Transformation of D-glucose to 1-deoxy-1-[4'-methoxyphenyl]-2R,3R,4R- pentitol template: Synthesis of Karalicin analogues

Article abstract of DOI:10.1016/S0957-4166(98)00017-2

Transformation of D-glucose to Karalicin isomers 1-1b is reported via the key chiron 5,6-anhydro-D-glucofuranose 2. Crucial protection and deprotection strategies of pentitol chiral template 6 are described.

Full text of DOI:10.1016/S0957-4166(98)00017-2

Pergamon
Tetrahedron: Asymmetry 9 (1998) 827–833
Transformation of D-glucose to 1-deoxy-1-[40-methoxyphenyl]-
2R,3R,4R-pentitol template: synthesis of Karalicin analogues
Hari Babu Mereyala ∗ and Rajendrakumar Reddy Gadikota
Organic Division III, Bio-organic Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 5 January 1998; accepted 13 January 1998
Abstract
Transformation of D-glucose to Karalicin isomers 1–1b is reported via the key chiron 5,6-anhydro-D-
glucofuranose 2. Crucial protection and deprotection strategies of pentitol chiral template 6 are described. © 1998
Elsevier Science Ltd. All rights reserved.
The increasing occurrence of the life threatening herpes virus infection in children with inherited T-
cell deficiencies and in patients who are immunosuppressed because of AIDS infection, transplantation
or cancer therapy has given great importance to the rapid development of chemotherapeutic agents.1
Chemotherapeutic agents that act specifically on viral rather than on host macromolecular synthesis
are being developed. Thus, acyclovir, vidarabine, cytovene, famvir and cidofovir have been the present
drugs of choice for oral and genital herpes.1 Recently Karalicin 1 a p-methoxyphenyl pentitol derivative
whose absolute stereochemical structure has not been determined was isolated from Pseudomonas fluo-
rescens/putida strains collected from sewer channels.2 Earlier, other bioactive compounds pyrrolnitrin3
pyoluteorin,4 and pyoverdine siderophore5 had been isolated from these strains. Karalicin 1 has been
shown to possess antiviral activity against herpes viruses, whilst polio and vaccinia viruses were found
to be less sensitive.6 Karalicin 1 has shown inhibitory effects on the multiplication of the herpes virus
in vitro. Due to these interesting antiviral properties the synthesis of 1 and its analogues were taken up
as a part of our programme to obtain selective and effective antiviral compounds. In order to establish
the absolute stereochemical structure of 1 synthesis by chiron approach starting from D-glucose was
considered.
Retrosynthetic analysis (Scheme 1) to derive the 1-deoxy-pentitol template of 1 suggested car-
bon–carbon bond formation by regioselective nucleophilic opening of 5,6-anhydro-D-glucofuranose
derivative 2 by p-methoxy phenylmagnesium bromide followed by one carbon degradation of the
terminal diol (by periodate cleavage). This general strategy in principle would allow synthesis of all
the eight possible isomers of Karalicin 1 to establish unambiguously the absolute stereochemistry by
choice of monosaccharides that are available in appropriate chiral forms.
∗
Corresponding author. E-mail: root@csiict.ren.nic.in
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00017-2

828
H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
Scheme 1.
Thus D-glucose was transformed to the 5,6-anhydroepoxyglucofuranose derivative 2 by established7
procedures (Scheme 2). Regioselective nucleophilic opening of epoxide 2 by p-methoxy phenylmagne-
1
sium bromide8 in THF at 0°C for 2 h gave 3 in 81% yield, which as characterised from the H-NMR
spectrum from the appearance of benzylic protons H-6 (2H) at δ 2.7 (1H, dd, Jgem 13.6 Hz, J5,6 7.7 Hz)
0
and δ 2.96 (1H, dd, J5,6 2.8 Hz), aromatic OCH3 at δ 3.78 and anomeric proton H-1 at δ 5.9 (1H, d,
J1,2 4.1 Hz). Benzylation BnBr–NaH/DMF of 3 gave 4 which on subsequent deprotection of acetonide
(TFA/H2O/CH2Cl2) gave 5 in high yield, which on oxidative cleavage with NaIO4 followed by reduction
with NaBH4 gave the diol 6 as a crystalline compound m.p. 65–67°C. A one pot regioselective silylation
of 6 with tert-butyldimethylsilyl chloride followed by acetylation (Ac2O/Py/1 h) gave the 3-O-acetyl-5-
O-silyl derivative 7 which was characterised by the 1H-NMR spectrum from the appearance of the acetyl
group at δ 2.03 (3H, s, OCOCH3) and H-3 at δ 5.27 (1H, t, J2,3=J3,4 4.8 Hz) shifted downfield due to
acetylation.
