First stereoselective total synthesis of cryptomoscatone D2 and syntheses of (5 R,7 S)-kurzilactone and (+)-cryptofolione by an asymmetric acetate aldol approach

Article abstract of DOI:10.1055/s-0031-1290771

An efficient concise stereoselective total synthesis of cryptomoscatone D2 and syntheses of (5R,7S)-kurzilactone and (+)-cryptofolione, based on an asymmetric acetate aldol reaction starting from trans-cinnamaldehyde, are described. The other key reaction

Full text of DOI:10.1055/s-0031-1290771

PAPER
▌1365
paper
First Stereoselective Total Synthesis of Cryptomoscatone D2 and Syntheses of
(5R,7S)-Kurzilactone and (+)-Cryptofolione by an Asymmetric Acetate Aldol
Approach
Jhillu Singh Yadav,* Bogonda Ganganna, Dinesh Chandra Bhunia
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160387; E-mail: yadavpub@iict.res.in
Received: 29.12.2011; Accepted after revision: 22.02.2012
O
O
Abstract: An efficient concise stereoselective total synthesis of
cryptomoscatone D2 and syntheses of (5R,7S)-kurzilactone and
(+)-cryptofolione, based on an asymmetric acetate aldol reaction
starting from trans-cinnamaldehyde, are described. The other key
reactions are a Horner–Wadsworth–Emmons reaction, a Brown’s
asymmetric allylation and a ring-closing metathesis.
OH OH
O
OH OH
O
cryptomoscatone D2 (1)
(Z)-cryptomoscatone D2 (2)
O
Key words: lactones, stereoselective synthesis, total synthesis, al-
dol reactions, cyclizations
O
OH
O
Naturally occurring 6-(ω-arylalkenyl)-5,6-dihydro-α-py-
rones and styrylpyrones have been isolated from Crypto-
carya species (Figure 1).1–3 Many of these α-pyrones
exhibit important biological properties, such as anti-
inflammatory action,4 antiproliferative activity,5 and inhi-
bition of the growth of breast-cancer cell lines.6 Crypto-
moscatone D2, isolated from the stem bark of
Cryptocarya moschata (Lauraceae)2 and C. mandiocanna,7
is a highly potent inhibitor of the G2 check point. These
inhibitors enhance killing of cancer cells by ionization ra-
diation and DNA-damaging chemotherapeutic agents,
particularly in cells lacking a p53 function.8 Cryptomo-
scatone D2 has also been found to display high dose- and
time-dependent antiproliferative activity against several
human cervical carcinoma cell lines (HeLa, SiHa, C33A,
and MRC-5).7 (5R,7S)-Kurzilactone, isolated from the
ethyl acetate extract of the leaves of C. kurzii, displays
significant cytotoxicity against KB cell lines, with an IC50
value of 1 μg·mL–1,9 whereas cryptofolione, isolated from
various Cryptocarya species,1–3 exhibits remarkable ac-
tivity against trypomastigotes of Trypanosoma cruzi, re-
ducing their number by 77% at 250 μg·mL–1.10
(+)-(5R,7S)-kurzilactone (3)
O
OH OH
O
O
(+)-cryptofolione (4)
OH OH
O
(Z)-(+)-cryptofolione (5)
O
O
OAc
O
OAc
O
(+)-(6R,2S)-cryptocaryalactone (6)
(–)-(6S,2S)-epi-cryptocaryalactone (7)
Figure 1 Natural products containing styrylpyrones
Our retrosynthetic analysis is shown in Scheme 1. We en-
visaged that (+)-cryptofolione, (5R,7S)-kurzilactone, and
cryptomoscatone D2 might be prepared from the common
intermediate 9. (5R,7S)-Kurzilactone and cryptomosca-
tone D2 could be prepared from lactone 8, which, in turn,
would be derived from the common intermediate 9 by
Brown’s asymmetric allylation followed by acryloylation
and ring-closing metathesis. (+)-Cryptofolione could be
obtained from 9 by sequential Horner–Wadsworth–
Emmons reaction, Brown’s asymmetric allylation, acry-
loylation and ring-closing metathesis. The two stereocen-
ters in compound 10 could be obtained from a double
asymmetric acetate aldol reaction starting from commer-
cially available trans-cinnamaldehyde (12) and (4S)-3-
acetyl-4-benzyl-1,3-thiazolidine-2-thione (13).
The activities of this class of molecules therefore make
them attractive synthetic targets. Whereas there are four
reports on syntheses of (+)-cryptofolione11 and three re-
ports on syntheses of (5R,7S)-kurzilactone,12 there are
none on syntheses of cryptomoscatone D2. In a continua-
tion of our efforts in the total syntheses of biologically ac-
tive lactone-containing natural products,13 we report here
a concise approach to the syntheses of cryptomoscatone
D2, (5R,7S)-kurzilactone and (+)-cryptofolione, which
contain a 1,3-polyol functionality.
SYNTHESIS 2012, 44, 1365–1372
Advanced online publication: 05.04.2012
DOI: 10.1055/s-0031-1290771; Art ID: SS-2011-Z1191-OP
© Georg Thieme Verlag Stuttgart · New York
Our synthesis began with the diastereoselective asymmet-
ric acetate aldol reaction between trans-cinnamaldehyde
(12) and thione 13 in the presence of titanium(IV) chlo-
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1366
J. S. Yadav et al.
PAPER
O
O
OH OH
O
O
OH
O
(+)-cryptofolione (4)
(5R,7S)-kurzilactone (3)
O
TBSO
OTBS
OH
OH OH
O
20
cryptomoscatone D2 (1)
O
TBSO
OTBS
O
TBSO
OTBS O
Me
N
OMe
19
8
TBSO
OTBS O
H
9
TBSO
OH
O
S
N
S
10
Ph
O
O
S
H
N
S
+
12
Ph
13
Scheme 1 Retrosynthetic analysis
ride and ethyl(diisopropyl)amine to introduce the first ste- [(+)-Ipc2B(allyl)] to give the required homoallylic alcohol
reogenic center, yielding 11 as the major diastereomer in 17 in 90% yield as a single diastereomer (Scheme 3).16
a 9:1 ratio (Scheme 2). The secondary hydroxy group was The protected homoallylic alcohol 17 was treated with ac-
protected as the corresponding silyl ether 14 by treatment ryloyl chloride and triethylamine at 0 °C to give acrylate
with tert-butyl(dimethyl)silyl triflate and 2,6-lutidine in 18 in 83% yield. Ring-closing metathesis of 18 with
84% yield.
