Stereoselective synthesis of 2-epi-jaspine B via base-catalyzed intramolecular oxy-Michael conjugate addition approach

Article abstract of DOI:10.1016/j.tetasy.2009.07.004

2-epi-Jaspine B has been synthesized starting from (-)-diethyl tartrate in 12 simple steps and 26.6% overall yield. The key intermediate was obtained via stereoselective base-catalyzed intramolecular oxy-Michael conjugate addition followed by tandem hydro

Full text of DOI:10.1016/j.tetasy.2009.07.004

Tetrahedron: Asymmetry 20 (2009) 1802–1805
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of 2-epi-jaspine B via base-catalyzed
intramolecular oxy-Michael conjugate addition approach
*
Gowrisankar Reddipalli, Mallam Venkataiah, Mithilesh Kumar Mishra, Nitin W. Fadnavis
Biotransformations Laboratory, Organic Division-I, Indian Institute of Chemical Technology, Habsiguda, 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:
2-epi-Jaspine B has been synthesized starting from (ꢀ)-diethyl tartrate in 12 simple steps and 26.6% over-
all yield. The key intermediate was obtained via stereoselective base-catalyzed intramolecular oxy-
Michael conjugate addition followed by tandem hydrogenation/hydrogenolysis.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 2 June 2009
Accepted 1 July 2009
Available online 29 July 2009
1. Introduction
68% yield. Treatment of 2 with benzyl bromide in Ag2O/DCM gave
3 in 95% yield. Reduction of 3 with lithium aluminum hydride in
Phytosphingosine is present in large quantities in yeast and
plants, as both the free sphingoid base and an integral component
of (glyco)phytosphingolipids.1 Several biological processes, includ-
ing heat–stress response and endocytic events involve phytosphin-
gosine.2 Sphingosine-1-phosphate has been found to induce a
rapid and relevant release of arachidonic acid, and increase phos-
pholipase D activity in A549 cells.3 Phytosphingosine has also been
found to be a key intermediate from which more complex metab-
olites are derived.4 Apart from the linear structures, phytosphingo-
sine derivatives also exist as anhydro forms that were shown to be
potent inhibitors of a variety of glycosidase activities.5 One of the
naturally occurring anhydrophytosphingosine derivatives isolated
from marine sponges, Pachastrissa sp. and Jaspis sp.,6 exhibited a
significant cytotoxicity against P388, A549, HT29, and MEL28 car-
cinoma cell lines in vitro.7 The impressive biological activity and
novel structural features have prompted several research groups
to explore the preparation of this compound.6,8,9 As part of our
research program in the synthesis and evaluation of enzyme inhib-
itors we have carried out the stereoselective total synthesis of 2-
epi-jaspine B 12, a diastereomer of jaspine B 11 (Fig. 1).
THF, followed by N-Boc protection in a single-pot reaction gave
diol 4 in 90% overall yield. Acetonide protection by treatment with
2,2-dimethoxy propane gave regioselective product 5 in 85%
yield.11 Oxidation of 5 with Dess–Martin periodinane followed by
Wittig olefination with ethoxycarbonyl methylene triphenylphos-
phorane gave 6 in 92% yield. Deprotection of the acetonide with
PTSA in MeOH gave N-protected amino alcohol 7 (97%) which
was treated with 0.1 equiv of sodium hydride in THF at 0 °C for
1 h to obtain the diastereoselective intramolecular oxy-Michael
H2N
OH
H2N
OH
C14H29
2-epi-jaspine B 12
C14H29
jaspine B 11
O
O
Figure 1.
BocHN
OBn
Our approach to 2-epi jaspine B 12 is depicted retrosynthetically
in Scheme 1. The syn-(S,S)-stereochemical center in commercially
available (ꢀ)-diethyl tartrate can be utilized in the preparation of
protected anti-aminoalcohols,10 which can be subjected to a
base-catalyzed intramolecular oxy-Michael conjugate addition.11
TFA− +H3N
OH
O
OEt
O
C
14H29
O
10
OH
8
2. Results and discussion
OBn
OEt
EtOOC
O
Commercially available (ꢀ)-diethyl tartrate was treated with
thionyl chloride to form cyclic sulfite 1, which was treated with
sodium azide in DMF10 at room temperature to yield azide 2 in
COOEt
OH
NBoc
O
(−)-DET
6
* Corresponding author. Tel.: +91 40 27191631; fax: +91 40 27160512.
