Synthesis of Unsymmetrical Linear Diarylheptanoids and their Enantiomers and Antiproliferative Activity Studies

Article abstract of DOI:10.1002/ejoc.201801211

Successful synthesis of unsymmetrical linear diarylheptanoids with syn-1,3-diol unit and their enantiomers have been achieved using acyl anion and Wittig olefination chemistry. The syn disposition of the two hydroxyl groups in the linear diarylheptanoids

Full text of DOI:10.1002/ejoc.201801211

A Journal of
Accepted Article
Title: Synthesis of Unsymmetrical Linear Diarylheptanoids and their
Enantiomers and Antiproliferative Activity Studies
Authors: Sudarshan Kasireddy, Govindaraj Perumal, Indrapal Singh
Aidhen, and Mukesh Doble
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10.1002/ejoc.201801211
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Synthesis of Unsymmetrical Linear Diarylheptanoids and their
Enantiomers and Antiproliferative Activity Studies
Kasireddy Sudarshan,[a] Govindaraj Perumal,[b] Indrapal Singh Aidhen*[a] and Mukesh Doble[b]
Dedication ((optional))
Abstract: Successful synthesis of unsymmetrical linear
diarylheptanoids with syn-1,3- diol unit and their enantiomers have
been achieved using acyl anion and Wittig olefination chemistry. The
syn disposition of the two hydroxyl groups in the linear
diarylheptanoids was achieved with the use of D-xylose as starting
material. The synthesized compounds were tested for anti-
proliferative activity on HeLa cells using MTT assay at 50µM
concentration.
Due to eminent biological significance of linear diarylheptanoids
several synthetic methods has been reported mainly focusing on
the synthesis of symmetrical linear diarylheptanoids.[3] There are
some reports available for synthesis of unsymmetrical
diarylheptanoids with anti-configuration of 1,3-diol unit 4.[4]
However, very few reports are available for the synthesis of
unsymmetrical diarylheptanoids 5[5] with syn-orientation of the
1,3-diol unit therein. Given the biological significance of linear
diarylheptanoids in general and the absence of a general method
enabling access to unsymmetrical diarylheptanoids and
corresponding enantiomers prompted us to undertake this study.
We targeted the synthesis of 5 through a strategy wherein the
terminal aryl units were envisaged to be installed via acyl-anion
and Wittig reaction chemistry onto a D-xylose derived building
block, ensuring the required syn orientation of the 1,3-diol unit in
the target. The synthesized diarylheptanoids 5 were aimed for
anti-proliferative activity. We presented herein the method
developed for the synthesis of 5 and biological studies of the
synthesized compounds.
Introduction
Diarylheptanoids are the natural secondary plant metabolites,
whose characteristic structural feature is the presence of two aryl
rings tethered by a seven carbon chain. These class of
compounds are mainly found in plants of the genera Curcuma,
Zingiber, Alpinia and Renealmia.[1] The linear diarylheptanoids
having 1,3-diol system 1 are known to exhibit various biological
activities such as antioxidative, antiproliferative, hepatoprotective
and antiemetic activities.[2] Depending on the substituents on the
aryl rings, linear diarylheptanoids can be further classified into two
types, symmetrical linear diarylheptanoids 2 in which both the aryl
groups are same and unsymmetrical linear diarylheptanoids 3 in
which aryl groups are different (Figure 1).
Results and Discussion
The envisaged scheme for the synthesis of linear unsymmetrical
diarylheptanoids 5 banked on the use of acyl anion and Wittig
olefination chemistry for the introduction of aryl-residues (Figure
2). The successful use of aryl-acyl anion for the synthesis of
tetrahydropyran diarylheptanoid (+)-centrolobine[6] inspired us to
avail its efficacy for linear diarylheptanoids 5. The synthetic
scheme, demanded availability of key building block which would
ensure delivery of syn 1,3-diol unit. This architecture was readily
recognized in D-Xylose 6, as commercially and abundantly
available starting material.
Figure 1. General structures of linear diarylheptanoids.
[a]
[b]
Dr. Kasireddy Sudarshan, Prof. Dr. Indrapal Singh Aidhen*
Department of Chemistry
Indian Institute of Technology, Madras
Chennai, India-600036.