Scheme 2. (a) p-OMePhMgBr/CuI/THF/0°C/2 h, 81%; (b) BnBr/NaH/DMF/O°C–RT/1 h, 94%; (c) TFA:H2O:CH2Cl2
(2:1:2)/35°C/6 h, 80%; (d) NaIO4/MeOH:H2O (2:1)/0°C–RT/1 h; NaBH4/isopropyl alcohol/ RT/1 h, 83%; (e) TBDM-
SCl/Py/RT/3 h; Ac2O/Py/1 h, 90%; (f) TBAF/THF/0°C/30 min. 98%; (g) 1% p-TsOH in MeOH:CH2Cl2 (1:3)/−20°C/18 h, 87%
(h) PdO/H2/1atm/EtOAc/2 h, 90%; (i) Ac2O/Py/1 h, 95%; (j) 10% Pd–BaSO4/H2/1atm/ MeOH/4 h, 93%; (k) Ph3CCl/Py/RT/6
h; Ac2O/RT/1 h, 92% yield
Desilylation of 7 with tetrabutylammonium fluoride resulted in the exclusive isolation of the unwanted
8a due to migration of the C-3-O acetyl group to the C-5 hydroxyl group, formation of 8b was not
observed. In order to prevent isomerisation of the acetyl group during base catalysed desilylation a
recently reported method9 of desilylation by use of I2, MeOH at reflux temperature was also tried
unsuccessfully resulting in the isolation of a mixture of 8a:8b in a ratio of 4:1. After trying several
methods of desilylation the best procedure established was by use of 1% p-TsOH in MeOH–CH2Cl2
strictly at −20°C for 18 h, quenching the reaction mixture with triethylamine and evaporation of solvent

H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
829
1
in high vacuum (0.01 Torr) gave 8a:8b in a ratio of 1:6 (by H-NMR). Formation of 8a was evident
1
from the H-NMR spectrum from the appearance of an acetyl group at δ 2.02 (3H, s) and H-5 (2H)
shifted downfield to δ 4.1–4.3 (m, 3H, merged with H-4) and also from the upfield shift of H-3 proton
1
to δ 3.4 due to deacetylation. Compound 8b was characterised by the H-NMR spectrum from the
appearance of an acetyl group at δ 2.10 (s, 3H), and H-3 at δ 5.15 (1H, dd, J2,3 4.2 Hz, J3,4 4.0 Hz).
However, the problem of isomerisation continued even during hydrogenolysis. Thus when, 8a:8b was
hydrogenated in ethyl acetate at 1 atm pressure at 0°C using PdO as a catalyst resulted in the isolation
1
of 1:1a in a ratio of 1:1 (by H-NMR). Attempts to isolate 1 by preparative thin layer chromatography
also met with failure because of rapid isomerisation of 1 to 1a (1:1 ratio) while removing the solvent.