E-mail addresses: fadnavisnw@yahoo.com, fadnavis@iict.res.in (N.W. Fadnavis).
Scheme 1.
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.07.004

G. Reddipalli et al. / Tetrahedron: Asymmetry 20 (2009) 1802–1805
1803
OBn
OBn
O
O
OH
O
O
OH
OEt
OEt
HO
d
EtO
EtO
c
OEt
a
b
EtO
(−)-DET
NHBoc
O
O
N3
N3
O
O
4
1
2
3
e
OBn
OBn
OBn
OEt
OEt
g
f
OH
O
HO
O
NBoc
O
NHBoc
O
NBoc
7
6
5
h
TFA − +H3N
OH
OBn
BocHN
OBn
BocHN
j
O
i
C
14H29
O
O
C11H23
OEt
O
10
8
9
Scheme 2. (a) SOCl2, TEA, DCM, 0 °C, 3 h; (b) NaN3, DMF, rt, 5 h (68%); (c) BnBr, Ag2O, DCM, rt, 10 h, 95%; (d) LAH/THF, 4 h reflux, 2 m NaOH, (Boc)2O, rt, 30 min, 90%; (e) 2,2-
DMP, DCM, rt, 3 h, 85%; (f) (i) Dess–Martin periodinane, DCM, rt, 1 h; (ii) Ph3P@CH–COOEt, DCM, rt, 30 min, 92%; (g) PTSA/MeOH, rt, 2 h, 97%; (h) NaH/THF, 0 °C to rt 1 h, 90%;
(i) i) DIBAL-H/THF, ꢀ78 °C, 1.5 h; (ii) Brꢀ+PPh3C12H25, n-BuLi, ꢀ78 °C to rt, 3 h (73%); (j) Pd(OH)2/C, H2, MeOH, TFA, rt 5 h, 92%.
product12 8 in 90% yield. The formation of anti product 8 was
deduced from the 13C NMR spectra in which the anti-C2 resonates
at 78.5 ppm. In the case of a syn-product, the C2 is expected to
resonate at 70 ppm (Scheme 2).
measured with a Horiba-SEPA-300 digital polarimeter. Mass spec-
tra were recorded on a Q STAR mass spectrometer (Applied Biosys-
tems, USA).
Having attained the required stereochemistry in the terahydrof-
uranyl ring, the attachment of the alkyl side chain was achieved by
reduction of the ester group with DIBAL-H to the aldehyde,
followed by a Wittig olefination with dodecanylidene triphenyl
phosphorane. Thus, 8 was successfully transformed into 9 in 73%
yield. Tandem hydrogenation/hydrogenolysis of 9 over palladium
hydroxide on carbon in MeOH/TFA gave the corresponding TFA salt
of 2-epi-jaspine B 10 in 92% yield. The formation of anti-product 10
was confirmed from the 13C NMR spectra in which the anti-C3
resonates at 74.3 ppm. In the case of the syn-product, C3 is
expected to resonate at 71 ppm as reported in the literature.6,8a Dat-
ta et al. have previously reported the preparation of 2,3-syn-11 by an
oxy-Michael approach,8d but critical analysis of their spectroscopic
data by Davies et al. has shown that the product is an anti-product
formed via retro-Michael/Michael epimerization pathway. Our re-
sultsareinfullagreementwiththeproposedmechanismof Davies,8a
which predicts a thermodynamically favorable 2,3-anti product
after the attack of the oxy-anion during the Michael addition.
4.1.1. 1-[(1R,2S)-3-Ethoxy-1-(ethoxycarbonyl)-2-hydroxy-3-
oxopropyl]-1,2-triazadien-2-ium 2
Thionyl chloride (2.2 mL, 30.1 mmol) was added drop wise to a
stirred solution of diethyl (S,S)-tartrate (3.1 g, 15.0 mmol) and
anhydrous triethylamine (4.9 mL, 31.1 mmol) in 30 mL of dry
CH2Cl2 at 0 °C. The temperature was allowed to reach room tem-
perature in 2 h. Next, CH2Cl2 (20 mL) and saturated NaCl (40 mL)
were added to the reaction mixture, after which the layers were
separated, and the aqueous phase was extracted thoroughly with
CH2Cl2 (2 ꢁ 50 mL). The combined organic phases were dried with
anhydrous Na2SO4. The solvent was removed under reduced pres-
sure to yield 1 quantitatively as brown oil which was used without
further purification.