E-mail: isingh@iitm.ac.in
Mr. Govindaraj Perumal, , Prof. Dr. Mukesh Doble*
Department of Biotechnology, Bhupat and Jyoti Mehta School of
Biosciences,
Indian Institute of Technology, Madras
Chennai, India-600036.
E-mail: mukeshd@iitm.ac.in
Figure 2. Synthetic Scheme for syn-unsymmetrical linear diarylheptanoids.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801211
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The judicious change of the substituents on the aryl rings present
in aryl aminonitriles 7 and ylide 8, allows synthesis of both syn
unsymmetrical linear diarylheptanoids 5a-e and their
corresponding enantiomers 9a-e, respectively, via a common
electrophilic intermediate 12 obtained from D-xylose (Figure 3).
The success of the envisaged scheme is described herein.
hydrated CuSO4 in aqueous methanol at 60 oC.[8] Clean hydrolysis
ensued furnishing the desired aryl ketones 11a-f in good yields
(Scheme 1). With the synthesis of ketones 11a-f, successful
incorporation of first aryl group, en route synthesis of
diarylheptanoids 5 was realized.
Figure 3. Schematic representation of proposed route.
The synthesis of key building block, bromide 12 was achieved in
five steps, starting from commercially available D-xylose 6. The
literature describes 4-step protocol on L-xylose[7] for
deoxygenation at C-3 position. The same method was employed
for the synthesis of the deoxy derivative 13 using D-xylose.
(Scheme 1). The desired bromide 12 was obtained through
bromination with the use of CBr4/PPh3. The stage was now set for
the incorporation of aryl group through aryl acyl anion chemistry.
Several aryl -aminonitriles 7a-f underwent clean alkylation with
the bromide 12 affording the alkylated intermediates 14a-f as
diastereoisomeric mixtures. Without any further purification, these
intermediates, 14a-f were directly subjected to hydrolysis using
The carbonyl functionality in ketones 11a-f was removed by
catalytic hydrogenation using palladium hydroxide on carbon and
ethanol as solvent. Hydrolysis of acetonide groups in 15a-f was
carried out using 10 % H2SO4 in THF at 60 ºC, which resulted in
anomeric mixtures of hemiacetals 10a-f respectively. For the
incorporation of second aryl ring, the obtained mixture of
hemiacetals 10a-f was subjected to Wittig olefination[9] with the
ylide 8f generated from benzyl triphenyl phosphonium bromide
and potassium carbonate in the presence of 18-crown-6 in
dichloromethane at 40 ºC. The desired olefinated product 16a-f
respectively was obtained in good yields as E/Z mixture. (Scheme
2). With the synthesis of olefins 16a-f, the linear seven carbon
framework, syn disposition 1, 3 diol unit and incorporation of the
aryl residues at the terminal carbon atoms have been achieved.
Reduction of the double bond in 16a-f was carried out by
hydrogenation using H2 (1 atm) in the presence of catalytic
amount of 10% Pd/C in EtOAc which furnished the targeted syn-
unsymmetrical linear diarylheptanoids with 1,3-diols 5a-e, and
symmetrical linear diarylheptanoid Yashabushidiol A, 5f[10]
(Scheme 2).
In the developed synthetic scheme, sequential introduction of aryl
residues, the first one as aryl acyl-anion and the second aryl unit
through benzyl phosphonium ylide, at different stages enabled
convenient synthesis of unsymmetrical diarylheptanoids. While
maintaining the same sequence and methodology for
incorporation of aryl residues, but judicious changing of the
substituents on the aryl residue in phosphonium ylide 8a-e
allowed for the synthesis of corresponding enantiomers of 5a-e.
As a proof and versatility of the concept, the anomeric mixture of
diol 10f obtained through the use phenyl aminonitrile 7f, was
Scheme 1. Synthesis of aryl ketones 11a-f. Reagents and conditions: a) Ref.
.
[7]; b) CBr4, Ph3P, Et3N, CH2Cl2, 65%; c) NaH, 12, dry. DMF; d) CuSO4 5H2O,
MeOH/H2O, 60 ºC.
