Stereoselective total synthesis of decarestrictine-J via Ring Closing Metathesis (RCM)

Article abstract of DOI:10.1016/j.tet.2009.10.100

Stereoselective total synthesis of decarestrictine-J, a polyketide natural product is described. The synthesis involves the Prins cyclisation and Ring Closing Metathesis (RCM) as key steps.

Full text of DOI:10.1016/j.tet.2009.10.100

Tetrahedron 66 (2010) 334–338
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective total synthesis of decarestrictine-J via Ring Closing
Metathesis (RCM)
*
J.S. Yadav , K. Anantha Lakshmi, N. Mallikarjuna Reddy, Attaluri R. Prasad, Basi V. Subba Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective total synthesis of decarestrictine-J, a polyketide natural product is described. The syn-
thesis involves the Prins cyclisation and Ring Closing Metathesis (RCM) as key steps.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 17 July 2009
Received in revised form
23 October 2009
Accepted 27 October 2009
Available online 31 October 2009
Keywords:
Prins cyclisation
Ring Closing Metathesis
Natural products
1. Introduction
natural products.6 However, there are no reports on the use of
Prins cyclisation to generate and conserve the stereocenters of 7
Decanolides1a,b have attracted special attention over the last few
years. Of these, decarestrictine family is one of the most important
classes of compounds (Fig. 1). The decarestrictines2 are secondary
metabolites that were isolated from various penicillium strains and
identified as bioactive compounds by chemical screening.3 Several
members of the decarestrictine family have been shown to inhibit
the biosynthesis of cholesterol. Hence, these compounds are used
for developing cholesterol lowering drugs.4
in decarestrictine-J. Recently, we have explored the utility of
Prins cyclisation in the synthesis of some natural products.7 As
a part of this ongoing program, we have attempted the total
synthesis of decarestrictine-J utilizing the Prins cyclisation as
a key step.
2. Results and discussions
In our retrosynthetic analysis (Scheme 1), we envisioned that
the target molecule I could be achieved from 13 through Ring
Closing Metathesis (RCM). The compound 13 could in turn be
obtained via esterification of compound 7 with relevant acid 12.
The required 1,3-diol 7 was proposed to obtain from homoallylic
alcohol 1 by Prins cyclisation with acetaldehyde.
O
O
OH
O
O
O
OH
HO
O
HO
O
OH
II
I
III
The total synthesis of decarestrictine-J is described in Scheme
2 with 7.4% overall yield. Accordingly, regioselective ring opening
of (R)-benzyl glycidal ether with vinyl magnesium bromide using
copper cyanide gave the homoallylic alcohol 1.8a The Prins cycli-
sation of 1 with acetaldehyde in presence of TFA followed by hy-
drolysis of the resulting trifloroacetate afforded tetrahydropyran 2
in 52% yield.8b TBS protection of 2 with TBSCl, DMAP and imid-
azole provided the corresponding TBS ether 3 in 87% yield. The
secondary hydroxyl group of 3 was protected as its benzyl ether
using NaH, BnBr in THF to afford compound 4. Deprotection of TBS
ether gave the pyranyl methanol 5 in 81% yield. The primary
hydroxyl group of 5 was subjected to iodination using Ph3P,
Figure 1. Decarestrictine-J (I), decarestrictine L (II), decarestrictine D (III).
Consequently, there have been some reports on the total
synthesis of decarestrictines.5 The Prins cyclisation has emerged
as a powerful synthetic tool for the construction of six-mem-
bered ring. It has been utilized in the synthesis of several
* Corresponding author. Tel.: þ91 40 27193030; fax: þ91 40 27160512.
E-mail address: yadavpub@iict.res.in (J.S. Yadav).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.100

J.S. Yadav et al. / Tetrahedron 66 (2010) 334–338
335
O
O
O
OTBS
O
O
OH
OH
+
HO
HO
O
BnO
OTBS
BnO
7
12
I
13
+
HO
O
OH
HO
O
1
2
Scheme 1. Retrosynthetic analysis of decarestrictine-J.
OH
O
imidazole and iodine to give 6 in 92%, which upon reductive
opening using Zn in ethanol furnished the homoallyl alcohol
7 in 88%.9
OH
O
a
b
c
HO
HO
TBSO
OH
Next, the synthesis of fragment 12 was achieved as described in
Scheme 2. Accordingly, aldehyde 8 was treated with vinyl magne-
sium bromide and CuCN in THF gave the corresponding alcohol 9 in
80% yield. Protection of free OH group using TBSCl, DMAP, and
imidazole gave the corresponding TBS ether 10 in 92% yield.
Debenzylation of 10 using sodium in liq. ammonia gave the cor-
responding alcohol 11, which was subsequently oxidized with IBX
in DMSO/DCM system to yield the corresponding aldehyde 11a in
68% yield. Oxidation of 11a with NaClO2, NaH2PO4, 2-methyl-2-
butene in t-BuOH/H2O afforded the acid fragment 12 in 83% yield
(Scheme 3).10
Finally, we have attempted the coupling of two fragments 12
and 7. Thus, esterification of the free OH group of 7 with acid 12 in
the presence of DCC11 and a catalytic amount of DMAP gave the
diene 13 as depicted in Scheme 3 and set a stage for macro-
cyclisation by Ring Closing Metathesis.12 The diene upon treat-
ment with 5 mol % Grubb’s II catalyst under high dilution
conditions (0.001 M in DCM) afforded the cyclic ester 14 in 64%
yield. Deprotection of TBS ether in 14 using TBAF in dry THF
provided the corresponding alcohol 15 in 92% yield. Treatment of
compound 15 with IBX in DMSO yielded the corresponding ketone
16 in 85% yield. Upon treatment of 16 with Pd/C13 in EtOAc under
hydrogen atmosphere afforded the target molecule, decar-
estrictine-J (I) in 81% yield. The spectral data of thus synthesized
decarestrictine-J (I) were identical with the natural product
(Scheme 4).4
1
2
3
OBn
OBn
OBn
f
d
e
7
HO
I
TBSO
O
O
O
5
6
4
Scheme 2. Reagents and conditions: (a) Acetaldehyde, TFA, DCM then K2CO3, MeOH rt,
3 h, 52%; (b) TBSCl, Imidazole, DMAP, DCM, 0 ꢀC-rt, 3 h, 87%; (c) NaH, BnBr, dry THF, rt,
6 h, 90%; (d) CSA, MeOH, 0 ꢀC, 10 min, (e) Ph3P, imidazole, I2, THF, 0 ꢀC-rt, 2 h, 92%; (f)
Zn, EtOH, reflux, 1 h, 88%.
