Highly Selective Biocatalytic Transesterification Reactions on Aryl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoates

Article abstract of DOI:10.1007/s10562-014-1447-6

Acid anhydrides have been used to carry out the regioselective acylation of primary hydroxyl group in benzyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate and 4-fluorobenzyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate and deacylation of their diesters in the presence of Lipozyme TL IM in diisopropyl ether. Amongst different acid anhydrides used, butanoic anhydride was found to be the best acylating agent as compared to others. Both acylation and deacylation reactions were highly selective and efficient yielding exclusively the monoacylated products in 70-88 % yields.

Full text of DOI:10.1007/s10562-014-1447-6

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Catal Lett (2015) 145:919–929
DOI 10.1007/s10562-014-1447-6
Highly Selective Biocatalytic Transesterification Reactions
on Aryl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoates
•
Gaurav Kumar Ashish Dhawan Brajendra K. Singh Nawal K. Sharma
•
•
•
•
•
•
Sunil K. Sharma Ashok K. Prasad Erik V. Van der Eycken Christophe Len
•
•
Arthur C. Watterson Virinder S. Parmar
Received: 7 September 2014 / Accepted: 15 November 2014 / Published online: 14 February 2015
Ó Springer Science+Business Media New York 2015
Abstract Acid anhydrides have been used to carry out
the regioselective acylation of primary hydroxyl group in
benzyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate
and 4-fluorobenzyl 3-hydroxy-2-(hydroxymethyl)-2-methyl-
propanoate and deacylation of their diesters in the presence
of LipozymeÒ TL IM in diisopropyl ether. Amongst dif-
ferent acid anhydrides used, butanoic anhydride was found
to be the best acylating agent as compared to others. Both
acylation and deacylation reactions were highly selective
and efficient yielding exclusively the monoacylated prod-
ucts in 70–88 % yields.
1 Introduction
Enzymes have been established as valuable catalysts in or-
ganic synthesis for performing chemo-, regio- and stere-
oselective chemical transformations during the last three
decades, lipases in particular are known for their low cost and
wide tolerance towards their substrates. Lipase-catalyzed
regioselective esterifications offer an alternative to the poor
selectivity in chemical syntheses, which suffers from many
shortcomings like high reaction temperatures causing poly-
merization of the products and hence low yields, coloration
of the final products and dehydration or cyclization side re-
actions leading to formation of many undesirable side
products. Furthermore, generally regioselective chemical
synthesis can only be achieved by protection/deprotection
strategies, which are highly cumbersome and not suitable for
industrial processes. These shortcomings can be overcome
by the use of enzymatic catalysis because of the high degree
of regioselectivity exhibited by enzymes and mild reaction
conditions under which they work.
Keywords Aryl 3-hydroxy-2-(hydroxymethyl)-2-
methylpropanoates ꢀ Lipase ꢀ LipozymeÒ TL IM ꢀ
Acylation ꢀ Deacylation ꢀ Regioselectivity
Dedicated with affection to our Friend and Collaborator, Professor
Kalle Levon (NYU Polytechnic School of Engineering, Brooklyn,
New York, USA) in commemoration of the completion of his
26 years in active research.
G. Kumar ꢀ A. Dhawan ꢀ B. K. Singh ꢀ N. K. Sharma ꢀ
S. K. Sharma ꢀ A. K. Prasad ꢀ V. S. Parmar (&)
Bioorganic Laboratory, Department of Chemistry, University of
Delhi, Delhi 110 007, India
N. K. Sharma
Department of Chemical and Biomolecular Engineering, NYU
Polytechnic School of Engineering (NYU-Poly), Six Metrotech
Center, Brooklyn, NY 11201, USA
e-mail: virparmar@gmail.com
C. Len
Sorbonne Universites, Universite de Technologie de Compiegne
G. Kumar ꢀ A. Dhawan ꢀ S. K. Sharma ꢀ
A. C. Watterson ꢀ V. S. Parmar
´
(UTC), CS 60319, 60203 Compiegne Cedex, France
´
`
`
Department of Chemistry, Institute of Nanoscience
and Nanomedicine (INSET), University of
Massachusetts Lowell, One University Avenue, Lowell,
MA 01854, USA
C. Len
Universite de Technologie de Compiegne (UTC), Ecole
´
`
Superieure de Chimie Organique et Minerale (ESCOM),
´
EA4297 Transformations Chimiques de La Matiere
´
`
B. K. Singh ꢀ E. V. Van der Eycken ꢀ V. S. Parmar
Laboratory for Organic & Microwave-Assisted Chemistry
(LOMAC), University of Leuven (KU Leuven), Celestijnenlaan
200F, 3001 Leuven, Belgium
`
Renouvelable, 60205 Compiegne Cedex, France
C. Len
Department of Chemistry, University of Hull, Hull HU6 7RX, UK
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G. Kumar et al.
