Facile total synthesis of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide from carbohydrate, a mosquito oviposition attractant pheromone

Article abstract of DOI:10.1016/j.carres.2012.05.009

Total synthesis of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide, a major component of mosquito oviposition attractant pheromones is reported. The key synthetic steps involve epoxide opening by lithiated salt of ethylpropionate and acid catalysed lactonization.

Full text of DOI:10.1016/j.carres.2012.05.009

Carbohydrate Research 358 (2012) 7–11
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Facile total synthesis of (ꢀ)-(5R,6S)-6-acetoxy-5-hexadecanolide
from carbohydrate, a mosquito oviposition attractant pheromone
Saibal Das a, Anand Kumar Mishra a, Ashish Kumar a, Ahamad Al Khazim Al Ghamdi b, Jhillu Singh Yadav a,
⇑
a Division of Natural Product Chemistry, Indian Institute of Chemical Technology (CSIR), Hyderabad 500 607, AP, India
b Engineer Abdullah Baqshan for Bee Research, King Saudi University, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
Total synthesis of (ꢀ)-(5R,6S)-6-acetoxy-5-hexadecanolide, a major component of mosquito oviposition
attractant pheromones is reported. The key synthetic steps involve epoxide opening by lithiated salt of
ethylpropionate and acid catalysed lactonization. The total synthesis was achieved in 11 linear steps star-
ing from a readily available carbohydrate d-gluconolactone in 18% overall yield making it simple, practi-
cal and elegant.
Received 13 April 2012
Received in revised form 8 May 2012
Accepted 10 May 2012
Available online 18 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Total synthesis
Pheromone
Carbohydrate
Lactone
Hydrazone
1. Introduction
appropriate side chain followed by terminal epoxide respectively.
Subsequently, compound 4 could be obtained from readily avail-
In 1979, (ꢀ)-(5R,6S)-6-acetoxy-5-hexadecanolide 1 was isolated
by the group of Pickett and Laurence from apical droplets formed on
the egg of the mosquito Culex pipens fatigans1 and was established as
a major component of mosquito oviposition attractant pheromones.
The first synthesis of the two enantiomers of 1 was reported by
Fuganti et al. in the year 1982.2 Since then numerous synthesis of
1 have been reported3–39 realizing its need and importance. In pur-
suit of our earlier efforts40 and owing to the significance of 1 herein
we disclosed a facile synthesis starting from an easily available
carbohydrate d-gluconolactone.
able d-gluconolactone 6 as reported earlier by our group41 via
intermediate 5.
We began our synthesis from a known diol 5 (Scheme 2) ob-
tained in two steps from commercially available d-gluconolactone
as developed earlier in our group.41 The oxidative cleavage of diol 5
with NaIO4 provided the corresponding terminal aldehyde as ex-
pected, which upon treatment with tosylhydrazine in MeOH led
to the formation of aldehyde hydrazone 4 in 78% yield (for two
subsequent steps).
The conversion of hydrazone 4 to its allyl alcohol was accom-
plished by its treatment with 3 equiv of n-octylmagnesiumbro-
mide and desired compound 7 was achieved in 76% yield.42
Significantly, exclusive formation of E-olefin was observed and
confirmed by its 1H NMR at d = 5.35 (dd, J = 15.4, 6.2 Hz) ppm.
The secondary hydroxyl group of compound 7 was then protected
as its benzyl ether 8 in 98% yield as planned followed by the depro-
tection of primary acetonide group by the treatment with catalytic
p-TSA in MeOH to obtain the anticipated diol 9 in 80% yield. Then
the conversion of diol 9 to its corresponding epoxide 3 was ob-
tained in 75% yield (for two steps) via usual selective tosylation
of primary alcohol, followed by its treatment with NaH in anhy-
drous THF.43 Now the opening of the epoxide was executed using
lithium salt of ethyl propiolate to provide the homopropargylic
alcohol 10 in 80% yield (Scheme 3).44
2. Results and discussion
The retrosynthetic plan for the target compound 1 is depicted in
Scheme 1. The compound (ꢀ)-(5R,6S)-6-acetoxy-5-hexadecanolide
1 was envisaged from the intramolecular cyclization of hydroxyl
ester compound 2 wherein the terminal ester and secondary alco-
hol could lead to the preferred six member lactone. Compound 2
was planned to be obtained from an intermediate 3 by the epoxide
opening with ethylpropiolate followed by saturation of the termi-
nal alkyne chain. In continuation, epoxide 3 was visualized to be
obtained from hydrazone compound 4 in simple steps including
Grignard reaction and epoxide formation to incorporate the
Towards the construction of desired six-membered saturated
lactone, a two step sequence was performed, which consisted in
hydrogenation of intermediate 10 using Pd/C in presence of H2 to
⇑
Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512.