Hydrogenolysis by change of solvents (MeOH, cyclohexane) and catalysts (Pd/C, Pd/BaSO4) also did
not prevent isomerisation. Thus, hydrogenolysis of 8a at 1 atm pressure with Pd/BaSO4 in MeOH gave a
crystalline Karalicin analogue 1a, m.p. 103–105°C, in quantitative yield and was characterised from the
1H-NMR spectrum. In order to synthesise Karalicin 1 an alternative route devoid of alkaline and acidic
reaction conditions was considered. Diol 6 was converted in a one pot reaction to the trityl derivative 9
by reaction with Ph3CCl/Py followed by acetylation. Compound 9 was hydrogenated with Pd–BaSO4
catalyst in EtOAc to isolate 1:1a in a ratio of 1:4 due to migration of the acetyl group. In order to
characterise 1/1a and other isomeric monoacetylated derivatives 7, 8a and 8b, 1/1a was converted to the
1
tetra-acetate 1b by acetylation. The H-NMR spectrum of 1b exhibited four acetyl group singlets at δ
0
1.90 (2/4 –OAc), δ 2.01 (5 –OAc), δ 2.03 (3 –OAc), 2.04 (2/4 –OAc), 3.89 (dd, 1H, J5,5 11.2, J4,5 6.4
Hz, H-5), 4.25 (dd, 1H, J4,5 4.5 Hz, H-50), 5.24 (ddd, 1H, J2,3 6.7 Hz, H-2), 5.28 (dd, 1H, J3,4 5.6 Hz,
0
H-3) and 5.37 (ddd, 1H, H-4).
In conclusion, a simple, high yielding method based on a protection–deprotection strategy to prepare
Karalicin anologues from D-glucose has been described by a chiron approach. Synthesis of Karalicin 1
could not be achieved due to facile migration of the acetyl group from secondary to the terminal primary
alcohol.
1. Experimental section
All moisture sensitive reactions were performed under a nitrogen atmosphere using flame-dried
1
glassware. Solvents were dried over standard drying agents and freshly distilled prior to use. H-NMR
spectra were measured with a Varian Gemini (200 and 400 MHz) spectrometer, with tetramethylsilane
as an internal standard for solutions in deuteriochloroform. J values are given in hertz. Optical rotations
were measured with a JASCO DIP-370 instrument, and [α]D values are in units of 10−1 deg cm2 g−1. IR
spectra were taken with a Perkin–Elmer 1310 spectrometer. Organic solutions were dried over anhydrous
Na2SO4 and concentrated below 40°C in vacuo.
1.1. 3-O-Benzyl-1,2-O-isopropylidine-6-C-(40 -methoxyphenyl)-α-D-glucopentofuranose 3
To a solution of 5,6-anhydro-3-O-benzyl-1,2-O-isopropylidine-α-D-glucopentofuranose 2 (3.5 g, 11.9
mmol) in dry THF (30 cm3) was added copper(I) iodide (0.03 g) and the reaction mixture was cooled to
0°C. Freshly prepared 4-methoxyphenylmagnesium bromide (4.45 g of fresh 4-bromoanisole and 0.57
g of magnesium in 20 ml of dry THF, 23.95 mmol) was added dropwise over 30 min. to the reaction
mixture and stirred for 2 h at 0°C. After completion of the reaction (monitored by TLC) it was quenched
by addition of saturated aqueous ammonium chloride solution (20 cm3) and then filtered through a bed of
Celite and washed with ethyl acetate. The filtrate was concentrated to a syrupy residue and was extracted

830
H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
into ethyl acetate (2×75 ml). Combined organic phases were dried (Na2SO4), filtered and concentrated
to obtain a residue which was filtered on a bed of silica gel [60–120 mesh, hexane:EtOAc (4:1)] to obtain
the title compound (3.81 g, 81%) as a syrup. [α]D −39.2 (c 1.32, CHCl3): υmax/cm−1 3430 (OH): 1H-
NMR (CDCl3, 200 MHz ): δ 1.35, 1.45 (2s, 6H, 2×CH3), 2.7 (dd, 1H, Jgem 13.6 Hz, J5,6 7.7 Hz, H-6),
2.96 (dd, 1H, J5,6 2.8 Hz, H-60), 3.78 (s, 3H, OCH3), 3.85–4.15 (m, 3H, H-3,4 and H-5), 4.45–4.65 (m,
0
2H, H-2 and C6H5CH2), 4.70 (d, 1H, Jgem 12.7 Hz, C6H5CH2), 5.9 (d, 1H, J1,2 4.1 Hz, H-1), 6.8 (d, 2H,
J 8.5 Hz, ArH), 7.15 (d, 2H, ArH), 7.2–7.4 (m, 5H, ArH). Anal. calcd for C23H28O6: C=68.98; H, 7.05.
Found: C, 68.92; H, 7.02.