Grubbs’ first-generation catalyst17 gave lactone 8 in 87%
yield. Finally, treatment of lactone 8 with 4 M hydrochlo-
ric acid in tetrahydrofuran at room temperature gave cryp-
tomoscatone D2 in 91% yield.
The chiral auxiliary 14 was reduced with DIBAL-H in an-
hydrous dichloromethane to afford an aldehyde that, with-
out purification, was subjected to a further aldol reaction
with
(4R)-3-acetyl-4-benzyl-1,3-thiazolidine-2-thione With enough material in hand, we extended our work with
(15), following an earlier procedure,14 to give the easily cryptomoscatone D2 to the preparation of (5R,7S)-kurzi-
separable diastereomers 10 and 10a (dr 9:1) in 85% over- lactone (3; Scheme 3). Allylic oxidation of cryptomosca-
all yield for the two steps.
tone D2 with manganese dioxide in dichloromethane gave
(5R,7S)-kurzilactone (3) in 89% yield.
The free hydroxy group was masked by reaction with tert-
butyl(dimethyl)silyl triflate and 2,6-lutidine to give the The key intermediate 9 was also used in a synthesis of (+)-
protected disilyl ether 16, which was reduced with cryptofolione (Scheme 4). Horner–Wadsworth–Emmons
DIBAL-H to give the aldehyde 9 in 96% yield (Scheme reaction18 of compound 9 with diethyl {2-[methoxy(meth-
2).
yl)amino]-2-oxoethyl}phosphonate (21)19 gave the α,β-
unsaturated Weinreb amide 19 exclusively as the E-iso-
mer. Reduction of amide 19 with DIBAL-H in tetrahydro-
The aldehyde 9 was subjected to Brown’s asymmetric
allylation15 with (+)-allylbis(isopinocampheyl)borane
Synthesis 2012, 44, 1365–1372
© Georg Thieme Verlag Stuttgart · New York

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Cryptomoscatone D2, (5R,7S)-Kurzilactone, and (+)-Cryptofolione
1367
OH
O
OH
O
S
S
S
O
S
O
N
TiCl4, DIPEA, CH2Cl2
0 °C to –78 °C, 10 min
N
S
H
S
+
+
N
11
syn (88%)
11a
anti (9%)
12
Ph
dr 9:1
Ph
Ph
13
TBSO
OH
O
S
O
TBSO
S
i) DIBAL-H, CH2Cl2
TBSOTf
2,6-lutidine
–78 °C, 5 min
N
anti-10a
(8%)
N
S
+
S
CH2Cl2, 0 °C to r.t.
5 min, 84%
ii) 15, TiCl4, DIPEA
CH2Cl2, 0 °C to –78 °C
10 min, 85%
Ph
(overall for 2 steps)
Ph
14
10
syn (77%)
dr 9:1
TBSO
OTBS O
TBSO
OTBS O
S
DIBAL-H, CH2Cl2
–78 °C, 5 min, 96%
TBSOTf, 2,6-lutidine
H
N
S
CH2Cl2, 0 °C to r.t.
5 min, 88%
9
Ph
16
S
O
S
N
Ph
15
Scheme 2 Synthesis of key intermediate 9
furan at –78 °C gave the corresponding aldehyde, which overall yields of 28.4%, 25.3%, and 15.3%. Biological
was then subjected to Brown’s asymmetric allylation15 studies on the products and further studies to improve the
with (+)-Ipc2B(allyl) to give corresponding homoallylic efficiency of the syntheses are currently underway.
alcohol 20 in 86% as a single diastereomer.16 Alcohol 20
was treated with acryloyl chloride, triethylamine, and a
Air- and/or moisture-sensitive reactions were carried out in anhyd
catalytic amount of 4-(N,N-dimethylamino)pyridine to
give the acrylate 22 in 81% yield. The compound 22, with
two terminal double bonds, was subjected to ring-closing
metathesis in the presence of Grubbs’ first-generation
catalyst17 to give the lactone 23 in 80% yield. The two si-
lyl groups in lactone 23 were cleaved with 4 M hydrochlo-
ric acid in tetrahydrofuran to provide (+)-cryptofolione
(4) in 83% yield. The target compounds cryptomoscatone
D2, (5R,7S)-kurzilactone, and (+)-cryptofolione were
characterized by means of spectroscopic analysis and by
comparison with the data from the literature, and were
found to be identical in all respects.2,11,12
solvents under argon in oven- or flame-dried glassware. All anhyd
solvents were distilled before to use. THF, toluene, and Et2O were
distilled from Na and benzophenone, and CH2Cl2 and DMSO were
distilled from CaH2. Commercial reagents were used without puri-
fication. Column chromatography was carried out on ACME silica
gel (60–120 mesh). Specific optical rotations [α]D were determined
by using a Jasco DIP-360 digital polarimeter and are given in 10–1
deg·cm2·g–1. IR spectra were recorded on a Perkin-Elmer 683 spec-
trometer using neat products or solutions in CHCl3. 1H NMR were
recorded on a Bruker 300 or Varian Unity 500 spectrometer, and 13
C
NMR spectra were recorded on a Bruker 300 spectrometer. Chemi-
cal shifts are reported in ppm downfield from TMS. Melting points
were determined by using a Barnstead electrothermal melting point
apparatus.
In conclusion, an efficient strategy for the enantioselec-
tive synthesis of anti-1,3-polyols was used in the synthe-
ses of several natural products. Total syntheses of A dry round-bottomed flask was charged under argon with a soln of
cryptomoscatone D2, (5R,7S)-kurzilactone, and (+)-cryp-
tofolione were accomplished by a concise synthetic ap-
proach involving three key steps: an asymmetric acetate
aldol reaction, a Brown’s asymmetric allylation and a
(4S)-4-Benzyl-3-[(3R,4E)-3-hydroxy-5-phenylpent-4-enoyl]-
1,3-thiazolidine-2-thione (11)
thiazolidinethione 13 (2 g, 7.96 mmol) in CH2Cl2 (30 mL). The soln
was cooled to 0 °C and TiCl4 (1.05 mL, 9.56 mmol) was added
dropwise. The thick yellow suspension was stirred for 10 min be-
fore i-Pr2NEt (1.63 mL, 9.56 mmol) was added dropwise at 0 °C.
