Short stereoselective synthesis of (+)-monocerin via a palladium-catalysed intramolecular alkoxycarbonylation

Article abstract of DOI:10.3184/174751916X14636665341699

A concise stereoselective total synthesis of (+)-monocerin has been accomplished using cross metathesis, tandem dihydroxylation-S_N2 cyclisation and intramolecular alkoxycarbonylation as key steps. Cross-metathesis of 2-iodo-3,4,5-trimethoxyvinylbenzene and (R)-hepten-4-ol, followed by tandem dihydroxylation-S_N2 cyclisation generated a tri-substituted tetrahydrofuran ring. Finally, the dihydroisocoumarin was obtained by an intramolecular alkoxycarbonylation. In this paper, we have developed an expedient operationally simple Pd(OAc)₂/bathocuproine catalysed alkoxycarbonylation under atmospheric pressure of carbon monoxide. The catalytic system developed here can be useful for the synthesis of various dihydroisocoumarins and phthalides.

Full text of DOI:10.3184/174751916X14636665341699

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 JUNE, 375–378
RESEARCH PAPER 375
Short stereoselective synthesis of (+)-monocerin via a palladium-catalysed
intramolecular alkoxycarbonylation
Surendra R. Punganurua*, Sivaprasad Aviraboinab and Kalkunte S. Srivenugopala
aDepartment of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter Dr., Amarillo, TX 79106, USA
bSadhvi Pharma, Plot No: 55, Kukatpally IE, Hyderabad-500072, India
A concise stereoselective total synthesis of (+)-monocerin has been accomplished using cross metathesis, tandem dihydroxylation-
SN2 cyclisation and intramolecular alkoxycarbonylation as key steps. Cross-metathesis of 2-iodo-3,4,5-trimethoxyvinylbenzene
and (R)-hepten-4-ol, followed by tandem dihydroxylation-SN2 cyclisation generated a tri-substituted tetrahydrofuran ring. Finally, the
dihydroisocoumarin was obtained by an intramolecular alkoxycarbonylation. In this paper, we have developed an expedient operationally
simple Pd(OAc) /bathocuproine catalysed alkoxycarbonylation under atmospheric pressure of carbon monoxide. The catalytic system
developed here 2can be useful for the synthesis of various dihydroisocoumarins and phthalides.
Keywords: (+)-monocerin, total synthesis, alkoxycarbonylation, palladium, cross metathesis
Epidemiological, clinical, and experimental evidence suggests
thatmanyofthetherapeuticagentscurrentlyusedhavetheirroots
in natural products.1 Dihydroisocoumarins and their derivatives
occur widely in nature and serve as key intermediates in the
synthesis of biologically active molecules.2 As these compounds
are known to have a wide range of interesting activities such
as antifungal, antiallergenic and antimalarial activities, they
are regarded as highly attractive targets in organic chemistry.
Monocerin is one such compound that has been isolated as an
antifungal, insecticidal, antimalarial and phytotoxic secondary
metabolite from several fungal sources including Drechslera
monoceras and Fusarium larvarum.3 Structural features
such as having 2,3,5-trisubstituted tetrahydrofuran unit with
an all cis stereochemistry and its potential for application in
pharmaceutical industry, meant that monocerin has attracted
the attention of many synthetic chemists. Biosynthetically,
monocerin was found to have a heptaketide origin and a recent
study demonstrated that cis-fused furanobenzopyranones arose
by intramolecular nucleophilic trapping of a quinonemethide
intermediate by a pendant alcohol.4
key step.7 Recently, Lee et al. used a radical cyclisation of a
vinyl ether to construct the cis-fused sub-unit of monocerin
and achieved its total synthesis.8 Fujita et al. synthesised
monocerin via a stereoselective oxylactonisation of ortho-
alkenylbenzoate with chiral hypervalent iodine.9 Through
intramolecular trapping of quinonemethide by She et al.10,11 and
copper mediated tandem cyanation-lactonisation by Nookaraju
et al.12 we synthesised a monocerin. Herein, we report a short
stereoselective total synthesis of monocerin 1 by a palladium
catalysed intramolecular carbonylation using carbon monoxide.
Results and discussion
The retrosynthetic analysis of (+)-monocerin has been
presented in Scheme 1. We envisioned that the lactone skeleton
of the monocerin 1 could be readily obtained from aryl iodide
having trisubstituted tetrahydrofuran with hydroxyl group 2
via palladium catalysed intramolecular alkoxycarbonylation.