OH
OTBS
O
b
a
BnO
BnO
BnO
H
9
10
8
OTBS
O
OTBS
c
e
d
12
HO
H
11a
11
Scheme 3. Reagents and conditions: (a) vinyl magnesium bromide, CuCN, THF, 0 ꢀC-rt,
4 h, 80%; (b) TBSCl, imidazole, DMAP, DCM, 0 ꢀC-rt, 3 h, 94%; (c) Na, liq. NH3, THF,
ꢁ78 ꢀC, 30 min (d) IBX, DMSO, DCM, 0 ꢀC-rt, 2 h, 72%; (e) NaClO2, NaH2PO4, 2-methyl-
2-butene, t-BuOH, 6 h, 83%.
O
OBn OH
O
OTBS
O
b
a
+
HO
BnO
OTBS
7
13
12
O
O
O
O
d
O
c
O
O
BnO
BnO
OH
BnO
OTBS
16
14
15
e
I
Scheme 4. Reagents and conditions: (a) DCC, DMAP, DCM, 83% (b) Grubb’s II catalyst, DCM, reflux, 16 h, 64%; (c) TBAF, THF, 0 ꢀC-rt, 4 h, 92%; (d) IBX, DMSO, DCM, 0 ꢀC-rt, 2 h, 85%;
(e) Pd/C, EtOH, 6 h, 81%.

336
J.S. Yadav et al. / Tetrahedron 66 (2010) 334–338
3. Conclusion
300 MHz): d 0.04 (6H, s, Me2Si), 0.86 (9H, s, terbutyl), 1.21 (3H, d,
J¼6.1 Hz, CH3), 1.89–1.96 (2H, dd, J¼3.77, 2.26 Hz, 2CHa), 2.01–2.07
In summary, the stereoselective total synthesis of decar-
estrictine-J has been achieved for the first time via the Prins cyc-
lisation. Further applications of the Prins cylisation in the synthesis
of natural products are in progress and will be disclosed in due
course.
(2H, dd, J¼3.21, 2.45 Hz, 2CHe) 3.35–3.54 (3H, m, OCH), 3.69–3.86
(2H, m, OCH); 13C NMR (CDCl3, 75 MHz):
d
ꢁ5.5, ꢁ3.6, 18.2, 21.5,
25.7, 37.6, 42.9, 66.3, 68, 71.6, 76.1; LC-MS: m/z: 283 (60, MþNaþ),
129(35), 111(40), 92(53); HRMS (ESI): m/z 283 [MþNa]þ calcd for
C7H14O3Na: 283.1705; found: 283.1708.
4. Experimental section
4.1. General
4.1.3. {[(2R,4S,6R)-4-(Benzyloxy)-6-methyl-tetrahydro-2H-pyran-2-
yl]methoxy}(tert-butyl)dimethylsilane (4). To a stirred solution of
alcohol 3 (4 g, 15.38 mmol) in THF (40 ml), NaH (0.92 g, 38.3 mmol)
was added at 0 ꢀC and stirred for 30 min at the same temperature.
Then, benzyl bromide (2.63 mL, 15.38 mmol) was added and stirred
for 2 h. After completion of the reaction as indicated by TLC, the
mixture was quenched with aq NH4Cl (40 mL) and the extracted
with EtOAc (3ꢂ40 mL). The combined organic layers were washed
with brine (50 mL), dried over anhydrous Na2SO4 and concentrated
in vacuo. The crude residue was purified by column chromatogra-
phy (silica gel, 60–120 mesh, EtOAc: hexane, 1:9) to afford 4 (4.84 g,
Commercial reagents were used without further purification, all
solvents were purified by standard techniques and Infrared spectra
were recorded on Perkin–Elmer 683 spectrometer. Optical rota-
tions were obtained on Jasco Dip 360 digital polarimeter. NMR
spectra were recorded in CDCl3 solvent on Varian Gemini 200,
Brucker 300 and Varian Unity 400 NMR spectrometers. Chemical
shifts (d) are quoted in parts per million and are referenced to
tetramethylsilane (TMS) as an internal standard. Coupling con-
stants (J) are quoted in Hertz. Column chromatographic separations
were carried out on silica gel (60–120 mesh) and flash chromato-
graphic separations were carried out using 230–400 mesh, silica
gel. Mass spectra were recorded on Micromass VG-7070H for EI and
VG Autospec M for FABMS.
90%) as a light yellow syrup.
