Lipase-catalysed regio- and enantioselective deacetylation of 2,4-diacetoxyphenyl alkyl ketones

Article abstract of DOI:10.1016/S0968-0896(99)00109-1

Porcine pancreatic lipase in tetrahydrofuran catalyses the deacetylation of 2,4-diacetoxyphenyl alkyl ketones in a highly regioselective fashion. The strategy of regioselective deacetylation of diacetoxyphenyl alkyl ketones has also resulted in the enanti

Full text of DOI:10.1016/S0968-0896(99)00109-1

Bioorganic & Medicinal Chemistry 7 (1999) 1973±1977
Lipase-Catalysed Regio- and Enantioselective Deacetylation of
2,4-Diacetoxyphenyl Alkyl Ketones
Ashok K. Prasad,* Hari N. Pati, Abul Azim, Smriti Trikha and Poonam
Department of Chemistry, University of Delhi, Delhi-110 007, India
Received 17 February 1999; accepted 8 April 1999
AbstractÐPorcine pancreatic lipase in tetrahydrofuran catalyses the deacetylation of 2,4-diacetoxyphenyl alkyl ketones in a highly
regioselective fashion. The strategy of regioselective deacetylation of diacetoxyphenyl alkyl ketones has also resulted in the enan-
tiomeric resolution of a racemic diacetoxyphenyl alkyl ketone, i.e. (‹)-2,4-diacetoxyphenyl (1-ethyl)pentyl ketone, a precursor for
the synthesis of an antifungal coumarin, 7-acetoxy-4-(1-ethyl)pentyl-3-phenyl-2H-1-benzopyran-2-one. # 1999 Elsevier Science
Ltd. All rights reserved.
Introduction
the selective deacetylation of one of two acetoxy func-
tions of a racemic diacetoxyphenyl alkyl ketone, this
perhaps is the ®rst report of the recognition of phenolic
acetoxy function by lipase as a remote handle for chiral
discrimination.
Polyphenolics occur widely in nature and being the sec-
ondary metabolites of plants possess a variety of biolo-
gical activities.1±5 Polyhydroxyaryl alkyl ketones are
versatile starting materials for the synthesis of di€erent
classes of natural polyphenolics, e.g. coumarins,6 chal-
cones,7 ¯avones,8 ¯avanones,9 chromones,10 etc. Synth-
esis of these natural products requires selective
protection/deprotection of the starting compounds
leading to multistep synthetic protocols and hence
overall low yields. Lipases are the most frequently used
enzymes in organic synthesis11,12 to carry out regio-
selective and/or enantioselective acylation of polyols13
and synthesis of chiral intermediates and target mole-
cules.14 Recently, we have demonstrated that the lipases
from porcine pancreas (PPL) and Aspergillus species15
can be used for the regioselective de-esteri®cation of
peracetates of di€erent classes of polyphenolics, e.g.
acetophenones,16,17 chalcones,17 desoxybenzoins,18 cou-
marins,19 ¯avones,19 and esters and amides of aromatic
carboxylic acids.20,21 Earlier studies had revealed that
PPL in tetrahydrofuran (THF) is the best combination
to carry out ecient, regioselective deacetylation on
di€erent polyphenolic peracetates. We wish to report
herein the regioselective deacetylation of 2,4-diacetoxy-
phenyl alkyl ketones mediated by PPL in THF. This
system also exhibited enantioselectivity while catalysing
Results and Discussion
The starting aryl alkyl ketones, i.e. 2,4-dihydroxyphenyl
undecyl ketone (1), 2,4-dihydroxyphenyl pentadecyl
ketone (2), 2,4-dihydroxyphenyl isopropyl ketone (3),
2,4-dihydroxyphenyl isobutyl ketone (4) and 2,4-dihy-
droxyphenyl (1-ethyl)pentyl ketone (5) were prepared by
Friedel±Crafts acylation of resorcinol with the corres-
ponding acids in the presence of fused ZnCl2 at 150ꢀC.