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10.1002/ejoc.201801211
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reacted with the ylides 8a-e generated from corresponding benzyl
phosphonium salts. The reaction afforded the corresponding
olefinated products, 17a-e which on hydrogenation furnished
linear diarylheptanoids 9a-e respectively, these being the
enantiomers of diarylheptanoids 5a-e (Scheme 3).
added to each well and incubated for 4 h. Subsequently, each well
containing the MTT reagent was replaced with DMSO to dissolve
the formazan crystals that are formed and the absorbance was
measured at 570 nm using a microplate reader (Enspire, Perkin
Elmer, USA).
Scheme 2. Synthesis of syn-unsymmetrical linear diarylheptanoids 5a-f. Reagents and conditions: a) H2, Pd(OH)2/C, EtOH, 10 h; b) PhCH2Br, K2CO3, acetone; c)
10% aq H2SO4, THF, 60 ºC, 4 h; d) [(benzyl)P(Ph)3]Br, 18-crown-6, K2CO3, CH2Cl2, 40 ºC, 6 h; e) H2, Pd/C, EtOAc, 6 h.
The results shows that all the tested compounds decreased the
cell viability to less than 75 % in 24 h. Among all the tested
compounds, linear diarylheptanoids 5a-c inhibits the cell
proliferation by 50 % (Figure 4, 36.03 % for 5a, 44.18% for 5b and
48.69% for 5c). The common structural moiety in these
compounds is the presence of methoxyl group at para position. In
compound 5a, methoxyl group is present at the para position.
Increase in the number of methoxyl groups on the aryl ring as in
compounds 5b and 5c increases the percentage cell viability
thereby decrease in the cytotoxic nature. Interestingly,
enantiomers (9a-c) of compounds 5a-c has shown less cytotoxic
activity than 5a-c (Figure 4, 51.19 % for 9a, 57.93% for 9b and
59.80% for 9c). Although, synthesized unsymmetrical linear
diarylheptanoid compounds 5a-c showed moderate cytotoxic
activity, it was symmetrical linear diarylheptanoid 5f, a natural
product named as Yashabushidiol A, was found to be most active.
The cell proliferation with compound 5f was 29.1 % at 50 µM
concentration, indicating that it has potent anticancer activity.
Scheme 3. Synthesis of diarylheptanoids 9a-e; Reagents and conditions: (a)
More symmetrical linear diarylheptanoids would be worthy of
[(ArCH2)P(Ph)3]Br, 18-crown-6, K2CO3, CH2Cl2, 40 ºC, 6 h (b) H2, Pd/C, EtOAc,
synthesis for unravelling significance of substituents, if any.
6 h.
100
Biological Studies
75
The antiproliferative activity of the synthesized compounds (5a-f
and 9a-e) were evaluated with HeLa cells (National Centre for Cell
Sciences, Pune, India) by MTT [3-(4, 5-dimethylthiazole-2-yl)-2,
50
25
5-diphenyl tetrazolium bromide] assay at a concentration of 50µM.
Cells of density 1×103 were added as triplicate to each well of 96
well tissue culture plate and incubated at 37 C with 5 % CO2 for
0
5a 5b 5c 5d 5e 9a 9b 9c 9d 9e 5f
Compounds
o
24 h and incubated with various compounds (5a-f and 9a-e) at
Figure 4. Antiproliferative activity of the synthesized compounds with HeLa cells.
50µM concentration. After 24 h of treatment, MTT reagent was
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10.1002/ejoc.201801211
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NH4Cl solution (15 mL) was added to the reaction mixture and was
extracted with ethyl acetate (3×20 mL). The ethyl acetate layer was
washed with water (3×20 mL), dried over Na2SO4 and concentrated to
obtain alkylated compounds 14a-f. Without further purification a solution
of CuSO4.5H2O (5 equiv.) in CH3OH:H2O (7:3, 15 volumes) was added to
the 14a-f and refluxed at 60 ˚C for 90 min. The solvents were evaporated
under reduced pressure, to the obtained residue water (10 mL) was added.
The aqueous layer was extracted with ethyl acetate (3×20 mL), combined
organic layer washed with saturated NaHSO3 solution (3×15 mL), brine (10
mL) and dried over Na2SO4. The solvent was evaporated and the obtained
residue was purified by silica gel column chromatography (ethyl acetate:
hexanes, 2:8) to afford the aryl ketones 11a-f.