The soln was stirred for 10 min at 0 °C, cooled to −78 °C, and a soln
ring-closing metathesis. The α-pyrones cryptomoscatone
D2, (5R,7S)-kurzilactone and (+)-cryptofolione were ob-
tained in ten, eleven and twelve steps, respectively, in
of freshly distilled aldehyde 12 (1.05 g, 7.96 mmol) in CH2Cl2 (8
mL) was added. The mixture was stirred for 10 min and then the re-
action was quenched with sat. aq NH4Cl. The mixture was warmed
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1365–1372

1368
J. S. Yadav et al.
PAPER
TBSO
OTBS
O
TBSO
TBSO
OTBS OH
Me
N
(+)-(Ipc)2BCH2CH=CH2
Et2O, –100 °C, 1 h, 90%
21, DBU, LiCl
9
9
O
MeCN–CH2Cl2 (3:1)
r.t., 3 h, 81 %
Me
17
19
TBSO
O
OTBS
OTBS
OTBS
OH
OTBS
O
i) DIBAL-H, THF
–78 °C, 5 min
Et3N, acryloyl chloride
CH2Cl2, 0 °C, 30 min, 83%
ii) (+)-(Ipc)2BCH2CH=CH2
Et2O, –100 °C, 1 h, 86%
(overall for 2 steps)
18
20
22
O
O
TBSO
O
TBSO
OTBS O
Et3N, acryloyl chloride
PhCH=RuCl2(PCy3)2
DMAP, CH2Cl2, 0 °C
30 min, 81%
CH2Cl2, reflux, 4 h, 87%
8
O
O
TBSO
O
OH OH
O
MnO2, CH2Cl2
4 M HCl, THF
r.t., 2 h, 91%
PhCH=RuCl2(PCy3)2
r.t., 30 min, 89%
CH2Cl2, reflux, 4 h, 80%
23
cryptomoscatone D2 (1)
O
O
O
OH OH
O
OH
O
4 M HCl, THF
r.t., 2 h, 83%
(+)-cryptofolione (4)
(5R,7S)-kurzilactone (3)
O
O
Scheme 3 Syntheses of cryptomoscatone D2 and (5R,7S)-kurzilac-
tone
P
O
EtO
N
Me
OEt
Me
21
to r.t. and the layers were separated. The aqueous layer was extract-
ed with CH2Cl2 (2 × 30 mL) and the combined organic layer was
dried (Na2SO4), filtered, and concentrated under reduced pressure.
The crude product was purified by flash column chromatography
(silica gel, 2–5% EtOAc–hexane) to provide the product 11 as a yel-
low liquid; yield: 2.7 g (88%); Rf = 0.4 (20% EtOAc–hexane); [α]D
+127.4 (c 1.34, CHCl3). Compound 11a was also obtained; yield:
2.7 g (88%).
Scheme 4 Synthesis of (+)-cryptofolione (4)
29
tography (silica gel, 2% EtOAc–hexane) to give a yellow solid;
yield: 2.2 g (84%); mp 76–78 °C; Rf = 0.8 (10% EtOAc–hexane);
[α]D29 +167.5 (c 1.28, CHCl3).
IR (neat): 3453, 2953, 2929, 2855, 1697, 1255, 1161, 834 cm–1.
IR (neat): 3391, 3026, 1688, 1344, 1162, 749, 698 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.14–7.37 (m, 10 H), 6.65 (d, J =
15.4 Hz, 1 H), 6.24 (dd, J = 5.8, 15.4 Hz, 1 H), 5.36 (m, 1 H), 4.83
(br m, 1 H), 3.69 (dd, J = 2.9, 17.3 Hz, 1 H), 3.34–3.44 (m, 2 H),
3.24 (dd, J = 3.8, 12.5 Hz, 1 H), 3.04 (dd, J = 1.9, 10.6 Hz, 1 H),
2.88 (d, J = 11.5, 1 H).
1H NMR (300 MHz, CDCl3): δ = 7.16–7.38 (m, 10 H), 6.56 (d, J =
15.8 Hz, 1 H), 6.21 (dd, J = 6.8, 15.8 Hz, 1 H), 5.21 (m, 1 H), 4.86–
4.97 (m, 1 H), 3.69–3.80 (m, 1 H), 3.16–3.36 (m, 3 H), 3.02 (dd, J =
2.3, 10.6 Hz, 1 H), 2.86 (d, J = 11.3 Hz, 1 H), 0.89 (s, 9 H), 0.11 (s,
3 H), 0.08 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 201.3, 172.4, 136.4, 136.3, 130.6,
129.8, 129.4, 129.0, 128.5, 127.8, 127.3, 126.5, 68.6, 68.3, 45.7,
36.8, 32.1.
13C NMR (75 MHz, CDCl3): δ = 201.1, 171.3, 136.5, 131.7, 129.8,
129.3, 128.8, 128.5, 127.5, 127.1, 126.4, 70.5, 68.6, 46.7, 36.5,
32.1, 25.7 (3 × C), 18.0, –4.2, –4.9.
MS (ESI): m/z = 520 [M + Na]+.
MS (ESI): m/z = 406 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H21NNaO2S2: 406.0911;
HRMS (ESI): m/z [M + Na]+ calcd for C27H35NNaO2S2Si:
520.1776; found: 520.1779.
found: 406.0906.
(4R)-4-Benzyl-3-[(3R,5R,6E)-5-{[tert-butyl(dimethyl)silyl]oxy}-
3-hydroxy-7-phenylhept-6-enoyl]-1,3-thiazolidine-2-thione (10)
A 25 wt% soln of DIBAL-H in toluene (10 mL) was added slowly
over 10 min to a stirred soln of compound 14 (3.54 g, 7.11 mmol)
in anhyd CH2Cl2 (50 mL) at –78 °C and the mixture was stirred at
–78 °C for 10 min. When the reaction was complete, sat. aq sodium
potassium tartrate soln (10 mL) was added and the mixture was
stirred vigorously at r.t. for an additional 1 h then extracted with
CH2Cl2 (3 × 30 mL). The combined organic layer was washed with
brine (30 mL), dried (Na2SO4), and concentrated under reduced
(4S)-4-Benzyl-3-[(3R,4E)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-
phenylpent-4-enoyl]-1,3-thiazolidine-2-thione (14)
2,6-Lutidine (0.79 mL, 6.78 mmol) was added to a soln of alcohol
11 (2 g, 5.22 mmol) in anhyd CH2Cl2 (25 mL) and the mixture was
stirred at 0 °C under N2. After 5 min, TBSOTf (1.4 mL, 6.26 mmol)
was added dropwise and the mixture was stirred at 0 °C for 10 min.