20
Rf¼0.8 (10% EtOAc/Hexane). [
a]
¼þ2 (c 0.5, CHCl3); IR (neat):
y
D
3030, 2931, 2857, 1460, 1253, 1122, 1073, 837 cmꢁ1; 1H NMR (CDCl3,
300 MHz): 0.05 (6H, s, Me2Si), 0.89 (9H, s, terbutyl), 1.21 (3H, d,
d
J¼6.1 Hz, CH3), 1.95–2.01 (2H, dd, J¼7.5, 2.2 Hz, 2CHa), 2.04–2.1 (2H,
dd, J¼8.3, 2.2 Hz, 2CHe), 3.28–3.55 (4H, m, 2ꢂOCH and OCH2), 3.65–
3.7 (1H, m, OCH), 4.54 (2H, s, OCH2Ph), 7.21–7.30 (5H, m, ArH); 13
C
4.1.1. (2R,4S,6R)-Tetrahydro-2-(hydroxymethyl)-6-methyl-2H-pyran-
4-ol (2). Trifluoroacetic acid (95 mL) was added slowly to a solution
of the homoallylic alcohol 1 (5 g, 49.01 mmol) and acetaldehyde
(5.4 g, 122 mmol) in CH2Cl2 (150 mL) at 25 ꢀC under nitrogen at-
mosphere. The reaction mixture was stirred for 3.0 h and then
quenched with saturated sodium hydrogen carbonate solution
(300 mL) and the pH was adjusted to >7 by addition of triethyl-
amine. The mixture was extracted with CH2Cl2 (4ꢂ100 mL) and the
combined organic layers were concentrated under reduced pres-
sure. The resulting trifluoroacetate was directly used in the next
reaction without purification. The residue was dissolved in meth-
anol (75 mL) and treated with potassium carbonate (17.9 g) for
0.5 h. The solvent was removed under reduced pressure and then
diluted with water (40 mL). The resulting mixture was extracted
with CH2Cl2 (3ꢂ50 mL) and the combined organic layers were dried
over anhydrous Na2SO4 and the solvent was removed under re-
duced pressure. Purification of the crude by column chromatogra-
NMR (CDCl3, 75 MHz):
d
ꢁ5.2, ꢁ5.3, 18.3, 21.7, 25.9, 34.6, 39.9, 66.4,
69.5, 71.7, 74.6, 76.24, 127.5, 128.3, 138.6; LC-MS: m/z 373 (100,
MþNaþ), 368 (55), 351 (40); HRMS (ESI): m/z [MþH]þ calcd for
C20H35O3Si: 351.2277; found: 351.2361.
4.1.4. [(2R,4S,6R)-4-(Benzyloxy)-6-methyl-tetrahydro-2H-pyran-
2yl]methanol (5). To a stirred solution of compound 4 (4.84 g,
13.82 mmol) in MeOH (40 mL), was added a catalytic amount of
CSA at 0 ꢀC and stirred for 10 min at the same temperature. Upon
completion, the mixture was quenched with NaHCO3, extracted
with EtOAc (2ꢂ50 mL) and concentrated under reduced pressure.
The resulting crude residue was purified by column chromatogra-
phy to afford the alcohol 5 (3.92 g, 81%) as colourless oil Rf¼0.3 (20%
20
EtOAc/Hexane). [
a
]
D
¼ꢁ10.7 (c 0.5, CHCl3); IR (neat):
y 3446, 3030,
2934, 2861, 1452, 1365, 1115, 1072, 740 cmꢁ1
300 MHz):
1.24 (3H, d, J¼6.1 Hz, CH3), 1.84–2.0 (4H, m, 2ꢂCH2),
3.35–3.55 (5H, m, 3ꢂOCH and CH2), 4.5 (2H, s, OCH2Ph), 7.18–7.27
;
1H NMR (CDCl3,
d
phy on silica gel gave the product 2 (3.718 g, 52%) as a colourless
(5H, m, ArH); 13C NMR (CDCl3, 75 MHz):
d 21.6, 33.5, 39.8, 66, 69.5,
20
liquid. Rf¼0.3 (60% EtOAc/Hexane). [
(neat):
1H NMR (CDCl3, 300 MHz):
a
]
D
¼ꢁ13.3 (c 0.5, CHCl3); IR
71.8, 74.3, 76, 127.5, 128.3, 138.5; LC-MS: m/z 291 (100, MþNaþ);
HRMS (ESI): m/z [MþH]þ calcd for C14H21O3: 236.1416; found:
237.1489.
y
3398, 2925, 2856, 1722, 1452, 1363, 1178, 1030, 976 cmꢁ1
;
d
1.25 (3H, d, J¼6.1 Hz, CH3), 1.81–1.87
(2H, dd, J¼3.7, 2.2 Hz, 2CHa), 1.92–1.98 (2H, dd, J¼3.9, 2.4 Hz, 2CHe),
3.45–3.65 (4H, m, OCH), 3.78–3.87 (1H, m, OCH); 13C NMR (CDCl3,
4.1.5. (2R,4S,6R)-4-(Benzyloxy)-tetrahydro-2-(iodomethyl)-6-
methyl-2H-pyran (6). To a stirred solution of alcohol 5 (3.5 g,
14.83 mmol) in dry THF (35 mL) were added imidazole (2.42 g,
35.5 mmol) and triphenylphosphine (4.66 g, 17.79 mmol) and I2
(4.57 g, 17.796 mmol) successively at 0 ꢀC. The resulting reaction
mixture was stirred for 2 h at room temperature and then
quenched by adding water (15 mL), and extracted with DCM
(3ꢂ30 mL). The organic layers were washed with brine (15 mL),
dried over anhydrous Na2SO4 and concentrated in vacuo. Purifica-
tion of the crude residue by column chromatography gave the pure
75 MHz):
d 21.6, 36.5, 42.3, 65.8, 67.3, 71.6, 76.05; LC-MS: m/z: 169
(100, MþNaþ), 102 (68), 79 (20); HRMS (ESI): m/z [MþNa]þ calcd
for C7H14O3Na: 169.0840; found: 169.0839.