The cis-fused tetrahydrofuran 2 can be prepared by a tandem
dihydroxylation-SN2 cyclisation sequence from 3. The requisite
allyl alcohol 3 was obtained by cross metathesis of the allyl
alcohol 4 and styrene 5 by using Grubbs 2nd generation catalyst.
The synthesis of (+)-monocerin commenced with the
preparation of the homoallylic alcohol 4 by asymmetric
allylation of the commercially available butyraldehyde 6 with
allyltributylstannane 7 using Ti(OiPr)4 as shown in Scheme
Mori et al.5 first reported the total synthesis of monocerin,
followed by Simpson using a radical benzylic bromination to
initiate the formation of cis-tetrahydrofuran.6 Mallreddy et
al. reported a total synthesis of monocerin and its analogues
from D-glucose by using intramolecular C-glycosidation as a
O
I
O
H
H
3CO
3CO
H
H
3CO
3CO
H
H
3CO
3CO
OH
OH
I
O
OCH3
OCH3
OH
O
2
3
(+)-Monocerin 1
OH
H
H
3CO
+
I
3CO
OCH3
5
4
Scheme 1 Retrosynthetic analysis of (+)-monocerin.
* Correspondent. E-mail: surendra.r.punganuru@ttuhsc.edu

376 JOURNAL OF CHEMICAL RESEARCH 2016
2. 2-Iodo-3,4,5-trimethoxy-1-vinylbenzene 5 was prepared
from 3,4,5-trimethoxybenzaldehyde 8 by iodination using
N-iodosuccinimide/trifluoro acetic acid followed by a Wittig
reaction with methyltriphenylphosphonium bromide (Scheme
3). The coupling of the key intermediates 5 and 6 was achieved by
a Grubbs cross-metathesis reaction, which led to 3 in 70% yield.
Mesylation of 3 with methanesulfonyl chloride in the presence
of diisopropylethylamine, gave 10 in excellent yield. Using the
procedure reported by Marshall et al.15 the intermediate 10 was
converted to the cis-substituted tetrahydrofuran 2 by AD-mix-β
with a catalytic amount of potassium osmate (VI) in a tandem
asymmetric dihydroxylation and SN2 cyclisation.
advantages of this method include the broad availability of
substrates and the high tolerance of palladium catalysts of a
variety of functional groups.
With 2 in hand, we next set to investigate different reactions
to generate the lactone 11 and envisioned that palladium
catalysed intramolecular carbonylation would be a good
method. Generally, phosphine ligands are used to complex
and activate the palladium species. However, the use of such
ligands is undesirable because of their toxicity and air as
well as moisture sensitive with conversion to, for example,
phosphine oxide species.17 For these reasons, we examined
the use of less expensive nitrogen ligands in place of the
phosphines. The reaction conditions were optimised using
different catalysts in combination with different solvents and
bases. First to test the different ligands, we used palladium
acetate as catalyst, potassium carbonate as base and DMF as
The introduction of a carbonyl group into arenes using
carbonylation reactions in the presence of a suitable nucleophile
is an interesting method among the array of catalytic conversions
of aryl halides performed by palladium complexes.16 The
Ti(OiPr)4
O
OH
(S,S)-BINOL
SnBu3
+
H
4°
CH2Cl2
MS
,
4
7
6
to
–78 °C –20 °C
75
%
Scheme 2 Asymmetric allylation.
O
O
H
3CO
3CO
H
3CO
3CO
H
H
3CO
3CO
Br
CH3PPh3
H
H
NIS, TFA
H
I
Acetonitrille
rt, 6 h, 91%
H
I
0
°
C, 2h
OCH3
OCH3
OCH3
68
%
8
9
5
2
H
3CO
3CO
H
H
3CO
3CO
Grubbs (II) cat
MsCl, DCM
NEt3, rt, 95%
OH
CH2Cl2, reflux
OMs
H
I
I
70
%
3
OCH3
OCH3
10
AD-mix
Pot. osmate
(one crystal)
β
O
Pd(OAc)2/ BCP
O
I
H
H
3CO
3CO
CO (baloon)
H
3CO
3CO
O
NH
CH3SO2
CsCO3, DMA, 12 h, 72%
OH
2
H
tBuOH/H2O,
0 °C, 95%
OCH3O
11
OCH3
2
BBr3
55%
CH Cl2 –20
°
C
,
2
O
H
3CO
3CO
O
H
OH O
1
Scheme 3 Synthesis of (+)-monocerin.