The dihydroxy ketones 1±5 were characterised on the
basis of their spectral analysis and comparison of their
physical data with those reported in the literature.22±24
The diacetates of compounds 1±5, i.e. 2,4-diacetoxy-
phenyl undecyl ketone (6), 2,4-diacetoxyphenyl penta-
decyl ketone (7), 2,4-diacetoxyphenyl isopropyl ketone
(8), 2,4-diacetoxyphenyl isobutyl ketone (9) and 2,4-
diacetoxyphenyl (1-ethyl)pentyl ketone (10) were pre-
pared by the acetic anhydride/pyridine method in more
than 80% yields. The new diacetoxy compounds 6 and
8±10 were identi®ed from their spectral data (1H NMR,
13C NMR, IR, UV and MS, cf. Experimental), whereas
the known diacetate 7 was characterised on the basis of
its spectral data and comparison of physical data with
those reported in literature.25,26
* Corresponding author.
0968-0896/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved.
PII: S0968-0896(99)00109-1

1974
A. K. Prasad et al. / Bioorg. Med. Chem. 7 (1999) 1973±1977
with our earlier proposed hypothesis on the mechanism
of action of PPL in THF involving a dynamic Schi€'s
base complex formation between the e-amino group of
the lysine residue in the active site of the PPL and the
keto group directly attached to the benzenoid ring.27
The formation of this complex causes the ortho acetoxy
function to be embedded under the hydrophobic bulk of
the active site of the enzyme and the serine-OH takes
part in deacetylation of other more suitably placed
acetoxy function(s) (para acetoxy function in the present
study) in the same molecule.
In order to investigate the possibility of enantiomeric
resolution through the de-esteri®cation of the acetoxy
function in the phenyl ring of racemic aryl alkyl
ketones, 2,4-diacetoxyphenyl (1-ethyl)pentyl ketone (10)
was incubated with PPL in THF and the reaction was
stopped by ®ltering o€ the enzyme after about 45%
conversion of the diacetate to monoacetate. It was
observed that the enzyme selectively deacetylates the
para acetoxy function over the ortho acetoxy function of
the chiral ketone 10 as in the case of achiral ketones 6±
9. In addition to the regioselectivity in deacetylation of
compound 10, the lipase also showed enantioselectivity
and deacetylated the para acetoxy function of one
enantiomer leading to optically active ( )-2-acetoxy-4-
hydroxyphenyl alkyl ketone 15 (Table 1). The detailed
study of enantioselectivity of the enzymatic deacetyla-
tion is in progress. The products of all enzymatic dea-
cetylation reactions, i.e. 2-acetoxy-4-hydroxyphenyl
alkyl ketones 11±15 are new compounds and have been
fully characterised on the basis of their spectral (1H
NMR, 13C NMR, IR, UV and MS) analysis (cf.
Experimental). The presence of hydroxyl function at the
para position with respect to the nuclear carbonyl group
in the compounds 11±15 was further supported by the
observance of bathochromic shifts in their UV absorp-
tion maxima in the presence of NaOAc and no change
in their lmax values on the addition of AlCl3 and HCl.28
No deacetylation reaction was observed on any of the
above substrates by carrying out the reactions under
identical conditions but without addition of the lipase.
The enzymatic deacetylation of 2,4-diacetoxyphenyl
undecyl ketone (6) and 2,4-diacetoxyphenyl pentadecyl
ketone (7) with PPL in THF gave exclusively the
2-acetoxy-4-hydroxyphenyl undecyl ketone (11) and
2-acetoxy-4-hydroxyphenyl pentadecyl ketone (12) in 45
and 60% yields, respectively (Table 1). In both cases the
enzyme selectively deacetylates the acetoxy group para
to the nuclear carbonyl group. The result that the ortho
acetoxy function is inert to PPL-catalysed deacetylation
is in conformity with our earlier ®ndings.16±19 Further,
the results indicate that the increase in the lipophilicity
of the substrate due to increase in chain length of the
alkyl moiety does not a€ect the regioselectivity of PPL
in THF. This is the ®rst example of enzymatic de-ester-
i®cation of long-chain alkyl (C11-C15) aryl ketones.