Conclusions
Synthesis of unsymmetrical linear diarylheptanoids and their
enantiomers with syn-1,3-diols has been achieved via a common
intermediate. The developed synthetic route used acyl anion
chemistry and Wittig olefination for the incorporation of the aryl
residues. The developed route is convenient and opened up new
vistas for more diversified library of new compounds towards
biological studies and applications. Synthesis of more
functionalized linear diarylheptanoid compounds are underway
for the better biological applications.
Ketone (11a): Yield: 81% (0.300 g) from 12 (0.300 g), Rf: 0.31 (3:7,
EtOAc/Hexanes). Pale yellow solid, Melting point: 76-78 ºC. [α]20D = - 5.71
(c = 0.1, CHCl3), 1H NMR (CDCl3, 500 MHz) :1.30 (s, 3 H, CH3), 1.51 (s,
3 H, CH3), 1.54-1.58 (m, 1 H), 2.38 (dd, J = 13.4, 4.2 Hz, 1 H), 3.02 (dd, J
= 16.2, 7.5 Hz, 1 H), 3.44 (dd, J = 16.1, 5.2 Hz, 1 H), 3.85 (s, 3 H, OCH3),
4.68-4.72 (m, 1 H), 4.74 (t, J = 4.2 Hz, 1 H), 5.79 (d, J = 3.7 Hz, 1 H), 6.92
(d, J = 8.7 Hz, 2 H, ArH), 7.93 (d, J = 8.7 Hz, 2 H, ArH) ppm. 13C NMR (125
MHz, CDCl3) δ : 26.3 (CH3), 26.8 (CH2), 39.3 (CH2), 42.9 (CH2), 55.6
(OCH3), 74.6 (CH), 80.8 (CH), 105.1 (CH), 111.2 (C), 113.9 (CH), 130.1
(C), 130.6 (CH), 163.7 (C), 196.0 (CO) ppm. IR (KBr): max 2988, 2856,
1727, 1596, 1468, 1308 cm-1. HRMS (ESI): Calcd. for C16H20O5Na
[M+Na]+: 315.1208; found: 315.1203.
Experimental Section
General information: All reactions were carried out in oven dried
glassware. Reactions requiring inert atmosphere were carried out under
nitrogen atmosphere. Dry DMF was prepared by stirring with calcium
hydride and was stored over 4 Å molecular sieves after downward
distillation. Solvents used for chromatography were LR grade. All the
reactions were monitored by TLC on precoated silica gel ‘MERCK F254
’
plates. The solvent system used throughout, unless otherwise specified,
was ethyl acetate-hexanes with various percentage of polarity depending
on the nature of the substrate. The spot detection on TLC was done by
exposure of plate under UV radiation both in 235 nm and 350 nm. Melting
points were determined in capillaries and are uncorrected. 1H NMR (400
MHz, 500 MHz) and 13C NMR (100 MHz, 125 MHz) spectra were recorded
with CDCl3 or DMSO-d6 as solvent and tetramethyl silane (TMS) as
reference. Chemical shifts were reported in delta ()units, parts per million
(ppm). Coupling constants (J) were reported in Hertz (Hz). Mass spectra
were recorded on a MICRO-Q TOF mass spectrometer by using the ESI
technique at 10 eV. IR spectra were recorded on JASCO-FT/IR-4100
spectrometer and absorptions were reported in wavenumber (cm-1). The
starting -aminonitriles 7a-f were prepared using the literature known
protocol[11] and were fully characterized before use.