E-mail address: yadavpub@iict.res.in (J.S. Yadav).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.05.009

8
S. Das et al. / Carbohydrate Research 358 (2012) 7–11
OAc
O
OH
OBn
O
OEt
7
7
7
O
O
OH
3
1
O
2
TsHNN
OH
O
O
O
O
HO
HO
O
O
O
HO
OH
O
O
OH
4
6
5
Scheme 1. Retrosynthetic strategy for 1.
Ref. 11
OH
O
O
O
1. 2,2-DMP, pTSA, acetone
MeOH, rt, 12h, 86%
HO
HO
HO
O
O
OH
O
OH
2. LiAlH4, THF
0oC-rt, 4h, 96%
5
δ-glucono lactone
TsHNN
O
(i) NaIO4, AcCN/H2O (6:1), rt, 5 h
(ii) NH2NHTs, MeOH, rt, 5h,
O
O
O
78% (for two steps)
4
Scheme 2. Synthesis of hydrazone intermediate 4.
OBn
n-C8H17MgBr,
ether
NaH, BnBr,
DMF
OH
O
4
7
7
O
O
O
0oC-rt, 3h,
76%
0oC-rt, 2h,
98%
8
7
(i) TsCl, N(Et)3, Bu2SnO(cat),
DCM, 0oC-rt, 12h
p-TSA,
MeOH
OBn
OBn OH
OH
(ii) NaH, THF, 0oC 1h,
O
7
rt, 5h,
80%
7
75% (for two steps)
3
9
Ethyl propiolate, n-BuLi,
BF3.OEt2
OBn
7
THF, -78 0oC,
80%
CO2Et
OH
10
Scheme 3. Synthesis of homo propargylic alcohol intermediate 10.
attain saturated compound 2 followed by lactonization via catalytic
p-TSA to obtain the desired six-membered lactone 11 (Scheme 4) as
a sole product in 87% yield (for two steps).44,45
3. Conclusion
In conclusion we have accomplished a facile total synthesis of
(ꢀ)-(5R,6S)-6-acetoxy-5-hexadecanolide 1, of mosquito oviposi-
tion attractant pheromones in 11 linear steps with 18% overall
yield from d-gluconolactone. The synthesis involves simple and
convenient reactions like epoxide opening by lithiated salt of
ethylpropiolate, acid catalysed lactonization to form six-mem-
Finally, the total synthesis of (ꢀ)-(5R,6S)-6-acetoxy-5-hexade-
canolide 1 was achieved by acetylation of the alcohol 12 using
Ac2O, DMAP, in 90% yield.15 The synthetic material showed IR,
1H, 13C NMR spectral data and optical rotation {½a 3D2
ꢀ33 (c 0.4,
ꢁ
CHCl3)} in good agreement with the literature reports.2,4,15

S. Das et al. / Carbohydrate Research 358 (2012) 7–11
9
p-TSA (cat),
benzene
OH
H2, Pd/C, MeOH,
O
10
7
rt, 12h
87.2%
(for two steps)
OH
OEt
2
OH
OAc
O
Ac2O, DMAP,
DCM,
7
7
O
20oC, 1h
90 %
O
O
11
1
Scheme 4. Synthesis of homo propargylic alcohol intermediate 10.
bered lactone making it practical and elegant for further
development.