JOURNAL OF CHEMICAL RESEARCH 2016 377
layer chromatography was performed on Merck-precoated silica gel
60-F254 plates. All other chemicals and solvents were obtained from
commercial sources and purified using standard methods. The IR
spectra of all compounds were recorded on a Perkin-Elmer Spectrum
GX FTIR spectrometer. The IR values are reported in reciprocal
centimetres (cm–1). The 1H NMR and 13C NMR spectra were recorded
on a Bruker-Avance 300 MHz spectrometer. Chemical shifts (δ) are
reported in ppm, using TMS (δ = 0) as an internal standard in CDCl3.
ESI mass spectra was recorded on AB sciex QTRAP 5500 mass
spectrometer.
solvent. Tetramethylguanidine, DABCO and bipyridine did
not give any product under these reaction conditions (Table 1,
entry 1), whereas, 1,10-phenanthroline gave the product in less
yield. However, bathocuproine (BCP) gave the desired product
in good yield when compared to other phenanthroline ligands
(Table 1, entries 2–5). Following further optimisation by using
different bases, we found that Cs2CO3 gave the product in good
yield when compared to other bases used (Table 1, entries 6–8).
Amongst the different solvents that were used DMA was found
to be the best solvent for the carbonylation (Table 1, entries
9 and 10). Other palladium catalysts used in this study were
ineffective only generating the product in low yield (Table 1,
entries 11–13). In summary, 11 was generated in good yield
via alkoxycarbonylation using Pd(OAc)2 as catalyst, Cs2CO3
as a base, BCP as a ligand and DMA as a solvent. Finally
(+)-monocerin was obtained from 11 by partial demethylation
with borontribromide in 55% yield and 20% of the starting
material recovered. The characterisation data of (+)-monocerin
1 was consistent with that previously reported.
(R)-Hept-1-en-4-ol (4): To (S,S)-BINOL (0.85 g, 3.1 mmol) in
CH2Cl2 (8.0 mL) was added Ti(OiPr)4 (0.67 mL, 2.1 mmol) in the
presence of molecular sieves (2.5 g) and stirred at reflux temperature.
After 1 h, the reaction mixture was cooled to room temperature and
butyaldehyde 6 (1.5 g, 21 mmol) in CH2Cl2 was added and stirred
for 10 min. After 10 min the reaction mixture was cooled to –78 °C
and allyltri-n-butyltin 7 (7 mL, 21 mmol) was added and the reaction
was continued for 24 h at –20 °C. After completion of the reaction,
saturated aqueous solution of sodium bicarbonate was added to quench
the reaction mixture, and then extracted with dichloromethane (3 × 50
mL). The organic phase was washed with water and dried over Na2SO4,
and the crude product was purified by column chromatography using
In conclusion, we have achieved a concise stereoselective
total synthesis of (+)-monocerin from commercially available
starting materials. The intramolecular alkoxy carbonylation
described in this paper can be used for the synthesis of a wide
variety of dihydroisocoumarins.
hexane and ethyl acetate. Colourless liquid: yield 75%; [α]25 –18.2
D
(c 1.0, CHCl3) [lit.13[α]25D –22.5 (c 0.65, CHCl3)]. IR (neat) max 3250,
2895, 1644, 1501, 1199, 746 cm–1. 1H NMR (CDCl3, 300 MHz): δ 0.96
(t, 3H, J = 7.2 Hz), 1.28–1.49 (m, 4H), 2.1–2.29 (m, 2H), 3.56–3.69
(m, 1H), 5.01–5.12 (m, 2H), 5.65–5.75 (m, 1H). 13C NMR (CDCl3, 75
MHz): δ 14.3, 18.6, 40.2, 42.6, 70.9, 115.6, 134.9. ESI MS (m/z): 115
(M + H). Anal. calcd for C7H14O: C 73.34, H 12.36; found: C 73.15, H
12.52%.
Experimental
All chemicals were purchased from Sigma-Aldrich and S.D.
