First total synthesis of salinipyrone A using highly stereoselective vinylogous Mukaiyama aldol reaction

Article abstract of DOI:10.1016/j.tet.2012.08.035

A synthetic approach for the total synthesis of salinipyrone A has been developed. Key steps involve the TiCl₄-mediated vinylogous Mukaiyama aldol reaction (VMAR) of chiral ketene silyl N,O-acetal with propionaldyhyde, an aldol condensation, Witting olefination, and a cyclization. The synthesis proceeds in eight steps.

Full text of DOI:10.1016/j.tet.2012.08.035

Tetrahedron 68 (2012) 9289e9292
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
First total synthesis of salinipyrone A using highly stereoselective vinylogous
Mukaiyama aldol reaction
*
Palakuri Ramesh, Harshadas Mitaram Meshram
Natural Product Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 May 2012
Received in revised form 10 August 2012
Accepted 13 August 2012
Available online 14 September 2012
A synthetic approach for the total synthesis of salinipyrone A has been developed. Key steps involve the
TiCl4-mediated vinylogous Mukaiyama aldol reaction (VMAR) of chiral ketene silyl N,O-acetal with
propionaldyhyde, an aldol condensation, Witting olefination, and a cyclization. The synthesis proceeds in
eight steps.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Aldol reaction
Wittig olifination
Cyclization
Salinipyrones
Pacificanones
1. Introduction
Our retrosynthetic analysis of salinipyrone A (1) is outlined in
Scheme 1. We envisioned that Weinreb amide 5 could be stereo-
Polyketides are a large family of natural products produced by
step-wise decarboxylative Claisen type condensation of acyl-CoA
precursors, catalyzed by polyketide synthases (PKSs). The carbon
skeleton of polyketides may be further reduced and modified
based on the programming encoded by different domains present
in PKSs with ketoreductase, dehydratase, and enoylreductase ac-
tivities. A large number of type I polyketides with antitumor ac-
tivity have been isolated from marine actinomycetes.1,2 Four new
type I polyketides (Fig. 1), salinipyrones (A and B) and pacif-
icanones (A and B) have been isolated from cultures of the obligate
marine actinomycete Salinispora pacifica CNS-2373 found in
a sediment sample collected from Palau island, Western Pacific
Ocean. The biological activity of these compounds is currently
being examined in diverse bioassays. In initial screening, the sal-
inipyrones and the pacificanones displayed no significant activity
in a cancer cytotoxicity assay using HCT-116 human colon cancer
cells. In an isolated mouse splenocyte model of allergic in-
flammation, salinipyrone A displayed moderate inhibition of
selectively prepared by the vinylogous Mukaiyama aldol reaction.
According to above retrosynthetic analysis, compound 4 could be
accessed from propionaldehyde
2
and the vinylketene silyl
N,O-acetal 3.
OH
HO
OH
O
O
O
OH
O
Salinipyrone B(2)
1
Salinipyrone A( )
OH
OH
OH
OH
interleukin-5 production by 50% at 10
human cell cytotoxicity.
mg/mL without measurable
O
O
Pacificanones B
Pacificanones A
* Corresponding author. Fax: þ91 40 27193275; e-mail address: hmmeshram@
yahoo.com (H.M. Meshram).
Fig. 1. Chemical structures of salinipyrones A and B and pacificanones A and B.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.035

9290
P. Ramesh, H.M. Meshram / Tetrahedron 68 (2012) 9289e9292
as tert-butyldimethylsilyl (TBS) ether by reacting with TBDMSOTf in
the presence of 2,6-lutidine.
HO
OH
TBSO
O
O
Reductive removal of the chiral auxiliary from 4 using DIBALeH in
O
N
CH2Cl2 at ꢀ78 ꢁC, gave 7, which was homologated to (E)-
a,b-un-
5
O
saturated ester 8 (90% yield) by Wittig olifination using Ph3P]
CHCO2Et in CH2Cl2.The ester 8 was converted to the Weinreb amide 5
in 84% yield by using N-methoxy,N-methyl amine$HCl, and 2 equiv
iPrMgCl in THF.6 The dianion generated from ethyl 2-methyl-3-
oxopentanoate using LDA and followed by addition to a solution of
5 at 0 ꢁC gave corresponding tricarbonyl intermediate smoothly,
which on boiling with DBU in toluene effected cyclization to produce
9 in 58% yield.6,7 Subsequent deprotection of TBS with TBAF afforded
salinipyrone A (1) in 90% yield (Scheme 2). The physical and spectral
dataofoursynthetic1wereinexcellentagreementwiththeliterature
Salinipyrone A(1)
O
OTBS
O
O
N
4
Bn
OTBS
N
O
O
+
reports.3 Weobservedavalueof[
a]
25 ꢀ88.68(c0.35,MeOH),whereas
CHO
D
25 ꢀ87.00 (c 0.33, MeOH).