In addition to the selective deacetylation study on
ketones 6 and 7 with straight chain alkyl groups, 2,4-
diacetoxyphenyl isopropyl ketone (8) and 2,4-diacetoxy-
phenyl isobutyl ketone (9) were also incubated with PPL
in THF to investigate the e€ect of branching in the alkyl
chain on the regioselectivity of the enzymatic reaction.
It was observed that the enzyme deacetylates the para
acetoxy group of compounds 8 and 9 exclusively over
the ortho acetoxy group in the same fashion leading to
the formation of 2-acetoxy-4-hydroxyphenyl isopropyl
ketone (13) and 2-acetoxy-4-hydroxyphenyl isobutyl
ketone (14), respectively (Table 1). This result indicates
that the di€erent array of carbon atoms of the alkyl
group does not a€ect the selectivity of the enzymatic
reaction, i.e. the enzyme and alkyl group interaction
does not play any crucial role in the de-esteri®cation of
phenolic acetoxy function. These results are in accordance
The enzymatic method developed for the selective dea-
cetylation of polyacetoxyphenyl alkyl ketones may o€er
a signi®cant advantage over the chemical method for
selectively protecting the chelated hydroxyl function en
route to the synthesis of bioactive polyphenolic com-
pounds. This strategy of selective de-esteri®cation has
been applied fruitfully in the enantiomeric separation of
a chiral ketone. This is the ®rst example of resolution of
a polyphenolic compound involving the phenolic acetoxy
Table 1. Regioselective deacetylation of diacetoxyphenyl alkyl ketones mediated by PPL in THF at 42±45ꢀC in the presence of n-butanola
Substrate
Time (h)
Product (% yield)
2,4-Diacetoxyphenyl undecyl ketone (6)
2,4-Diacetoxyphenyl pentadecyl ketone (7)
2,4-Diacetoxyphenyl isopropyl ketone (8)
2,4-Diacetoxyphenyl isobutyl ketone (9)
2,4-Diacetoxyphenyl (1-ethyl)pentyl ketone (10)
24
24
48
48
48
2-Acetoxy-4-hydroxyphenyl undecyl ketone (11)29 (45)
2-Acetoxy-4-hydroxyphenyl pentadecyl ketone (12) (60)
2-Acetoxy-4-hydroxyphenyl isopropyl ketone (13)29 (55)
2-Acetoxy-4-hydroxyphenyl isobutyl ketone (14)29 (45)
(
)-2-Acetoxy-4-hydroxyphenyl (1-ethyl)pentyl ketone (15)29 (45)
a
All these reactions, when performed under identical conditions but without adding the lipase, did not yield any product.

A. K. Prasad et al. / Bioorg. Med. Chem. 7 (1999) 1973±1977
1975
function situated far away from the asymmetric centre
as remote site for chiral recognition by the lipase. Further
work in this direction is in progress in our laboratory. The
chiral ketone (10) resolved herein is a precursor for the
synthesis of a highly potent antifungal coumarin, 7-
acetoxy-4-(1-ethyl)pentyl-3-phenyl-2H-1-benzopyran-2-
one (16).6 Since it is well established that the biological
activities of two enantiomers are not the same, the
strategy of enantiomeric separation via enzymatic dea-
cetylation of an acetoxy function can be used to syn-
thesise (R)- and (S)-forms of the active coumarin to
study their comparative antifungal activity. Further, in
the course of this enzymatic de-esteri®cation study nine
new compounds, i.e. 6 and 8±15, have been obtained.