hydrazone 4 (10 g, 25 mmol) in ether (100 mL). The mixture was
allowed to reach room temperature slowly and was stirred for
3 h, quenched with aqueous saturated NH4Cl, extracted with Et2O
(3 ꢂ 200 mL), brine wash, dried over anhydrous Na2SO4 and re-
moval of the solvent followed by purification gave product 7
4. Experimental section
4.1. General methods
(5.15 g, 76%) as a viscous liquid. ½a D30
ꢁ
+15.4 (c 2.37, CHCl3); IR
(KBr):
m
(cmꢀ1) 3454, 2925, 2855, 1460, 1067, 917. 1H NMR
(300 MHz, CDCl3): d (ppm) 5.68–5.81 (m, 1H), 5.35 (dd, J = 15.4,
6.2 Hz, 1H), 4.15–4.23 (m, 1H), 3.98–4.06 (m, 1H), 3.81–3.93 (m,
2H), 1.97–2.09 (m, 2H), 1.41 (s, 3H), 1.18–1.38 (m, 15H), 0.89 (t,
3H, J = 6.7 Hz). 13C NMR (CDCl3, 75 MHz): d (ppm) 134.3, 127.1,
109.1, 78.4, 71.5, 64.6, 32.2, 31.7, 29.3, 29.1, 29.0, 28.9, 26.3,
25.0, 22.5, 13.9. (LC–MS): m/z = 293 [M+Na]+. HRMS: calcd for
Reactions were conducted under N2 in anhydrous solvents such
as CH2Cl2, THF, and AcOEt as mentioned. Yields refer to chromato-
graphically and spectroscopically (1H and 13C NMR) homogeneous
material. Air-sensitive reagents were transferred by syringe or
double-ended needle. Column chromatography (CC): silica gel
(60–120 mesh. Acme Chemical Co., India). TLC: Merck 60 F-254 sil-
ica gel plates and light petroleum ether (bp 60–808) for reaction
monitoring; detection by UV light. IR spectra were recorded on a
Perkin–Elmer FT-IR 240-c spectrophotometer using KBr optics. 1H
NMR and 13C spectra were recorded on Varian Bruker-300 spec-
trometer in CDCl3 using TMS as internal standard. Mass spectra
were recorded on a Finnigan MAT 1020 mass spectrometer operat-
ing at 70 eV. HR-ESI-MS: QSTAR-XL hybrid ms/ms system (Applied
Biosystems/MDS Sciex, Foster City, USA), equipped with an ESI
source (IICT, Hyderabad); in m/z. The optical rotations were mea-
sured on a Jasco Dip 360 Digital polarimeter.
C
16H30NaO3 [M+Na]+ 293.2087; found: 293.2101.
4.4. (R)-4-[(S,E)-1-(Benzyloxy)undec-2-enyl]-2,2-dimethyl-1,3-
dioxolane (8)
To a stirred solution of 7 (1 g, 3.69 mmol) in dry DMF (12 mL),
NaH (142 mg, 5.91 mmol) and benzyl bromide (759 mg, 4.4 mmol)
were added at 0 °C. The reaction mixture was stirred for 2 h at
room temperature. Excess NaH and benzyl bromide were removed
by addition of methanol and Et3N. The reaction mixture was evap-
orated, diluted with dichloromethane, washed with water
(3 ꢂ 100 mL), dried over anhydrous Na2SO4 and evaporated. Col-
umn chromatography gave product 8 (1.306 g, 98%) as a colorless
4.2. 4-Methyl-N0-[{(4S,40R,5R)-2,2,20,20-tetramethyl-4,40-bi(1,3-
dioxolan)-5-yl}methylene] benzenesulfono hydrazide (4)
oil. ½a 3D0
ꢁ
+42.9 (c 1, CHCl3); IR (KBr): m
(cmꢀ1) 2926, 2855, 1457,
1374, 1073, 737, 698. 1H NMR (CDCl3, 300 MHz): d (ppm) 7.20–
7.37 (m, 5H), 5.64–5.76 (m, 1H), 5.33–5.45 (m, 1H), 4.64 (d, 1H,
J = 12 Hz), 4.36 (d, 1H, J = 11.3 Hz), 3.99–4.13 (m, 2H), 3.80–3.86
(m, 1H), 3.65–3.72 (m, 1H), 2.11 (q, 2H, J = 6.79 Hz), 1.19–1.46
(m, 18H), 0.88 (t, 3H, J = 6.79 Hz), 13C NMR (CDCl3, 75 MHz): d
(ppm) 138.3, 137.2, 128.9, 127.8, 127.4, 126.3, 109.3, 80.4, 77.8,
69.9, 66.7, 32.4, 31.8, 29.4, 29.2, 29.1, 26.5, 25.4, 22.6, 14.0. (LC–
MS): m/z = 383[M+Na]+. HRMS: calcd For C16H30NaO3 [M+Na]+
383.2562; found: 383.2567.