Bn
reported value for natural product was [a]
D
2
3
3. Conclusion
Scheme 1. Retrosynthesis of salinipyrone A.
In summary, we have described the stereoselective first total
syntheses of salinipyrone A (1). Key transformations in the sequence
included construction of d-hydroxy-a-methyl-a,b-unsaturated car-
2. Results and discussions
bonyl unit using the vinylogous Mukaiyama aldol reaction followed
by a seven-step synthetic sequence with 14% overall yield starting
from vinylketene silyl N,O-acetal 3.
Thus, starting vinylketene silyl N,O-acetal 3 was prepared by
unifying (S)-(þ)-4-benzyl-2-oxazolidinone and E-2-methyl-2-
pentenoic acid by using the known procedure.4 The vinylogous
aldol reaction of 3 with propionaldehyde 2 in the presence of TiCl4,
yielded anti-adduct 6 in 91% yield and in a >20:1 diastereomeric
ratio (as revealed by 1H NMR). The product 6 arose through the
anti-aldol transition state (Scheme 2) as proposed by Kobayashi.4,5
The secondary hydroxyl group of the aldol adduct 6 was protected
4. Experimental section
4.1. General remarks
All reactions were conducted under an atmosphere of nitrogen
(IOLAR Grade I). Progress of the reactions was monitored by TLC on
precoated Merck Silica Gel 60 F-254. Evaporation of solvents was
performedat reduced pressure ona Buchi rotaryevaporator. Column
chromatography was carried out with silica gel grade 60e120 and
Me
Bn
H
O
TBS
Cl4Ti
N
O
O
Me
100e200 mesh. 1H NMR spectra were recorded at 300 MHz and 13
C
O
Et
NMR spectra at 75 MHz in CDCl3 or CD3OD. J values were recorded
in hertz and abbreviations used were sdsinglet, dddoublet,
a
Favourable T.S in the anti-selective
Kobayashi aldol reaction
OTBS
N
O
mdmultiplet, and brdbroad. Chemical shifts (
d) are reported rela-
O
O
HO
tive toTMS (
d
¼0.0) as an internal standard. IR spectra were recorded
O
O
+
H
Me
H
Bn
Bn
on Thermo Nicolet FT/IR-5700. Mass spectral data were obtained
using MS (ESI), HRMS data obtained using quadrupole time-of-flight
(QTOF) mass spectrometer (QSTAR XL, Applied Biosystems MDS
Sciex, Foster City, USA). One or more of the following methods were
used for visualization: UV absorption by fluorescence quenching;
iodine staining; anisaldehyde stain (ethanol (135 mL)/H2SO4
(5 mL)/AcOH (1.5 mL)/p-anisaldehyde 3.7 mL). Ethyl acetate and
hexane were the common eluents used unless specified.
Et
N
O
N
O
TBS
2
3
O
O
6
Bn
Me
Cl Ti
4
O
Alternative Kobayashi T.S exbhiting
unfavourable interaction
TBSO
O
O
TBSO
O
d
b
c
N
O
H
O
4.2. Procedures and analytical data
7
Bn
4
4.2.1. (S)-4-Benzyl-3-((4S,5R,E)-5-hydroxy-2,4-dimethylhept-2-
enoyl)oxazolidin-2-one (6). TiCl4 (1.0 M in CH2Cl2, 11.8 mL,
11.8 mmol, 1.0 equiv) was slowly added to a solution of propio-
naldehyde 2 (1.70 mL, 23.6 mmol, 2.0 equiv) in CH2Cl2 (60 mL) at
ꢀ78 ꢁC and the mixture was stirred at same temperature for 10 min.
