t., 3 h, 88%; (e) 1. (COCl)2, anhyd DMSO, Et3N, CH2Cl2, –78 °C,
3 h; 2. PhMgBr, anhyd THF, 0 °C to r.t., 3 h, 76% (overall yield for two steps); (f) TESCl, imidazole, CH2Cl2, 0 °C to r.t., 4 h, 85%; (g) DDQ,
CH2Cl2: H2O (19:1), 0 °C, 1 h, 90%; (h) acryloyl chloride, Et3N, DMAP (cat.), CH2Cl2, 0 °C to r.t., 6 h, 92%; (i) 20 mol% Grubbs first-gene-
ration catalyst, [(PCy3)2Cl2Ru=CHPh], CH2Cl2, reflux, 6 h, 85%; (j) TBAF, CH2Cl2, 0 °C to r.t., 86%.
OBn
OBn
OBn
OBn
OBn
a
c
d
f
b
e
9a
BnO
O
BnO
HO
BnO
BnO
O
MsO
i
HO
HO
BnHN
19
20
21
23
22
OBn
OH
OBn
OH
OBn
OH
OH
g
h
COOH
COOH
BnO
BnO
HO
NBn
NH2
(–)-galantinic acid (5)
NBn
NBn
Cbz
Cbz
Cbz
11
dr = 9:1 (anti/syn)
24
12a:12b
Scheme 3 Reagents and conditions: (a) BnBr, NaH, THF, 0 °C to r.t., 4 h, 90%; (b) 2 M HCl, THF, 0 °C to r.t., 90%; (c) Bu2SnO, BnBr,
benzene, reflux, 18 h, 88%; (d) MsCl, DIPEA, CH2Cl2, 0 °C to r.t, 3 h, 82%; (e) BnNH2, 120 °C, 12 h, 85%; (f) CbzCl, sat. NaHCO3, EtOH,
0 °C, 3 h, 90%; (g) 1. OsO4 (cat.), NMO, acetone–H2O (4:1), 6 h, 2. NaIO4, THF–H2O, (4:1) 30 min; 3. allyl(tributyl)stannane, MgBr2·Et2O,
CH2Cl2, 0 °C, 3 h, overall yield 72%; (h) 1. OsO4 (cat.), NMO, t-BuOH, 6 h; 2. NaIO4, THF–H2O (4:1), 30 min; 3. NaClO2, 20%
NaH2PO4·2H2O, t-BuOH, 0 °C to r.t., 4 h, overall yield 85%; (i) 10% Pd/C, H2 gas, MeOH, 8 h, 86%.
Ph
H
H
OBn OH
O
OBn
O
SnBu3
MgBr2•OEt2
SnBu3
M
R
R
R
H
H
O
H
1,3-anti chelation
Scheme 4 1,3-Asymmetric induction model
corresponding carboxylic acid 24 in 85% yield by NaClO2 In summary, we have developed a simple, convenient, and
in the presence of 20% NaH2PO4·2H2O in t-BuOH. The efficient approach to leiocarpin A (1) and (–)-galantinic
removal of benzyl and Cbz groups in compound 24 by acid (5) by a sequence of reactions starting from the three-
catalytic hydrogenolysis afforded the target compound, carbon chiral synthon (R)-2,3-O-isopropylidineglyceral-
(–)-galantinic acid (5) in 86% yield; the spectral and ana- dehyde (10). This approach provides a high stereoselec-
lytical data for the product were consistent with those re- tivity, uses a readily available and inexpensive starting
ported in the literature.6–7
material, and requires simple experimental conditions,
making it a useful and attractive approach to the total syn-
theses of leiocarpin A (1) and (–)-galantinic acid (5).
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York

PAPER
Total Syntheses of Leiocarpin A and (–)-Galantinic Acid
1389
dried (Na2SO4), filtered, and concentrated. The residue was purified
by column chromatography (EtOAc–hexane, 1:9) to give a color-
less liquid; yield: 7.6 g (88%); [a]D25 –4.08 (c = 0.5, CHCl3).
Melting points were recorded on a Büchi R-535 apparatus and are
uncorrected. IR spectra were recorded on a Perkin-Elmer FTIR 240-
c spectrophotometer using KBr optics. 1H NMR and 13C NMR spec-
tra were recorded on Gemini-200 (200 MHz), Bruker Avance-300
(300 MHz), and Unity-400 (400 MHz) spectrometers, respectively,
in CDCl3 using TMS as internal standard. Mass spectra were re-
corded on a Finnigan MAT 1020 mass spectrometer operating at 70
eV. Column chromatography was performed using E. Merck 60-
120 mesh silica gel. All solvents were distilled, dried over CaH2 and
stored under N2 prior to use. Starting materials and reagents used in
the reactions, obtained commercially from Aldrich, Lancaster, and
Fluka were used without purification unless otherwise indicated.
IR (neat): 2954, 2878, 1613, 1513, 1461, 1246, 1087, 1009, 739
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.18 (d, J = 8.3 Hz, 2 H), 6.78 (d,
J = 8.3 Hz, 2 H), 5.89–5.76 (m, 1 H), 5.08–4.98 (m, 2 H), 4.46 (q,
J = 17.3, 11.3 Hz 2 H), 3.77 (s, 3 H), 3.75–3.72 (m, 1 H), 3.64–3.59
(m, 1 H), 3.52–3.37 (m, 2 H), 2.34–2.24 (m, 2 H), 0.97–0.92 (m, 18
H), 0.63–0.54 (m, 12 H).