Fine Chemicals Pvt. Ltd. and used as received. ACME silica gel
(100–200 mesh) was used for column chromatography and thin-
2-Iodo-3,4,5-trimethoxybenzaldehyde (9): Commercially available
3,4,5-trimethoxybenzaldehyde (0.93 g, 5 mmol) and TFA (0.5 mL)
was dissolved in acetonitrile (5 mL) and N-iodosuccinimide (1.35 g,
6 mmol) was added in portions over 1 h at 0 °C. The reaction was then
continued at room temperature until the completion of reaction was
indicated by TLC. It was quenched by the addition of saturated sodium
bicarbonate and extracted with ethyl acetate (3 × 20 mL). The organic
phase was washed with sodium thiosulfate solution, concentrated and
the crude product was purified by silica gel column chromatography
using hexane/ethyl acetate as an eluent. Half-white solid (1.45 g,
90.6%); m.p.: 65–68 °C [lit.14 67–68 °C]. IR (KBr): 2989, 1685, 1564,
1481, 1380, 1281, 1045, 945 cm–1. 1H NMR (300 MHz, CDCl3): δ 3.91
(s, 3 H), 3.92 (s, 3 H), 3.98 (s, 3 H), 7.32 (s, 1H), 10.15 (s, 1H). 13C NMR
(75 MHz, CDCl3): 56.2, 61.1, 61.2, 91.5, 107.4, 128.8, 148.7, 150.6,
152.9, 190.9. ESI MS (m/z): 323 (M + H). Anal. calcd for C10H11IO4: C
37.29, H 3.44; found: C 37.35, H 3.61%.
Table 1 Optimisation of the reaction conditions for the intramolecular
alkoxycarbonylation with carbon monoxidea
O
O
Pd(OAc)2/ ligand
H
H
3CO
3CO
H
H
3CO
3CO
CO (baloon)
Base,
130 °C
Solvent,
OH
O
I
OCH3O 11
OCH3
2
Entry
1
2
3
4
5
6
7
8
Catalyst
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Ligand
L1 or L2 or L3
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
NEt3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Solvent Yield (%)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMA
DMA
DMA
DMA
0
26
40
42
55
20
0
65
25
72
10
34
20
L4
L5
L6
L7
L7
L7
L7
L7
L7
L7
L7
L7
2-Iodo-3,4,5-trimethoxy-1-vinylbenzene (5): Methyltriphenylphos-
phonium bromide (1.78 g, 5 mmol) and potassium tert-butoxide
(1.1 g, 10 mmol) were placed in a round-bottomed flask and dry THF
was added under a nitrogen atmosphere. When the reaction turned a
deep yellow colour, 2-iodo-3,4,5-trimethoxybenzaldehyde (1.28 g,
4 mmol) was added in THF and the reaction was stirred for 3 h at room
temperature. After completion of the reaction, the reaction mixture was
filtered and the filtrate was evaporated. The crude product was purified
by column chromatography using hexane and ethyl acetate. White solid
(0.87 g, 68%); m.p.: 61–63 °C. IR (KBr): 3512, 2918, 1566, 1415, 1375,
9
10
11
12
13
Pd(CH3CN)2
Pd(acac)2
NH
1
1159 cm–1. H NMR (300 MHz, CDCl3): δ 3.83 (s, 3H), 3.90 (s, 3H),
N
N
N
3.95 (s, 3H), 5.26 (dd, J = 1.2, 11.2 Hz), 5.51 (d, 1H, J = 18.1 Hz), 6.86
(s, 1H), 6.93 (dd, J = 11.2, 18.1 Hz). 13C NMR (75 MHz, CDCl3): 56.3,
60.9, 61.1, 89.2, 106.3, 116.2, 136.1, 141.2, 141.9, 154.1, 154.6. ESI
MS (m/z): 321 (M + H). Anal. calcd for C11H13IO3: C 41.27, H 4.09;
found: C 41.29, H 4.11%.
N
N
N
N
N
L1
L2
L3
L4
Ph
Ph
Ph
Ph
(R,E)-1-(2-Iodo-3,4,5-trimethoxyphenyl)hept-1-en-4-ol (3): To a
solution of 2-iodo-3,4,5-trimethoxy-1-vinylbenzene (0.8 g, 2.5 mmol)
and (R)-hept-1-en-4-ol (0.34 g, 3 mmol) in anhydrous dichloromethane
(10 mL) was added Grubbs-II catalyst (250 mg, 6 mol%) and stirred
at reflux for 6 h. It was then stirred for an additional 1 h at room
temperature in the open air to deactivate the catalyst. The reaction
N
N
N
N
N
N
L6
L5
L7
aReaction conditions: 2 (0.1 mmol), Pd catalyst (3 mol%), ligand (6 mol%), CO (1 Atm),
base (1.2 equiv.), 24 h.