A solution of vinylketene silyl N,O-acetal 3 (4.43 g, 11.8 mmol,
1.0 equiv) in CH2Cl2 (60 mL) was added at ꢀ78 ꢁC and the reaction
mixture was stirred for 20 h at same temperature. The reaction
mixture was quenched by the addition of a saturated solution of
Rochelle’s salt (50 mL) and the mixture was extracted with CH2Cl2
(3ꢂ50 mL). The combined organic layers were sequentially washed
with a saturated solution of NaHCO3 (150 mL), brine (100 mL), and
then dried over MgSO4. The solvent was removed under reduced
pressure and the residue was purified by flash column chromatog-
raphy on silica gel (15% ethyl acetate/hexane) to provide 6-anti
TBSO
TBSO
f
e
O
CO2Et
N
5
8
TBSO
HO
OH
OH
g
O
O
9
O
O
Salinipyrone A (1)
Scheme 2. Reagents and conditions: (a) 2 (2.0 equiv), TiCl4 (1.0 equiv), CH2Cl2, ꢀ78 ꢁC,
20 h, 91% (>20:1 dr); (b) TBSeOTf, 2,6-lutidine, CH2Cl2, 0 ꢁC, 90%; (c) DIBALeH, CH2Cl2,
ꢀ78 ꢁC, 72%; (d) Ph3P]CHCO2Et, CH2Cl2, rt, 90%; (e) N-methoxy,N-methyl amine$HCl,
i
2 equiv PrMgCI, THF, ꢀ20 ꢁC to 0 ꢁC, 84%; (f) ethyl 2-methyl-3-oxopentanoate, LDA,
THF, 0 ꢁC, 3 h, 62%; (ii) DBU, toluene, reflux, 6 h, 56%; (g) TBAF, THF, 0 ꢁC to rt, 90%.

P. Ramesh, H.M. Meshram / Tetrahedron 68 (2012) 9289e9292
9291
25
(3.21 g, 91%) as a colorless oil. Rf (20% EtOAc/hexanes) 0.40. [
a
]
11.5 mmol) in CH2Cl2 (20 mL) was treated with Ph3P]CHCO2Et
(5.20 g, 15.0 mmol) and stirred for 2 h. The solvent was evaporated
and the residue purified by column chromatography (5% EtOAc/
D
þ28.8 (c 1, CHCl3). 1H NMR (300 MHz, CDCl3):
¼0.98e1.04 (6H, m,
d
CH2Me, CHMe), 1.35e1.50 (1H, m, CHaHbCH3), 1.60e1.75 (1H, m,
CHaHbCH3), 1.95 (3H, s, ]CeMe), 2.50e2.60 (1H, m, ]CHeCHCH3),
2.83 (1H, dd, J¼9.06, 13.40 Hz, CHaHbeAr), 3.22 (1H, ddd, J¼2.26,
7.36, 10.73 Hz, CHeOH), 3.30 (1H, dd, J¼2.92, 10.73 Hz, CHaHb-Ar),
4.13 (dd, 1H, J¼6.61, 8.87 Hz, OCHaHbCH), 4.26 (t, 1H, J¼8.87 Hz,
OCHaHbCH), 4.68e4.79 (1H, m, CHeN), 5.75 (1H, d, J¼10.38 Hz,
HC]CCH3eCO), 7.17 (2H, d, J¼7.55 Hz, AreH), 7.23e7.35 (3H, m,
hexane) to give 8 (3.51 g, 90%) as a colorless liquid. Rf (5% EtOAc/
25
hexanes) 0.40. [
d
a]
ꢀ12.6 (c 1, CHCl3). 1H NMR (300 MHz, CDCl3):
D
¼0.02 (6H, s, Si(Me)2), 0.82 (3H, t, J¼6.79 Hz, CH2CH3), 0.88 (9H, s,
SiC(Me)3), 0.98 (3H, d, J¼6.79 Hz, CH3CH), 1.30 (3H, t, J¼6.79 Hz,
OCH2CH3), 1.35e1.48 (2H, m, CH2CH3), 1.77 (3H, s, ]CeMe),
2.62e2.72 (1H, m, ]CeCHMe), 3.44e3.51 (1H, m, HCeOTBS), 4.20
(2H, q, J¼6.79 Hz, OCH2CH3), 5.76 (1H, d, J¼15.10 Hz, CHb]
CHaeCO2Et), 5.87 (1H, d, J¼9.82 Hz, CHb]CHaeCO2Et), 7.32 (1H, d,
AreH). 13C NMR (75 MHz, CDCl3):
d
¼9.83, 13.69, 16.00, 26.55, 37.24,
39.52, 54.89, 66.15, 76.32, 127.24, 128.75, 129.37, 130.77, 134.69,
142.44, 153.98, 171.48. IR (KBr): nmax¼3521(br), 2963, 2927, 1775,
1682 (C]O), 1310, 1213, 1102, 766 cmꢀ1. ESI-MS: m/z¼332 [Mþ1],
354 [MþNa]. ESI-HRMS: m/z calculated for C19H25NO4Na: 354.1681;
found: 354.1675.