LC–MS (EI, 70 eV): m/z (%) = 503.3 (100%) [M + Na]+.
(1S)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]but-3-en-1-ol (9a)
To a mixture of activated Zn dust (5.5 g, 84.6 mmol) and anhyd
THF (30 mL) under N2 was added a solution of (R)-2,3-O-isopropy-
lidineglyceraldehyde (10) (5.5 g, 42.3 mmol) in THF (25 mL) at
0 °C, followed by allyl bromide (7.15 mL, 84.6 mmol) added drop-
wise over 10 min. The mixture was then stirred for 4 h at 0 °C until
the reaction was complete (TLC). The reaction was quenched by ad-
dition of sat. aq NH4Cl (17 mL) at 0 °C over 30 min and the mixture
was stirred for 1 h then filtered. The filtrate was concentrated in vac-
uo to give a crude product that was partitioned between H2O (50
mL) and EtOAc (100 mL). The organic layer was washed with brine
(30 mL), dried (anhyd Na2SO4), and concentrated. The residue was
further purified by column chromatography to give the pure com-
pound 9a as a yellowish oil; yield: 8.3 g (92%); [a]D25 +5.58
(c = 0.5, MeOH).
(1R,2R,3S)-3-[(4-Methoxybenzyl)oxy]-1-phenyl-2-[(triethylsi-
lyl)oxy]hex-5-en-1-ol (8a)
A solution of oxalyl chloride (5.0 mL, 58.3 mmol) in CH2Cl2 (25
mL) was added dropwise to DMSO (8.2 mL, 116.6 mmol) in
CH2Cl2 (40 mL) at –78 °C. After 15 min, a solution of compound
15 (7.0 g, 14.5 mmol) in CH2Cl2 (15 mL) was added, and stirring
was continued for 40 min at –78 °C and then for 20 min at –40 °C.
Et3N (24 mL, 176 mmol) was added at –78 °C, and the reaction was
allowed to reach r.t. The mixture was diluted with H2O (50 mL) and
extracted with CH2Cl2 (150 mL). The organic layer was separated,
washed with brine (30 mL), and dried (Na2SO4). The crude alde-
hyde was added to PhMgBr (1.2 equiv) in THF (50 mL) at 0 °C and
the mixture was stirred for 3 h at 0 °C to r.t until the reaction was
complete (TLC). The reaction was quenched with sat. aq NH4Cl (20
mL) at 0 °C, and then mixture was concentrated. The crude product
was extracted with Et2O (200 mL), and the organic layer was
washed with H2O (50 mL) and brine (30 mL) then dried (Na2SO4),
filtered, and concentrated. The residue was purified by column
chromatography to give pure compound 8a as a pale yellow oil;
yield: 5.1 g (76% overall); [a]D25 –9.10 (c = 0.4, CHCl3).
IR (neat): 3454 (br, OH), 2986, 1375, 1214, 1064 cm–1.
1H NMR (200 MHz, CDCl3): d = 5.90–5.70 (m, 1 H), 5.20–5.00 (m,
2 H), 4.00–3.90 (m, 3 H), 3.75–3.65 (m, 1 H), 2.40–2.20 (m, 2 H),
1.38 (s, 3 H), 1.36 (s, 3 H).
13C NMR (50 MHz, CDCl3): 134, 118, 109, 88, 71, 65, 38, 27, 25.
MS (EI, 70 eV): m/z (%) = 172 (5) [M]+, 157 (10), 141 (13), 101
IR (neat): 3452, 2924, 2877, 1708, 1639, 1613, 1513, 1459, 1246,
1085, 1040, 738, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.18 (m, 5 H), 7.12 (d, J =
8.30 Hz, 2 H), 6.77 (d, J = 8.30 Hz, 2 H), 5.86–5.73 (m, 1 H), 5.07–
4.97 (m, 2 H), 4.65 (dd, J = 6.79, 2.26 Hz, 1 H), 4.36 (q, J = 10.57
Hz, 2 H), 3.94–3.91 (dd, J = 6.79, 2.26 Hz, 1 H), 3.78 (s, 3 H), 3.51–
3.46 (m, 1 H), 2.37 (t, J = 6.79 Hz, 2 H), 0.83 (t, J = 8.30 Hz, 9 H),
0.45–0.35 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 142.9, 129.3, 127.7, 127.6, 127.3,
115.9, 113.4, 79.1, 76.6, 76.2, 70.9, 34.0, 6.9, 4.8.
LC–MS (EI, 70 eV): m/z (%) = 465.3 [M + Na]+.
(70), 59 (35), 43 (100).
(2R,3S)-3-[(4-Methoxybenzyl)oxy]hex-5-ene-1,2-diol (14)
To a solution of acetonide 13 (6 g, 20.5 mmol) in THF (60 mL) was
added 1 M HCl (2 mL) at 0 °C and the mixture was allowed to warm
to r.t., stirred for 6 h, and cooled to 0 °C. Solid Na2CO3 (0.5 g) was
then added in portions to neutralize the mixture. The solvent was re-
moved in vacuo, and the residue was partitioned between H2O (50
mL) and EtOAc (150 mL). The organic layer was washed with aq
NaHCO3 (50 mL) and brine (20 mL) then dried (Na2SO4). Filtra-
tion, concentration, and flash chromatography (EtOAc–hexane,
3:7) gave the required product 14 as a pale yellow oil; yield: 4.9 g
(95%); [a]D25 +8.20 (c = 0.4, CHCl3).