In the past, in our laboratory we have used a battery of
lipases, viz. porcine pancreatic Lipase (PPL), Candida
rugosa Lipase (CRL), Amano PS, Candida antarctica Li-
pase (CAL), Theremomyces lanuginous (LipozymeÒ TL
IM) and from Pseudomonas sp. for carrying out selective
manipulations of hydroxyl groups in different classes of
compounds [1–8], viz. aryl alkyl ketones [1, 2], hydrox-
ymethylated phenolic compounds [3], amides and esters
[4], sugar derivatives [5], benzoxazines [6], dihydro-
coumarins [7], chromanones [8], etc. In addition to carry-
ing out selective manipulations of similar functional groups
in the small molecules, we have used these lipases exten-
sively for the development of novel amphiphilic co-poly-
mers useful in drug encapsulation and drug delivery
applications. More specifically, we have exploited C.
antarctica lipase-B (CAL-B) to co-polymerize poly-
ethylene glycol (PEG), with different aromatic diesters,
aliphatic diesters, naturally occurring dibasic amino acid
diesters and hydroxy diesters under solvent-free conditions,
thus providing a greener route to the synthesis of these
polymers [9–12].
2 Experimental
2.1 General
The IR spectra were recorded either on a Perkin–Elmer
1
model 2000 FT-IR or RXI FT-IR spectrometer. The H
NMR and 13C NMR spectra were recorded on a Bruker
AC-300 Avance spectrometer at 300 and at 75.5 MHz,
respectively using TMS as internal standard. The che-
mical shift values are on d scale and the coupling con-
stant (J) are in Hz. The FAB-HRMS spectra of all the
compounds were recorded on a micro TOF-Q instrument
from Bruker Daltonics, Bremen high resolution mass
spectrometer in positive mode using the matrix HEDS
(bishydroxyethylsulfide) doped with sodium acetate.
Candida antarctica lipase B and LipozymeÒ TL IM
immobilized on silica were gifted by Novozymes Inc.,
Copenhagen. The enzymes, C. rugosa lipase (CRL, Type
VII) and porcine pancreatic lipase (PPL, Type II) were
purchased from Sigma Chemical Co. (USA). All en-
zymes were used after storing under vacuum over P2O5
for 24 h. Diisopropyl ether (DIPE) was distilled over
The desymmetrization reactions on prochiraldiols, e.g.
serinol analogues have been reported earlier [13–16].
Herein we are reporting a novel strategy to carry out re-
gioselective acylation reactions on aryl 1,3-dihydroxy-2-
methylpropanoates 1 and 2 using acid anhydrides as acy-
lating agents. Of the six lipases screened in this study, we
found LipozymeÒ TL IM to be the best catalyst. We have
also successfully demonstrated the efficacy of LipozymeÒ
TL IM in regioselective deacylation of the corresponding
diacyl derivatives 5a–5e and 6a–6e. Diacyl derivatives
were synthesized from 1 and 2 chemically by treating them
with the anhydrides of acetic, propanoic, butanoic, pen-
tanoic and hexanoic acids as acylating agents and 4-N,N-
dimethylaminopyridine (DMAP) as catalyst in anhydrous
dichloromethane. Four different lipases were screened, viz.