cm 1: 2990, 1780, 1700, 1615, 1190, 1010 and 900; UV
(MeOH) nM: 259 and 273; H NMR (CDCl3): d 0.87
1
(3H, t, J=6.7 Hz, CH3), 1.26 (16H, brs, (CH2)8), 1.66
(2H, m, CO CH2 CH2), 2.28 and 2.31 (6H, 2s, 3H
each, 2ÂOCOCH3), 2.84 (2H, t, J=7.0 Hz, COCH2),
6.94 (1H, d, J=2.2 Hz, C 3H), 7.07 (1H, dd, J=8.6
and 2.2 Hz, C 5H) and 7.78 (1H, d, J=8.6 Hz, C 6H);
13C NMR (CDCl3): d 13.97 (CH3), 20.92 (CH3-CH2),
22.55 and 23.98 (2ÂOCOCH3), 28.72, 29.13, 29.20,
29.32, 29.37 and 29.49 (7ÂCH2), 31.78 (COCH2CH2),
41.27 (COCH2), 117.24 and 118.92 (C-3 and C-5),
128.34 (C-1), 130.58 (C-6), 149.76 (C-2), 153.54 (C-4),
168.20 and 168.87 (2ÂCOCH3) and 199.08 (CO); EIMS,
m/z (% rel. int.): 376 [M+] (22), 334 (20), 315 (60), 273
(90), 235 (85), 220 (40), 206 (25), 193 (90), 178 (85), 165
(65), 152 (95), 137 (100), 123 (22), 81 (10), 69 (10) and 55
(14).
Experimental
Melting points were determined in a bath and are
uncorrected. The UV and IR spectra were recorded on a
Beckman DU-2 spectrophotometer and Shimadzu
model 435 spectrophotometer, respectively. The 1H
NMR and the 13C NMR spectra were recorded on a
Bruker AC-250 spectrometer at 250 and 62.9 MHz,
respectively using TMS as an internal standard. The
chemical shift values are on d scale and the coupling
constants (J) are in Hz. The EI mass spectra were
recorded on a Jeol AX 505 W instrument at 70 eV. The
enzyme, porcine pancreatic lipase (PPL) (Type-II), was
purchased from Sigma Chemical Co. (USA) and used
after keeping in vacuo over P2O5 for 12 h. The organic
solvents used were redistilled and dried over molecular
sieves (4 A). Analytical thin layer chromatography (TLC)
was performed on silica gel coated on 5Â20 cm glass
plates and/or Merck silica gel 60 F254 plates. Solvent
systems used were A (benzene:ethyl acetate, 17:3) and B
(benzene:ethyl acetate, 9:1). The developing agents were
alcoholic FeCl3 solution (3%) or iodine vapour. The
diacetates 6±10 of dihydroxy ketones 1±5 were prepared
in high yields by the acetic anhydride±pyridine method
either at room temperature or by heating to 80ꢀC.
2,4-Diacetoxyphenyl isopropyl ketone (8). Obtained as
an oil; Rf 0.4 (solvent A); IR (®lm) cm 1: 3000, 1780,
1690, 1620, 1250, 1190, 1140, 1110, 1010, 990, 910 and
1
820; UV (MeOH) nM: 259 and 276; H NMR (CDCl3):
d 1.13 (6H, d, J=6.8 Hz, CH(CH3)2), 2.27 and 2.29 (6H,
2s, 3H each, 2ÂOCOCH3), 3.33 (1H, m, CH(CH3)2),
6.96 (1H, d, J=2.1 Hz, C 3H), 7.09 (1H, dd, J=8.5
and 2.1 Hz, C-5H) and 7.73 (1H, d, J=8.5 Hz, C-6H);
13C NMR (CDCl3): d 18.47 (2ÂCH3), 20.73 and 20.82
(2ÂOCOCH3), 38.03 (CH), 117.28 and 118.86 (C-3 and
C-5), 127.81 (C-1), 130.25 (C-6), 149.78 (C-2),153.27 (C-
4), 168.23 and 168.86 (2ÂCOCH3) and 203.44 (CO);
EIMS, m/z (% rel. int.): 264 [M+] (7), 222 (80), 221 (90),
180 (95), 137 (100), 108 (15), 81 (25), 69 (10) and 53 (8).