J¼15.86 Hz, CHd]CH). 13C NMR (75 MHz, CDCl3):
¼ꢀ4.57, ꢀ4.34,
d
9.46, 12.33, 14.25, 16.59, 25.80, 27.43, 27.92, 37.59, 60.01, 76.74,
115.47, 144.43, 149.81, 156.73, 167.48. IR (KBr): nmax¼2958, 2932,
2857, 1715 (C]O), 1625, 1465, 1254, 1168, 1031, 837, 773 cmꢀ1. ESI-
MS: m/z¼363 [MþNa]. ESI-HRMS: calculated for C19H36O3NaSi:
363.2331; found: 363.2328.
4.2.2. (S)-4-Benzyl-3-((4S,5R,E)-5-(tert-butyldimethylsilyloxy)-2,4-
dimethylhept-2-enoyl)oxazolidin-2-one (4). To a stirred alcohol 6
(1.12 g, 3.4 mmol) and 2,6-lutidine (0.57 g, 8.5 mmol) in CH2Cl2
(15 mL) was added TBDMSOTf (1.02 g, 3.74 mmol) at ꢀ78 ꢁC portion
wise over a period of 10 min. The reaction mixture was stirred at
ꢀ78 ꢁC for 20 min. The mixture was then diluted with CH2Cl2 and
washed with water, brine. The organic layer was dried over anhy-
drous Na2SO4, filtered, and concentrated. The crude product was
purified by column chromatography using (5% ethyl acetate/hexane)
to afford TBS protected compound 4 (1.39 g, 3.12 mmol, 92%) as
4.2.5. (2E,4E,6S,7R)-7-(tert-Butyldimethylsilyloxy)-N-methoxy-
N,4,6-trimethylnona-2,4-dienamide (5). To a solution of compound
8 (0.680 g, 2 mmol) and N-methoxy,N-methyl amine$HCl (0.292 g,
i
3 mmol) in dry THF (10 mL) was added 2 equiv PrMgCl, (2 mL,
4.0 mmol, 2 M solution in THF) dropwise at ꢀ20 ꢁC and the mixture
was stirred for 6 h. The reaction mixture was quenched with sat-
urated NH4Cl and the mixture was extracted with Et2O. The organic
extracts were washed with brine and dried over anhydrous Na2SO4.
Evaporation of the solvent in vacuum to give the crude product,
which was purified by flash chromatography (15% EtOAc/hexanes)
a colorless oil. Rf (5% EtOAc/hexanes) 0.50. [
a
]
25 þ7.52 (c 0.5, CHCl3).
D
1H NMR (300 MHz, CDCl3):
d
¼0.05 (6H, s, Si(Me)2), 0.87 (3H, t,
J¼7.36 Hz, CH2CH3), 0.90 (9H, s, SiC(Me)3), 1.02 (3H, d, J¼6.79 Hz,
CH3CH), 1.42e1.48 (2H, m, CH2CH3), 1.90 (3H, s, ]CeMe), 2.62e2.68
(1H, m, ]CeCHMe), 2.77 (dd,1H, J¼9.63,13.21 Hz, CHaHbeAr), 3.35
(dd,1H, J¼10.76,13.40 Hz, CHaHbeAr), 3.50e3.58 (1H, m, HCeOTBS),
4.10 (1H, dd, J¼5.28, 8.68 Hz, OCHaHbCH), 4.20 (1H, t, J¼8.30 Hz,
OCHaHbCH), 4.60e4.66 (1H, m, CHeN), 5.95 (1H, d, J¼9.82 Hz, HC]
CCH3eCO), 7.17 (2H, d, J¼7.55 Hz, AreH), 7.22e7.35 (3H, m, AreH).