A solution of diol 5 (12 g, 45.7 mmol) in AcCN and water (6:4,
200 mL) was treated with NaIO4 (14.7 g, 68.6 mmol) portion wise
at 0 °C and stirred at room temperature for 5 h, then filtered and
acetonitrile was evaporated under reduced pressure, washed with
DCM (250 mL) and the solvent was evaporated to afford the de-
sired aldehyde (10 g, 95%) as a yellowish oil, which was immedi-
ately used for the next reaction without additional purification. A
mixture of aldehyde (10 g, 43.42 mmol) and p-toluene sulfonyl
hydrazine (8.08 g, 43.42 mmol) in 100 ml of methanol was stirred
for 5 h at room temperature under N2. Methanol was evaporated
under reduced pressure, petroleum ether (75 mL) was added and
the precipitated white solid was filtered and dried under vacuum
to yield tosylhydrazone 4 (14.188 g, 82%). Mp 153–155 °C. 1H
NMR (CDCl3, 300 MHz): dH (ppm) 7.10–7.80 (m, 5H), 6.52 (br s,
1H), 3.50–4.25 (m, 5H), 2.41 (s, 3H), 1.42 (s, 6H), 1.38 (s, 6H).
(ESI): m/z = 399 [M+H]+. HRMS: calcd for C18H27N2O6S [M+H]+
399.1589; found: 399.1600.
4.5. (2R,3S,E)-3-(Benzyloxy)tridec-4-ene-1,2-diol (9)
To a stirred solution of 8 (1 g, 2.77 mmol) in MeOH (12 mL) at
0 °C was added PTSA (cat.) and stirred for 8 h at room temperature.
The reaction mixture was quenched by saturated aqueous NaHCO3
and evaporated under reduced pressure, then extracted with ethyl
acetate (3 ꢂ 30 ml), washed with brine, dried over anhydrous
Na2SO4, and evaporated under reduced pressure. The crude residue
was chromatographed to give diol 9 (711 mg, 80%) as a viscous li-
4.3. (S,E)-1-[(R)-2,2-Dimethyl-1,3-dioxolan-4-yl]undec-2-en-1-
ol (7)
quid. ½a 3D0
ꢁ
+27.7 (c 1, CHCl3); IR (KBr): m
(cmꢀ1) 3408, 2924, 2854,
1458, 1092, 1061, 753, 697. 1H NMR (CDCl3, 300 MHz): d (ppm)
7.26–7.38 (m, 5H), 5.70–5.82 (m, 1H), 5.41 (dd, 1H, J = 15.1,
8.3 Hz), 4.61 (d, 1H, J = 11.3 Hz), 4.34 (d, 1H, J = 11.3 Hz), 3.86
(dd, 1H, J = 8.3, 4.5 Hz), 3.63–3.76 (m, 3H), 2.64 (br s, 1H), 2.47
To a solution of Grignard reagent [prepared in situ from Mg
(1.86 g, 75.2 mmol) and n-octylbromide (14.5 g, 75.2 mmol) in
ether (300 mL)] at 0 °C was added a solution of the aldehyde

10
S. Das et al. / Carbohydrate Research 358 (2012) 7–11
(br s, 1H), 2.11 (q, 2H, J = 6.7 Hz), 1.19–1.47 (m, 12H), 0.88 (t, 3H,
J = 7.5 Hz). 13C NMR (CDCl3, 75 MHz): d (ppm) 137.9, 128.3,
127.7, 126.1, 81.1, 73.3, 70.1, 63.2, 32.3, 31.7, 29.3, 29.2, 29.1,
29.0, 22.6, 14.2. (LC–MS): m/z = 343 [M+Na]+. HRMS: calcd for
atmosphere. Reaction mixture was filtered over celite, the filtrate
was concentrated under reduced pressure, purification by silica-
gel column chromatography afforded 2 (71 mg, 90%) as a white so-
lid. Mp 90–92 °C, (lit.15 91–93 °C); ½a D30
ꢁ
+1.0 (c 0.8, CH2Cl2); [lit.15
C
16H30NaO3 [M+Na]+ 343.2249; found: 343.2261.