378 JOURNAL OF CHEMICAL RESEARCH 2016
mixture was filtered through Celite, concentrated, and the residue was
purified by column chromatography on silica gel using hexane and
ethylacetate as an eluent. Pale yellow solid (0.56 g, 70%); [α]25D –11.2
(c 1.2, CHCl3). M.p.: 58–59 °C. IR (KBr): 3371, 2929, 1718, 1599, 1258,
filtered through a plug of Celite (eluting with ethyl acetate), and
concentrated under reduced pressure. The crude product was purified
by column chromatography on silica gel using hexane/ethyl acetate as
an eluent to afford the pure product. Clear oil (231 mg, 72%); [α]25
D
1
1021 cm–1. H NMR (300 MHz, CDCl3): δ 0.96 (t, 3H, J = 7.2 Hz),
+13.1 (c 1.0, CHCl3) [lit12 [α]25 +23.2 (c 0.56, CHCl3)]. IR: 3451,
D
2926, 2855, 1469, 1337, 1168, 1102, 908 cm–1. H NMR (300 MHz,
1
1.38–1.59 (m, 4H), 1.65–1.67 (m, 1H), 2.19–2.40 (m, 2H), 3.81 (s, 3H),
3.83 (s, 3H), 3.84 (s, 3H), 5.82–5.92 (m, 1H), 6.47 (d, 1H, J = 15.6 Hz),
6.69 (s, 1H). 13C NMR (75 MHz, CDCl3): 14.1, 18.9, 26.6, 39.1, 40.8,
56.3, 60.7, 71.2, 106.2, 127.6, 128.9, 129.6, 134.9, 136.9, 152.3, 153.8.
ESI MS (m/z): 307 (M + H). Anal. calcd for C16H23IO4: C 47.30, H 5.71;
found: C 47.33, H 5.79%.
CDCl3): δ 0.97 (t, 3H, J = 7.2 Hz), 1.36–1.57 (m, 4H), 1.81–1.91 (m,
1H), 2.52–2.60 (m, 1H), 3.85 (s, 6H), 3.95 (s, 3H), 4.35–4.41 (m, 1H),
4.68 (d, 1H, J = 2.4 Hz), 4.92–5.01 (m, 1H), 6.71 (s, 1H). 13C NMR (75
MHz, CDCl3): 14.0, 19.1, 37.5, 38.2, 56.3, 60.8, 61.1, 74.3, 79.2, 90.8,
106.5, 132.4, 141.2, 152.3, 157.4, 169.2. ESI MS (m/z): 323 (M + H).
Anal. calcd for C17H22O6: C 63.34, H 6.88; found: C 63.31, H 6.74%.
(+)-Monocerin (1): To the compound 11 (0.1 g, 0.3 mmol) in
dichloromethane, boron tribromide (1.0 M in hexanes, 0.1 mL, 1
mmol) was added at –25 °C. The reaction mixture was warmed to
room temperature and stirred for 2 h. The reaction was quenched by the
addition of saturated aqueous NaHCO3 solution and the product was
extracted with dichloromethane (3 × 20 mL). The combined organic
phases were washed with water, and dried over Na2SO4. The crude
product was purified by column chromatography using hexane and
(R,E) -1- (2-iodo-3,4,5-trimethoxyphenyl) hept-1-en- 4-yl
methanesulfonate (10): To the dichloromethane solution of (R,E)-
1-(2-iodo-3,4,5-trimethoxyphenyl)hept-1-en-4-ol (0.5 g, 1.2 mmol),
diisopropylethylamine (0.1 mL, 1.5 mmol) was added and stirred
for 30 min at room temperature. Methanesulfonyl chloride (0.1 mL
1.5 mmol) was added slowly at 0 °C and the reaction was monitored
by TLC. After completion of the reaction, it was diluted with
dichloromethane and washed with water, and concentrated. The crude
product was purified by column chromatography using hexane and
ethyl acetate as eluents. White solid (0.52 g, 95%); [α]25D –12.2 (c 1.0,
CHCl3). M.p.: 64–66 °C. IR: 2926, 2855, 1469, 1337, 1168, 1102, 908
cm–1. 1H NMR (300 MHz, CDCl3): δ 0.98 (t, 3H, J = 7.2 Hz), 1.39–1.57
(m, 2H), 1.62–1.83 (m, 2H), 2.54–2.65 (m, 2H), 2.94 (s, 3H), 3.82 (s,
3H), 3.83 (s, 3H), 3.86 (s, 3H), 4.77–4.83 (m, 1H), 5.84–5.91 (m, 1H),
6.62 (d, 1H, J = 15.4 Hz), 6.84 (s, 1H). 13C NMR (75 MHz, CDCl3):
13.7, 18.6, 37.0, 38.4, 38.7, 55.7, 60.4, 81.9, 95.9, 105.5, 125.9, 127.1,
136.1, 137.4, 144.1, 151.6, 152.3. ESI MS (m/z): 485 (M + H). Anal.