When the starting material was completely consumed, the reaction
was quenched by addition of H2O (10 mL) and the mixture was ex-
tracted with CH2Cl2 (2 × 30 mL). The organic extract was washed
with brine (20 mL), dried (Na2SO4), filtered, and concentrated un-
der reduced pressure. The residue was purified by column chroma-
Synthesis 2012, 44, 1365–1372
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PAPER
Cryptomoscatone D2, (5R,7S)-Kurzilactone, and (+)-Cryptofolione
1369
pressure to give a crude aldehyde, which was used in the aldol reac-
tion without further purification; Rf = 0.7 (10% EtOAc–hexane).
(3R,5R,6E)-3,5-Bis{[tert-butyl(dimethyl)silyl]oxy}-7-phenyl-
hept-6-enal (9)
A 25% soln of DIBAL-H in toluene (2.7 mL) was slowly added
over 5 min to a stirred soln of compound 16 (1.25 g, 1.90 mmol) in
anhyd CH2Cl2 (15 mL) at –78 °C, and the mixture was stirred at
–78 °C for 10 min. When the reaction was complete, sat. aq sodium
potassium tartrate soln (10 mL) was added and the mixture was
stirred vigorously at r.t. for additional 1 h. The mixture was then ex-
tracted with CH2Cl2 (3 × 15 mL) and the combined organic layers
were washed with brine (20 mL), dried (Na2SO4), and concentrated
under reduced pressure. The crude product was purified by flash
column chromatography (silica gel, 3% EtOAc–hexane) to give a
clear liquid; yield: 0.82 g (96%); Rf = 0.7 (10% EtOAc–hexane);
[α]D29 +24.3 (c 1.08, CHCl3).
A dry round-bottomed flask was charged with a soln of thione 15
(1.7 g, 6.77 mmol) in CH2Cl2 (25 mL) under argon. The soln was
cooled to 0 °C and TiCl4 (0.89 mL, 8.12 mmol) was added drop-
wise. The thick yellow suspension was stirred for 10 min before i-
Pr2NEt (1.39 mL, 8.12 mmol) was added dropwise at 0 °C. The soln
was stirred for 10 min at 0 °C then cooled to −78 °C. To the reaction
mass was added a soln of the freshly prepared aldehyde (6.09 mmol)
in CH2Cl2 (8 mL). The mixture was stirred for 15 min and then the
reaction was quenched with sat. aq NH4Cl and the mixture was
warmed to r.t. The layers were separated and the aqueous layer was
extracted with CH2Cl2 (3 × 30 mL). The combined organic layers
were dried (Na2SO4), filtered, and concentrated under reduced pres-
sure. The crude product was purified by flash column chromatogra-
phy (silica gel, 2–5% EtOAc–hexane) to give product 10; yield:
IR (neat): 2954, 2931, 2857, 1726, 1254, 1082, 835, 776 cm–1.
1H NMR (300 MHz, CDCl3): δ = 9.77 (t, J = 2.3 Hz, 1 H), 7.16–7.35
(m, 5 H), 6.43 (d, J = 15.8 Hz, 1 H), 6.09 (dd, J = 7.5, 15.8 Hz, 1 H),
4.29–4.41 (m, 2 H), 2.48–2.66 (m, 2 H), 1.74–1.90 (m, 2 H), 0.90
(s, 9 H), 0.88 (s, 9 H), 0.10 (s, 3 H), 0.07 (s, 3 H), 0.06 (s, 3 H), 0.04
(s, 3 H).
29
2.97 g (77%; two steps); Rf = 0.5 (20% EtOAc–hexane); [α]D
–62.4 (c 0.64, CHCl3). The diastereoisomer 10a was also obtained;
yield: 0.32 g (8%; two steps).
IR (neat): 3486, 2953, 2930, 2856, 1689, 1258, 1161, 835, 751 cm–1.
13C NMR (75 MHz, CDCl3): δ = 202.0, 136.6, 132.7, 129.9, 128.6,
127.6, 126.4, 71.2, 65.7, 51.5, 46.7, 26.0 (3 × C), 25.7 (3 × C), 18.1,
18.0, –3.7, –4.3, –4.4, –4.6.
MS (ESI): m/z = 471 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C25H44NaO3Si2: 471.2726;
1H NMR (300 MHz, CDCl3): δ = 7.14–7.40 (m, 10 H), 6.54 (d, J =
15.8 Hz, 1 H), 6.20 (dd, J = 6.4, 16.0 Hz, 1 H), 5.35 (m, 1 H), 4.60–
4.70 (m, 1 H), 4.38–4.51 (m, 1 H), 3.32–3.51 (m, 2 H), 3.16–3.30
(m, 2 H), 3.03 (dd, J = 2.3, 10.8 Hz, 1 H), 2.87 (d, J = 11.3 Hz, 1 H),
1.67–1.87 (m, 2 H), 0.94 (s, 9 H), 0.14 (s, 3 H), 0.08 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 201.2, 172.3, 136.6, 136.4, 131.7,
129.7, 129.3, 128.8, 128.5, 127.5, 127.1, 126.4, 71.6, 68.4, 64.8,
46.3, 43.4, 36.6, 32.1, 25.8 (3 × C), 18.1, –4.4, –5.0.
found: 471.2717.
(4R,6S,8R,9E)-6,8-Bis{[tert-butyl(dimethyl)silyl]oxy}-10-
phenyldeca-1,9-dien-4-ol (17)
MS (ESI) m/z = 564 [M + Na]+.
A mixture of a 1.0 M soln of (+)-Ipc2B(allyl) in pentane (1 mL, 1.00
mmol) and anhyd Et2O (5 mL) was cooled to –100 °C and then a
soln of the aldehyde 9 (0.410 g, 0.915 mmol) in Et2O (10 mL) was
slowly added. The mixture was stirred at –100 °C for 1 h then
warmed to 0 °C. The reaction was then quenched by dropwise addi-
tion of 30% aq H2O2 (1 mL) and 1 M aq NaOH (1 mL). The mixture
was extracted with EtOAc (10 mL) and the layers were separated.