(1R,2S,3S)-3-[(4-Methoxybenzyl)oxy]-1-phenyl-1,2-bis[(tri-
ethylsilyl)oxy]hex-5-ene (16)
TESCl (3.5 g, 22.9 mmol) in anhyd CH2Cl2 (10 mL) was added
dropwise to a stirred solution of alcohol 8a (4.6 g, 10.4 mmol) and
imidazole (2.8 g, 41.6 mmol) in anhyd CH2Cl2 (20 mL) at 0 °C un-
der N2. The mixture was stirred for 4 h at 0 °C to r.t. When the re-
action was complete (TLC), the mixture was filtered, the residue
was washed with CH2Cl2 (20 mL), and the combined organic layers
were concentrated. The crude product was diluted with H2O (30
mL) and extracted with EtOAc (125 mL). The combined organic
layers were washed with brine (20 mL), dried (Na2SO4), filtered,
and concentrated to give a residue that was purified by column chro-
matography (EtOAc–hexane, 1:9) to give compound 16 as a yel-
lowish oil; yield: 4.8 g (85%); [a]D25 +4.80 (c = 1.2, CHCl3).
IR (neat): 3410, 2931, 1612, 1513, 1462, 1301, 1248, 1078, 1034,
821 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.18 (d, J = 8.3 Hz, 2 H), 6.81 (d,
J = 8.3 Hz, 2 H), 5.90–5.76 (m, 1 H), 5.14–5.05 (m, 2 H), 4.58–3.35
(m, 2 H), 3.77 (s, 3 H), 3.65–3.41 (m, 4 H), 2.69 (br s, 2 H, –OH),
2.39–2.27 (m, 2 H).
LC–MS (EI, 70 eV): m/z (%) = 275.1 (100%) [M + Na]+.
(1S,5R)-1-(1-{1,2-Bis[(triethylsilyl)oxy]ethyl}but-3-enyloxy-
methyl)-4-methoxybenzene (15)
TESCl (7.3 mL, 45.5 mmol) was added dropwise to a stirred solu-
tion of diol 14 (4.6 g, 18.2 mmol) and imidazole (7.4 g, 109.5 mmol)
in anhyd CH2Cl2 (25 mL) at 0 °C under N2, and the mixture was
stirred for 6 h at 0 °C to r.t. After completion of the reaction (TLC),
the mixture was filtered, the residue was washed with CH2Cl2 (2 ×
20 mL), and the organic layer was concentrated. The crude product
was diluted with H2O (50 mL) and extracted with EtOAc (100 mL).
The combined organic layers were washed with brine (30 mL),
IR (neat): 2954, 2878, 1612, 1513, 1459, 1245, 1089, 1008, 737
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.19 (m, 5 H), 7.16 (d, J =
8.3 Hz, 2 H), 6.78 (d, J = 8.3 Hz, 2 H), 5.91–5.76 (m, 1 H), 5.08–
4.96 (m, 2 H), 4.47–4.44 (m, 2 H), 4.32 (d, J = 11.3 Hz, 1 H), 3.90
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York

1390
K. Nagaiah et al.
PAPER
(m, 1 H), 3.79 (s, 3 H), 3.66–3.60 (m, 1 H), 2.40–2.29 (m, 2 H), 0.81
(t, J = 8.3 Hz, 9 H), 0.75 (t, J = 8.3 Hz, 9 H); 0.48–028 (m, 12 H).
13C NMR (50 MHz, CDCl3): d = 163.4, 144.9, 144.5, 127.1, 127.0,
126.4, 119.9, 76.9, 76.6, 28.8, 5.9, 3.9.
13C NMR (75 MHz, CDCl3): d = 128.8, 127.2, 127.1, 126.8, 115.4,
112.9, 78.6, 76.1, 75.7, 70.4, 33.5, 6.4, 4.3.
LC–MS (EI, 70 eV): m/z (%) = 485.2 [M + Na]+.
Leiocarpin A (1)
LC–MS (EI, 70 eV): m/z (%) = 579.3 (100%) [M + Na]+.
A 1.0 M solution of TBAF in THF (1.2 mL) was added to a stirred
solution of lactone 7 (200 mg, 0.43 mmol) in THF at 0 °C. The mix-
ture was stirred for 8 h at 0 °C to r.t. until the reaction was complete
(TLC). The solvent was removed in vacuo, and then the residue was
partitioned between H2O (5 mL) and CH2Cl2 (10 mL). The organic
layer was washed with H2O (5 mL) and brine (5 mL), dried
(Na2SO4), filtered, and concentrated. The residue was purified by
flash chromatography (EtOAc–hexane, 4:6) to give the target com-
pound 1 as a colorless solid; yield: 87 mg (86%); [a]D25 –94.9
(c = 0.4, CHCl3).
(1R,2S,3S)-1-Phenyl-1,2-bis[(triethylsilyl)oxy]hex-5-en-3-ol
(17)
DDQ (1.8 g, 8.1 mmol) was added portionwise to a stirred solution
of 16 (3.8 g, 6.8 mmol) in CH2Cl2– H2O (19:1) at 0 °C. The mixture
was stirred for 30 min until the reaction was complete (TLC) and
then solid NaHCO3 (0.84 g, 10 mmol) was added. The mixture was
then filtered and washed with H2O (10 mL) and brine. The solvent
was removed in vacuo, and the residue was partitioned between
H2O (30 mL) and CH2Cl2 (50 mL). The organic layer was washed
with H2O (20 mL) and brine (20 mL), dried (Na2SO4), filtered, and
concentrated to give a residue that was purified by flash chromatog-
raphy (EtOAc–hexane, 2:8) to give the required alcohol 17 as a yel-
lowish oil; yield: 2.7 g (90%); [a]D25 +12.0 (c = 0.4, CHCl3).