4.1.2. [(2R,4S,6R)-2-(tert-Butyldimethylsilyloxy)methyl]-6-methyl-
tetrahydro-2H-pyran-4-ol (3). To a solution of 2 (3.7 g, 25.34 mmol)
in dry CH2Cl2 (40 mL) were added catalytic amount of DMAP
(15 mg) and imidazole (3.10 g, 45.6 mmol) in one portion followed
by TBSCl (3.8 g, 25.3 mmol) in three portions at 0 ꢀC. The resulting
mixture was stirred for 4 h and slowly warmed to room tempera-
ture. Then, the mixture was quenched by addition of water (15 mL),
diluted with CH2Cl2 (3ꢂ40 mL), washed with brine (20 mL), and
dried over anhydrous Na2SO4 and concentrated in vacuo. Purifica-
tion of the crude by column chromatography (SiO2, 10% EtOAc in
product 6 (4.97 g, 92%) as a pale yellow liquid. Rf¼0.7 (SiO2, 30%
28
EtOAc in hexane). [
a
]
¼ꢁ14.9 (c 0.5, CHCl3); IR (neat):
y 3029,
D
2939, 2856, 1451, 1660, 1362, 1159, 1081, 739 cmꢁ1; 1H NMR (CDCl3,
300 MHz):
d
1.24 (3H d, J¼5.8 Hz, CH3), 1.93–1.98 (2H, m, CH2),
2.25–2.29 (2H, m, CH2), 3.11–3.21 (2H, m, ICH2), 3.28–3.35(1H, m,
hexane) afforded TBS ether 3 (5.7 g, 87%) as a colourless oil. Rf¼0.7
OCH), 3.42–3.57 (2H, m, 2ꢂOCH), 4.54 (2H, s, OCH2Ph), 7.24–7.3
20
(20% EtOAc/Hexane). [
a
]
¼ꢁ4.5 (c 0.55, CHCl3); IR (neat):
y
3379,
(5H, m, ArH); 13C NMR (CDCl3, 75 MHz):
d 8.8, 21.6, 37.5, 39.4, 69.6,
D
2932, 2858, 1464, 1372, 1129, 1033, 837 cmꢁ1
;
1H NMR (CDCl3,
72.1, 74.1, 75, 127.5, 128.4, 138.4; LC-MS: m/z 369 (25, MþNaþ), 301

J.S. Yadav et al. / Tetrahedron 66 (2010) 334–338
337
(20), 263(20), 249 (35); HRMS (ESI): m/z [MþNH4]þ calcd for
the mixture was quenched with NH4Cl (10 g) and then extracted
with DCM (2ꢂ30 mL). The combined organic layers were washed
with brine (25 mL), dried over Na2SO4 and concentrated in vacuo.
The crude residue was purified by column chromatography to af-
ford alcohol 11 (3.12 g, 68%) as a pale yellow liquid. Rf¼0.35 (10%
C14H23INO2: 364.0768; found: 364.0769.
4.1.6. (2R,4R)-4-(Benzyloxy)hept-6-en-2-ol (7). To the iodide 6 (3 g,
8.287 mmol) in ethanol (80 mL), zinc dust (10.93 g, 165.6 mmol)
was added. The resulting mixture was refluxed for 1 h and then
cooled to 25 ꢀC. Addition of solid ammonium chloride (10 g) and
ether (200 mL) followed by stirring for 5 min gave a grey suspension
which was filtered through Celite. The filtrate was concentrated in
vacuo and purified by flash chromatography to give compound 7
EtOAc/Hexane). IR (neat):
1467, 1254, 1085, 1023, 922, 837, 776 cmꢁ1
300 MHz): 0.05 (3H, s, MeSi), 0.08 (3H, s, MeSi), 0.9 (9H, s, ter-
y
3371, 3080, 2954, 2931, 2889, 2858,
;
1H NMR (CDCl3,
d
butyl), 1.66–1.90 (2H, m, CH2), 2.39 (1H, br s, OH), 3.67–3.85 (2H, m,
OCH2), 4.38–4.43 (1H, m, OCH), 5.07–5.24 (2H, m, olefin), 5.8–5.9
(1.62 g, 88%) as a pale yellow liquid. Rf¼0.4 (10% EtOAc/Hexane).
(1H, m, olefin); 13C NMR (CDCl3, 75 MHz):
d
ꢁ5.3, ꢁ5.1, 18.1, 25.8,
20
[
a]
¼ꢁ21.8 (c 0.5, CHCl3); IR (neat):
y
3427, 3070, 3031, 2967, 2930,
39.2, 60, 73.1, 114.3, 140.6; LC-MS: m/z 239 (100, MþNaþ); HRMS
(ESI): m/z [MþH]þ calcd for C11H25O2Si: 217.1618; found: 217.1609.
D
1640, 1453, 1093, 1066, 914, 739 cmꢁ1; 1H NMR (CDCl3, 300 MHz):
d
1.18 (3H, d, J¼6.4 Hz, CH3), 1.51–1.56 (2H, t, J¼5.5 Hz, CH2), 2.07
(1H, br s, OH), 2.20–2.41 (2H, m, allylic CH2) 3.65–3.71 (1H, m, OCH),
3.99–4.05 (1H, m, OCH), 4.36–4.65 (2H, m, OCH2Ph), 4.99–5.06 (2H,
m, olefin), 5.66–5.8 (1H, m, olefin), 7.17–7.28 (5H, m, ArH); 13C NMR
4.1.10. 3-(tert-Butyldimethylsilyloxy)pent-4-enoic acid (12). To a stir-
red solution of IBX (8.283 g, 29.58 mmol) in DMSO (30 mL) was
added compound 11 (2.13 g, 9.86 mmol) in CH2Cl2 (10 mL) at 0 ꢀC.
After complete conversion, the reaction mixture was filtered through
Celite pad, washed with water (30 mL) and extracted with ether
(3ꢂ40 mL), dried over anhydrous Na2SO4 and concentrated in vacuo
and purified by flash column chromatography to afford aldehyde 11a.
To a stirred solution of aldehyde 11a (1.3 g, 6.07 mmol) in t-
BuOH (10 mL) were added solutions of 2-methyl-2-butene (10 mL),
NaClO2 (0.829 g, 9.11 mmol) and NaH2PO4 (1.09, 9.112 mmol) in
water (5 mL) and stirred over 6 h at room temperature. The solvent
was removed under reduced pressure and extracted with EtOAc
(3ꢂ10 mL). The combined organic layers were washed with brine
(5 mL), dried over Na2SO4 and concentrated in vacuo. The crude
residue was purified by column chromatography to afford acid 12
(1.162 mg, 83%) as a light yellow liquid. Rf¼0.2 (10% EtOAc/Hexane).