The aqueous layer was extracted with EtOAc (3 × 10 mL) and the
combined organic layers were washed with brine (2 × 4 mL), dried
(Na2SO4), filtered, and concentrated. The crude reaction mixture
was further purified by column chromatography (silica gel, 2%
EtOAc–hexane) to give a clear liquid: yield: 0.405 g (90%); Rf = 0.4
(5% EtOAc–hexane); [α]D30 +5.3 (c 1.5, CHCl3).
HRMS (ESI): m/z [M + Na]+ calcd for C29H39NNaO3S2Si:
564.2038; found: 564.2034.
(4R)-4-Benzyl-3-[(3S,5R,6E)-3,5-bis{[tert-butyl(dimethyl)si-
lyl]oxy}-7-phenylhept-6-enoyl]-1,3-thiazolidine-2-thione (16)
2,6-Lutidine (0.4 mL, 3.47 mmol) was added to a soln of alcohol 10
(1.45 g, 2.67 mmol) in anhyd CH2Cl2 (20 mL) and the mixture was
stirred at 0 °C under N2. After 15 min, TBSOTf (0.73 mL, 3.21
mmol) was added dropwise and the mixture was stirred at 0 °C for
10 min. When the starting material was completely consumed, the
reaction was quenched with H2O (8 mL) and the mixture was ex-
tracted with CH2Cl2 (2 × 20 mL). The organic extract was washed
with brine (20 mL), dried (Na2SO4), filtered, and concentrated un-
der reduced pressure. The residue was purified by column chroma-
tography (silica gel, 2% EtOAc–hexane) to give a yellow solid;
yield: 1.54 g (88%); mp 75–77 °C; Rf = 0.8 (10% EtOAc–hexane);
[α]D30 –76.4 (c 1.07, CHCl3).
IR (neat): 3453, 2953, 2931, 2857, 1070, 834, 773 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.17–7.33 (m, 5 H), 6.41 (d, J =
16.0 Hz, 1 H), 6.08 (dd, J = 7.0, 16.0 Hz, 1 H), 5.73–5.83 (m, 1 H),
5.01–5.09 (m, 2 H), 4.24–4.31 (m, 1 H), 4.07–4.14 (m, 1 H), 3.90–
3.98 (m, 1 H), 2.95 (br s, 1 H, OH), 2.10–2.24 (m, 2 H), 1.89–1.97
(m, 1 H), 1.77–1.85 (m, 1 H), 1.57–1.70 (m, 2 H), 0.90 (m, 9 H),
0.89 (s, 9 H), 0.09 (s, 3 H), 0.08(s, 3 H), 0.07 (s, 3 H), 0.04 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 136.6, 135.0, 132.6, 129.9, 128.5,
127.6, 126.3, 117.3, 71.4, 69.0, 67.9, 45.0, 42.2, 41.3, 26.0 (3 × C),
25.8 (3 × C), 18.2, 17.9, –3.8, –4.5, –4.6, –4.6.
IR (neat): 2955, 2928, 2854, 1703, 1364, 1255, 1157, 1070, 834
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.16–7.37 (m, 10 H), 6.46 (d, J =
15.8 Hz, 1 H), 6.13 (dd, J = 6.8, 15.8 Hz, 1 H), 5.22 (m, 1 H), 4.36–
4.52 (m, 2 H), 3.59 (dd, J = 7.5, 16.6 Hz, 1 H), 3.17–3.35 (m, 3 H),
2.87 (dd, J = 1.5, 11.3 Hz, 1 H), 2.84 (d, J = 12.1 Hz, 1 H), 1.73–
1.93 (m, 2 H), 0.91 (s, 9 H), 0.86 (s, 9 H), 0.12 (s, 3 H), 0.10 (s, 3
H), 0.06 (s, 3 H), 0.05 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 201.0, 171.8, 136.8, 136.6, 133.0,
129.6, 129.4, 128.8, 128.5, 127.4, 127.1, 126.4, 71.2, 68.6, 66.8,
46.8, 46.7, 36.4, 32.0, 26.0 (3 × C), 25.8 (3 × C), 18.2, 18.1, –3.8,
–4.2, –4.3, –4.5.
MS (ESI): m/z = 513 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C28H50NaO3Si2: 513.3196;
found: 513.3178.
(1R,3S,5R,6E)-1-Allyl-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-7-
phenylhept-6-en-1-yl Acrylate (18)
Acryloyl chloride (0.08 mL, 1.01 mmol) was added dropwise under
N2 to a soln of alcohol 17 (0.33 g, 0.678 mmol) and Et3N (0.14 mL,
1.01 mmol) in CH2Cl2 (5 mL), and the mixture was stirred at 0 °C
for 30 min. When the reaction was complete, the mixture was
poured into brine (3 mL) and extracted with CH2Cl2 (2 × 5 mL). The
organic phase was washed with brine (2 × 5 mL), dried (Na2SO4),
and concentrated. The crude product was purified by column chro-
matography (silica gel, 2% EtOAc–hexane) to give a colorless oil;
MS (ESI): m/z = 679 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C35H53NNaO3S2Si2:
678.2903; found: 678.2891.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1365–1372

1370
J. S. Yadav et al.
PAPER
yield: 307 mg (83%); Rf = 0.8 (5% EtOAc–hexane); [α]D30 +5.93 (c
3.7, CHCl3).
(6R)-6-[(2S,5E)-2-Hydroxy-4-oxo-6-phenylhex-5-en-1-yl]-5,6-
dihydro-2H-pyran-2-one (3) [(5R,7S)-Kurzilactone]
MnO2 (0.187 g, 2.15 mmol) was added to a stirred soln of crypto-
moscatone D2 (1; 31 mg, 0.107 mmol) in CH2Cl2 (5 mL) at 25 °C,
and the mixture was stirred at 25 °C for 1 h. The mixture was then
filtered through a pad of Celite and concentrated under reduced
pressure. The residue was purified by column chromatography (sil-
ica gel, 60% EtOAc–hexane) to give a white solid; yield: 26 mg
(89%); mp 76–78 °C; Rf = 0.5 (EtOAc); [α]D26 +81 (c 0.3, CHCl3)
{Lit.12a [α]D20 +84 (c 0.231, CHCl3)}.