Ketone (11b): Yield: 72% (0.295 g) from 12 (0.300 g), Rf: 0.46 (3:7,
EtOAc/Hexanes). Pale yellow solid, Melting point: 85-87 ºC. [α]20D = - 6.90
(c = 0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) :1.31 (s, 3 H, CH3), 1.52 (s,
3 H, CH3), 1.54-1.62 (m, 1 H), 2.38 (dd, J = 13.3, 4.2 Hz, 1 H), 3.04 (dd, J
= 16.1, 7.4 Hz, 1 H), 3.45 (dd, J = 16.1, 5.3 Hz, 1 H), 3.92 (s, 3 H, OCH3),
3.93 (s, 3 H, OCH3), 4.68-4.71 (m, 1 H), 4.74 (t, J = 4.1 Hz, 1 H), 5.80 (d,
J = 3.7 Hz, 1 H), 6.88 (d, J = 8.4 Hz, 1 H, ArH), 7.51 (d, J = 2.0 Hz, 1H,
ArH), 7.58 (dd, J = 8.3, 2.0 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3)
δ : 26.3 (CH3), 26.8 (CH2), 39.3 (CH2), 42.8 (CH2), 56.1 (OCH3), 56.2
(OCH3), 74.6 (CH), 80.8 (CH), 105.2 (CH), 110.1 (CH), 110.3 (CH), 111.3
(C), 123.2 (CH), 130.2 (C), 149.2 (C), 153.6 (C), 196.1 (CO) ppm. IR (KBr):

max 3022, 2994, 2891, 1742, 1596, 1468, 1317 cm-1. HRMS (ESI): Calcd.
for C17H22O6Na [M+Na]+: 345.1314. Found: 345.1340.
Ketone (11c): Yield: 64% (0.288 g) from 12 (0.300 g), Rf: 0.28 (1:4,
EtOAc/Hexanes). White solid, Melting point: 75-76 ºC. [α]20D = - 11.65 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) :1.32 (s, 3 H, CH3), 1.53 (s, 3 H,
CH3), 1.56-1.63 (m, 1 H), 2.41 (dd, J = 13.4, 4.0 Hz, 1 H), 3.06 (dd, J =
16.4, 7.4 Hz, 1 H), 3.48 (dd, J = 16.4, 5.2 Hz, 1 H), 3.911 (s, 6 H, 2×OCH3),
3.916 (s, 3 H, OCH3), 4.70-4.74 (m, 1 H), 4.76 (t, J = 4.1 Hz, 1 H), 5.82 (d,
J = 3.6 Hz, 1 H), 7.22 (s, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3) δ :
26.2 (CH3), 26.7 (CH2), 39.2 (CH2), 43.0 (CH2), 56.4 (2×OCH3), 61.0
(OCH3), 74.5 (CH), 80.8 (CH), 105.1 (CH), 105.8 (CH), 111.3 (C), 132.1
(C), 153.1 (C), 196.3 (CO) ppm. IR (KBr): max 2976, 2884, 1719, 1536,
1468, 1321 cm-1. HRMS (ESI): Calcd. for C18H24O7Na [M+Na]+: 375.1420,
found: 375.1425.
Procedure for preparation of bromide (12): To a stirred and cooled
solution of CBr4 (2 equiv.), 13 (1 equiv.) and Et3N (2 equiv.) in CH2Cl2 (7
mL) was added Ph3P (2 equiv.) in CH2Cl2 (7 mL) portion wise over a period
of 45 min at 0 °C under inert atmosphere. After 3 h of stirring, the reaction
mixture was diluted with hexane, and poured in ice-cold saturated aqueous
NaHCO3 solution. The organic layer was separated and the aqueous layer
extracted with hexane (3×10 mL). The combine organic extracts were
dried over Na2SO4 and concentrated. The residue thus obtained was
purified by silica-gel column chromatography (ethyl acetate: hexanes, 1:9)
to furnish the corresponding bromide 12. Yield: 65% (1.301 g) from 13
(1.500 g), Rf: 0.81 (1:4, EtOAc/Hexanes). Pale yellow liquid. 1H NMR
(CDCl3, 400 MHz) :1.31 (s, 3 H, CH3), 1.51 (s, 3 H, CH3), 1.69-1.76 (m, 1
H), 2.23 (dd, J = 13.6, 4.4 Hz, 1 H), 3.48-3.50 (m, 2 H), 4.39-4.45 (m, 1 H),
4.76 (t, J = 4.2 Hz, 1 H), 5.84 (d, J = 3.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3) δ : 26.3 (CH3), 26.9 (CH2), 33.9 (CH2), 37.8 (CH2), 80.6 (CH), 105.9
(CH) 111.6 (C) ppm. IR (CHCl3): max 2986, 2853, 1341, 1013, 656 cm-1.
HRMS (ESI): Calcd for C8H13BrO3Na [M+Na]+: 258.9946; found: 258.9951.