IR (KBr): 3437, 2924, 2854, 1716, 1631, 1459, 1379, 1274, 1080,
758 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.27 (m, 5 H), 4.89 (br s, 1
H), 4.44 (m, 1 H), 4.39 (d, J = 9.82 Hz, 1 H), 3.52 (dd, J = 9.82, 3.02
Hz, 1 H), 2.96 (d, J = 18.88 Hz, 1 H), 2.86 (dd, J = 18.88, 5.28 Hz,
1 H), 2.22 (br s, 2 H).
IR (neat): 3432, 2923, 2853, 1638, 1459, 1238, 1063, 1007, 736
cm–1.
1H NMR (200 MHz, CDCl3): d = 7.32–7.23 (m, 5 H), 5.92–5.72 (m,
1 H), 5.21–5.08 (m, 2 H), 4.59 (d, J = 6.6 Hz, 1 H), 3.81–3.74 (m, 1
H), 3.70–3.71 (m, 1 H), 2.23–2.02 (m, 2 H), 0.89–0.78 (m, 18 H),
0.50–0.29 (m, 12 H).
13C NMR (75 MHz, CDCl3): 168.8, 137.7, 128.7, 128.6, 127.3,
77.1, 74.4, 72.5, 65.8, 36.5, 22.6.
LC–MS (EI, 70 eV): m/z = 257.1 [M + Na]+.
LC–MS (EI, 70 eV): m/z (%) = 459.2 (100%) [M + Na]+.
(4R)-4-[(1S)-1-(Benzyloxy)but-3-en-1-yl]-2,2-dimethyl-1,3-di-
oxolane (19)
(1R,2S,3S)-1-Phenyl-1,2-bis[(triethylsilyl)oxy]hex-5-en-3-yl
Prop-2-enoate (18)
A solution of alcohol 9a (5.5 g, 31.9 mmol) in anhyd THF (20 mL)
was added to a stirred solution of NaH (1.53 g, 38.3 mmol) in anhyd
THF (40 mL) at 0 °C under N2, and the mixture was stirred for 20
min. BnBr (4.6 mL, 38.3 mmol) was added, and the mixture was
stirred for 4 h at r.t. The reaction was then quenched with ice-cold
H2O (20 mL) at 0 °C, and the mixture was concentrated and then di-
luted with H2O (50 mL). The aqueous layer was extracted with
EtOAc (3 × 30 mL), and the combined organic layers were washed
with brine (30 mL), dried (Na2SO4), and concentrated. The residue
was further purified by column chromatography to give pure com-
pound 19 as a yellowish oil; yield 7.5 g (90%).16f
Et3N (2.0 mL, 15.0 mmol) was added dropwise over 15 min to a so-
lution of alcohol 17 (2.2 g, 5.0 mmol) in anhyd CH2Cl2 (10 mL) at
0 °C, and the mixture was stirred for 30 min at 0 °C. Acryloyl chlo-
ride (0.45 mL, 5.5 mmol) in anhyd CH2Cl2 (5 mL) was added drop-
wise at 0 °C, and the mixture was stirred at 0 °C to r.t. for 6 h. When
the reaction was complete (TLC), the mixture was quenched with
sat. aq NaHCO3 (5 mL) at 0 °C and then diluted with CH2Cl2 (20
mL). The organic layer was washed with H2O (10 mL) and brine (10
mL), dried, and concentrated under reduced pressure. The residue
was purified by column chromatography (EtOAc–hexane, 1:9) to
give the required product 18 as a yellow oil; yield: 2.2 g (92%).
(2R,3S)-3-(Benzyloxy)hex-5-ene-1,2-diol (20)
To a stirred solution of acetonide 19 (1.0 g, 3.81 mmol) in THF (15
mL) was added 2 M HCl (1 mL) at 0 °C. The mixture was stirred for
3 h at r.t. then cooled to 0 °C and neutralized with solid NaHCO3
(0.168 g, 2 mmol). The solvent was removed in vacuo and diluted
with H2O (20 mL). The aqueous layer was extracted with EtOAc
(3 × 20 mL), and the combined organic layers were washed with aq
NaHCO3 and brine, then dried (Na2SO4) and concentrated. The res-
idue was further purified by flash chromatography (EtOAc–hexane,
3:7) to give pure 20 as a yellowish oil; yield: 0.76 g (90%).16f
1H NMR (200 MHz, CDCl3): d = 7.31–7.15 (m, 5 H), 6.38 (dd, J =
17.3, 2.2 Hz, 1 H), 6.08 (dd, J = 17.3, 10.5 Hz, 1 H), 5.82–5.74 (m,
2 H), 5.47–5.42 (m, 1 H), 5.07–4.95 (m, 2 H), 4.41 (d, J = 8.3 Hz, 1
H), 3.89 (m, 1 H), 2.54–2.41 (m, 2 H), 0.85 (t, J = 8.3 Hz, 9 H), 0.76
(t, J = 8.3 Hz, 9 H), 0.49–0.41 (m, 6 H), 0.30–0.20 (m, 6 H).