2,4-Diacetoxyphenyl isobutyl ketone (9). Obtained as an
oil; Rf 0.5 (solvent B); IR (®lm) cm 1: 3000, 2930, 1780,
1690, 1610, 1590, 1500, 1420, 1300, 1250, 1120, 1010,
970, 910, 815 and 670; UV (MeOH) nM: 259 and 276;
1H NMR (CDCl3):
d 0.95 (6H, d, J=6.7 Hz,
CH(CH3)2), 2.27 (1H, m, CH(CH3)2), 2.29 and 2.32
(6H, 2s, 3H each, 2ÂOCOCH3) 2.72 (2H, d, J=6.8 Hz,
CH2), 6.94 (1H, d, J=2.2 Hz, C-3H), 7.08 (1H, dd, J=
8.6 and 2.2 Hz, C-5H) and 7.77 (1H, d, J=8.6 Hz, C-
6H); 13C NMR (CDCl3): d 20.97 and 22.50 (2ÂCH3 and
2ÂOCOCH3), 24.68 (CH), 50.18 (COCH2), 117.28 and
118.95 (C-3 and C-5), 128.64 (C-1), 130.59 (C-6), 149.69
(C-2), 153.49 (C4), 168.27 and 168.94 (2ÂCOCH3) and
198.89 (CO); EIMS, m/z (% rel. int.): 278 [M+] (3), 236
(28), 221 (14). 194 (52), 179 (43), 152 (33), 137 (100) and
43 (21).
General procedure of enzymatic deacetylation of
2,4-diacetoxyphenyl alkyl ketones 6±10
To a solution of 2,4-diacetoxyphenyl alkyl ketone (1±
2 mmol) in dry THF (20±25 mL) containing n-butanol
(5 molar equivalent), PPL (200±300 mg) was added and
the suspension was stirred at 42±45ꢀC. The progress of
the reaction was monitored by TLC. The reaction was
quenched on completion (in the case of chiral ketone 10
the reaction was quenched after about 45% conversion
of the diacetate to a product) by ®ltering o€ the enzyme,
solvent was removed under reduced pressure and the
crude product was puri®ed by column or preparative
TLC and/or by crystallisation a€ording pure mono-
acetoxyphenyl alkyl ketones 11±15. All diacetoxyphenyl
alkyl ketones and their enzymatic reaction products
were characterised on the basis of their spectroscopic
data.
2,4-Diacetoxyphenyl (1-ethyl)pentyl ketone (10). Obtained
1
as a viscous oil; Rf 0.45 (solvent B); IR (®lm) cm
:
3000, 2950, 1780, 1690, 1620, 1490, 1420, 1250, 1200,
1140, 1110, 1010, 905 and 820; UV (MeOH) nM: 259
1
and 275; H NMR (CDCl3): d 0.87 (6H, m, 2ÂCH3),
1.26 (4H, m, C-30H and C-40H), 1.53 (2H, m, C-20H),
1.70 (2H, m, C-100H), 2.29 and 2.31 (6H, 2s, 3H each,
2ÂOCOCH3), 3.14 (1H, m, C-10H), 6.95 (1H, d,
J=2.2 Hz, C-3H), 7.08 (1H, dd, J=8.6 and 2.2 Hz, C-
5H) and 7.73 (1H, d, J=8.6 Hz, C-6H); 13C NMR
(CDCl3): d 11.55 and 13.78 (C-50 and C-200), 20.82 and
20.96 (C-30 and C-40), 22.75 and 24.55 (2ÂOCOCH3),
29.47 (C-20), 30.78 (C-100), 50.41 (C-10), 117.55 and
2,4-Diacetoxyphenyl undecyl ketone (6). Obtained as a
white solid, mp 50±51ꢀC; Rf 0.5 (solvent B); IR (nujol)

1976
A. K. Prasad et al. / Bioorg. Med. Chem. 7 (1999) 1973±1977
1
118.89 (C-3 and C-5), 129.11 (C-1), 130.32(C-6), 149.86
(C-2), 153.29 (C-4), 168.26 and 168.93 (2ÂCOCH3) and
203.13 (CO); EIMS, m/z (% rel. int.): 320 [M+] (10),
278 (15), 263 (85), 236 (5), 234 (10), 221 (95), 178 (85),
137 (100), 108 (10), 81 (15), 69 (8) and 57 (25).