½
a 3D2
ꢁ
+0.9 (c 0.7, CH2Cl2)]; IR (KBr):
m
(cmꢀ1) 3283, 2922, 2854,
1730, 1466, 1381, 1071. 1H NMR (300 MHz, CDCl3): d (ppm) 4.12
(q, J = 7.1 Hz, 2H), 3.49–3.58 (m, 2H), 2.30–2.37 (m, 2H), 1.61–
1.90 (m, 4H), 1.21–1.53 (m, 21H), 0.88 (t, 3H, J = 6.7 Hz). 13C NMR
(CDCl3, 75 MHz): d (ppm) 173.8, 74.6, 74.0, 60.3, 34.0, 31.9, 31.4,
30.4, 29.6, 29.5, 29.3, 25.9, 22.6, 21.1, 14.2, 14.0. (LC–MS): m/
z = 339 [M+Na]+. HRMS: calcd for C16H30NaO3 [M+Na]+ 339.2511;
found: 339.2523.
4.6. (R)-2-[(S,E)-1-(Benzyloxy)undec-2-enyl]oxirane (3)
To diol 9 (500 mg, 1.56 mmol) in dry CH2Cl2 were added trieth-
ylamine (173 mg, 1.72 mmol), p-toluenesulfonyl chloride (327 mg,
1.72 mmol) and dibutyltin oxide (cat.). The resulting solution was
stirred for 12 h at room temperature. After complete conversion
as confirmed by TLC, the mixture was quenched with satd NH4Cl
solution and extracted with CH2Cl2 (3 ꢂ 20 mL). Removal of sol-
vent followed by purification on silica gel column chromatography
gave the pure tosyl derivative. To a stirred suspension of freshly
activated sodium hydride (67 mg, 2.79 mmol) in dry THF (10 mL)
at 0 °C, tosyl derivative in dry THF (8 mL) was added dropwise.
After completion of the reaction (2 h), the reaction mixture was
quenched with saturated aqueous NH4Cl solution and extracted
with EtOAc. The organic layer was washed with brine solution,
dried over anhydrous Na2SO4, and concentrated under reduced
pressure, purification by silica-gel column chromatography affor-
4.9. (R)-6-[(S)-1-Hydroxyundecyl]tetrahydro-2H-pyran-2-one
(11)
To a stirred solution of 2 (50 mg) in benzene PTSA (cat.) was
added. Reaction mixture was allowed to be stirred for 12 h at rt,
was quenched by saturated aqueous solution of NaHCO3 and ex-
tracted with EtOAc. The organic layer was washed with brine solu-
tion, dried over anhydrous Na2SO4 and concentrated under
reduced pressure, purification by silica-gel column chromatogra-
phy afforded 11 (41 mg, 96.7%) as a white solid. Mp 67–68 °C,
(lit.15 67–68 °C); ½a 3D0
ꢁ
ꢀ11.0 (c 0.8, CH2Cl2); [lit.15
½
a 3D2
ꢁ
ꢀ12.6 (c
ded 3 (350 mg, 75% for two steps) as a viscous liquid. ½a D30
ꢁ
+19.5
m
(cmꢀ1) 2925, 2854, 14.59, 1067, 973. 1H
1.05, CH2Cl2)]; IR (KBr):
m
(cmꢀ1) 3279, 2921, 2853, 1715, 1458,
(c 1, CHCl3); IR (KBr):
1283, 1071. 1H NMR (CDCl3, 300 MHz): d (ppm) 4.15–4.25 (m,
2H), 3.74–3.81 (m, 1H), 2.41–2.61 (m, 2H), 1.74–2.03 (m, 4H),
1.18–1.57 (m, 18H), 0.88 (t, 3H, J = 6.98 Hz). 13C NMR (CDCl3,
75 MHz): d (ppm) 171.7, 83.4, 72.3, 31.8, 31.6, 29.7, 29.5, 29.2,
25.8, 22.6, 21.0, 18.2, 14.0 ppm. (LC–MS): m/z = 293 [M+Na]+.