C. antarctica lipase-B (Novozyme-435), porcine pancreatic
lipase (PPL), C. rugosa lipase (CRL) and LipozymeÒ TL
IM for selective deacylation of the diacyl compounds 5a–
5e and 6a–6e in different organic solvents in the presence
of n-butanol as the acyl group scavenger. LipozymeÒ TL
IM in diisopropyl ether was found to be the most efficient
biocatalyst for the regioselective deacylation of compounds
5a–5e and 6a–6e (Scheme 2; Table 2). No clear selectivity
or conversion was observed with Novozyme-435, PPL and
CRL. The monoacylated products 3a–3e and 4a–4e
formed, by either lipase catalyzed acylation of the diols 1
and 2, or by the deacylation of their corresponding diacyl
derivatives 5a–5e and 6a–6e,were fully characterized from
their spectral data and all twenty compounds are novel and
are being reported here for the first time. These compounds
may find applications in the synthesis of copolymers for
drug encapsulation and targeted drug delivery.
˚
activated molecular sieves (4 A) prior to use. Analytical
TLCs were performed on pre-coated Merck silica gel
60F254 plates; the spots were detected under UV light.
Silica gel (100–200 mesh) was used for column
chromatography.
2.2 Synthesis of 4-Fluorobenzyl 3-hydroxy-2-
(hydroxymethyl)-2-methylpropanoate (2)
2,2-Bis(hydroxymethyl)propanoic acid (5 g, 37.28 mmol)
and KOH (3.13 g, 55.91 mmol) were taken in DMF
(25 mL), 4-fluorobenzyl bromide (11.21 g, 59.64 mmol)
was then added. After 15 h of stirring at 100 °C, DMF was
evaporated under reduced pressure. The residue was dis-
solved in CH2Cl2 (100 mL) and extracted with water
(2 9 50 mL). The crude product was recrystallized from
hexane/CH2Cl2 to give 4-fluorobenzyl 3-hydroxy-2-(hy-
droxymethyl)-2-methylpropanoate as viscous oil (6.5 g,
1
82 %). H NMR (300 MHz, CDCl3): d 1.06 (3H, s, C-2
methyl), 2.97 (2 brs 9 OH), 3.72 (2H, d, J = 11.4 Hz,
C-10Ha and C-3Ha), 3.92 (2H, d, J = 11.4 Hz C-10Hb and
C-3Hb) 5.16 (2H, s, C-100H), 7.02-7.08 (2H, m, C-3000 and
C-5000), 7.31–7.36 (2H, m, C-2000 and C-6000); 13C NMR
(75.5 MHz, CDCl3): d 17.08 (C-2 CH3), 49.25 (C-2) 65.97
(C-100), 68.14 (C-10 and C-3), 115.44 & 115.72 (C-3000
&
C-5000), 129.84 & 129.95 (C-2000 & C-6000), 131.50 & 131.54
(C-1000), 161.03 & 164.30 (C-4000), 175.65 (C=O); IR (KBr):
3234 (OH), 1729 (C=O), 1513, 1224, 1047 and 831 cm-1
;
FAB-HRMS: m/z 265.0848 ([M?Na]?, C12H15FO4Na
calcd 265.0847).