to give the title compound 5 (0.596 g, 84%) as a light yellow oil. Rf
25
(15% EtOAc/hexanes) 0.30. [
(300 MHz, CDCl3):
a
]
D
ꢀ8.5 (c 3, CHCl3). 1H NMR
d
¼0.26 (6H, s, Si(Me)2), 1.07 (3H, t, J¼7.55 Hz,
CH2CH3), 1.12 (9H, s, SiC(Me)3), 1.23 (3H, d, J¼6.79 Hz, CH3CH),
1.58e1.66 (2H, m, CH2CH3), 2.03 (3H, s, ]CeMe), 2.90 (1H, m, ]
CeCHMe), 3.46 (3H, s, NeMe), 3.70 (1H, dd, J¼4.53, 9.82 Hz,
HCeOTBS), 3.94 (3H, s, NeOMe), 6.07 (1H, d, J¼9.82 Hz, CHb]
CHaeCO), 6.54 (1H, d, J¼15.86 Hz, CHb]CHaeCO), 7.54 (1H, d,
13C NMR (75 MHz, CDCl3):
d
¼ꢀ4.60, ꢀ4.34, 10.07, 13.50,15.68, 18.00,
25.81, 25.55, 27.28, 37.38, 55.34, 66.21, 76.57, 127.14, 128.73, 129.32,
J¼15.86 Hz, CHd]CH). 13C NMR (75 MHz, CDCl3):
¼ꢀ4.41, ꢀ4.19,
d
130.24, 135.08, 140.92, 152.84, 171.93. IR (KBr): nmax¼2958, 2931,
9.84, 12.70, 16.65, 18.14, 25.95, 27.37, 32.49, 37.33, 61.51, 76.86,
113.01, 132.39, 143.83, 148.76, 167.64. IR (KBr): nmax¼2958, 2931,
2857, 1657 (C]O), 1610, 1464, 1374, 1104, 1008, 836, 774 cmꢀ1. ESI-
MS: m/z¼356 [Mþ1]. ESI-HRMS: m/z calculated for C19H38NO3Si:
356.2620; found: 356.2614.
2857, 1789, 1682 (C]O), 1461, 1352, 1253, 1211, 1105, 836, 772 cmꢀ1
.
ESI-MS: m/z¼446 [Mþ1], 468 [MþNa]. ESI-HRMS: m/z calculated for
C25H39NO4NaSi: 468.2546; found: 468.2546.
4.2.3. (4S,5R,E)-5-(tert-Butyldimethylsilyloxy)-2,4-dimethylhept-2-
enal (7). To a solution of DIBAL-H (1 M in hexane) (6.1 mL,
6.1 mmol) in CH2Cl2 (20 mL) was added a solution of compound 4
(1.357 g, 3.05 mmol) in CH2Cl2 (25 mL) at ꢀ78 ꢁC with dropwise
and the mixture was stirred for 30 min. The reaction mixture was
quenched by the addition of MeOH (0.5 mL) and saturated sodium
potassium tartarate solution, and the resulting mixture was diluted
with CH2Cl2, and then stirred for another 30 min. The mixture was
dried over MgSO4 and filtered through a pad of Celite, and the fil-
trates were concentrated in vacuo. The residue was chromato-
graphed on silica gel (hexane) to give aldehyde 7 (592 mg, 72%) as
4.2.6. 6-((1E,3E,5S,6R)-6-(tert-Butyldimethylsilyloxy)-3,5-dimethyl-
octa-1,3-dienyl)-4-hydroxy-3,5-dimethyl-2H-pyran-2-one
(9). To
a freshly prepared 1.0 M solution of LDA (1.20 mL) in anhydrous
THF at ꢀ20 ꢁC was added a solution of ethyl 2-methyl-3-oxo-
pentanoate (83 mg, 0.53 mmol) in anhydrous THF (5 mL) dropwise
and allowed to stir for 30 min at 0 ꢁC. To this mixture, a solution of 5
(376 mg, 1.06 mmol) in anhydrous THF (5 mL) was added dropwise
at 0 ꢁC and allowed to stir for another 30 min at the same tem-
perature. After completion, the reaction mixture was quenched
with saturated aqueous NH4Cl (6 mL) at 0 ꢁC and allowed to warm
to room temperature. The aqueous layer was separated and washed
with EtOAc (2ꢂ5 mL). The combined organic layers were dried over
anhydrous Na2SO4 and concentrated in vacuo to afford the tri-
carbonyl compound (280 mg, 62%) as a liquid. Without further
purification, the crude tricarbonyl compound was treated with DBU
(1.0 mL, 6.81 mmol) in anhydrous toluene under reflux for 6 h. The
solvent was removed under reduced pressure and then the residue
was diluted with CH2Cl2 (10 mL) and washed with water (3 mL).