(CDCl3, 75 MHz): d 23.6, 37.9, 41.7, 64.5, 71.2, 76.2, 117.4, 127.7, 128.4,
134.4, 138.8; LC-MS: m/z 243 (30, MþNaþ); HRMS (ESI): m/z
[MþH]þ calcd for C14H21O2: 221.1536; found: 221.1525.
4.1.7. 5-(Benzyloxy)pent-1-en-3-ol (9). To a solution of compound 8
(7 g, 42.68 mmol) in dry THF (100 mL) was added a commercially
available vinyl magnesium bromide (6.658 g, 51.21 mmol) in THF at
0 ꢀC. The mixture was warmed to 40 ꢀC and then allowed to stir for
4 h at 40 ꢀC. Upon completion, saturated NH4Cl solution (100 mL)
was added and the mixture was extracted with EtOAc (3ꢂ30 mL).
The combined organic layers were washed with brine (50 mL),
dried over Na2SO4 and concentrated under reduced pressure. Pu-
rification by column chromatography afforded the pure product 9
(6.47 g, 80%) as a pale yellow liquid. Rf¼0.45 (10% EtOAc/hexane). IR
IR (neat):
y
2956, 2858, 1714, 1467, 1254, 1088, 835, 777 cmꢁ1
;
1H
(neat):
y
3420, 3030, 2922, 2862, 1640, 1452, 1098, 740, 697 cmꢁ1
;
NMR (CDCl3, 300 MHz): d
0.07 (3H, s, MeSi), 0.08 (3H, s, MeSi), 0.89
1H NMR (CDCl3, 300 MHz):
d
1.73–1.8 (2H, m, CH2), 3.53–3.68 (2H,
(9H, s, terbutyl), 2.56 (2H, d, J¼6.0 Hz, CH2), 4.55–4.61 (1H, q,
J¼6.1 Hz, OCH), 5.11–5.3 (2H, m, olefin), 5.79–5.9 (1H, m, olefin); 13C
m, OCH2), 4.27 (1H, m, OCH), 4.46 (2H, s, OCH2Ph), 5.03 (1H, d,
J¼10.5 Hz, olefin), 5.2 (1H, d, J¼17.3 Hz, olefin), 5.74–5.85 (2H, m,
NMR (CDCl3, 75 MHz):
d
ꢁ5.2, ꢁ4.4, 18.1, 25.6, 42.8, 70.5, 115.4,
olefin), 7.2–7.27 (5H, m, ArH); 13C NMR (CDCl3, 75 MHz):
d
36.2,
139.2, 174.7; LC-MS: m/z 253 (52, MþNaþ); HRMS (ESI): m/z
[MþH]þ calcd for C11H23O3Si: 231.1411; found: 231.1416.
68.2, 71.8, 73.2, 114.3, 127.6, 128.5, 137.8, 140.5; LC-MS: m/z 215 (90,
MþNaþ), 157 (20), 129 (35), 91 (100); HRMS (ESI): m/z [MþNa]þ
calcd for C12H16NaO2: 215.1043; found: 215.1041.
4.1.11. (3R)-(2R,4R)-4-(Benzyloxy)hept-6-en-2yl-3-hydroxypent-4-
enoate (13). To a stirred solution of alcohol 7 (0.4 g, 1.81 mmol) in
CH2Cl2 (10 mL) were added compound 12 (0.5 g, 2.18 mmol) fol-
lowed by DCC (0.74 g, 3.63 mmol) and DMAP (0.44 g, 3.63 mmol) at
room temperature and allowed to stir for 15 h. After completion,
the mixture was filtered and the resulting filtrate was evaporated in
vacuo. The crude residue was purified by column chromatography
to afford ester 13 (567 mg, 81%) as colourless oil. Rf¼0.2 (20% EtOAc/
4.1.8. 5-(Benzyloxy)pent-1-en-3-yloxy(tert-butyl)dimethylsilane
(10). To a solution of 9 (2.10 g, 13.4 mmol) in dry CH2Cl2 (30 mL)
were added a catalytic DMAP (10 mg) and imidazole (1.37 g,
20.0 mmol) in one portion followed by TBSCl (2.43 mg,16.0 mmol)
in three portions at 0 ꢀC. The reaction mixture was stirred for 4 h
and slowly warmed to room temperature. Upon completion, the
mixture was quenched by the addition of saturated NH4Cl solution
(15 mL), diluted with CH2Cl2 (30 mL), washed with brine (15 mL),
dried over Na2SO4 and concentrated in vacuo. Purification of the
crude by column chromatography afforded TBS ether 10 (3.34 g,
Hexane). IR (neat):
1088, 835, 778 cmꢁ1; [
300 MHz):
y 3073, 2930, 2857, 1734, 1641, 1463, 1369, 1254,
20
a]
¼ꢁ30.8 (c 0.5, CHCl3); 1H NMR (CDCl3,
D
d
0.04 (3H, s, MeSi), 0.06 (3H, s, MeSi), 0.84 (9H, s, ter-
butyl), 1.21 (3H, d, J¼6.2 Hz, CH3), 1.59–1.75 (2H, m, CH2), 2.2–2.47
(4H, m, 2ꢂCH2), 3.38–3.49 (1H, m, OCH), 4.34–4.44 (1H, m, OCH),
4.47–4.55 (2H, m, OCH2Ph), 4.98–5.20 (5H, m, OCHMe and olefin),
5.7–5.8 (2H, m, olefin), 7.18–7.3 (5H, m, ArH); 13C NMR (CDCl3,
92%) as a colourless oil. Rf¼0.7 (10% EtOAc/Hexane). IR (neat):
3030, 2953, 2857, 16.43, 14.64, 1361, 1253, 1092, 837, 776 cmꢁ1; 1H
NMR (CDCl3, 300 MHz): 0.03 (3H, s, MeSi), 0.05 (3H, s, MeSi),
y
d
0.82 (9H, s, terbutyl), 1.75–1.81 (2H, m, CH2), 3.4–3.62 (2H, m,
OCH2), 4.27–4.33 (1H, m, OCH), 4.43–4.54 (2H, s, OCH2Ph), 4.99–
5.04 (1H, dt, J¼7.5, 1.3 Hz, olefin), 5.11–5.18 (1H, dt, J¼17.1, 1.5 Hz,
olefin), 5.75–5.86 (1H, m, olefin), 7.27–7.35 (5H, m, ArH); 13C NMR
75 MHz):
d
ꢁ4.9, ꢁ4.5, 18.1, 20.8, 25.8, 38.3, 41.1, 43.8, 68.3, 70.6,
71.4, 74.8, 114.6, 117.4, 127.6, 128, 128.3, 134.1, 140.2, 170.5; LC-MS:
m/z 455 (100, MþNaþ); HRMS (ESI): m/z [MþNa]þ calcd for
C25H40O4SiNa: 455.2593; found: 455.2579.