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Highly Selective Biocatalytic Transesterification Reactions
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2.3 General Procedure of LipozymeÒ TL IM Lipase
Catalyzed Acylation of Benzyl 3-Hydroxy-2-
(hydroxymethyl)-2-methylpropanoate (1) and 4-
Fluorobenzyl 3-hydroxy-2-(hydroxymethyl)-2-
methylpropanoate (2) with Acid Anhydrides
2.3.3 Benzyl 2-(butanoyloxymethyl)-3-hydroxy-2-
ethylpropanoate (3c)
It was obtained as a viscous oil (812 mg, 88 %).1H NMR
(300 MHz, CDCl3): 0.91 (3H, t, J = 7.5 Hz,
d
OCO(CH2)2CH3), 1.25 (3H, s, C-2 methyl), 1.55–1.65 (2H,
m, OCOCH2CH2CH3), 2.23 (2H, t, J = 7.5 Hz,
OCOCH2CH2CH3), 3.65 (1H, d, J = 12 Hz, C-3Ha), 3.72
(1H, d, J = 12 Hz, C-3Hb), 4.21 (1H, d, J = 11.1 Hz,
C-10Ha), 4.35 (1H, d, J = 11.1 Hz, C-10Hb), 5.17 (2H, s,
C-100H), 7.34 (5H, s, aromatic protons); 13C NMR
(75.5 MHz, CDCl3): d 13.62 (OCO(CH2)2CH3), 17.51 (C-2
CH3), 18.35 (OCOCH2CH2CH3), 35.99 (OCOCH2CH2-
CH3), 48.30 (C-2), 65.00, 65.66 & 66.68 (C-100, C-3 &
C-10), 127.99 (C-3000 & C-5000), 128.33 (C-2000 & C-6000),
128.60 (C-4000), 135.62 (C-1000), 173.77 & 174.27 (29
C=O); IR (KBr): 3502 (OH), 2966, 1732 (C=O), 1457,
1178, 1049 and 698 cm-1; FAB-HRMS: m/z 317.1353
([M?Na]?, C16H22O5Na calcd 317.1359).
To a mixture of 1or 2 (1 mmol) in dry diisopropyl ether
(40 mL), appropriate acid anhydride (1.2 mmol) was
added, followed by LipozymeÒ TL IM lipase (350 mg).
The reaction mixture was stirred at 37–42 °C in an incu-
bator shaker and progress of the reaction was monitored
periodically by TLC. On completion, the reaction was
stopped by filtering off the enzyme and solvent evaporated
to dryness under vacuum. The crude products 3a–3e and
4a–4e thus obtained were purified by column chromatog-
raphy on silica gel using a mixture of petroleum ether-ethyl
acetate for elution.
2.3.1 Benzyl 2-(acetoxymethyl)-3-hydroxy-2-
methylpropanoate (3a)
2.3.4 Benzyl 2-(pentanoyloxymethyl)-3-hydroxy-2-
It was obtained as a viscous oil (635 mg, 77 %).1H NMR
(300 MHz, CDCl3): d 1.22 (3H, s, C-2 methyl), 1.98 (3H,
s, OCOCH3), 3.66 (1H, d, J = 12.3 Hz, C-3Ha), 3.72 (1H,
d, J = 12.3 Hz, C-3Hb), 4.22 (1H, d, J = 12 Hz, C-10Ha),
4.32 (1H, d, J = 12 Hz, C-10Hb), 5.17 (2H, s, C-100H), 7.34
(5H, s, aromatic protons); 13C NMR (75.5 MHz, CDCl3): d
17.81 (C-2 CH3), 21.01(OCOCH3), 48.57 (C-2), 65.32,
66.25 & 67.02 (C-100, C-10 & C-3), 128.33 (C-3000 & C-5000),
128.67 (C-2000 & C-6000), 128.94 (C-4000), 135.98 (C-1000),
171.47 & 174.57 (29 C=O); IR (KBr): 3502 (OH), 2946,
1732 (C=O), 1456, 1243, 1042 and 698 cm-1; FAB-
HRMS: m/z 289.1054 ([M?Na]?, C14H18O5Na calcd
289.1046).