1.2. 3,5-Di-O-benzyl-1,2-O-isopropylidine-6-C-(40 -methoxyphenyl)-α-D-glucopentofuranose 4
To a slurry of hexane washed sodium hydride (0.25 g, 10.45 mmol) in dry DMF (3 cm3) a solution
of 3 (3.5 g, 8.7 mmol) in DMF (4 cm3) was added at 0°C followed by benzyl bromide (1.78 g, 10.45
mmol). The reaction mixture was stirred for 30 min. at room temperature and then poured into cold water
(50 cm3) and extracted into diethyl ether (2×75 cm3). Combined ethereal extracts were dried (Na2SO4),
filtered and concentrated to obtain a residue which was filtered on a bed of silica gel [60–120 mesh,
hexane:EtOAc (5:1)] to obtain the title compound (4.06 g, 94%) as a syrup. [α]D −59 (c 2.2, CHCl3):
1H-NMR (CDCl3, 200 MHz ): δ 1.3, 1.42 (2s, 6H, 2×CH3), 2.81 (dd, 1H, Jgem 13.2 Hz, J5,6 7.6 Hz,
H-6), 3.12 (dd, 1H, J5,6 2.8 Hz, H-60), 3.78 (s, 3H, OCH3), 3.95–4.09 (m, 3H, H-3,4 and H-5), 4.3–4.7
0
(m, 5H, H-2 and 2×C6H5CH2), 5.9 (d, 1H, J1,2 4.2 Hz, H-1), 6.8 (d, 2H, J 8.5 Hz, ArH), 7.1–7.45 (m,
12H, ArH). Anal. calcd for C30H34O6: C, 73.45; H, 6.99. Found: C, 73.42; H, 6.89.
1.3. 3,5-Di-O-benzyl-6-C-(40-methoxyphenyl)-α/β-D-glucopentofuranose 5
To a solution of 4 (3.1 g, 6.3 mmol) in dichloromethane (20 cm3), 60% aqueous trifluoro acetic acid
(15 cm3) was added and stirred for 6 h at 35°C. After completion of the reaction, it was cooled to 10°C
and neutralised with saturated aqueous sodium hydrogen carbonate solution (10 cm3). The organic phase
was separated and the aqueous layer extracted into dichloromethane (2×50 cm3). The combined organic
phases were dried (Na2SO4), filtered and concentrated to obtain the title compound 5 (2.3 g, 80%) as
1
a syrup. υmax/cm−1 3500 (OH): H-NMR (CDCl3, 200 MHz ): δ 2.69–2.88 (m, 1H, H-6), 3.05–3.25
(m, 1H, H-60), 3.78 (s, 3H, OCH3), 3.88–4.09 (m, 2H, H-2 and H-4), 4.12–4.20 (m, 2H, H-3 and H-5)
4.3–4.65 (m, 4H, 2×C6H5CH2), 5.1 (s, 0.4H, H-1), 5.49–5.55 (m, 0.6H, H-1), 6.8 (d, 2H, J 8.5 Hz, ArH),
7.09–7.4 (m, 12H, ArH). Anal. calcd for C27H30O6: C, 71.98; H, 6.71. Found: C, 71.93; H, 6.66.
1.4. 2,4-Di(benzyloxy)-5-(4-methoxyphenyl)-(2R,3R,4R)-pentane-1,3-diol 6
To a solution of 5 (1.9 g, 4.2 mmol) at 0°C in 50% aqueous methanol (25 cm3) was added in one portion
sodium metaperiodate (1.35 g, 6.32 mmol) and stirred at 0°C for 1 h. After completion of the reaction,
solvent was removed on a rotary evaporator to obtain a residue which was dissolved in dichloromethane
and filtered through Celite and bed washed with dichloromethane (2×25 cm3). Combined organic phases
were dried (Na2SO4), filtered and concentrated to a syrup, which was dissolved in isopropanol (10 cm3),
cooled to 0°C and sodium borohydride (0.26 g, 6.8 mmol) was added. The reaction mixture was stirred
for 1 h and then quenched with a few drops of acetic acid and was gradually brought to room temperature.