HRMS: calcd for C16H30NaO3 [M+Na]+ 293.2087; found: 293.2102.
NMR (CDCl3, 300 MHz): d (ppm) 7.18–7.34 (m, 5H), 5.61–5.76
(m, 1H), 5.39 (dd, 1H, J = 15.8, 7.5 Hz), 4.58 (d, 1H, J = 12.0 Hz),
4.4 (d, 1H, J = 12.0 Hz), 3.70 (dd, 1H, J = 7.5, 3.7 Hz), 2.94–3.01 (m,
1 H), 2.70 (t, J = 4.5 Hz, 1 H), 2.58–2.68 (m, 1 H), 2.09 (q,
J = 6.7 Hz, 2 H), 1.19–1.46 (m, 12 H), 0.89 (t, 3H, J = 6.7 Hz). 13C
NMR (CDCl3, 75 MHz): d (ppm) 137.2, 128.2, 127.6, 127.5, 125.7,
79.0, 70.4, 53.5, 44.8, 32.3, 31.8, 29.6, 29.3, 29.3, 29.1, 28.9, 22.6,
14.0. (LC–MS): m/z = 325 [M+Na]+. HRMS: calcd for C20H30NaO2
[M+Na]+ 325.2138; found: 325.2153.
4.10. (5R,6S)-6-Acetoxy-5-hexadecanolide (1)
To 11 (20 mg, 0.073 mmol) in CH2C12 (5 mL), at 25 °C, was
added 4,4-dimethylamino pyridine (54 mg, 0.44 mmol) and acetic
anhydride (45 mg, 0.44 mmol). After 1 h at 20 °C, the reaction
was quenched with brine. Extraction with CH2C12 (3 ꢂ 10 mL),
drying with Na2SO4, filtration, concentration under reduced pres-
sure and flash chromatography afforded 1 (21 mg, 90%) as a color-
4.7. (5R,6S,E)-Ethyl-6-(benzyloxy)-5-hydroxyhexadec-7-en-2-
ynoate (10)
To a solution of lithium salt of ethyl propiolate [prepared in situ
from ethyl propiolate (130 m g, 1.32 mmol) and n-butyl lithium
(85 mg, 1.32 mmol) in THF (5 mL) at ꢀ78 °C, 0.5 h] at ꢀ78 °C was
added BF3ꢃOEt2 (85 mg, 1.32 mmol). The resulting mixture was
stirred for 5 minutes. Then the solution of epoxide 3 (200 mg,
0.66 mmol), in dry THF was added to reaction mixture and the
mixture was stirred for 3 h at same temperature. After completion
of the reaction, the reaction mixture was quenched with saturated
aqueous NH4Cl solution and extracted with EtOAc. The organic
layer was washed with brine solution, dried over anhydrous
Na2SO4, and concentrated under reduced pressure, purification
by silica-gel column chromatography afforded 10 (212 mg, 80%)
less oil. ½a 3D2
ꢁ
ꢀ33 (c 0.4, CHCl3); [lit.4 ½a D20
ꢀ35.4 (c 0.85, CHCl3)]; IR
ꢁ
(KBr):
m
(cmꢀ1) 2924, 2853, 1737, 1373, 1240, 1073. 1H NMR
(CDCl3, 300 MHz): d (ppm) 4.93–5.03 (m, 1H), 4.35 (ddd, J = 3.0,
7.5, 10.5 Hz, 1H), 2.55–2.66 (m, 1H), 2.40–2.51 (m, 1H), 2.08 (s,
3H), 1.75–2.06 (m, 2H), 1.52–1.74 (m, 4H), 1.13–1.40 (m, 16H),
0.88 (t, 3H, J = 7.5 Hz). 13C NMR (CDCl3, 75 MHz): d (ppm) 170.8,
170.4, 80.5, 74.3, 31.9, 29.6, 29.5, 29.4, 29.3, 25.2, 23.5, 22.7,
21.0, 18.2, 14.1. (LC–MS): m/z = 335 [M+Na]+. HRMS: calcd for
C18H32NaO4 [M+Na] 335.2198; found: 335.2195.