methylpropanoate (3d)
It was obtained as a viscous oil (780 mg, 81 %).1H NMR
(300 MHz, CDCl3):
d
0.89 (3H, t, J = 7.2 Hz,
OCO(CH2)3CH3), 1.22 (3H, s, C-2 methyl), 1.24–1.29 (2H,
m, OCO(CH2)2CH2CH3), 1.52-1.61 (2H, m, OCOCH2-
CH2CH2CH3), 2.21 (2H, t, J = 7.8 Hz, OCOCH2(CH2)2-
CH3), 3.65 (1H, d, J = 11.7 Hz, C-3Ha), 3.72 (1H, d,
J = 11.7 Hz, C-3Hb), 4.22 (1H, d, J = 11.1 Hz, C-10Ha),
4.33 (1H, d, J = 11.1 Hz, C-10Hb), 5.17 (2H, s, C-100H),
7.34 (5H, s, aromatic protons); 13C NMR (75.5 MHz,
CDCl3): d 13.64 (OCO(CH2)3CH3), 17.49 (C-2 CH3),
22.19 (OCO(CH2)2CH2CH3), 26.90 (OCOCH2CH2CH2-
CH3), 33.82 (OCOCH2(CH2)2CH3), 48.31 (C-2), 65.00,
65.69 & 66.67 (C-100, C-10 & C-3), 127.97 (C-3000 & C-5000),
128.31 (C-2000 & C-6000), 128.59 (C-4000), 135.64 (C-1000),
173.93 & 174.25 (29 C=O); IR (KBr): 3504 (OH), 2960,
1737 (C=O), 1457, 1173, 1052 and 697 cm-1; FAB-
HRMS: m/z 331.1509 ([M?Na]?, C17H24O5Na calcd
331.1516).
2.3.2 Benzyl 2-(propanoyloxymethyl)-3-hydroxy-2-
methylpropanoate (3b)
It was obtained as a viscous oil (720 mg, 83 %).1H NMR
(300 MHz, CDCl3): d 1.09 (3H, t, J = 7.5 Hz, OCOCH2-
CH3), 1.23 (3H, s, C-2 methyl), 2.24–2.31 (2H, q,
J = 7.2 Hz, OCOCH2CH3), 3.66 (1H, d, J = 12.0 Hz,
C-3Ha), 3.72 (1H, d, J = 12.0 Hz, C-3Hb), 4.22 (1H, d,
J = 11.1 Hz, C-10Ha) 4.36 (1H, d, J = 11.1 Hz, C-10Hb),
5.17 (2H, s, C-100H), 7.34 (5H, s, aromatic protons); 13C
NMR (75.5 MHz, CDCl3): d 9.0 (OCOCH2CH3), 17.46 (C-
2 CH3), 20.20 (OCOCH2CH3), 48.27 (C-2), 64.97, 65.69 &
66.64 (C-100, C-3 & C-10), 127.95 (C-3000 & C-5000), 128.29
(C-2000 & C-6000), 128.56 (C-4000), 135.59 (C-1000), 174.22 &
174.50 (29 C=O); IR (KBr): 3504 (OH), 2981, 1735
(C=O), 1459, 1192, 1052 and 698 cm-1; FAB-HRMS: m/z
303.1198 ([M?Na]?, C15H20O5Na calcd 303.1203).
2.3.5 Benzyl 2-(hexanoyloxymethyl)-3-hydroxy-2-
methylpropanoate (3e)
It was obtained as a viscous oil (755 mg, 76 %).1H NMR
(300 MHz, CDCl3): d 0.88 (3H, t, J = 6.9 Hz, OCO
(CH2)4CH3), 1.23 (3H, s, C-2 methyl), 1.25–1.31 (4H, m,
OCO(CH2)2CH2CH2CH3), 1.52–1.61 (2H, m, OCOCH2-
CH2(CH2)2CH3), 2.24 (2H, t, J = 7.8 Hz, OCOCH2(-
CH2)3CH3), 3.65 (1H, d, J = 11.4 Hz, C-3Ha), 3.72 (1H, d,
J = 11.4 Hz, C-3Hb), 4.22 (1H, d, J = 11.1 Hz, C-10Ha),
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G. Kumar et al.
4.33 (1H, d, J = 11.1 Hz, C-10Hb), 5.17 (2H, s, C-100H),
7.34 (5H, s, aromatic protons); 13C NMR (75.5 MHz,
CDCl3): d 13.88 (OCO(CH2)4CH3), 17.51 (C-2 CH3),
22.26 (OCO(CH2)3CH2CH3), 24.53 (OCO(CH2)2CH2CH2
CH3), 31.23 (OCOCH2CH2(CH2)2CH3), 34.06 (OCOCH2
(CH2)2CH3), 48.31 (C-2), 64.99, 66.68 & 65.67 (C-100, C-10
& C-3), 127.97 (C-3000 & C-5000), 128.32 (C-2000 & C-6000),
128.60 (C-4000), 135.62 (C-1000), 173.98 & 174.27 (29
C=O); IR (KBr): 3505 (OH), 2957, 1736 (C=O), 1458,
1166, 1050 and 697 cm-1; FAB-HRMS: m/z 345.1662
([M?Na]?, C18H26O5Na calcd 345.1672).