To a solution of 1 in 30 mL of DMF at room temperature, sodium
azide (1.35 g, 20.74 mmol) was added and the mixture was stirred
at rt for 5 h. The solvent was then evaporated under reduced pres-
sure, the residue was dissolved in 50 mL of EtOAc, washed with
saturated NaCl (3 ꢁ 30 mL), and dried with anhydrous Na2SO4.
After evaporation of the solvent, the residue was chromatographed
over silica gel (60–120 mesh, EtOAc/hexane, 1:3) yielding 2 (2.36 g,
3. Conclusion
68%) as a viscous oil. ½a D25
ꢂ
¼ ꢀ30:5 (c 1, EtOH). IR(neat)
mmax = 1211,
1744, 2119, 2931, 2986, 3485 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d
In conclusion, we have synthesized the epimer of jaspine B in
26.6% overall yield in 12 simple steps. The strategy of the stereose-
lective intramolecular oxy-Michael conjugate addition reaction can
be applied to synthesis of a variety of products.
1.30–1.39 (m, 6H), 3.21–3.25 (d, J = 6.0 Hz, 1H), 4.21–4.37 (m,
4H), 4.59 (qt, J = 3.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 13.9,
14.0, 62.3, 62.6, 64.3, 72.0, 166.9, 170.7. ESI-MS: m/z = 254 (M+Na).
4.1.2. 1-[(1R,2S)-2-(Benzyloxy)-3-ethoxy-1-(ethoxycarbonyl)-3-
oxopropyl]-1,2-triazadien-2-ium 3
4. Experimental
To a solution of 2 (2 g, 8.7 mmol) in 20 mL of dry CH2Cl2 was
added silver oxide (3.05 g, 13.0 mmol) followed by benzyl bromide
(1.23 mL, 10.4 mmol). The reaction mixture was stirred for 10 h at
room temperature and then filtered through a pad of Celite. The fil-
trate was evaporated to dryness and the residue was purified by
column chromatography on silica gel (60–120 mesh, EtOAc/hex-
4.1. General
All reagents were purchased from Aldrich. IR spectra were
recorded on
a
Perkin–Elmer RX-1 FT-IR system. 1H NMR
(300 MHz) and 13C NMR (75 MHz) spectra were recorded on a
Bruker Avance-300 MHz spectrometer. Optical rotations were

1804
G. Reddipalli et al. / Tetrahedron: Asymmetry 20 (2009) 1802–1805
ane, 4:96). Compound 3 was obtained as a colorless oil (2.64 g,
64.2, 65.3, 71.8, 78.4, 79.31, 80.4, 123.5, 124.1, 127.7, 127.9,
128.0, 128.4, 128.5, 137.33, 145.7, 165.8. ESI-MS: m/z = 442
(M+Na).
95%). ½a 2D5
ꢂ
¼ þ5:5 (c 1, CHCl3). IR(neat)
mmax = 1202, 1753, 2113,
2906, 2939, 2983 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 1.19 (m,
6H), 4.08–4.20 (m, 1H), 4.21–4.33 (m, 4H), 4.36–4.62 (m, 2H),
4.85–4.92 (m, 1H), 7.28–7.38 (m, 5H). 13C NMR (75 MHz, CDCl3):
d 14.0, 14.1, 61.6, 61.8, 62.3, 63.1, 73.3, 78.3, 127.9, 128.2, 128.4,
136.4, 167.0. ESI-MS: m/z = 344 (M+Na).