(CDCl3, 75 MHz):
d
ꢁ4.9, ꢁ4.3, 18.2, 25.8, 38.1, 66.7, 70.8, 73, 113.6,
127.6, 128.3, 138.5, 141.5; LC-MS: m/z 329 (60, MþNaþ);
HRMS (ESI): m/z [MþH]þ calcd for C18H31O2Si: 307.2088; found:
307.2082.
4.1.12. (8R,10R,E)-8-(Benzyloxy)-4-(tert-butyldimethylsilyloxy)-10-
methyl-3,4,7,8,9,10-hexahydrooxecin-2-one (14). Grubbs’ II catalyst
(0.88 mg, 5 mol %) was dissolved in CH2Cl2 (10 mL) and was added
drop wise to a solution of the acrylic ester 15 (0.2 g, 0.462 mmol) in
700 mL of CH2Cl2. The reaction mixture was stirred under reflux at
45 ꢀC for 12 h by which time all of the starting material was con-
sumed (TLC). The solvent was removed under vacuum and the
crude product was purified by silica gel column chromatography to
4.1.9. 3-(tert-Butyldimethylsilyloxy)pent-4-en-1-ol (11). To a stirred
solution of compound 10 (5.91 g, 19.31 mmol) in THF (20 mL) were
added liq. NH3 (40 mL), and Na metal (0.72 g, 31.3 mmol) and the
reaction mixture was stirred for 30 min at ꢁ78 ꢀC. On completion,

338
J.S. Yadav et al. / Tetrahedron 66 (2010) 334–338
obtain 14 (120 mg, 64%) as colourless oil. Rf¼0.6 (10% EtOAc/Hex-
(1H, m, 5Ha), 3.38 (2H, d, J¼2.8 Hz, 2Ha, 2Hb), 3.65–3.72 (1H, m, OCH),
5.15–5.22 (1H, m, OCHMe); 13C NMR (CDCl3, 75 MHz): 20.8, 21.4, 37,
39.3, 44.2, 51.8, 69.4, 71.6, 166.6, 202.9; LC-MS: m/z 223 (43, MþNaþ),
153 (100), 102 (72); HRMS (ESI): m/z [MþNa]þ calcd for C10H16O4Na:
223.0946; found: 223.0942.
28
ane). [
a
]
¼ꢁ2.0 (c 1, CHCl3); IR (neat):
y
2927, 2856, 1735, 1460,
0.05
D
1365, 1253, 1074, 836, 778 cmꢁ1; 1H NMR (CDCl3, 300 MHz):
d
(3H, s, MeSi), 0.07 (3H, s, MeSi), 0.87 (9H, s, terbutyl), 1.40 (3H, d,
J¼6.4 Hz),1.85–1.99 (2H, m, CH2), 2.22–2.47 (2H, m, CH2), 2.71–2.85
(2H, m, CH2), 4.42–4.57 (2H, m, OCH2Ph), 4.92 (1H, m, OCHMe),
5.22–5.56 (2H, m, olefin), 7.21–7.31 (5H, m, ArH); 13C NMR (CDCl3,
Acknowledgements
75 MHz):
d
ꢁ4.9, ꢁ4.5, 18.2, 20.3, 25.7, 34.8, 39.8, 44.3, 65.4, 69.8,
70.6, 78.3, 127.2, 127.4, 127.5, 128.4, 133.1, 138.4, 169.3; LC-MS: m/z
427 (45, MþNaþ); HRMS (ESI): m/z [MþNa]þ calcd for
C23H36O4SiNa: 427.228; found: 427.2289.
K.A.L and N.M.R thank UGC & CSIR, New Delhi for the award of
fellowships.
Appendix. Supplementary data
4.1.13. (8R,10R,E)-8-(Benzyloxy)-4-hydroxy-10-methyl-3,4,7,8,9,10-
hexahydrooxecin-2-one (15). A solution of compound 14 (120 mg,
0.297 mmol) in THF (10 mL) was treated with a 1.1 M solution of
TBAF in THF (3.5 mL, 0.35 mmol) at room temperature for 1 h. The
solvent was removed and then diluted with EtOAc (20 mL) and
water (20 mL). The mixture was saturated with sodium chloride
and extracted with EtOAc (4ꢂ20 mL). The combined organic layers
were dried over Na2SO4 and concentrated in vacuo. The crude
product was purified by column chromatography to afford
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2009.10.100.
References and notes
1. (a) Drager, G.; Kirschning, A.; Thiericke, R.; Zerlin, M. Nat. Prod. Rep. 1996, 13,
365–375; (b) Collins, I. J. Chem. Soc., Perkin Trans. I 1999, 1377–1395.
2. (a) Grabley, S.; Hammann, P.; Hutter, K.; Kluge, H.; Thiericke, R.; Wink, J.; Zeeck,
A. J. Antibiot. 1991, 44, 670–673; (b) Grabley, S.; Granzer, E.; Hutter, K.; Ludwig,
D.; Mayer, M.; Thericke, R.; Wink, J.; Philipps, S.; Zeeck, A. J. Antibiot. 1992, 45,
56–65; (c) Gohrt, A.; Zeeck, A.; Hutter, K.; Krisch, R.; Kluge, H.; Thericke, R.