2.3.8 4-Fluorobenzyl 2-(butanoyloxymethyl)-3-hydroxy-2-
methylpropanoate (4c)
It was obtained as a viscous oil (725 mg, 80 %).1H NMR
(300 MHz, CDCl3):
d
0.91 (3H, t, J = 7.5 Hz,
OCO(CH2)2CH3), 1.21 (3H, s, C-2 methyl), 1.52–1.65 (2H,
m, OCOCH2CH2CH3), 2.23 (2H, t, J = 7.5 Hz,
OCOCH2CH2CH3), 3.64 (1H, d, J = 11.4 Hz, C-3Ha),
3.70 (1H, d, J = 11.4 Hz, C-3Hb), 4.21 (1H, d,
J = 11.1 Hz, C-10Ha), 4.33 (1H, d, J = 11.1 Hz, C-10Hb),
5.13 (2H, s, C-100H), 7.07-7.01 (2H, m, C-2000H and
C-6000H), 7.30–7.35 (2H, m, C-3000H and C-5000H); 13C NMR
(75.5 MHz, CDCl3): d 13.59 (OCO(CH2)2CH3), 17.47 (C-2
CH3), 18.34 (OCOCH2CH2CH3), 35.98 (OCOCH2CH2-
CH3), 48.30 (C-2), 64.97, 65.59 & 65.96 (C-100, C-10 &
C-3), 115.39 & 115.68 (C-3000 & C-5000), 130.03 & 130.14
(C-2000 & C-6000), 131.47 & 131.51 (C-1000), 161.04 & 164.32
(C-4000), 173.73 & 174.18 (29 C=O); IR (KBr) 3505 (OH),
2967, 1732 (C=O), 1513, 1225, 1049 and 828 cm-1; FAB-
HRMS: m/z 335.1257 ([M?Na]?, C16H21FO5Na calcd
335.1265).
2.3.6 4-Fluorobenzyl 2-(acetoxymethyl)-3-hydroxy-2-
methylpropanoate (4a)
It was obtained as a viscous oil (625 mg, 76 %).1H NMR
(300 MHz, CDCl3): d 1.21 (3H, s, C-2 methyl), 1.99 (3H,
s, OCOCH3), 3.65 (1H, d, J = 11.4 Hz, C-3Ha), 3.71 (1H,
d, J = 11.4 Hz, C-3Hb), 4.21 (1H, d, J = 11.4 Hz,
C-10Ha), 4.37 (1H, d, J = 11.4 Hz, C-10Hb), 5.14 (2H, s,
C-100H), 7.01-7.08 (2H, m, C-2000H and C-6000H), 7.30–7.35
(2H, m, C-3000H and C-5000H); 13C NMR (75.5 MHz,
CDCl3): d 17.44 (C-2 CH3), 20.64 (OCOCH3), 48.23 (C-2),
64.97, 65.81 & 65.97 (C-100, C-10 & C-3),115.40 &
115.6912 (C-2000 & C-6000), 130.01 & 130 (C-3000 & C-5000),
131.47 & 131.51 (C-1000), 161.04 & 164.32 (C-4000), 171.08
& 174.14 (29 C=O); IR (KBr) 3502 (OH), 2948, 1732
(C=O), 1531, 1226, 1042 and 829 cm-1; FAB-HRMS: m/z
307.0942 ([M?Na]?, C14H17FO5Na calcd 307.0952).