4.1.6. Ethyl 2-((2R,3S,4S)-3-(benzyloxy)-4-[(tert-
pentyloxy)carbonyl] aminotetrahydro-2-furanyl) acetate 8
Compound 6 (0.49 g, 1.16 mmol) was stirred with a solution of
PTSA (13 mg, 0.05 mmol) in methanol (15 mL) for 2 h at room tem-
perature. Methanol was removed by evaporation under reduced
pressure, after which sodium carbonate solution (1 mL, 10%) was
added and the product was extracted with ethyl acetate
(3 ꢁ 15 mL). The ethyl acetate layer was dried over anhydrous so-
dium sulfate and evaporated. The deprotected product 7 obtained
as an oil (0.43 g, 1.14 mmol, 97%) was dissolved in 15 mL of dry
THF. Sodium hydride (catalytic amount, 60% dispersion in mineral
oil, 7 mg) was added at 0 °C, after which the reaction mixture was
allowed to return to room temperature and stirred for 1 h. The
reaction mixture was then cooled in ice and quenched with 2 mL
of saturated NH4Cl solution. The solvent was evaporated under re-
duced pressure, and the residue was extracted with EtOAc
(2 ꢁ 15 mL) and dried with anhydrous Na2SO4. After evaporation
of ethyl acetate, the residue was chromatographed over silica gel
(60–120 mesh, EtOAc/hexane, 1:9) yielding 8 (0.375 g, 90%) as a
4.1.3. tert-Butyl N-[(1S,2S)-2-(benzyloxy)-3-hydroxy-1-
(hydroxymethyl)propyl] carbamate 4
To a solution of lithium aluminum hydride (0.54 g, 14.6 mmol)
in 50 mL of dry THF was added azide 3 (1.55 g, 4.8 mmol) in dry
THF drop wise at 0 °C for 20 min, after which the reaction mixture
was refluxed for 4 h. The reaction was quenched with 10 mL of cold
saturated NH4Cl solution, after which a 1 M NaOH solution and
Boc-anhydride (1.58 mL, 7.2 mmol) were added to the reaction
mixture and stirred for 30 min. The reaction mixture was filtered
and the solvent was evaporated under reduced pressure. The resi-
due was extracted with EtOAc (2 ꢁ 20 mL) and dried over anhy-
drous Na2SO4. After evaporation of the solvent, the residue was
chromatographed over silica gel (60–120 mesh, EtOAc/hexane,
2:3) yielding 4 (1.35 g, 90%) as a white solid. ½a D25
ꢂ
¼ ꢀ45:45 (c 1,
CHCl3). IR (KBr)
m
max = 1674, 2884, 2944, 3251, 3475 cmꢀ1 1H
.
NMR (300 MHz, CDCl3): d 1.42 (s, 9H), 3.40–3.46 (m, 1H), 3.57–
3.66 (m, 2H), 3.70–3.86 (m, 2H), 3.88–3.97 (m, 1H), 4.53–4.64
(m, 2H), 7.26–7.38 (m, 5H). 13C NMR (75 MHz, CDCl3): d 28.3,
51.5, 60.1, 61.7, 71.6, 78.2, 80.1, 128.0, 128.1,128.5, 137.8, 156.6.
ESI-MS: m/z = 334 (M+Na).
colorless oil. ½a D25
ꢂ
¼ þ11:5 (c 1, CHCl3). IR(neat)
mmax = 1500,
1713, 2857, 2925, 2974, 3442 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d
1.25 (t, J = 7.2 Hz, 3H), 1.45 (s, 9H), 2.51(dd, J = 1.9, 6.8 Hz, 2H),
3.63 (t, J = 8.35 Hz, 1H), 3.80–3.85 (m, 1H), 4.04–4.19 (m, 3H),
4.21–4.32 (m, 2H), 4.53–4.64 (m, 2H), 5.12 (d, J = 7.7 Hz, NH),
7.28–7.40 (m, 5H). 13C NMR (75 MHz, CDCl3): d 14.1, 28.3, 29.6,
38.5, 51.1, 60.7, 71.2, 72.0, 78.5, 79.7, 80.7, 127.9, 128.0, 128.5,
137.3, 155.5, 170.5. ESI-MS: m/z = 380 (M+1), 402 (M+Na).
4.1.4. tert-Butyl (4S)-4-[(1S)-1-benzyloxyethyl]-2,2 dimethyl-
1,3-oxazolane-3-carbamate 5
To a solution of the amino-protected diol 4 (1.08 g, 3.5 mmol) in
20 mL of dry CH2Cl2, were added 2,2-dimethoxypropane (1.35 mL,
10.4 mmol) and PTSA (32 mg, 0.14 mmol) and the reaction mixture
was stirred at ambient temperature for 3 h. The organic layer was
evaporated under reduced pressure to afford the crude acetonide
which was purified by column chromatography on silica gel (60–
120 mesh, EtOAc/hexane, 2:8) to yield 5 (0.96 g, 85%) as a colorless
4.1.7. tert-Pentyl N-(3S,4S,5R)-4-(benzyloxy)-5-[(Z)-2-tetradecenyl]
tetrahydro-3-furanylcarbamate 9
To a stirred solution of compound 8 (0.210 g, 0.55 mmol) in
20 mL of dry THF, DIBAL-H (0.094 g, 0.66 mmol) was added at
ꢀ78 °C and the solution was stirred for 1.5 h. After the completion
of the reaction, a saturated solution of sodium potassium tartrate
in water (2 mL) was added to quench the reaction. The solvent
was then evaporated under reduced pressure, the reaction mixture
was extracted with EtOAc (2 ꢁ 15 mL), dried with anhydrous
Na2SO4, and concentrated. The aldehyde product was used as such
without further purification due to its instability on silica gel
column.
