2768 Kamidi et al.
Asian J. Chem.
via lipase enzyme mediated stereo-selective reduction from
chiral precursor Corey lactone diol. This method was found to
be an efficient with considerable yield, cost effective and minimized
the synthetic steps compared to reported procedures. This synthetic
route involves Swern oxidation, lipase enzymatic reduction and
Wittig reaction conditions as key steps.
0.5 mmol) was added at room temperature and the reaction mass
was heated to reflux at 42 ºC and maintained for 15 h under
reflux. After completion of the reaction, the mass was washed
with sodium thiosulphate solution and the collected organic layer
was washed with brine, dried over anhydrous Na2SO4 and the
solvent was evaporated under reduced pressure to afford crude
compound 8 asaliquid(200g).Thecrudecompoundwasdissolved
in ethanol (600 mL), cooled in refrigerator for 5 h and filtered
to obtain pure compound as solid (130 g). 1H NMR (400 MHz,
CDCl3): δ 2.9 (m, 2H), 3.1 (m, 2H), 3.8 (s, 2H), 7.2 (m, 3H), 7.3
(m, 2H).
EXPERIMENTAL
All the chemicals, reagents and solvents were purchased
fromAldrich (Sigma-Aldrich, USA). The progress of the reaction
was examined by thin layer chromatography (TLC), performed
on silica gel glass plates containing 60 F-254. The separation
of compounds was done by column chromatography using
Merck 60-120 mesh silica gel. Infrared spectra were recorded on
(3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-((S,E)-3-
triethylsilyloxy-5-phenylpent-1-enyl)cyclopenta[b]furan-2-
one (12): Compound 11 (30 g) was added to 0.1 M phosphate
buffer solution and maintained pH around 7-7.5 and stirred
solution for 20 min. CAL-B enzyme (3 g) was added slowly
at 27 ºC and stirred reaction mixture for 5 h at the same temper-
ature.After reaction completion, the reaction mixture was treated
with sodium bicarbonate solution and extracted with n-hexane
(2 × 300 mL), dried over Na2SO4. The solvent was removed
under vacuum to afford pure compound 12 as a liquid (20 g).
1H NMR (400 MHz, CDCl3): δ 0.5 (J/Hz = 7.86, q, 6H), 0.9 (J/
Hz = 8.0, t, 9H), 1.8 (m, 2H), 2.0 (m, 1H), 2.3 (m, 1H), 2.4 (m,
2H), 2.7 (m, 4H), 3.9 (J/Hz = 6.03, q, 1H), 4.1 (J/Hz = 6.26, q,
1H), 4.9 (m, 1H), 5.5 (m, 1H), 5.6 (m, 1H), 7.2 (J/Hz = 12.6,
t, 3H), 7.3 (J/Hz = 12.9, d, 2H).
1
a Perkin-Elmer RX-1 FT-IR spectrophotometer. H NMR
spectra were recorded on a Bruker UXNMR/XWI-NMR-400
MHz spectrometer and 13C NMR (75 MHz) spectra were recorded
on Bruker Avance-400 MHz spectrometer. All the chemical
shifts (δ) are accounted in parts per million (ppm) with reference
to an internal standard TMS. ESI spectra was recorded on
Micro mass, Quattro LC using ESI+ software with a capillary
voltage of 3.98 kV and ESI mode positive ion trap detector.
Optical rotations of the asymmetric molecules were measured
with a Horiba-SEPA-300 digital polarimeter.All the chemical
reactions were performed under inert atmosphere.
Synthesis: Compound 11 was prepared as reported
previously [12] from triethyl silyl protected (-)-Corey lactone
diol by employing well established Swern oxidation and
Wittig-Horner synthetic protocols.