Ketone (11d): Yield: 67% (0.340 g) from 12 (0.300 g), Rf: 0.31 (1:4,
EtOAc/Hexanes). White solid, Melting point: 85-87 ºC. [α]20D = - 8.30 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz)  :1.30 (s, 3 H, CH3), 1.49 (s, 3 H,
CH3), 1.57-1.62 (m, 1 H), 2.44 (dd, J = 13.2, 3.9 Hz, 1 H), 3.07 (dd, J =
16.1, 7.3 Hz, 1 H), 3.43 (dd, J = 16.1, 5.6 Hz, 1 H), 3.86 (s, 3 H, OCH3),
4.69-4.72 (m, 1 H), 4.73 (t, J = 4.2 Hz, 1 H), 5.11 (s, 2 H, OCH2Ph), 5.81
(d, J = 3.6 Hz, 1 H), 7.03-7.05 (m, 1 H, ArH), 7.39-7.43 (m, 4 H, ArH), 7.45-
7.48 (m, 2 H, ArH), 7.60-7.62 (m, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3) δ : 26.3 (CH3), 26.8 (CH2), 39.5 (CH2), 43.4 (CH2), 56.8 (OCH3),
72.1 (CH2), 74.6 (CH), 80.9 (CH), 105.4 (CH), 110.6 (C), 113.9 (CH), 114.7
(CH), 122.1 (CH), 127.1 (CH), 127.6 (CH), 128.9 (CH), 135.8 (C), 137.5
General procedure for alkylation of -aryl aminonitriles and
preparation of aryl ketones (11a-f): To a suspension of NaH (1.2 equiv.)
in DMF (8 mL) was added a solution of -aryl aminonitrile (7a-f 1.1 equiv.)
in DMF (9 mL) at 0 ˚C under inert atmosphere. After 20 min, a solution of
bromo compound 12 (1.2 mmol, 1 equiv.) in DMF (17 mL) was added, and
the reaction mixture was stirred for 2 h at room temperature. A saturated
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(C), 145.9 (C), 149.7 (C), 196.2 (CO) ppm. IR (KBr): max 2985, 2876, 1724,
1514, 1451, 1291 cm-1. HRMS (ESI): Calcd. for C23H26O6Na [M+Na]+:
421.1627, found: 421.1631.
Compound (15c): Yield: 81% (0.195 g) from 11c (0.250 g), Rf: 0.38 (1:4,
EtOAc/Hexanes). White solid, Melting point: 57-59 ºC. [α]20D = - 11.12 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) :1.30 (s, 3 H, CH3), 1.47 (m, 4 H,
CH3, CH), 1.80-1.92 (m, 2 H), 2.08 (dd, J = 13.2, 3.8 Hz, 1 H), 2.58-2.76
(m, 2 H), 3.80 (s, 3 H, OCH3), 3.83 (s, 6 H, 2×OCH3), 4.15-4.22 (m, 1 H),
4.71 (t, J = 4.0 Hz, 1 H), 5.82 (d, J = 3.6 Hz, 1 H), 6.41 (s, 2 H, ArH) ppm.
13C NMR (100 MHz, CDCl3)δ : 26.2 (CH3), 26.7 (CH2), 32.9 (CH2), 36.1
(CH2), 39.1 (CH2), 56.1 (2×OCH3), 60.9 (OCH3), 77.0 (CH), 80.6 (CH),
105.40 (CH), 105.49 (CH), 110.9 (C), 137.6 (C), 153.2 (C) ppm. IR (KBr):
Ketone (11e): Yield: 71% (0.360 g) from 12 (0.300 g), Rf: 0.31 (1:4,
EtOAc/Hexanes). White solid, Melting point: 80-82 ºC. [α]20D = - 12.61 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz)  : 1.32 (s, 3 H, CH3), 1.48 (s, 3 H,
CH3), 1.58-1.63 (m, 1 H), 2.45 (dd, J = 13.1, 3.6 Hz, 1 H), 3.05 (dd, J =
16.0, 7.2 Hz, 1 H), 3.41 (dd, J = 16.1, 5.6 Hz, 1 H), 3.87 (s, 3 H, OCH3),
4.65-4.67 (m, 1 H), 4.70 (t, J = 4.3 Hz, 1 H), 5.16 (s, 2 H, OCH2Ph), 5.79
(d, J = 3.8 Hz, 1 H), 7.01-7.03 (m, 1 H, ArH), 7.37-7.41 (m, 4 H, ArH), 7.43-
7.46 (m, 2 H, ArH), 7.58-7.60 (m, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3) δ : 26.1 (CH3), 26.7 (CH2), 39.7 (CH2), 43.5 (CH2), 56.8 (OCH3),
72.2 (CH2), 74.4 (CH), 80.7 (CH), 105.6 (CH), 111.1 (C), 113.6 (CH), 114.4
(CH), 121.9 (CH), 127.1 (CH), 127.5 (CH), 128.9 (CH), 135.6 (C), 137.5
(C), 145.7 (C), 149.9 (C), 196.4 (CO) ppm. IR (KBr): max2976, 2884, 1719,
1536, 1468, 1321 cm–1. HRMS (ESI): Calcd. for C23H26O6Na [M+Na]+:
421.1627, found: 421.1619.