oil. ½a 2D5
ꢂ
¼ ꢀ50:05 (c 1, CHCl3). IR(neat)
mmax = 1370, 1395, 1456,
1693, 2926, 2975, 3448 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 1.47–
1.53 (m, 15H), 3.32 (dd, J = 10, 16 Hz, 2H), 3.72–3.96 (m, 3H),
4.0–4.13 (m, 2H), 4.4–4.8 (m, 2H), 7.27–7.37 (m, 5H). 13C NMR
(75 MHz, CDCl3): d 24.1, 27.4, 28.1, 56.6, 58.2, 65.2, 71.2, 78.9,
81.2, 93.7, 127.5, 127.7, 128.2, 137.8, 153.9. ESI-MS: m/z = 374
(M+Na).
To a stirred solution of dodecyl triphenylphosphonium bromide
(1.13 g, 2.2 mmol) in 20 mL of dry THF at ꢀ78 °C was added n-
butyllithium (1.6 M solution in hexane 1.25 mL,1.87 mmol) drop-
wise and the resulting solution was stirred for 45 min. The crude
aldehyde obtained above was dissolved in dry THF (5 mL) and
added dropwise with stirring to the ylide solution at ꢀ78 °C. The
reaction mixture was then allowed to return to room temperature
and stirred for 3 h. The reaction was quenched with 6 mL of satu-
rated NH4Cl solution at 0 °C, the solvent was evaporated under re-
duced pressure, the residue was extracted with EtOAc (2 ꢁ 15 mL),
and dried with anhydrous Na2SO4. After evaporation of ethyl ace-
tate the residue was chromatographed (silica gel, 60–120 mesh,
EtOAc/hexane, 2:98) to obtain 9 (0.191 g, 73%) as a colorless oil.
4.1.5. tert-Butyl (4S)-4-[(1R,2E)-1-(benzyloxy)-4-ethoxy-4-oxo-
2-butenyl]-2,2-dimethyl-1,3-oxazolane-3-carboxylate (6)
To a stirred solution of compound 5 (0.756 g, 2.2 mmol) in
15 mL of dry CH2Cl2, Dess–Martin periodinane (1.20 g, 2.9 mmol)
was added and stirred at room temperature for 1 h. The reaction
mixture was then quenched with 5 mL of saturated Na2S2O3 solu-
tion, extracted with CH2Cl2 (2 ꢁ 20 mL), dried over anhydrous
Na2SO4, and concentrated under reduced pressure to obtain the
crude aldehyde. The crude aldehyde was dissolved in dichloro-
methane (15 mL) and treated with ethoxycarbonyl methylene tri-
phenylphosphorane (1.29 g, 3.0 mmol) for 30 min. The organic
layer was evaporated under reduced pressure and the residue
was purified by column chromatography on silica gel (60–120
mesh, EtOAc/hexane, 4:96) to yield compound 6 (0.81 g, 92%) as
½
a 2D5
ꢂ
¼ þ6:8 (c 1, CHCl3). IR(neat)
mmax = 1497, 1714, 2854, 2924,
3444 cmꢀ1 1H NMR (300 MHz, CDCl3): d 0.88 (t, J = 7.2 Hz, 3H),
.