nM: 320 and 325; +NaOAc: 323 and 345; H NMR
(CDCl3): d 0.95 (6H, d, J=6.7 Hz, CH(CH3)2) 2.20 (1H,
m, CH), 2.34 (3H, s, OCOCH3), 2.70 (2H, d, J=6.9 Hz,
COCH2), 6.50 (1H, d, J=2.4 Hz, C-3H), 6.66 (1H, dd,
J=8.7 and 2.4 Hz, C-5H) and 7.67 (1H, d, J=8.7 Hz, C-
6H); 13C NMR (CDCl3): d 21.21 and 22.62 (2ÂCH3 and
OCOCH3), 25.29 (CH), 49.68 (COCH2), 111.20 and
113.28 (C-3 and C-5), 122.70 (C-1), 132.32 (C-6), 150.98
(C-2), 160.93 (C-4), 170.57 (COCH3) and 199.38 (CO);
EIMS, m/z (% rel. int.): 236 [M+] (17), 194 (25), 179 (26),
152 (21), 137 (100), 108 (3), 81 (5) and 43 (12).
2-Acetoxy-4-hydroxyphenly undecyl ketone (11).
Obtained as a light yellow solid, mp 104ꢀC; Rf 0.5 (sol-
vent A); IR (nujol) cm 1: 3320, 2960, 1740, 1685, 1615,
1510, 1320, 1250, 1230, 1150, 1115, 1020, 955 and 910;
UV (MeOH) nM: 313 and 326;+NaOAc: 322 and 353;
1H NMR (CDCl3): d 0.87 (3H, t, J=7.6 Hz, CH3), 1.25
(16H, s, (CH2)8), 1.64 (2H, m, CO-CH2-CH2), 2.35 (3H,
s, OCOCH3), 2.81 (2H, t, J=7.6 Hz, COCH2), 6.48 (1H,
d, J=1.9 Hz, C-3H), 6.64 (1H, dd, J=8.0 and 1.9 Hz,
C-5H) and 7.70 (1H, d, J=8.0 Hz, C-6H), 13C NMR
2-Acetoxy-4-hydroxyphenyl (1-ethyl)pentyl ketone (15).
Obtained as a viscous oil; Rf 0.4 (solvent A); [a]d23
6.6ꢀ (c 0.66, CHCl3); IR (nujol) cm 1: 3350, 3000,
1780, 1740, 1670, 1610, 1510, 1320, 1250, 1150, 1110,
1010, 900 and 820; UV (MeOH) nM: 259 and 296;
(CDCl3):
d 14.08 (CH3), 21.22 (CH3CH2) 22.65
1
(OCOCH3), 24.44, 24.95, 26.04, 28.90, 29.23, 29.59 and
31.87 (8ÂCH2), 40.78 (COCH2), 111.17 and 113.24 (C-3
and C-5), 122.49 (C-1), 132.24 (C-6), 151.02 (C-2),
160.74 (C-4), 170.44 (COCH3) and 199.27 (CO); EIMS,
m/z (% rel. int.): 334 [M+] (6), 316 (7), 292 (8), 274 (30),
194 (20), 165 (25), 152 (78), 137 (100), 123 (5) and 43 (13).
+NaOAc: 323 and 337; H NMR (CDCl3): d 0.83 (6H,
m, 2ÂCH3), 1.25 (4H, m, C-30H and C-40H), 1.50 (2H,
m, C-20H), 1.70 (2H, m, C-100H), 2.34 (3H, s, OCOCH3),
3.17 (1H, m, C-10H), 6.47 (1H, d, J=2.4 Hz, C-3H),
6.65 (1H, dd, J=8.7 and 2.4 Hz, C-5H) and 7.65 (1H, d,
J=8.7 Hz, C-6H); 13C NMR (CDCl3): d 11.70 and
13.80 (C-50 and C-200), 21.75, 22.75 and 25.11 (OCOCH3,
C-30 and C-40), 31.39 and 32.01 (C-20 and C-100), 49.45
(C-10), 107.81 and 113.21 (C-3 and C-5), 123.07 (C-1),
131.89 (C-6), 150.93 (C-2), 160.79 (C-4), 170.72
(COCH3) and 203.79 (CO); EIMS, m/z (% rel. int.): 279
[M++1] (25), 278 [M+] (6), 264 (5), 237 (85), 234 (10),
222 (95), 180 (98), 138 (95), 137 (100), 109 (30), 97 (45),
81 (65), 71 (70), 57 (90) and 43 (8).