(3aR,4R,5R,6aS)-Hexahydro-4-((S,E)-3-triehylsilyloxy-
5-phenylpent-1-enyl)-2H-cyclopenta[b]furan-2,5-diol (13):
To a solution of compound 12 (31 g, 1 mmol) in THF (310 mL),
DIBAL-H (260 mL, 3.5 mmol) was added dropwise at 70 ºC
and continued stirring for 30-45 min. The reaction progress
was monitored by TLC, the reaction was quenched with
methanol (77.5 mL) below 70 ºC, then reaction temperature
was raised to 5 °C, water (77.5 mL), ethyl acetate (77.5 mL)
were added to reaction mixture and continued stirring for 30
min at room temperature (solid formed). The reaction mixture
was filtered through a celite pad and washed with ethyl acetate
(310 mL). The organic layer was treated with sodium chloride
solution, dried over anhydrous Na2SO4 and concentrated under
reduced pressure to give compound 13 as a colourless liquid
(31 g, 99.6%).
Synthesis of 1-bromo-4-phenylbutan-2-one (6):1-Bromo-
4-phenylbutan-2-one (6) was prepared by adding bromine
(38.2 mL, 1.1 mmol) in acetic acid (1 mL, 0.01 vol) at 0 ºC to
a solution of 4-phenylbutan-2-one (5) (100 g, 1 mmol) in methanol
(1000 mL). The mixture was stirred at 15 ºC for 2 h and reaction
mixture was diluted with water (1000 mL) and extracted with
dichloromethane (2 × 500 mL) to obtain desired compound 6.
The organic fraction was collected, washed with brine solution
and dried over anhydrous Na2SO4. The crude compound 6 was
resulted as a liquid (160 g) after solvent removal under reduced
pressure. The spectroscopic data of compound 6 matches with
the spectral data reported in our previous paper [12].
Synthesis of dimethyl 2-oxo-4-phenylbutylphosphonate
(7): Trimethyl phosphate (87.45 g, 1 mmol) was added to
compound 6 (160 g, 1 mmol) in acetonitrile (320 mL) at room
temperature and stirred for 3 h at 65 ºC. The reaction progress
was monitored with TLC. The reaction mixture was dissolved
in sodium bicarbonate solution (1000 mL) and extracted with
ethyl acetate (2 × 800 mL). The collected organic fractions were
washed with sodium chloride solution and dried over sodium
sulphate. The solvent was removed under vacuum to afford crude
product. The crude compound was chromatographed on silica gel
using ethyl acetate and hexane mixture (50:50) to give compound
7 as a liquid (72 g). 1H NMR, 13C NMR spectra of compound 7
matches with the spectral data reported in previous paper [12].
Synthesis of 1-iodo-4-phenylbutan-2-one (8): Iodine
(171.49 g, 1 mmol) was added to a stirred solution of 4-phenyl-
butan-2-one (5) (100 g, 1 mmol) in methanol (300 mL) and
MDC (700 mL) mixture. To this solution, copper oxide (26.87 g,
(5Z)-Methyl-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((S,E)-
3-hydroxy-5-phenylpent-1-enyl)cyclopentyl)hept-5-enoate
(14): To a solution of 4-carboxy butyltriphenyl phosphonium
bromide (114.87 g, 3.5 mmol), potassium t-butoxide (49.83
g, 6 mmol) in THF (248 mL), compound 13 was added (31 g,
1 mmol) in THF (64 mL) at 5 ºC and the reaction mixture was
stirred for 4 h. After reaction completion, reaction contents
were poured into the cold water (155 mL) and solution pH
was adjusted to 2 with NaHSO4 solution, continued stirring
for another 1 h. Aqueous layer was extracted with ethyl acetate
(2 × 155 mL), organic fractions were washed with brine solution,
dried over anhydrous Na2SO4 and removed solvent under
reduced pressure. The obtained crude acid derivative (40 g)
was used for the next step without further purification.
To a solution of crude acid compound (147 g) in acetone
(620 mL), methyl iodide (105 g, 10 mmol) and potassium
carbonate (153.48 g, 15 mmol) was added at room temperature