The aqueous layer was again washed with CH2Cl2 (2ꢂ10 mL). The
combined organic layers were dried over Na2SO4, the solvent was
removed by concentration on the rotary evaporator, and the crude
product was purified by flash chromatography (50% EtOAc/hex-
anes) to give title compound 9 (145 mg, 56 %) as a pale yellow
a colorless oil. Rf (2% EtOAc/hexanes) 0.50. [
a
]
25 ꢀ6.48 (c 2, CHCl3).
D
1H NMR (300 MHz, CDCl3):
d¼0.03 (6H, s, Si(Me)2), 0.83 (3H, t,
J¼7.36 Hz, CH2CH3), 0.87 (9H, s, SiC(Me)3), 1.03 (3H, d, J¼6.79 Hz,
CH3CH), 1.30e1.55 (2H, m, CH2CH3), 1.72 (3H, s, ]CeMe),
2.75e2.87 (1H, m, ]CeCHMe), 3.53 (1H, dd, J¼5.85, 9.82 Hz,
HCeOTBS), 6.40 (1H, d, J¼10.38 Hz, HC]CCH3eCO), 9.34 (1H, s,
CHO). 13C NMR (75 MHz, CDCl3):
d
¼ꢀ4.45, ꢀ4.22, 9.38, 9.52, 16.43,
18.07, 25.83, 27.97, 37.75, 76.50, 138.80, 156.88, 195.55. IR (KBr):
nmax¼2948, 1718 (C]O), 1465, 1252, 1168, 1031 cmꢀ1. ESI-MS:
m/z¼293 [MþNa].
4.2.4. (2E,4E,6S,7R)-Ethyl-7-(tert-butyldimethylsilyloxy)-4,6-
dimethylnona-2,4-dienoate (8). A solution of enal
7 (3.10 g,

9292
P. Ramesh, H.M. Meshram / Tetrahedron 68 (2012) 9289e9292
25
liquid. Rf (50% EtOAc/hexanes) 0.20. [
a]
ꢀ8.46 (c 2.3, CHCl3). 1H
(75 MHz, CDCl3):
d
¼9.12, 9.60, 10.82, 12.76, 17.50, 28.64, 40.00,
D
NMR (300 MHz, CDCl3):
d
¼0.04 (6H, s, Si(Me)2), 0.88 (3H, t,
78.02, 100.00, 110.06, 115.50, 134.90, 140.82, 142.12, 154.34, 167.56,
167.82. IR (KBr): nmax¼3390 (br), 1675 (C]O), 1555, 1253, 1105,
836 cmꢀ1. ESI-MS: m/z¼293 [Mþ1]. ESI-HRMS: m/z calculated for
C17H25O4: 293.1744; found: 293.1747.
J¼7.54 Hz, CH2CH3), 0.90 (9H, s, SiC(Me)3), 1.00 (3H, d, J¼6.79 Hz,
CH3CH), 1.28e1.52 (2H, m, CH2CH3), 1.82 (3H, s, ]CeMe), 1.92 (3H,
s, ]CeMe), 2.06 (3H, s, ]CeMe), 2.64e2.70 (1H, m, ]CeCHMe),
3.50 (1H, q, J¼6.00 Hz, HCeOTBS), 5.83 (1H, d, J¼9.84 Hz, CH]CH),
6.30 (1H, d, J¼15.86 Hz, CH]CH), 7.30 (1H, d, J¼15.86 Hz, CH]CH).