Acknowledgments
as a viscous liquid. ½a D30
ꢁ
+14.3 (c 0.75, CHCl3); IR (KBr): m )
(cmꢀ1
3453, 2924, 2853, 2237, 1711, 1460, 1368, 1251, 1072. 1H NMR
(CDCl3, 300 MHz): d (ppm) 7.21–7.35 (m, 5H), 5.73–5.84 (m, 1H),
5.40 (dd, 1H, J = 15.8, 8.3 Hz), 4.59 (d, 1H, J = 12.0 Hz), 4.34 (d,
1H, J = 11.3 Hz), 4.18 (q, 2H, J = 6.7 Hz), 3.75–3.91 (m, 2H), 2.54
(dd, 2H, J = 6.0, 2.2 Hz), 2.22 (br d, 1H, J = 3.7 Hz), 2.07–2.17 (m,
2H), 1.18–1.47 (m, 15H), 0.88 (t, 3H, J = 6.7 Hz). 13C NMR (CDCl3,
75 MHz): d (ppm) 153.5, 138.9, 138.0, 128.3, 127.7, 127.6, 125.2,
85.7, 81.8, 74.5, 71.2, 70.1, 61.8, 32.4, 31.8, 29.3, 29.2, 29.1, 29.0,
22.8, 22.6, 14.1, 14.0. (LC–MS): m/z = 423 [M+Na]+. HRMS: calcd
for C16H30NaO3 [M+Na]+ 423.2511; found: 423.2521.
A.K.M. thanks the CSIR, New Delhi and A.K.P. thanks the NIPER,
Hyderabad for financial support. Author acknowledges the partial
support by the King Saud University for Global Research Network
for Organic Synthesis (GRNOS).
References
1. Laurence, B. R.; Pickett, J. A. J. Chem. Soc., Chem. Commun. 1982, 59–60.
2. Fuganti, C.; Grasselli, P.; Servi, S. J. J. Chem. Soc., Chem. Commun. 1982, 1285–
1286.
3. Park, Y.; Tae, J. Synthesis 2010, 21, 3627–3630.
4. Singh, S.; Guiry, P. J. Eur. J. Org. Chem. 1896, 2009.
5. Quinn, K. J.; Curto, J. M.; McGrath, K. P.; Biddick, N. A. Tetrahedron Lett. 2009, 50,
7121–7123.
4.8. (5R,6S)-Ethyl-5,6-dihydroxyhexadecanoate (2)
6. Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18, 2479–2483.
7. Ikishima, H.; Sekiguchi, Y.; Ichikawa, Y.; Kotsuki, H. Tetrahedron 2006, 62, 311–
316.
Mixture of 10 (100 mg, 0.249 mmol) and Pd/C (10% Pd, 18 mg,
0.169 mmol) in MeOH was stirred for 12 h at rt under hydrogen

S. Das et al. / Carbohydrate Research 358 (2012) 7–11
11
8. Dhotare, B.; Goswami, D.; Chattopadhyay, A. Tetrahedron Lett. 2005, 46, 6219–
6221.
28. Hwang, Y.-S.; Mulla, M. S.; Chaney, J. D.; Lin, G.-G.; Xu, H.-J. J. Chem. Ecol. 1987,
13, 245–252.
9. Sun, B.; Peng, L.; Chen, X.; Li, Y.; Yamasaki Tetrahedron: Asymmetry 2005, 16,
1305–1307.
10. Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2003, 125, 9308–9309.
11. Gallos, J. K.; Mihelakis, D. S.; Dellios, C. C.; Pozarentzi, M. E. Heterocycles 2000,
53, 703–707.
29. Barua, N. C.; Schmidt, R. R. Tetrahedron 1986, 42, 4471–4474.
30. Jefford, C. W.; Jaggi, D.; Boukouvalas, J. Tetrahedron Lett. 1986, 27, 4011–4014.
31. Ko, K. Y.; Eliel, E. L. J. Org. Chem. 1986, 51, 5353–5362.
32. Laurence, B. R.; Mori, K.; Otsuka, T.; Pickett, J. A.; Wadhams, L. J. J. Chem. Ecol.
1985, 11, 643–648.