IR (neat): 2954, 2930, 2856, 1725, 1255, 1192, 1074, 835, 774 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.20–7.43 (m, 5 H), 6.27–6.49 (m,
2 H), 5.95–6.17 (m, 2 H), 5.67–5.81 (m, 2 H), 5.01–5.14 (m, 3 H),
4.33 (q, J = 6.8, 13.6 Hz, 1 H), 3.80–3.91 (m, 1 H), 2.37 (t, J = 6.8
Hz, 2 H), 1.62–1.93 (m, 4 H), 0.90 (s, 9 H), 0.88 (s, 9 H), 0.08 (s, 3
H), 0.05 (s, 3 H), 0.04 (s, 3 H), 0.02 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 165.6, 136.8, 133.3, 133.0, 130.3,
129.6, 128.7, 128.5, 127.5, 126.3, 118.0, 71.5, 71.1, 66.5, 47.1,
41.8, 38.8, 26.0 (3 C’s), 25.9 (3 C’s), 18.2, 18.0, –3.8, –4.0, –4.5,
–4.6.
IR (neat): 3450, 2923, 1710, 1641, 765 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.50–7.61 (m, 3 H), 7.35–7.43 (m,
3 H), 6.82–6.91 (m, 1 H), 6.70 (d, J = 16.0 Hz, 1 H), 6.01 (dd, J =
2, 10.0 Hz, 1 H), 4.68–4.80 (m, 1 H), 4.38–4.49 (m, 1 H), 3.52 (br
s, 1 H, OH), 2.94 (dd, J = 2.8, 17.4 Hz, 1 H), 2.75 (dd, J = 8.8, 17.4
Hz, 1 H), 2.28–2.50 (m, 2 H), 1.74–1.94 (m, 2 H).
MS (ESI): m/z = 567 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C31H52NaO4Si2: 567.3301;
found: 567.3304.
13C NMR (75 MHz, CDCl3): δ = 200.4, 164.2, 145.2, 144.0, 134.0,
(6R)-6-[(2S,4R,5E)-2,4-Bis{[tert-butyl(dimethyl)silyl]oxy}-6-
phenylhex-5-en-1-yl]-5,6-dihydro-2H-pyran-2-one (8)
A soln of Grubbs’ first-generation catalyst G-I (0.022 g, 0.027
mmol, 10 mol%) in CH2Cl2 (20 mL) was added dropwise to a soln
of 18 (0.15 g, 0.275 mmol) in CH2Cl2 (30 mL) at r.t. The soln was
degassed with argon for 10 min and then refluxed with stirring for
3 h. The solvent was evaporated and the crude product was purified
by column chromatography (silica gel, 8% EtOAc–hexane) to give
a clear liquid; yield: 124 mg (87%); Rf = 0.2 (10% EtOAc–hexane);
[α]D30 +17.4 (c 0.51, CHCl3).
130.8, 129.0, 128.4, 126.1, 121.3, 75.0, 64.0, 46.8, 41.6, 30.0.
MS (ESI): m/z = 309 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H18NaO4: 309.1102;
found: 309.1092.
(2E,5S,7R,8E)-5,7-Bis{[tert-butyl(dimethyl)silyl]oxy}-N-meth-
oxy-N-methyl-9-phenylnona-2,8-dienamide (19)
LiCl (0.117 g, 2.76 mmol) and DBU (0.41 mL, 2.76 mmol) were
added to a soln of 21 (0.66 g, 2.76 mmol) in anhyd MeCN (10 mL)
at r.t. The mixture was stirred for 20 min and then a soln of freshly
prepared aldehyde 9 (0.826 g, 1.84 mmol) in CH2Cl2 (3 mL) was
added dropwise. The mixture was stirred for 1 h and then the reac-
tion was quenched by addition of sat. aq NH4Cl. The mixture was
diluted with CH2Cl2 (10 mL), the layers were separated, and the
aqueous layer was extracted with CH2Cl2 (2 × 10 mL). The com-
bined organic layers were washed with brine, dried (Na2SO4), and
concentrated in vacuo to give a crude product that was purified by
column chromatography (silica gel, 8% EtOAc–hexane) to give a
colorless liquid; yield: 0.645 g (81%); Rf = 0.2 (10% EtOAc–
hexane); [α]D29 +23.4 (c 2.5, CHCl3).
IR (neat): 2952, 2857, 1729, 1251, 1068, 831, 772 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.16–7.34 (m, 5 H), 6.79–6.84 (m,
1 H), 6.45 (d, J = 16.0 Hz, 1 H), 6.09 (dd, J = 7.0, 16.0 Hz, 1 H),
5.98 (d, J = 10.0 Hz, 1 H), 4.54 (m, 1 H), 4.33 (q, J = 6.0, 7.0, 14.0
Hz, 1 H), 4.06–4.14 (m, 1 H), 2.26–2.32 (m, 2 H), 2.04–2.12 (m, 1
H), 1.77 (t, J = 6.0, 12.0 Hz, 2 H), 1.60–1.68 (m, 1 H), 0.90 (s, 9 H),
0.87 (s, 9 H), 0.09 (s, 3 H), 0.08 (s, 3 H), 0.05 (s, 3 H), 0.04 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 164.2, 145.1, 136.8, 132.9, 129.7,
128.6, 127.5, 126.4, 121.5, 74.6, 71.5, 65.8, 47.5, 43.3, 30.1, 26.0 (3
× C), 25.9 (3 × C), 18.2, 18.1, –3.8, –4.2, –4.5, –4.1.
IR (neat): 2954, 2931, 2856, 1666, 1253, 1076, 834, 775 cm–1.
MS (ESI): m/z = 539 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C29H48O4NaSi2: 539.2988;
1H NMR (500 MHz, CDCl3): δ = 7.13–7.31 (m, 5 H), 6.85–6.93 (m,
1 H), 6.37 (dd, J = 13.8, 15.8 Hz, 2 H), 6.06 (dd, J = 6.9, 15.8 Hz, 1
H), 4.31–4.38 (m, 1 H), 3.98 (t, J = 5.9 Hz, 1 H), 3.62 (s, 3 H), 3.17
(s, 3 H), 2.32–2.48 (m, 2 H), 1.71–1.79 (m, 1 H), 1.61–1.68 (m, 1
H), 0.87 (s, 18 H), 0.05 (s, 6 H), 0.04 (s, 6 H).
found: 539.2990.