2-Acetoxy-4-hydroxyphenyl pentadecyl ketone (12).
Obtained as a white solid, mp 105ꢀC; Rf 0.5 (solvent
A); IR (nujol) cm 1: 3330, 2960, 1740, 1690, 1250, 1230,
1115 and 960; UV (MeOH) nM: 296; +NaOAc: 323
1
and 332; H NMR (CDCl3): d 0.87 (3H, t, J=7.6 Hz,
CH3), 1.26 (24H, s, (CH2)12), 1.63 (2H, m, CO CH2
CH2), 2.35 (3H, s, OCOCH3), 2.81 (2H, t, J=7.6 Hz,
COCH2), 6.49 (1H, d, J=2.4 Hz, C-3H), 6.70 (1H, dd,
J=8.6 and 2.4 Hz, C-5H) and 7.72 (1H, d, J=8.6 Hz,
C-6H); 13C NMR (CDCl3): d 14.09 (CH3), 21.22 (CH3-
CH2), 22.68(OCOCH3), 24.42, 24.68, 29.22, 29.34,
29.42, 29.44, 29.58, 29.67, 31.91 and 33.95 (12ÂCH2),
40.82 (COCH2), 111.18 and 113.20 (C-3 and C-5),
122.67 (C-1), 132.22 (C-6), 151.06 (C-2), 160.57 (C-4),
170.27 (COCH3) and 199.06 (CO); EIMS, m/z (% rel.
int.): 392 (1), 390 [M+] (missing), 279 (4), 256 (100), 227
(10), 214 (12), 213 (34), 199 (10), 185 (22), 171 (15), 157
(20), 149 (18), 129 (45), 115 (20), 97 (22), 85 (27), 73 (80),
60 (65), 57 (63), 43 (55) and 41 (37).
Acknowledgements
We sincerely acknowledge the support and encourage-
ment extended by Professor V. S. Parmar during the
course of this research work. A.Z. and S.T. thank the
Council of Scienti®c and Industrial Research (CSIR,
New Delhi, India) for ®nancial support.
References
2-Acetoxy-4-hydroxyphenyl isopropyl ketone (13).
Obtained as a semi solid; Rf 0.4 (solvent B); IR (nujol)
cm 1: 3400, 3000, 1750, 1680, 1615, 1585, 1525, 1320,
1220, 1125, 1110, 980, 960 and 810; UV (MeOH) nM:
323 and 334; +NaOAc: 323 and 346; 1H NMR
(CDCl3): d 1.15 (6H, d, J=6.9 Hz, CH(CH3)2) 234 (3H,
s, OCOCH3), 3.37 (1H, m, CH(CH3)2) 6.50 (1H, d,
J=2.4 Hz, C-3H), 6.67 (1H, dd, J=8.7 and 2.4 Hz, C-
5H) and 7.67 (1H, d, J=8.7 Hz, C-6H); 13C NMR
(CDCl3): d 18.97 (2ÂCH3), 21.17 (OCOCH3), 37.29
(CH), 111.37 and 113.28 (C-3 and C-5), 121.82 (C-1),
131.96 (C-6), 151.22 (C-2), 160.66 (C-4), 170.63 (COCH3)
and 203.71 (CO); EIMS, m/z (% rel. int.): 222 [M+] (5),
180 (17), 179 (20), 137 (100), 81 (8), 69 (5) and 43 (7).
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2-Acetoxy-4-hydroxyphenyl isobutyl ketone (14).
1
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Obtained as an oil; Rf 0.4 (solvent B); IR (®lm) cm
:
3400, 3000, 1780, 1740, 1620, 1515, 1320, 1300, 1250,
1160, 1110, 1010, 970, 890, 850 and 810; UV (MeOH)

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amounts of the 2-acetoxy ketones. This may be due to the
migration of acetoxy function from ortho to para position
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