12. Couladouros, E. A.; Mihou, A. P. Tetrahedron Lett. 1999, 40, 4861–4862.
13. Lohray, B. B.; Venkateswarlu, S. Tetrahedron: Asymmetry 1997, 8, 633–638.
14. Carlo, B.; Checconi, M.; Righi, G.; Rossi, L. Tetrahedron 1995, 51, 4111–4116.
15. Gravier-Pelletier, C.; Le Merrer, Y.; Depezay, J. C. Tetrahedron 1995, 51, 1663–
1674.
16. Coutrot, P.; Bomont, C. G. Tetrahedron Lett. 1994, 35, 8381–8384.
17. Ramaswamy, S.; Oehlschlager, A. C. Tetrahedron 1991, 47, 1145–1156.
18. Wu, W.; Wu, Y. J. Carbohydr. Chem. 1991, 10, 279–281.
19. Wang, Z.-M.; Qian, X.-H.; Zhou, W.-S. Tetrahedron 1990, 46, 1191–1196.
20. Kotsuki, H.; Kadota, I.; Ochi, M. J. Org. Chem. 1990, 55, 4417–4422.
21. Kawamura, F.; Tayano, T.; Satoh, Y.; Hara, S.; Suzuki, A. Chem. Lett. 1989, 10,
1723–1726.
33. Machiya, K.; Ichimoto, I.; Kirihata, M.; Ueda, H. Agric. Biol. Chem. 1985, 49, 643–
649.
34. Ochiai, M.; Ukita, T.; Nagao, Y.; Fujita, E. J. Chem. Soc., Chem. Commun. 1985,
637–638.
35. Qiang, L. G.; Jian, X. H.; Chi, W. B.; Zhong, G. G.; Shan, Z. W. Tetrahedron Lett.
1985, 26, 1233–1236.
36. Yamaguchi, M.; Hirao, I. J. Chem. Soc., Chem. Commun. 1984, 202–203.
37. Sato, T.; Watanabe, M.; Honda, N.; Fujisawa, T. Chem. Lett. 1984, 1175–1176.
38. Mori, K.; Otsuka, T. Tetrahedron 1983, 39, 3267–3269.
39. Masaki, Y.; Nagata, K.; Kaji, K. Chem. Lett. 1983, 1835–1836.
40. Sabitha, G.; Swapna, R.; Reddy, E. V.; Yadav, J. S. Synthesis 2006, 24, 4242–4246.
41. Yadav, J. S.; Madhavarao, B.; Rao, K. S. Tetrahedron: Asymmetry 2009, 20, 1725–
1730.
42. Chandrasekhar, S.; Takhi, M.; Yadav, J. S. Tetrahedron Lett 1995, 36, 5071–5074.
43. Sabitha, G.; Fatima, N.; Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron:
Asymmetry 2009, 20, 184–191.
22. Ochiai, M.; Ukita, T.; Iwaki, S.; Nagao, Y.; Fujita, E. J. Org. Chem. 1989, 54, 4832–
4840.
23. Rahman, S. S.; Wakefield, B. J.; Roberts, S. M.; Dowle, M. D. J. Chem. Soc., Chem.
Commun. 1989, 303–304.
24. Kang, S.-K.; Cho, I.-H. Tetrahedron Lett. 1989, 30, 743–746.
25. Kamatani, T.; Tsubuki, M.; Tatsuzaki, Y.; Honda, T. Heterocycles 1988, 27, 2107–
2110.
26. Zhou, W.; Cheng, J.; Lin, G. Huaxue Xuebao 1988, 46, 274–280.
27. Lin, G.; Jiang, Y.; Guo, G.; Xia, K. Huaxue Xuebao 1987, 45, 602–605.
44. Chandrasekhar, S.; Balaji, S. V.; Rajesh, G. Tetrahedron Lett. 2010, 51, 5164–
5166.
45. Nishii, Y.; Higa, T.; Takahashi, S.; Nakata, T. Tetrahedron Lett. 2009, 50, 3597–
3601.