(6R)-6-[(2R,4R,5E)-2,4-Dihydroxy-6-phenylhex-5-en-1-yl]-5,6-
dihydro-2H-pyran-2-one (1) (Cryptomoscatone D2)
Five drops of a 4 M soln of HCl in THF were added to a stirred soln
of compound 8 (53 mg, 0.102 mmol) in THF (3 mL) at 0 °C. The
mixture was warmed to r.t. and then stirred for 3 h. The reaction was
then quenched with solid NaHCO3 (10 mg) and the mixture was fil-
tered. The solvent was removed under reduced pressure and the res-
idue was purified by column chromatography (silica gel, 80%
EtOAc–hexane) to give a brown liquid; yield: 27 mg (91%); Rf = 0.4
(EtOAc); [α]D26 +65.3 (c 2.6, CHCl3).
13C NMR (75 MHz, CDCl3): δ = 166.6, 144.1, 136.8, 133.2, 129.5,
128.5, 127.5, 126.3, 120.8, 71.3, 68.6, 61.6, 46.4, 41.1, 32.3, 26.0 (3
× C), 25.9 (3 × C), 18.2, 18.0, –3.6, –4.1, –4.3, –4.5.
MS (ESI): m/z = 556 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C29H51NNaO4Si2: 556.3254;
found: 556.3278.
(4R,5E,8S,10R,11E)-8,10-Bis{[tert-butyl(dimethyl)silyl]oxy}-
12-phenyldodeca-1,5,11-trien-4-ol (20)
IR (neat): 3423, 2924, 1707, 1258, 1053, 758 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.19–7.38 (m, 5 H), 6.83–6.89 (m,
1 H), 6.61 (d, J = 16.0 Hz, 1 H), 6.27 (dd, J = 6, 16.0 Hz, 1 H), 5.98
(d, J = 10.0 Hz, 1 H), 4.71–4.79 (m, 1 H), 4.60–4.66 (m, 1 H), 4.33–
4.40 (m, 1 H), 2.29–2.35 (m, 2 H), 1.70–1.90 (m, 4 H).
13C NMR (75 MHz, CDCl3): δ = 164.8, 145.7, 136.6, 131.8, 130.0,
128.5, 127.6, 126.5, 121.1, 75.0, 70.1, 64.2, 43.4, 42.4, 29.8.
MS (ESI): m/z = 311 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H20NaO4: 311.1259;
A 25 wt% soln of DIBAL-H in toluene (1.46 mL) was slowly added
over 5 min to a stirred soln of amide 19 (0.55 g, 1.03 mmol) in an-
hyd THF (10 mL) at –78 °C, and the mixture was stirred for 5 min
at –78 °C. When the reaction was complete, sat. aq sodium potassi-
um tartrate soln (8 mL) was added and the mixture was stirred vig-
orously at r.t. for an additional 1 h, then extracted with EtOAc (3 ×
10 mL). The combined organic layers were washed with brine (20
mL), dried (Na2SO4), and the concentrated under reduced pressure
to give the crude aldehyde, which was used in the next reaction
without further purification; Rf = 0.7 (10% EtOAc–hexane).
found: 311.1249.
A similar procedure to that used in the synthesis of compound 17
gave product 20 as a colorless oil; yield: 460 mg (86%, two steps);
Rf = 0.6 (5% EtOAc–hexane); [α]D29 +33.2 (c 2.5, CHCl3).
Synthesis 2012, 44, 1365–1372
© Georg Thieme Verlag Stuttgart · New York

PAPER
Cryptomoscatone D2, (5R,7S)-Kurzilactone, and (+)-Cryptofolione
1371
IR (neat): 3420, 2931, 2957, 1253, 1074, 834, 774 cm–1.
IR (neat): 3424, 2923, 2853, 1706, 1254, 1020, 967 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.15–7.36 (m, 5 H), 6.42 (d, J =
15.8 Hz, 1 H), 6.09 (dd, J = 7.5, 15.8 Hz, 1 H), 5.58–5.85 (m, 2 H),
5.44–5.54 (m, 1 H), 5.05–5.16 (m, 2 H), 4.30–4.40 (m, 1 H), 4.09
(q, J = 6.0, 12.0 Hz, 1 H), 3.90 (m, 1 H), 2.14–2.35 (m, 4 H), 1.68–
1.82 (m, 1 H), 1.52–1.65 (m, 1 H), 1.44 (br s, 1 H, OH), 0.90 (s, 18
H), 0.08 (s, 3 H), 0.07 (s, 3 H), 0.05 (s, 3 H), 0.03 (s, 3 H).
1H NMR (500 MHz, CDCl3): δ = 7.21–7.41 (m, 5 H), 6.83–6.90 (m,
1 H), 6.64 (d, J = 15.0 Hz, 1 H), 6.28 (dd, J = 6, 16.0 Hz, 1 H), 6.04
(d, J = 10.0 Hz, 1 H), 5.84–5.92 (m, 1 H), 5.71 (dd, J = 6, 16.0 Hz,
1 H), 4.90 (q, J = 6.0 Hz, 1 H), 4.63–4.69 (m, 1 H), 4.04–4.10 (m, 1
H), 2.50–2.63 (br s, 2 H, 2 × OH), 2.41–2.47 (m, 2 H), 2.28–2.35
(m, 2 H), 1.77–1.87 (m, 2 H).
13C NMR (75 MHz, CDCl3): 136.9, 134.5, 134.3, 133.4, 129.3,
128.5, 128.1, 127.4, 126.3, 118.1, 71.7, 71.4, 69.1, 46.1, 41.9, 40.6,
26.0 (3 × C), 25.9 (3 × C), 18.2, 18.1, –3.5, –4.0, –4.3, –4.5.
13C NMR (75 MHz, CDCl3): δ = 164.0, 144.6, 136.5, 131.6, 131.0,
130.2, 130.1, 128.6, 127.7, 126.5, 121.6, 77.7, 70.5, 68.2, 42.2,
40.4, 29.7.
MS (ESI): m/z = 539 [M + Na]+.
MS (ESI): m/z = 337 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H52NaO3Si2: 539.3352;
found: 539.3375.
HRMS (ESI): m/z [M + Na]+ calcd for C19H22O4Na: 337.1415;
found: 337.1411.