Isopropyl alcohol was removed under reduced pressure to obtain a residue which was extracted into ethyl
acetate (2×75 cm3). The combined organic extracts were dried (Na2SO4), filtered and concentrated to
obtain a residue which was filtered on a bed of silica gel [60–120 mesh, hexane:EtOAc (3:1)] to obtain

H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
831
the title compound (1.48 g, 83%) as a colorless crystalline solid, m.p. 65–67°C. [α]D −44.5 (c 1.12,
1
CHCl3): υmax/cm−1 3450 (OH): H-NMR (CDCl3, 200 MHz ): δ 2.16 (br. s, OH), 2.65 (d, 1H, J 7.2
Hz, OH), 2.85 (dd, 1H, Jgem 13.2 Hz, J1,2 6.2 Hz, H-1), 3.04 (dd, 1H, J1 ,2 3.5 Hz, H-10), 3.5–3.90 (m,
0
5H, H-2,3,4 and H-5), 3.78 (s, 3H, OCH3), 4.20–4.7 (m, 4H, 2×C6H5CH2), 6.8 (d, 2H, J 8.4 Hz, ArH),
7.10–7.4 (m, 12H, ArH). Anal. calcd for C26H30O5: C, 73.91; H, 7.16. Found: C, 73.86; H, 7.09.
1.5. 2,4-Benzyloxy-1-[1-benzyloxy-4-tert-butyldimethylsilyloxy-(1R)-ethyl]-3-(4-methoxyphenyl)-(1R,
2R)-propylacetate 7
To a solution of diol 6 (1.0 g, 2.36 mmol) in pyridine (1.0 cm3) at 0°C was added tert-butyldimethylsilyl
chloride (0.426 g, 2.84 mmol) and stirred for 3 h at room temperature. When silylation was complete,
acetic anhydride (0.3 cm3) was added and stirred for 1 h. The reaction mixture was diluted with water
and extracted into diethyl ether (2×25 cm3). The combined ethereal layer was washed with water, dried
(Na2SO4), filtered and concentrated to obtain a residue which was filtered on a bed of silica gel [60–120
mesh, hexane:EtOAc (6:1)] to obtain the title compound 7 (1.23 g, 90%) as a colorless syrup. [α]D 20.45
(c 1.44, CHCl3): υmax/cm−1 1742 (C_O): 1H-NMR (CDCl3, 200 MHz): δ 0.3 (s, 6H, 2×Me), 0.88 (s,
9H, CMe3), 2.03 (s, 3H, OCOCH3), 2.7–2.8 (m, 2H, H-1,10), 3.6–3.9 (m, 4H, H-2,4 and H-5,50), 3.75 (s,
3H, OCH3), 4.1–4.8 (m, 4H, 2×C6H5CH2), 6.8 (d, 2H, J 8.0 Hz, ArH), 7.0–7.38 (m, 12H, ArH). Anal.
calcd for C34H46O6Si: C, 70.55; H, 8.01. Found: C, 70.41; H, 7.99.
1.6. 2,4-Di(benzyloxy)-3-hydroxy-5(4-methoxyphenyl)-(2R,3R,4R)-pentylacetate 8a
To a solution of 7 (0.75 g, 1.3 mmol) in dry THF (10 cm3) was added tetrabutylammonium fluoride (0.4
g, 1.5 mmol) at 0°C and was stirred for 30 min. After completion of the reaction, solvent was removed
under reduced pressure to obtain a residue which was extracted into ethyl acetate (50 cm3). The organic
layer was washed with water (2×25 cm3), dried (Na2SO4), filtered and concentrated to obtain a residue
which was filtered on a bed of silica gel [60–120 mesh, hexane: EtOAc (6:4)] to obtain the title compound
8a (0.59 g, 98%) as a thick syrup. [α]D 37.3 (c 1.0, CHCl3): υmax/cm−1 1744 (C_O): 1H-NMR (CDCl3,
200 MHz ): δ 2.02 (s, 3H, OCOCH3), 2.31 (d, 1H, J 8.4 Hz, OH), 2.82 (dd, 1H, Jgem 13.0 Hz, J1,2 6.0 Hz,
H-1), 3.10 (dd, 1H, J1 ,2 2.7 Hz, H-10), 3.4 (dd, 1H, J2,3 7.9 Hz, J3,4 6.2 Hz, H-3), 3.55–3.70 (m, 1H, H-2),
0
3.78 (s, 3H, OCH3), 4.1–4.5 (m, 5H, H-5,50, 1.5×C6H5CH2), 4.65 (d, 1H, Jgem 12.5 Hz, C6H5CH2), 6.8
(d, 2H, J 8.0 Hz, ArH), 7.1–7.4 (m, 12H, ArH). Anal. calcd for C28H32O6: C, 72.39; H, 6.94. Found: C,
72.33; H, 6.89.