J. Antibiot. 1992, 45, 66–73.
pure compound 15 (79 mg, 92%). Rf¼0.3 (30% EtOAc/Hexane).
28
[
a]
¼þ15.2 (c 0.85, CHCl3); IR (neat):
y 2927, 2856, 1735, 1460,
D
1365, 1253, 1074, 836, 778 cmꢁ1; 1H NMR (CDCl3, 300 MHz):
d 1.32
3. (a) Zahner, H.; Drautz, H.; Weber, W. In ; Bulock, J. D., Ed.; 1982; pp 51–70; (b)
Grabley, S.; Wink, J.; Zeeck, A. In Biotechnology Focus 3; Finn, R. K., Prave, P.,
Eds.; Hanser Publisher: Munich: 1992; pp 359–370.
4. Grabley, S.; Hammann, P.; Huttert, K.; Krisch, R.; Kluge, H.; Thiericke, R.; Mayer,
M.; Zeeck, A. J. Antibiot. 1992, 45, 1176–1181.
(3H, d, J¼6.5 Hz, CH3),1.81–1.88 (2H, m, CH2), 2.2–2.33 (2H, m, CH2),
2.79–2.93 (2H, m, CH2), 3.38–3.43 (1H, m, OCH), 4.39–4.53 (2H, m,
OCH2Ph), 4.93–4.99 (1H, m, OCHMe), 5.29–5.46 (2H, m, olefin),
7.17–7.26 (5H, m, ArH); 13C NMR (CDCl3, 75 MHz):
d 20.3, 34.9, 37.4,
5. (a) Riatto, V. B.; Pilli, R. A.; Victor, M. M. Tetrahedron 2008, 64, 2279–2300; (b)
Clark, J. S.; Fessard, T. C.; Whitlock, G. A. Tetrahedron 2006, 62, 73–78; (c) Garcia,
I.; Gomez, G.; Teijeira, M.; Teran, C.; Fall, Y. Tetrahedron Lett. 2006, 47, 1333–
1335; (d) Radha Krishna, P.; Narasimha Reddy, P. V. Tetrahedron Lett. 2006, 47,
7473–7476; (e) Lukesh, J. M.; Donaldson, W. A. Tetrahedron: Asymmetry 2003, 14,
757–762; (f) Machinaga, N.; Kibayashi, C. Tetrahedron Lett. 1993, 34, 5739–5742; (g)
Yamada, S.; Tanaka, A.; Oritani, T. Biosci. Biotechnol. Biochem. 1995, 59, 1657–1660.
6. For the Prins cyclisation, see for example. (a) Barry, C. St. J.; Crosby, S. R.; Harding,
J. R.; Hughes, R. A.; King, C. D.; Parker, G. D.; Willis, C. L. Org. Lett. 2003, 5, 2429–
2432; (b) Yang, X.-F.; Mague, J. T.; Li, C.-J. J. Org. Chem. 2001, 66, 739–747; (c)
Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44, 3485–3488;
(d) Barry, C. S.; Bushby, N.; Harding, J. R.; Willis, C. S. Org. Lett. 2005, 7, 2683–2686;
(e) Cossey, K. N.; Funk, R. L. J. Am. Chem. Soc. 2004,126,12216–12217; (f) Crosby, S.
R.; Harding, J. R.; King, C. D.; Parker, G. D.; Willis, C. L. Org. Lett. 2002, 4, 3407–
3410; (g) Marumoto, S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky, S. D. Org. Lett. 2002, 4,
3919–3922; (h) Kozmin, S. A. Org. Lett. 2001, 3, 755–758; (i) Jaber, J. J.; Mitsui, K.;
Rychnovsky, S. D. J. Org. Chem. 2001, 66, 4679–4686; (j) Kopecky, D. J.; Rych-
novsky, S. D. J. Am. Chem. Soc. 2001, 123, 8420–8421; (k) Rychnovsky, S. D.;
Thomas, C. R. Org. Lett. 2000, 2, 1217–1219; (l) Rychnovsky, S. D.; Yang, G.; Hu, Y.;
Khire, U. R. J. Org. Chem. 1997, 62, 3022–3023; (m) Su, Q.; Panek, J. S. J. Am. Chem.
Soc. 2004, 126, 2425–2430; (n) Yadav, J. S.; Reddy, B. V. S.; Sekar, K. C.; Gunasekar,
D. Synthesis 2001, 6, 885–888; (o) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.; Nir-
anjan, N. J. Mol. Catal. A: Chem. 2004, 210, 99–103; (p) Yadav, J. S.; Reddy, B. V. S.;
Reddy, M. S.; Niranjan, N.; Prasad, A. R. Eur. J. Org. Chem. 2003, 1779–1783.
7. (a) Yadav, J. S.; Sridhar Reddy, M.; Purushothama Rao, P.; Prasad, A. R. Tetra-
hedron Lett. 2006, 47, 4397–4401; (b) Yadav, J. S.; Purushothama Rao, P.; Sridhar
Reddy, M.; Rao, N. V.; Prasad, A. R. Tetrahedron Lett. 2007, 48, 1469–1471; (c)
Yadav, J. S.; Purushothama Rao, P.; Sridhar Reddy, M.; Prasad, A. R. Tetrahedron
Lett. 2008, 49, 5427–5430.
43.3, 64.7, 69.9, 70.7, 78.3,127.3,127.6,128.4,129,132.2,138.4,168.8;
LC-MS: 329 (100, MþKþ), 308 (35, MþNHþ4 ); HRMS (ESI): m/z
[MþNa]þ calcd for C17H22O4Na: 313.1415; found: 313.1427.