calcd for C17H25IO6S: C 42.16, H 5.20, S 6.62; found: C 42.21, H 5.16,
S 6.64%.
ethyl acetate as an eluent. Colourless oil (0.058 g) 55%; [α]25 +54.1
D
(c 1.0, CHCl3) [lit.12 [α]26 +53 (c 1.0, CHCl3)]. IR: 2973, 2836, 1703,
D
1
1633, 1278, 1122, 989 cm–1. H NMR (300 MHz, CDCl3): δ 0.95 (t,
3H, J = 7.3 Hz), 1.34–1.48 (m, 2H), 1.59–1.66 (m, 1H), 1.69–1.81 (m,
1H), 2.13–2.21 (m, 1H), 2.45–2.62 (m, 1H), 3.83 (s, 3H), 3.95 (s, 3H),
4.12–4.25 (m, 1H), 4.56 (d, J = 3.2 Hz), 5.03–5.12 (m, 1H), 6.61 (s, 1H),
11.25 (s, 1H). 13C NMR (75 MHz, CDCl3): 14.1, 19.1, 37.5, 38.2, 56.1,
60.8, 74.3, 79.2, 81.8, 102.3, 105.0, 132.1, 137.5, 156.2, 157.4, 168.2.
ESI MS (m/z): 309 (M + H). Anal. calcd for C16H20O6: C 62.33, H 6.54;
found: C 62.28, H 6.61%.
(2S,3aR,9bR)-6,7,8-trimethoxy-2-propyl-2,3,3a,9b-tetrahydro-
5H-furo[3,2-c]isochromen-5-one (2): Methane sulfonamide (0.2 g,
2 mmol) and K2OsO2(OH)4 (5 mg) were added to AD-mix β (1.4 g) in
t-butanol/water (1:1) (9 mL). The solution was stirred thoroughly for
30 min until one phase was present. The reaction mixture was cooled
to 0 °C and a solution of (R,E)-1-(2-iodo-3,4,5-trimethoxyphenyl)
hept-1-en-4-yl methanesulfonate (0.48 g, 1 mmol) in 1 mL of
t-butanol/water (1:1) was added. The reaction mixture was warmed
to room temperature over 2 h and stirred overnight. The mixture
was quenched with a saturated solution of Na2SO3 and stirred for
1 h. The aqueous layer was extracted with dichloromethane (3 ×
20 mL) and the combined organic extracts were dried over Na2SO4,
and concentrated under reduced pressure. The product was purified by
column chromatography using hexane and ethyl acetate as an eluent.
Viscous oil (0.52 g, 95%); [α]25D –32.8 (c 1.0, CHCl3). M.p.: 64–66 °C.
IR: 3451, 2926, 2855, 1469, 1337, 1168, 1102, 908 cm–1. 1H NMR (300
MHz, CDCl3): δ 0.98 (t, 3H, J = 7.2 Hz), 1.35–1.61 (m, 4H), 1.65–1.70
(m, 1H), 1.81–1.91 (m, 1H), 2.15–2.28 (m, 1H), 3.81 (s, 3H), 3.83 (s,
3H), 3.84 (s, 3H), 4.41–4.51 (m, 1H), 4.71–4.81 (m, 1H), 5.01–5.12 (m,
1H), 6.98 (s, 1H). 13C NMR (75 MHz, CDCl3): 14.1, 19.2, 37.6, 41.0,
56.3, 60.4, 71.7, 75.4, 84.3, 92.8, 106.8, 132.8, 140.5, 151.6, 152.3. ESI
MS (m/z): 423 (M + H). Anal. calcd for C16H25IO5: C 45.51, H 5.49;
found: C 45.49, H 5.56%.
SA thank the Sadhvi Pharma for providing the financial
assistance to carry out part of this work.
Received 4 February 2016; accepted 7 April 2016
Paper 1603900 doi: 10.3184/174751916X14636665341699
Published online: 5 June 2016
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