1.7. 2-Benzyloxy-1-[1-benzyloxy-2-hydroxy-(1R)-ethyl]-3-(4-methoxyphenyl)-(1R,2R)-propylacetate 8b
To a solution of 7 (0.3 g, 0.51 mmol) in dichloromethane (10 cm3) was added 1% p-TsOH solution in
methanol (3.0 cm3) at −20°C. Reaction was monitered by TLC and when complete (18 h) triethylamine
(0.3 cm3) was added and solvent was removed under high vacuum (0.01 Torr) to obtain a residue which
was filtered on a short bed of silica gel to obtain the title compound 8b (0.21 g, 87%) as a syrup. 8b: [α]D
14.2 (c 2.0, CHCl3): υmax/cm−1 1740 (C_O): 1H-NMR (CDCl3, 200 MHz ): δ 2.10 (s, 3H, OCOCH3),
2.5 (br. s, 1H, OH), 2.81 (dd, 1H, Jgem 12.8 Hz, J1,2 7.2 Hz, H-1), 2.98 (dd, 1H, J1 ,2 2.2 Hz, H-10),
0
3.55–3.95 (m, 4H, H-2, H-4 and H-5), 3.80 (s, 3H, OCH3), 4.35 (s, 2H, C6H5CH2), 4.6 (d, 2H, Jgem 13.8
Hz, C6H5CH2), 5.15 (dd, 1H, J2,3 4.2 Hz, J3,4 4.0 Hz, H-3), 6.8 (d, 2H, J 8.0 Hz, ArH), 7.1–7.38 (m,
12H, ArH). Anal. calcd for C28H32O6: C, 72.29; H, 6.94. Found: C, 72.35; H, 6.89.

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H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
1.8. 2-Benzyloxy-1-[1-benzyloxy-2-(4-methoxyphenyl)-(1R)-ethyl]-3-trityloxy-(1R,2R)-propylacetate 9
To a solution of diol 6 (0.3 g, 0.71 mmol) in pyridine (1.0 cm3) was added trityl chloride (0.25 g, 0.92
mmol) at 0°C and the reaction mixture was stirred for 6 h at room temperature. After completion of the
reaction, acetic anhydride (0.3 cm3) was added and stirred for 1 h. The reaction mixture was diluted with
water and extracted into diethyl ether (2×30 cm3). The combined ethereal layer was washed with water,
dried (Na2SO4), filtered and concentrated to obtain a residue which was filtered on a bed of silica gel
[60–120 mesh, hexane:EtOAc (5:1)] to obtain the title compound 9 (0.46 g, 92%) as a thick syrup. [α]D
11.19 (c 1.06, CHCl3): υmax/cm−1 1744 (C_O): 1H-NMR (CDCl3, 200 MHz): δ 2.05 (s, 3H, OCOCH3),
2.40–2.95 (m, 2H, H-1,10), 3.35–3.68 (m, 4H, H-2, H-4 and H-5,50), 3.80 (s, 3H, OCH3), 4.12–4.78 (m,
4H, 2×C6H5CH2), 5.8 (dd, 1H, J2,3 4.3 Hz, J3,4 4.2 Hz, H-3), 6.6–7.5 (m, 29H, ArH). Anal. calcd for
C47H46O6: C, 79.86; H, 6.56. Found: C, 79.81; H, 6.53.