(1S,2R,6S)-6-{2-Phenyl-1,2-bis[(triethylsilyl)oxy]ethyl}-5,6-di-
hydro-2H-pyran-2-one (7)
A solution of diolefin 18 (1.8 g, 3.6 mmol) in anhyd CH2Cl2 (20
mL) was added dropwise over 1 h to a refluxing solution of ruthe-
nium catalyst Ru-I (630 mg, 0.72 mmol) in anhyd degassed CH2Cl2
(780 mL), and then the mixture was refluxed until the starting ma-
terial was consumed (10 h, TLC). Removal of the solvent in vacuo
and column chromatography of the residue on silica gel (EtOAc–
hexane, 1:9) gave the required lactone 7 as a pale yellow oil; yield:
1.6 g (85%); [a]D25 +20.00 (c = 0.5, CHCl3).
(2R,3S)-1,3-Bis(benzyloxy)hex-5-en-2-ol (21)
Bu2SnO (2.065 g, 8.30 mmol) and Bu4NI (696 mg, 1.89 mmol) were
added to a stirred solution of compound 20 (1.67 g, 7.55 mmol) in
benzene (150 mL) at r.t. The flask was then fitted with a Dean–Stark
trap (filled with 4-Å molecular sieves) and a reflux condenser. The
trap was filled with benzene, and the mixture was heated to reflux
until H2O evolution appeared to be complete. The mixture was
cooled to r.t., and BnBr (1.08 mL, 9.04 mmol) was added. The re-
sulting yellow solution was refluxed for 18 h. The mixture was then
diluted with Et2O (50 mL) and washed with 10% Na2S2O3 (50 mL).
The layers were separated, and the aqueous phase was extracted
with Et2O (3 × 50 mL). The combined organic layers were washed
with H2O (30 mL), dried (MgSO4), filtered, and concentrated in
vacuo. The residue was purified by silica gel chromatography to
give ether 21 as a colorless oil; yield: 2.06 g (88%).16f
IR (neat): 3445, 2923, 2853, 1738, 1633, 1461, 1482, 1244, 1085,
737 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.29–7.23 (m, 5 H), 6.91–6.84 (m,
1 H), 5.95 (dd, J = 9.82, 2.26 Hz, 1 H), 4.63 (m, 1 H), 4.51 (d, J =
6.04 Hz, 1 H), 4.06 (dd, J = 6.79, 2.26 Hz, 1 H) 2.79–2.68 (m, 1 H),
2.35–2.25 (m, 1 H), 0.81 (m, 18 H), 0.48–0.39 (m, 12 H).
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York

PAPER
Total Syntheses of Leiocarpin A and (–)-Galantinic Acid
1391
(2R,3S)-1,3-Bis(benzyloxy)hex-5-en-2-yl Methanesulfonate (22)
MeSO2Cl (0.86 mL, 11.06 mmol) was added to a stirred solution of
compound 21 (3.15 g, 10.06 mmol) and DIPEA (5.24 mL, 15.09
mmol) in anhydrous CH2Cl2 (15 mL) at 0 °C. The mixture was
stirred for 3 h then neutralized with K2CO3 (1.65 g, 12 mmol). The
resulting mixture was stirred for 15 min then washed with H2O (2 ×
15 mL), and extracted with CH2Cl2 (2 × 25 mL). The combined or-
ganic layers were washed with brine (20 mL), dried (Na2SO4), and
concentrated. The residue was further purified by column chroma-
tography EtOAc–hexane, 2:8) to give pure compound 22 as a pale
yellow oil; yield: 3.2 g (82%); [a]D25 +2.0 (c = 0.2, CHCl3).
Benzyl Benzyl[(2S,3S,5R)-1,3-bis(benzyloxy)-5-hydroxyoct-7-
en-2-yl]carbamate (12a)
To a solution of compound 11 (0.7 g, 1.30 mmol) in acetone–H2O
(3:1, 10 mL) were added OsO4 (0.5 mol%) and NMO (0.46 g, 3.92
mmol) at r.t. The mixture was stirred for 6 h, and then the reaction
was quenched with solid NaHSO4 (0.94 g, 7.84 mmol) and the mix-
ture was stirred for 15 min. Solid particles were separated by filtra-
tion and the filtrate was dried (Na2SO4) and concentrated. The
residue was dissolved in THF–H2O (4:1, 10 mL), and NaIO4 (0.84
g, 3.92 mmol) was added. After 30 min, the mixture was filtered,
dried (Na2SO4), and concentrated to give the crude aldehyde. A so-
lution of this crude aldehyde (0.6 g, 1.1 mmol) in anhydrous
CH2Cl2 (15 mL) was treated with MgBr2·Et2O (0.53 g, 3.31 mmol)
and allyl(tributyl)stannane (0.51 mL, 1.65 mmol) at 0 °C, and the
mixture was stirred for 3 h. The mixture was then washed with 2 M
HCl solution (5 mL) and extracted with CH2Cl2 (2 × 25 mL). The
combined organic layers were dried (Na2SO4) and concentrated.
The residue was purified by flash column chromatography (silica
gel) to give compound 12a as yellowish oil; yield: 0.40 g (64%);
[a]D25 – 6.2 (c = 0.75, CHCl3).
IR (neat): 3030, 2922, 2858, 1454, 1353, 1174, 1097, 919, 741, 698
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45–7.18 (m, 10 H), 5.90–5.73
(m, 1 H), 5.16–5.06 (m, 2 H), 4.88–4.83 (m, 1 H), 4.64–4.44 (m, 4
H), 3.79–3.69 (m, 3 H), 2.96 (s, 3 H), 2.48–2.14 (m, 2 H).
MS (EI, 70 eV): m/z (%) = 413.1 [M + Na]+.