(1R,2E,5S,7R,8E)-1-Allyl-5,7-bis{[tert-butyl(dimethyl)si-
lyl]oxy}-9-phenylnona-2,8-dien-1-yl Acrylate (22)
Acknowledgment
Acryloyl chloride (0.04 mL, 0.513 mmol) was added dropwise un-
der N2 to a soln of homoallyl alcohol 20 (177 mg, 0.342 mmol),
Et3N (0.07 mL, 0.513 mmol), and DMAP (cat.) in anhyd CH2Cl2 (5
mL). The mixture was stirred at 0 °C for 30 min until the reaction
was complete then washed with brine, dried (Na2SO4), and concen-
trated. The crude product was purified by column chromatography
(silica gel, 2% EtOAc–hexane) to give a colorless liquid; yield: 158
B.G. and D.C.B. thank the CSIR, New Delhi, India, for the award
of fellowships. J.S.Y. acknowledges partial support by the King
Saud University for the Global Research Network for Organic Syn-
thesis (GRNOS).
29
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.omnorinIftangonmSorniuifIatoprtngiSutpor
mg (81%); Rf = 0.8 (5% EtOAc–hexane); [α]D +35.2 (c 0.33,
CHCl3).
IR (neat): 2931, 2859, 1726, 1636, 768 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.16–7.35 (m, 5 H), 6.32–6.46 (m,
2 H), 6.00–6.14 (m, 2 H), 5.63–5.82 (m, 3 H), 5.40–5.51 (m, 1 H),
5.27–5.38 (m, 1 H), 4.99–5.11 (m, 2 H), 4.29–4.38 (m, 1 H), 3.89 (t,
J = 5.3 Hz, 1 H), 2.40 (t, J = 6.0 Hz, 2 H), 2.16–2.33 (m, 2 H), 1.67–
1.79 (m, 1 H), 1.52–1.64 (m, 1 H), 0.09 (s, 18 H), 0.07 (s, 3 H), 0.06
(s, 3 H), 0.05 (s, 3 H), 0.02 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 165.3, 137.0, 133.4, 133.3, 130.5,
130.3, 130.0, 129.3, 128.8, 128.5, 127.4, 126.4, 117.8, 73.7, 71.4,
69.0, 46.2, 40.7, 39.0, 26.0 (3Cs), 25.9 (3 × C), 18.2, 18.1, –3.5,
–4.1, –4.3, –4.5.
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MS (ESI): m/z = 594 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C33H54NaO4Si2: 593.3458;
found: 593.3440.
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(6R)-6-[(1E,4S,6R,7E)-4,6-bis{[tert-butyl(dimethyl)silyl]oxy}-8-
phenylocta-1,7-dien-1-yl]-5,6-dihydro-2H-pyran-2-one (23)
A similar procedure to that adopted for the synthesis of compound
8 gave compound 23 as a colorless liquid; yield: 80% (32 mg); Rf =
0.2 (20% EtOAc–hexane); [α]D29 +2.0 (c 0.32, CHCl3).
IR (neat): 2926, 1736, 1642, 1219, 1069 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.16–7.36 (m, 5 H), 6.79–6.87 (m,
1 H), 6.41 (d, J = 15.8 Hz, 1 H), 6.10 (dd, J = 7.5, 15.8 Hz, 1 H),
6.00 (dt, J = 1.5, 2.2, 9.8 Hz, 1 H), 5.73–5.87 (m, 1 H), 5.59 (dd, J
= 6.8, 15.8 Hz, 1 H), 4.84 (q, J = 7.5, 14.3 Hz, 1 H), 4.27–4.36 (m,
1 H), 3.88 (t, J = 5.3 Hz, 1 H), 2.13–2.41 (m, 4 H), 1.67–1.78 (m, 1
H), 1.58–1.65 (m, 1 H), 0.86 (s, 18 H), 0.01–0.06 (m, 12 H).
13C NMR (75 MHz, CDCl3): δ = 164.0, 144.6, 136.8, 133.2, 131.7,
129.5, 130.0, 128.5, 127.5, 126.3, 121.6, 78.2, 71.3, 68.7, 46.2,
40.6, 29.7, 26.0 (3 × C), 25.9 (3 × C), 18.2, 18.0, –3.5, –4.1, –4.3,
–4.5.
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(11) (a) Matsuoka, Y.; Aikawa, K.; Irie, R.; Katsuki, T.
Heterocycles 2005, 66, 187. (b) Sabitha, G.; Reddy, S. S. S.;
Reddy, D. V.; Bhaskar, V.; Yadav, J. S. Synthesis 2010,
3453. (c) Kumar, R. N.; Meshram, H. M. Tetrahedron Lett.
2011, 52, 1003. (d) Das, B.; Nagendra, S.; Reddy, C. R.
Tetrahedron: Asymmetry 2011, 22, 1249.
MS (ESI): m/z = 565 [M + Na]+.
(12) (a) Jiang, B.; Chen, Z. Tetrahedron: Asymmetry 2001, 12,
2835. (b) Kim, Y-J.; Tae, J. Synlett 2006, 61. (c) Sabitha, G.;
Gopal, P.; Reddy, C. N.; Yadav, J. S. Synthesis 2009, 3301.
(13) For our contributions on lactone-containing molecules, see:
(a) Yadav, J. S.; Mandal, S. S. Tetrahedron Lett. 2011, 52,
5747. (b) Yadav, J. S.; Mandal, S. S.; Reddy, J. S. S.; Srihari,
P. Tetrahedron 2011, 67, 4620. (c) Yadav, J. S.; Reddy, J. S.
HRMS (ESI): m/z [M + Na]+ calcd for C31H50NaO4Si2: 565.3145;
found: 565.3156.
(6R)-6-[(1E,4S,6R,7E)-4,6-dihydroxy-8-phenylocta-1,7-dien-1-
yl]-5,6-dihydro-2H-pyran-2-one (4) [(+)-Cryptofolione]
The procedure adopted for the synthesis of compound 1 gave com-
pound 4 as a brown liquid; yield: 83% (12 mg); Rf = 0.4 (EtOAc);
[α]D29 +47.5 (c 0.56, CHCl3) {Lit.11d [α]D25 +45.6 (c 0.44, CHCl3)}.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1365–1372

1372
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Synthesis 2012, 44, 1365–1372
© Georg Thieme Verlag Stuttgart · New York