13C NMR (75 MHz, CDCl3):
d
¼ꢀ4.43, ꢀ4.28, 7.67, 8.16, 10.26, 13.36,
Acknowledgements
16.66, 25.96, 27.38, 38.20, 78.82, 101.02, 110.22, 114.34, 133.92,
144.24, 148.10, 157.42, 166.90, 168.82. IR (KBr): nmax¼3178 (br),
2980, 1678 (C]O), 1569, 1378, 1265, 1180, 1056 cmꢀ1. ESI-MS:
m/z¼429 [MþNa]. ESI-HRMS: m/z calculated for C23H38O5NaSi:
429.2437; found: 429.2434.
P.R. thanks CSIR-UGC, New Delhi, India, for the award of fel-
lowships and Dr. J.S. Yadav, Director IICT, for his support and
encouragement.
References and notes
4.2.7. Salinipyrone A (1). To a solution of compound 9 (0.206 g,
0.5 mmol) in dry THF (5 mL) was added TBAF (0.5 mL, 0.5 mmol,
1 M solution in THF) dropwise at 0 ꢁC and the mixture was stirred
for 90 min, then H2O (1 mL) was added and the mixture was
extracted with AcOEt. The organic extracts were washed with brine
and dried over anhydrous Na2SO4. Evaporation of the solvent in
vacuum to give the crude product, which was purified by flash
1. Shen, B. Curr. Opin. Chem. Biol. 2003, 7, 285e295.
2. Gokhale, R. S.; Sankaranarayanan, R.; Mohanty, D. Curr. Opin. Struct. Biol. 2007, 17,
736e743.
3. Oh, D. C.; Gontang, E. A.; Kauffman, C. A.; Jensen, P. R.; Fenical, W. J. Nat. Prod.
2008, 71, 570e575.
4. (a) Nicolaou, K. C.; Sun, Y.-P.; Ramakrishna, G.; Biswadip, B.; David, Y.; Chen, K. J.
Am. Chem. Soc. 2008, 130, 3633e3644; (b) Shirokawa, S.-i.; Shinoyama, M.; Ooi,
I.; Hosokawa, S.; Nakazaki, A.; Kobayashi, S. Org. Lett. 2007, 9, 849e852.
5. (a) Gerrit, S.; Markus, K. Org. Lett. 2012, 14, 1608e1611; (b) Shirokawa, S.;
Kamiyama, M.; Nakamura, T.; Okada, M.; Nakazaki, A.; Hosokawa, S.; Kobayashi,
S. J. Am. Chem. Soc. 2004, 126, 13604e13605; (c) Bruce, H. L.; Benjamin, A. J. Am.
Chem. Soc. 2009, 131, 1396e1397; (d) Giovanni, C.; Lucia, B.; Claudio, C.; Gloria, R.;
Franca, Z. Chem. Rev. 2011, 111, 3076e3154; (e) Anke, S.; Sven, M. l.; Martin, E. M.
Tetrahedron 2008, 64, 6263e6269.
6. Anthony, A. B.; Dieter, E. Tetrahedron Lett. 1998, 39, 7823e7826.
7. (a) Yasuharu, I.; Shigeru, O.; Shigeru, N.; Shosuke, Y. Tetrahedron Lett. 1996, 37,
2997e3000; (b) Kathlyn, A. P.; Yeon-Hee, L. J. Am. Chem. Soc. 2004, 126,
15968e15969.
chromatography (70% EtOAc/hexanes) to give the title compound 1
25
(0.131 g, 90%) as a yellow syrup. Rf (70% EtOAc/hexanes) 0.35. [a]
D
ꢀ88.68 (c 0.35, MeOH). 1H NMR (300 MHz, CD3OD):
¼0.95 (3H, t,
d
J¼7.55 Hz, CH2CH3), 1.03 (3H, d, J¼7.00 Hz, CH3CH), 1.36e1.48 (2H,
m, CH2CH3), 1.85 (3H, s, ]CeMe), 1.94 (3H, s, ]CeMe), 2.06 (3H, s,
]CeMe), 2.60e2.68 (1H, m, ]CeCHMe), 3.36 (ddd, 1H, J¼8.76,
5.22, 4.00 Hz, CHOH), 5.80 (1H, d, J¼10.53 Hz, CH]CH), 6.35 (1H, d,
J¼15.57 Hz, CH]CH), 7.10 (1H, d, J¼15.57 Hz, CH]CH). 13C NMR