(2S,3S)-N-Benzyl-1,3-bis(benzyloxy)hex-5-en-2-amine (23)
A mixture of compound 22 (2.5 g, 6.41 mmol) and BnNH2 (10.5
mL, 96.15 mmol) was heated to 120 °C. After 12 h, the mixture was
cooled to r.t. and diluted with EtOAc. The resulting mixture was
washed with aq NaHCO3 and brine, dried (Na2SO4) and concentrat-
ed. The residue was further purified by column chromatography
(EtOAc–hexane, 1:8) to give compound 23 as a yellowish oil; yield:
2.0 g (85%); [a]D25 +7.5 (c = 0.1, CHCl3).
IR (neat): 3453(br, OH), 3063, 3030, 2920, 2854, 1692, 1452, 1414,
1241, 1067, 913, 734, 696 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.40–6.98 (m, 20 H), 5.85–5.53
(m, 1 H), 5.20–4.92 (m, 4 H), 4.71–3.92 (m, 8 H), 3.83–3.65 (m, 1
H), 3.55–3.24 (m, 2 H), 2.19–1.94 (m, 2 H), 1.67–1.45 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 157.0, 139.1, 136.4, 134.6, 128.8,
128.7, 128.3, 128.2, 128.1, 128.0, 127.8, 127.6, 127.4, 127.0, 126.6,
117.7, 77.0, 73.0, 72.7, 69.1, 67.8, 67.2, 60.0, 50.0, 42.5, 37.5..
IR (neat): 3063, 3029, 2923, 2853,1454, 1095, 913, 738, 698 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.45–7.06 (m, 15 H), 5.92–5.62
(m, 1 H), 5.19–4.96 (m, 2 H), 4.63–4.32 (m, 4 H), 3.89–3.71 (m, 2
H), 3.65–3.45 (m, 3 H), 2.92–2.83 (m, 1 H), 2.59–2.22 (m, 2 H).
LC–MS (EI, 70 eV): m/z (%) = 580.3 [M+ + 1], 602.3 [M + Na]+.
HRMS: m/z calcd for [M + Na]+ C37H41NO5Na: 602.2882; found:
602.2854.
13C NMR (75 MHz, CDCl3): d = 140.7, 138.5, 138.2, 135.4, 134.3,
129.6, 128.9, 128.4, 128.3, 128.2, 128.1, 127.7, 127.6, 127.5, 127.4,
126.7, 116.8, 78.9, 73.1, 72.2, 69.5, 58.4, 52.0, 35.0.
(3S,5S,6S)-6-[Benzyl(benzyloxycarbonyl)amino]-5,7-bis(ben-
zyloxy)-3-hydroxyheptanoic Acid (24)
MS (ESI, 3.5 kV): m/z (%) = 402.2 [M + 1]+.
To a solution of compound 12a (0.5 g, 0.86 mmol) in acetone–H2O
(3:1, 5 mL) were added OsO4 (0.5 mol%) and NMO (0.30 g, 2.59
mmol) at r.t. The mixture was stirred for 6 h, and the reaction was
quenched with solid NaHSO4 (0.62 g, 5.18 mmol) and the mixture
was stirred for 15 min. Solid particles were separated by filtration,
and the filtrate was dried (Na2SO4) and concentrated. The residue
was dissolved in THF/H2O (4:1, 5 mL), and NaIO4 (0.55 g, 2.59
mmol) was added. After 30 min, the mixture was filtered, dried
(Na2SO4), and concentrated to give the crude aldehyde. To a solu-
tion of this crude aldehyde (0.43 g, 0.74 mmol) in t-BuOH (5 mL)
were added NaClO2 (0.73 g, 8.14 mmol) and 20% aq
Na2H2PO4·2H2O (5 mL) at 0 °C, and the mixture was stirred for 4 h
at r.t. The mixture was then diluted with EtOAc (5 mL) and washed
with 5 M aq NaH2PO4 (1 mL). The organic layer was dried
(Na2SO4) and concentrated, and residue was purified by flash col-
umn chromatography (silica gel) to afford compound 24 as a yel-
lowish oil; yield: 0.43 g (85%); [a]D25 –6.0 (c = 0.23, CHCl3).
HRMS (EI): m/z [M + 1]+ calcd for C27H32NO2: 402.2433; found:
402.2438.
Benzyl Benzyl[(2S,3S)-1,3-bis(benzyloxy)hex-5-en-2-yl]car-
bamate (11)
Compound 23 (1.3 g, 3.25 mmol) was dissolved in EtOH–H2O
(10:1; 10 mL) and the mixture was stirred at 0 °C. NaHCO3 (1.09 g,
13 mmol) and CbzCl (0.56, 3.9 mmol) were added, and the mixture
was stirred for 3 h at 0 °C and then diluted with H2O (20 mL). The
resulting mixture was concentrated and extracted with EtOAc (2 ×
25 mL). The combined organic layers were washed with brine (20
mL), dried (Na2SO4), and concentrated. The residue was further pu-
rified by column chromatography (EtOAc–hexane, 2:8) to give
compound 11 as yellowish oil; yield: 1.48 g (90%); [a]D25 –4.5
(c = 0.1, CHCl3).
IR (neat): 3064, 3030, 2922, 2853, 1697, 1454, 1243, 1103, 914,
736, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33–6.99 (m, 20 H), 5.96–5.65
(m, 1 H), 5.14–4.89 (m, 4 H), 4.69–4.41 (m, 4 H), 4.35–4.17 (m, 3
H), 4.12–4.05 (m, 1 H), 3.92–3.65 (m, 1 H), 3.56–3.33 (m, 1 H),
2.44–2.21 (m, 2 H).