2.3.9 4-Fluorobenzyl 2-(pentanoyloxymethyl)-3-hydroxy-
2-methylpropanoate (4d)
It was obtained as a viscous oil (660 mg, 70 %).1H NMR
(300 MHz, CDCl3): d 0.89 (3H, t, J = 7.2 Hz, OCO(CH2)3
CH3), 1.21 (3H, s, C-2 methyl), 1.25–1.37 (2H, m, OCO
(CH2)2CH2CH3), 1.49–1.59 (2H, m, OCOCH2CH2CH2-
CH3), 2.24 (2H, t, J = 7.5 Hz, OCOCH2(CH2)2CH3), 3.64
(1H, d, J = 11.4 Hz, C-3Ha), 3.70 (1H, d, J = 11.4 Hz,
C-3Hb), 4.21 (1H, d, J = 11.4 Hz, C-10Ha), 4.32 (1H, d,
J = 11.4 Hz, C-10Hb), 5.13 (2H, s, C-100H), 7.01-7.07 (2H,
m, C-2000H & C-6000H), 7.30–7.34 (2H, m, C-3000H &
2.3.7 4-Fluorobenzyl 2-(propanoyloxymethyl)-3-hydroxy-
2-methylpropanoate (4b)
C-5000H); 13C NMR (75.5 MHz, CDCl3):
d 13.62
It was obtained as a viscous oil (630 mg, 74 %).1H
NMR (300 MHz, CDCl3): d 1.09 (3H, t, J = 7.8 Hz,
OCOCH2CH3), 1.21 (3H, s, C-2 methyl), 2.23–2.31
(2H, q, J = 7.5 Hz, OCOCH2CH3), 3.65 (1H, d,
J = 11.7 Hz, C-3Ha), 3.71 (1H, d, J = 11.7 Hz,
C-3Hb), 4.22 (1H, d, J = 11.4 Hz, C-10Ha), 4.33 (1H, d,
J = 11.4 Hz, C-10Hb), 5.13 (2H, s, C-100H), 7.01-7.07
(2H, m, C-2000H and C-6000H), 7.30-7.34 (2H, m, C-3000H
and C-5000H); 13C NMR (75.5 MHz, CDCl3): d 9.01
(OCOCH2CH3), 17.45 (C-2 CH3), 27.39 (OCOCH2-
CH3), 48.31 (C-2), 64.97, 65.64 & 65.95 (C-100, C-10 &
C-3), 115.39 & 115.67 (C-3000 & C-5000), 130.0 & 130.11
(C-2000 & C-6000), 131.48 & 131.52 (C-1000), 161.04 &
164.32 (C-4000), 174.17 & 174.49 (29 C=O); IR (KBr):
3508 (OH), 2945, 1732 (C=O), 1513, 1225, 1051 and
(OCO(CH2)3CH3), 17.46 (C-2 CH3), 22.18 (OCO(CH2)2-
CH2CH3), 26.90 (OCOCH2CH2CH2CH3), 33.81 (OCOCH2
(CH2)2CH3), 48.30 (C-2), 64.96, 65.59 & 65.95 (C-100, C-10
& C-3), 115.38 & 115.67 (C-3000 & C-5000), 130.00 & 130.10
(C-2000 & C-6000), 131.48 & 131.52 (C-1000), 161.04 & 164.31
(C-4000), 173.90 & 174.17 (29 C=O); IR (KBr): 3502 (OH),
2961, 1732 (C=O), 1514, 1225, 1052 and 827 cm-1; FAB-
HRMS: m/z 349.1418 ([M?Na]?, C17H23FO5Na calcd
349.1422).
2.3.10 4-Fluorobenzyl 2-(hexanoyloxymethyl)-3-hydroxy-
2-methylpropanoate (4e)
It was obtained as a viscous oil (730 mg, 73 %).1H NMR
(300 MHz, CDCl3): d 0.90 (3H, t, J = 6.9 Hz, OCO
(CH2)4CH3), 1.21 (3H, s, C-2 methyl), 1.24–1.34 (4H, m,
OCO(CH2)2CH2CH2CH3), 1.51–1.66 (2H, m, OCOCH2
828 cm-1
;
FAB-HRMS: m/z 321.1098 ([M?Na]?,
C15H19FO5Na calcd 321.1109).
123