4.1.14. (E,8R,10R)-8-(Benzyloxy)-7,8,9,10-tetrahydro-10-methyl-3H-
oxecine-2,4-dione (16). To
a stirred solution of IBX (0.202 g,
0.72 mmol) in DMSO (10 mL) was added compound 15 (70 mg) in
CH2Cl2 (2 mL) at 0 ꢀC. After completion of the reaction as indicated
by TLC, the reaction mixture was filtered through a small Celite pad
and washed with water (10 mL) and then extracted with ether
(3ꢂ10 mL). The combined organic layers were dried over anhy-
drous Na2SO4, concentrated in vacuo and then purified by column
chromatography to afford compound 16 (1.44 g, 72%). Rf¼0.6 (30%
28
EtOAc/Hexane). [
a]
¼ꢁ76 (c 0.15, CHCl3); IR (neat):
y
3443, 2979,
1H
D
2924, 2856, 1742, 1705, 1451, 1262, 1174, 1094, 969, 741 cmꢁ1
NMR (CDCl3, 300 MHz):
;
d
1.30 (3H, d, J¼6.1 Hz, CH3), 1.85–1.88 (2H,
m, CH2), 1.97–2.04 (1H, m, CH), 2.32–2.38 (1H, m, CH), 2.48–2.53
(1H, m, CH), 2.67–2.75 (1H, m, CH), 3.48–3.52(1H, m, OCH), 4.42–
4.53 (2H, m, OCH2Ph), 4.91–4.95 (1H, m, OCHMe), 5.79–6.14 (2H, m,
olefin), 7.22–7.33 (5H, m, ArH); 13C NMR (CDCl3, 75 MHz):
d 20.6,
34.6, 38.3, 51, 68.8, 70.6, 71.3, 127.4, 127.7, 128.4, 130.4, 135.3, 138.1,
166.1, 196.5; LC-MS: m/z 311 (80, MþNaþ) HRMS (ESI): m/z
[MþNa]þ calcd for C17H2 0O4Na: 311.1259; found: 311.1255.
8. (a) Yadav, J. S.; Hissana, A.; Gayathri, K. U.; Rao, N. V.; Prasad, A. R. Synthesis
2008, 24, 3945–3950; (b) Bonini, C.; Chiummiento, L.; Lopardo, M. T.; Pullex,
M.; Colobert, F.; Solladie, G. Tetrahedron Lett. 2003, 44, 2695–2697.
4.1.15. (8R,10R)-8-Hydroxy-10-methyl oxecane-2,4-dione (1). To a sol-
ution of 16 (40 mg, 0.138 mmol) in EtOAc (2 ml), was added 10% Pd/C
(catalytic) and stirred under hydrogen atmosphere for 6 h. Then, the
reaction mixture was filtered through a small Celite pad and con-
centrated in vacuo. The crude residue thus obtained was purified by
column chromatography (SiO2, 30% EtOAc/Hexane) to afford decar-
estrictine-J¼(I) (33 mg, 81%). Rf¼0.15 (30% EtOAc/Hexane). Its melting
9. Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2005, 46, 2133–2136.
10. (a) Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567–569; (b) Yadav, J. S.;
Thrimurtulu, N.; Uma Gayathri, K.; Reddy, B. V. S.; Prasad, A. R. Tetrahedron Lett.
2008, 49, 6617–6620; (c) Sabitha, G.; Padmaja, P.; Sudhakar, K.; Yadav, J. S.
Tetrahedron: Asymmetry 2009, 20, 1330–1336.
11. Boruwa, J.; Gogoi, N.; Barua, N. C. Org. Biomol. Chem. 2006, 4, 3521–3525.
12. (a) Maier, M. E. Angew. Chem., Int. Ed. 2000, 39, 2073–2076; (b) Furstner, A.; Muller,
T. Synlett 1997, 1010–1012; (c) Chang, S.; Grubbs, R. H. Tetrahedron Lett. 1997, 38,
4757–4760; (d) Delgado, M.; Martin, J. D. J. Org. Chem. 1999, 64, 4798–4816; (e)
Nakashima, K.; Ito, R.; Sono, M.; Tori, M. Heterocycles 2000, 53, 301–314; (f) Oishi,
T.; Nagumo, Y.; Hirama, M. Chem. Commun. 1998, 1041–1042; (g) Furstner, A.;
Piquet, M.; Bruneau, C.; Dixneuf, P. H. Chem. Commun. 1998, 1315–1316; (h) Ger-
lach, K.; Quitschalle, M.; Kalesse, M. Tetrahedron Lett. 1999, 40, 3553–3556; (i)
Barrett, A. G. M.; Baugh, S. P. D.; Braddock, D. C.; Flack, K.; Gibson, V. C.; Giles, M. R.;
Marshall, E. L.; Procopiou, P. A.; White, A. J. P.; Williams, D. J. J. Org. Chem.1998, 63,
7893–7907; (j) Furstner, A.; Thiel, O. R.; Blanda, G. Org. Lett. 2000, 2, 3731–3734.
13. Sabitha, G.; Fatima, N.; Reddy, E. V.; Yadav, J. S. Tetrahedron Lett. 2008, 42,
6087–6089.
5g
28
point was 51–54 ꢀC; (lit.:
54–55 ꢀC) and [
a
]
¼ꢁ141 (c 0.15,
MeOH); (lit.: 5g ꢁ154 (c 0.1, MeOH)).The 1H NMR, 13DC NMR and mass
spectral data were in good agreement with those of reported natural
decarestrictine-J¼(1).4 IR (neat):
y
3422, 2924, 2854, 1738, 1706, 1448,
1259, 1074, 966 cmꢁ1 1H NMR (CDCl3, 300 MHz):
; d 1.30 (3H, d,
J¼6.2 Hz, CH3), 1.51–1.74 (3H, m, 6Hb, 7Ha, 7Hb), 1.83–1.92 (2H, m,
9Ha, 9Hb), 2.0–2.08 (1H, m, 6Ha), 2.25–2.34 (1H, m, 5Hb), 2.66–2.76