IR (neat): 3435(br, OH), 3029, 2923, 2854, 1693, 1454, 1243, 1103,
738, 697 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.63–7.06 (m, 20 H), 5.13 (br s, 2
H), 4.79–4.04 (m, 9 H), 3.74–3.37 (m, 2 H), 2.51–2.24 (m, 2 H),
1.80–1.46 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 157.2, 138.8, 137.5, 136.2, 128.4,
128.2, 128.0, 127.8, 127.7, 127.6, 127.0, 126.8, 77.1, 73.1, 72.8,
70.1, 69.0, 67.5, 59.8, 49.9, 41.5, 37.2.
LC–MS (EI, 70 eV) (ESI, 3.5 kV): m/z (%) = 620.3 [M + Na]+.
HRMS: m/z = [M + Na]+ calcd for C36H39NO7Na: 620.2624; found:
13C NMR (75 MHz, CDCl3): d = 139.4, 137.9, 136.5, 134.3, 134.1,
128.2, 128.0, 127.7, 127.6, 127.4, 127.0, 126.5, 117.4, 78.5, 72.8,
72.5, 69.2, 67.2, 59.4, 49.7, 35.8.
MS (ESI, 3.5 kV): m/z (%) = 536.2 [M + 1]+, 558.2 [M + Na]+.
HRMS: m/z [M + Na]+ calcd for C35H37NO4Na: 558.2620; found:
620.2646.
558.2620.
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York

1392
K. Nagaiah et al.
PAPER
(–)-Galantinic Acid (5)
Tetrahedron 1999, 55, 2493. (o) Surivet, J. P.; Vatele, J. M.
Tetrahedron 1999, 55, 13011. (p) Sabitha, G.; Sudhakar, K.;
Yadav, J. S. Synthesis 2007, 385. (q) Prasad, K. R.; Gholap,
S. L. Tetrahedron Lett. 2007, 48, 4679. (r) Chen, J.; Lin,
G. Q.; Wang, Z. M.; Liu, H. Q. .
To a solution of acid 24 (0.23 g, 0.38 mmol) in MeOH (10 mL) was
added 10% Pd/C (0.01 g) under a H2 atmosphere (0.1 mPa), and the
mixture was stirred for 8 h. The mixture was then filtered and con-
centrated to give a residue that was purified on Dowex 50W×4, elut-
ing with 1 M aq NH3, to give a colorless solid; yield: 0.06 g (86%);
[a]D25 –28.2 (c = 0.5, H2O).
(4) (a) Mu, Q.; Tang, W.; Li, C.; Lu, Y.; Sun, H.; Zheng, X.; Wu,
N.; Lou, B.; Xu, B. Heterocycles 1999, 12, 2969. (b) Mu,
Q.; Li, C. M.; He, Y. N.; Sun, H. D.; Zheng, H. L.; Lu, Y.;
Zheng, Q. T.; Jiang, W. Chin. Chem. Lett. 1999, 10, 135.
(c) Chen, J.; Lin, G. Q.; Liu, H. Q. Tetrahedron Lett. 2004,
45, 8111.
IR (KBr): 3448, 2923, 2851, 1637, 1458, 1215, 759 cm–1.
1H NMR (400 MHz, D2O): d = 4.26–4.17 (m, 1 H), 3.94–3.89 (m, 1
H), 3.78 (dd, J = 4, 12 Hz, 1 H), 3.64 (dd, J = 7, 12 Hz, 1 H), 3.18
(ddd, J = 4, 7, 7 Hz, 1 H), 2.59–2.44 (m, 2 H), 1.68–1.55 (m, 2 H).
(5) Shoji, j.; Sakajaki, R.; Koizumi, K.; Mayama, M.; Matsurra,
S. J. J. Antibiot. 1975, 28, 122.
LC/MS (EI, 70 eV): m/z (%) = 194.1 [M + 1]+, 216.1 [M + Na]+.
(6) Sakai, N.; Ohfune, Y. Tetrahedron Lett. 1990, 31, 4151.
(7) Sakai, N.; Ohfune, Y. J. Am. Chem. Soc. 1992, 114, 998.
(8) Ikota, N. Heterocycles 1991, 32, 521.
HRMS: m/z [M + Na]+ calcd for C7H15NO5Na: 216.0847; found:
216.0839.
(9) Kumar, J. S. R.; Datta, A. Tetrahedron Lett. 1999, 40, 1381.
(10) Kiyooka, S.; Goh, K.; Nakamura, Y.; Takesue, H.; Hena,
M. A. Tetrahedron Lett. 2000, 41, 6599.
(11) Moreau, X.; Campagne, J. Tetrahedron Lett. 2001, 42, 4467.
(12) Raghavan, S.; Ramakrishna Reddy, S. J. Org. Chem. 2003,
68, 5754.
Acknowledgment
D.S. and K.V.P. thank CSIR, New Delhi, for the award of fel-
lowships.
(13) Bethuel, Y.; Gademann, K. Synlett 2006, 1580.
(14) Kumar, P.; Pandey, S. K.; Kandula, S. V. Tetrahedron Lett.
2004, 45, 5877.
(15) (a) Nagaiah, K.; Sreenu, D.; Srinvasa Rao, R.; Yadav, J. S.
Tetrahedron Lett. 2007, 48, 7173. (b) Praveen Kumar, S.;
Nagaiah, K. Tetrahedron Lett. 2007, 48, 1391.
(c) Praveen Kumar, S.; Nagaiah, K.; Chorgade, M. S.
Tetrahedron Lett. 2006, 40, 7149.