1.9. 1-[1,2-Dihydroxy-(1R)-ethyl]-2-hydroxy-3-(4-methoxyphenyl)-(1R,2R)-propylacetate 1 and 2,3,4-
trihydroxy-5-(4-methoxyphenyl)-(2R,3R,4R)-pentylacetate 1a
A solution of 8a:8b (1:6 by NMR, 0.2 g, 0.43 mmol) and PdO (10 mg) in ethyl acetate (5.0 cm3) was
stirred under a hydrogen atmosphere (1 atm) for 2 h at room temperature. The catalyst was filtered off
and solvent removed under reduced pressure to obtain an inseparable mixture of 1:1a (1:1, 0.11 g, 90%)
as a thick syrup. Anal. calcd for C14H20O6: C, 59.14; H, 7.09. Found: C, 59.06; H, 7.02.
Compound 1a: To a solution of 8a (0.5 g, 1.07 mmol) in methanol (10 cm3) was added 10% Pd–BaSO4
(10 mg) and stirred under a hydrogen atmosphere (1 atm) for 4 h at room temperature. The catalyst
was filtered off and the solvent removed under reduced pressure to obtain the title compound 1a (0.285
g, 93%) as a colorless crystalline solid, m.p. 103–105°C: υmax/cm−1 1744 (C_O): [α]D 19.6 (c 1.0,
1
CHCl3): H-NMR (CDCl3, D2O exchanged, 200 MHz ): δ 2.12 (s, 3H, OCOCH3), 2.72 (dd, 1H, Jgem
13.0 Hz, J1,2 9.0 Hz, H-1), 2.95 (dd, 1H, J1 ,2 3.8 Hz, H-10), 3.41 (dd, 1H, J2,3 4.0 Hz, J3,4 4.5 Hz, H-3),
0
3.78 (s, 3H, OCH3), 3.92 (ddd, 1H, H-2), 4.1–4.3 (m, 3H, H-4 and H-5,50), 6.8 (d, 2H, J 8.0 Hz, ArH),
7.15 (d, 1H, ArH). Anal. calcd for C14H20O6: C, 59.14; H, 7.09. Found: C, 59.11; H, 7.01.
1.10. 1-[1,2-Di(methylcarbonyloxy)-(1R)-ethyl]-3-(4-methoxyphenyl)-2-methylcarbonyloxy-(1R,
2R)-propylacetate 1b
To a solution of 1/1a (0.1 g, 0.35 mmol) in pyridine (1.0 cm3) was added acetic anhydride (0.3 cm3) at
0°C and stirred for 1 h at room temperature. After completion of the reaction, the reaction mixture was
diluted with water (5 cm3) and extracted into diethyl ether (2×10 cm3). The combined organic phase was
washed with water, dried (Na2SO4), filtered and concentrated to obtain a residue which was filtered on a
bed of silica gel [60–120 mesh, hexane:EtOAc (3:1)] to obtain the title compound 1b (0.137 g, 95%) as
a thick syrup. 1b: [α]D 42.1 (c 0.75, CHCl3): υmax/cm−1 1742 (C_O): 1H-NMR (CDCl3, 400 MHz ): δ
1.90 (2/4 –OAc), 2.01 (5 –OAc), 2.03 (3 –OAc), 2.04 (2/4 –OAc), 2.77 (dd, 1H, Jgem 14.4, J1,2 6.2 Hz,
H-1), 2.82 (dd, 1H, J1 ,2 3.4 Hz, H-10), 3.76 (s, 3H, OCH3), 3.89 (dd, 1H, J5,5 11.2 Hz, J4,5 6.4 Hz, H-5),
0
0
4.25 (dd, 1H, J4,5 4.5 Hz, H-50), 5.24 (ddd, 1H, J2,3 6.7 Hz, H-2), 5.28 (dd, 1H, J3,4 5.6 Hz, H-3), 5.37
0
(ddd, 1H, H-4). Anal. calcd for C20H26O9: C, 58.33; H, 6.39. Found: C, 58.29; H, 6.32.

H. B. Mereyala, R. R. Gadikota / Tetrahedron: Asymmetry 9 (1998) 827–833
833
Acknowledgements
RRG thanks University Grants Commission, New Delhi for the financial assistance in the form of a
Senior Research Fellowship.
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