a colorless oil. ½a D25
ꢂ
¼ ꢀ22:2 (c 1, CHCl3). IR(neat)
mmax = 1375,
1.21–1.37 (m, 8H), 1.45 (s, 9H), 2.00 (q, J = 6.6,13.0 Hz, 2H), 2.28
(q, J = 6.8,14.2 Hz, 2H), 3.57 (t, J = 7.55 Hz, 1H), 3.65–3.74 (m, 1H),
3.91 (q, J = 3.6, 9.1 Hz, 1H), 4.07–4.16 (m, 1H), 4.17–4.30 (m, 1H),
4.45–4.58 (m, 2H), 5.13 (d, J = 5.84 Hz, NH), 5.30–5.42 (m,1H),
5.45–5.58 (m, 1H), 7.26–7.41 (m, 5H). 13C NMR (75 MHz, CDCl3):
d 14.0, 22.6, 27.4, 28.3, 29.3, 29.5, 29.6, 31.4, 31.8, 51.4, 71.1,
1699, 2929, 2977, 3449 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 1.23–
1.57 (m, 18H), 3.80–4.06 (m, 4H), 4.13–4.28 (qt, J = 7.35 Hz, 2H),
4.30–4.43 (m, 1H), 4.54–4.64 (m, 2H), 5.94 (d, J = 15.43, 1H), 6.83
(dd, J = 5.9, 9.55 Hz, 1H), 7.26–7.35 (m, 5H). 13C NMR (75 MHz,
CDCl3): d 14.2, 23.0, 24.7, 27.0, 28.2, 28.3, 29.7, 59.8, 60.5, 60.6,

G. Reddipalli et al. / Tetrahedron: Asymmetry 20 (2009) 1802–1805
1805
Bobak, D. A.; Bruni, P.; Moss, J.; Vaughan, M. J. Biol. Chem. 1999, 274, 18605–
18612.
4. Liao, J.; Tao, J.; Lin, G.; Liu, D. Tetrahedron 2005, 61, 4715–4733.
5. (a) Shibano, M.; Tsukamoto, D.; Kusano, G. Heterocycles 2002, 57, 1539–1553;
(b) Lynch, D. V.; Dunn, T. M. New Phytol. 2004, 161, 677–702.
6. Sudhakar, N.; Kumar, A. R.; Prabhakar, A.; Jagadeesh, B.; Rao, B. V. Tetrahedron
Lett. 2005, 46, 325–327.
7. (a) Kuroda, I.; Musman, M.; Ohtani, I. I.; Ichiba, T.; Tanaka, J.; Cravalos, D. C.;
Higa, T. J. Nat. Prod. 2002, 65, 1505–1506; (b) Ledroit, V.; Debitus, C.; Lavaud, C.;
Massiot, G. Tetrahedron Lett. 2003, 44, 225–228.
8. For synthetic strategies and structural assignment of jaspine B and 2-epi-
jaspine B, see: (a) Abraham, E.; Davies, S. G.; Roberts, P. M.; Russell, A. J.;
Thomson, E. Tetrahedron: Asymmetry 2008, 19, 1027–1047; (b) van den Berg, R.
J. B. H. N.; Boltje, T. J.; Verhagen, C. P.; Litjens, R. E. J. N.; Van der Marel, G. A.;
Overkleeft, H. S. J. Org. Chem. 2006, 71, 836–839; (c) Lee, T.; Lee, S.; Kwak, Y. S.;
Kim, D.; Kim, S. Org. Lett. 2007, 9, 429–432; (d) Bhaket, P.; Morris, K.; Stauffer,
C. S.; Datta, A. Org. Lett. 2005, 7, 875–876; (e) Passiniemi, M.; Koskinen, A. M. P.
Tetrahedron Lett. 2008, 49, 980–983; (f) Reddy, L. V. R.; Reddy, P. V.; Shaw, A. K.
Tetrahedron: Asymmetry 2007, 18, 542–546; (g) Du, Y.; Liu, J.; Linhardt, R. J. J.
Org. Chem. 2006, 71, 1251–1253; (h) Liu, J.; Du, Y.; Dong, X.; Meng, S.; Xiao, J.;
Cheng, L. Carbohydr. Res. 2006, 341, 2653–2657; (i) Ramana, C. V.; Giri, A. G.;
Suryawanshi, S. B.; Gonnade, R. G. Tetrahedron Lett. 2007, 48, 265–268; (j)
Ribes, C.; Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2006, 62, 5421–5425;
(k) Prasad, K. R.; Chandrakumar, A. J. Org. Chem. 2007, 72, 6312–6315.
9. (a) Abraham, E.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson, R. L.;
Roberts, P. M.; Russell, A. J.; Sánchez-Fernández, E. M.; Smith, A. D.; Thomson, J.