(16) (a) Marton, D.; Stivanello, D.; Tagliavini, G. J. Org. Chem.
1996, 61, 2731. (b) Christian, P.; Jean, L. L. J. Org. Chem.
1985, 50, 910. (c) Molas, P.; Matheu, M. I.; Castillón, S.
Tetrahedron Lett. 2004, 45, 3721. (d) Miranda, L. S. M.;
Meireles, B. A.; Costa, J. S.; Pereira, V. L. P.; Vasconcellos,
M. L. A. A. Synlett 2005, 869. (e) Paterson, I.; Anderson,
E. A.; Dalby, S. M.; Genovino, J.; Lim, J. H.; Moessner, C.
Chem. Commun. 2007, 1852. (f) Radha Krishna, P.;
Ramana Reddy, V. V.; Srinivas, R. Tetrahedron 2007, 63,
9871.
References and Notes
(1) (a) Wu, Y. C.; Duh, C. Y.; Chang, F. R.; Wang, S. K.; Chang,
J. J.; McPhail, D. T.; Lee, K. H. J. Nat. Prod. 1991, 54,
1077. (b) Sam, T. W.; Saw-Yeu, C.; Matsjeh, S.; Gan, E. K.;
Razak, D.; Mohamed, A. L. Tetrahedron Lett. 1987, 28,
2541. (c) Talapatra, S. K.; Basu, D.; Goaiwami, S.;
Talapatra, B. Indian J. Chem. Sect. B: Org. Chem. Incl. Med.
Chem. 1985, 24, 29.
(2) For reviews on the cytotoxic activity and other bioactivity of
styryl lactones see: (a) Mereyala, H. B.; Joe, M. Curr. Med.
Chem. Anti-Cancer Agents 2001, 1, 293. (b) Blázquez, M.
A.; Bermejo, A.; Zafra-Polo, M. C.; Cortes, D. Phytochem.
Anal. 1999, 10, 161. (c) Mohd Ridzuan, M. A. R.;
Ruenruetai, U.; Noor Rain, A.; Khozirah, S.; Zakiah, I. Trop.
Biomed. 2006, 23, 140.
(3) (a) Surivet, J. P.; Vatele, J. M. Tetrahedron Lett. 1998, 39,
7299. (b) Prasad, K. R.; Dhaware, M. G. Synlett. 2007,
1112. (c) Mukai, C.; Hirai, S.; Hanaoka, M. J. Org. Chem.
1997, 62, 6619. (d) Dixon, D. J.; Ley, S. V.; Tate, E. W.
J. Chem. Soc., Perkin Trans. 1 1998, 3125. (e) Tate, E. W.;
Dixon, D. J.; Ley, S. V. Org. Biomol. Chem. 2006, 4, 1698.
(f) Banwell, M. G.; Coster, M. J.; Edwards, A. J.;
(17) (a) Yong, X.; Glenn, D. P. J. Org. Chem. 2002, 67, 7158.
(b) Jackson, D. Y. Synth. Commun. 1988, 18, 337.
(c) Janusz, J.; Stanislaw, P.; Tomasz, B. Tetrahedron 1986,
42, 447.
(18) Rodriguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J. J.
Tetrahedron Lett. 1999, 40, 5161.
Karunaratne, O. P.; Smith, J. A.; Welling, L. L.; Willis,
A. C. Aust. J. Chem. 2003, 56, 585. (g) Banwell, M. G.;
Coster, M. J.; Karunaratne, O. P.; Smith, J. A. J. Chem. Soc.,
Perkin Trans. 1 2002, 1622. (h) Ramachandran, P. V.;
Chandra, J. S.; Reddy, M. V. R. J. Org. Chem. 2002, 67,
7547. (i) Viroleaud, M. A.; Bressy, C.; Piva, O. Tetrahedron
Lett. 2003, 44, 8081. (j) Nakashima, K.; Kikuchi, N.;
Shirayama, D.; Miki, T.; Ando, K.; Sono, M.; Suziki, S.;
Kawase, M.; Kondoh, M.; Sato, M.; Tori, M. Bull. Chem.
Soc. Jpn. 2007, 80, 387. (k) Prasad, K. R.; Dhaware, M. G.
Synlett 2007, 1112. (l) Yamshita, Y.; Saito, S.; Kobayashi,
S. J. Am. Chem. Soc. 2003, 125, 3793. (m) Chen, J.; Lin,
G.-Q.; Wang, Z.-M.; Liu, H.-Q. Synlett 2002, 1265.
(n) Tsubaki, M.; Kanai, K.; Nagase, H.; Honda, T.
(19) Rama Rao, A. V.; Mysorekar, S. V.; Gurjar, M. K.; Yadav,
J. S. Tetrahedron Lett. 1987, 28, 2183.
(20) Quinn, K. J.; Smith, A. G.; Cammrano, C. M. Tetrahedron
2007, 63, 4881.
(21) Prashad, M.; Kim, H. Y.; Lu, Y.; Liu, Y.; Har, D.; Repic, O.;
Blacklock, T. J.; Giannousis, P. J. Org. Chem. 1999, 64,
1750.
(22) For the use of magnesium bromide diethyl etherate in the
allylstannane reaction, see: (a) Lee, E.; Jeong, E. J.; Kang,
E. J.; Sung, L. T.; Hong, S. K. J. Am. Chem. Soc. 2001, 123,
10131. (b) Keck, G. E.; Abbott, D. E. Tetrahedron Lett.
1984, 25, 1883.
Synthesis 2009, No. 8, 1386–1392 © Thieme Stuttgart · New York