E. Tetrahedron: Asymmetry 2007, 18, 2510–2513; (b) Abraham, E.; Brock, E. A.;
Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson, R. L.; Perkins, J. H.;
Roberts, P. M.; Russell, A. J.; Sánchez-Fernández, E. M.; Scott, P. M.; Smith, A. D.;
Thomson, J. E. Org. Biomol. Chem. 2008, 6, 16651673; (c) Yakura, T.; Sato, S.;
Yoshimoto, Y. Chem. Pharm. Bull. 2007, 55, 1284–1286; (d) Venkatesan, K.;
Srinivasan, K. V. Tetrahedron: Asymmetry 2008, 19, 209–215; (e) Chandrasekhar,
S.; Tiwari, B.; Prakash, S. J. ARKIVOC 2006, 155–161.
72.0, 79.6, 80.7, 82.4, 123.8, 127.8, 128.0, 128.5, 133.1, 137.4,
155.6. ESI-MS: m/z = 488 (M+1), 510 (M+Na).
4.1.8. TFA salt of 2-epi-jaspine B 10
To a stirred solution of compound 9 (0.106 g, 0.2 mmol) in
20 mL of methanol, trifluoroacetic acid (0.2 mL, 2.6 mmol) and pal-
ladium hydroxide/C (10 mg, catalytic amount) were added. The
reaction mixture was stirred under hydrogen atmosphere at rt
for 5 h. The reaction mixture was filtered through a pad of Celite,
and the filtrate was evaporated to dryness. The residue was chro-
matographed (silica gel, 60–120 mesh, EtOAc/methanol, 9:1) to ob-
tain 10 (0.080 g, 92%) as a white solid. ½a D25
¼ þ13:6 (c 1, EtOH)
ꢂ
{lit.6 +14.5 (c 1.5, EtOH)}. IR(KBr)
mmax = 1713, 2925, 2974,
3442 cmꢀ1 1H NMR (300 MHz, CD3OD): d 0.89 (t, J = 7.3 Hz, 3H),
.
1.22–1.39 (m, 22H), 1.41–1.68 (m, 4H), 3.63–3.76 (m, 3H), 3.98–
4.05 (m, 1H), 4.09–4.17 (m, 1H); 13C NMR (75 MHz, CD3OD): d
14.3, 23.6, 26.8, 30.3, 30.6, 30.7, 33.0, 34.0, 53.7, 69.3, 74.3, 85.2.
ESI-MS: m/z = 300 (M+1_CF3COOH).
Acknowledgments
We are thankful to UGC-New Delhi, and CSIR-New Delhi for
financial assistance.
References
10. (a) Caldern, F.; Doyagez, E. G.; Fernandez-Mayoralas, A. J. Org. Chem. 2006, 71,
6258–6261; (b) Byun, H.-S.; He, L.; Bittman, R. Tetrahedron 2000, 56, 7051–
7091.
1. (a) Lynch, D. V.; Dunn, T. M. New Phytol. 2004, 161, 677–702; (b) Dickson, R. C.;
Lester, R. L. Biochim. Biophys. Acta 1999, 1438, 305–321; (c) Dickson, R. C.;
Lester, R. L. Biochim. Biophys. Acta 1999, 1426, 347–357; (d) Sweely, C. C. In
Biochemistry of Lipids, Lipoproteins, and Membranes; Vance, D. E., Vance, J. E.,
Eds.; Elsevier: Amsterdam, 1991.
2. Jenkins, G. M. Cell. Mol. Life Sci. 2003, 60, 701–710.
3. (a) Vasta, V.; Meacci, E.; Catarzi, S.; Donati, C.; Farnararo, M.; Bruni, P. Biochim.
Biophys. Acta 2000, 1483, 154–160; (b) Meacci, E.; Vasta, V.; Moorman, J. P.;
11. The acetonide carbon attached to N and O resonated at 93.7 ppm in 13C NMR
spectrum thus indicating the formation of a five-membered acetonide.
12. For recent examples of the oxy-Michael reaction, see: (a) Honda, T.; Ishikawa,
F. J. Org. Chem. 1999, 64, 5542–5546; (b) Kubota, T.; Tsuda, M.; Kobayashi, J.
Org. Lett. 2001, 3, 1363–1366; (c) Kigoshi, H.; Kita, M.; Ogawa, S.; Itoh, M.;
Uemura, D. Org. Lett. 2003, 5, 957–960.