max 2995, 2867, 1547, 1468, 1317, 1017 cm–1. HRMS (ESI): Calcd. for
C18H26O6Na [M+Na]+: 361.1627; found: 361.1623.
Compound (15f): Yield: 91% (0.215 g) from 11f (0.250 g), Rf: 0.65 (1:4,
EtOAc/Hexanes). White solid, Melting point: 48-50 ºC. [α]20D = - 5.41 (c =
0.1, CHCl3), (literature [α]25 = - 7.7 (c = 1.0, CHCl3)[12] 1H NMR (CDCl3,
D
400 MHz) :1.31 (s, 3 H, CH3), 1.43-1.47 (m, 1 H), 1.49 (s, 3 H, CH3), 1.78-
1.87 (m, 1 H), 1.89-1.99 (m ,1 H), 2.08 (dd, J = 13.2, 4.1 Hz, 1 H), 2.63-
2.70 (m, 1 H), 2.75-2.82 (m, 1 H), 4.19-4.23 (m, 1 H), 4.71 (t, J = 4.3 Hz, 1
H), 5.82 (d, J = 3.8 Hz, 1 H), 7.17-7.20 (m, 3 H, ArH), 7.25-7.29 (m, 2 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3)δ : 26.3 (CH3), 26.7 (CH2), 32.5
(CH2), 36.1 (CH2), 39.1 (CH2), 77.3 (CH), 80.7 (CH), 105.4 (CH), 110.9 (C),
126.0 (CH), 128.5 (CH), 141.8 (C) ppm. IR (KBr): max 2994, 2919, 2856,
1547, 1457, 1309 cm–1. HRMS (ESI): Calcd. for C15H20O3Na [M+Na]+:
271.1310. Found: 271.1311.
Ketone (11f): Yield: 74% (0.248 g) from 12 (0.300 g), Rf: 0.49 (1:4,
EtOAc/Hexanes). White solid, Melting point: 120-122 ºC. [α]20D = - 1.94 (c
= 0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) :1.31 (s, 3 H, CH3), 1.52 (s, 3
H, CH3), 1.54-1.59 (m, 1 H), 2.41 (dd, J = 13.5, 4.2 Hz, 1 H), 3.09 (dd, J =
16.4, 7.4 Hz, 1 H), 3.50 (dd, J = 16.5, 5.2 Hz, 1 H), 4.70-4.77 (m, 2 H), 5.81
(d, J = 3.7 Hz, 1 H), 7.44-7.48 (m, 2 H, ArH), 7.54-7.58 (m, 1 H, ArH), 7.94-
7.96 (m, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3) δ : 26.3 (CH3), 26.8
(CH2), 39.3 (CH2), 43.2 (CH2), 74.4 (CH), 80.8 (CH), 105.2 (CH), 111.3 (C),
128.3 (CH), 128.7 (CH), 133.4 (CH), 136.9 (C), 197.5 (CO) ppm. IR (KBr):
Compound (15g): Prepared from benzylation reaction of 15d; Yield: 70%
(0.274 g) from 15d (0.300 g), Rf: 0.46 (1:4, EtOAc/Hexanes). White solid,
Melting point: 42 ºC. [α]20 = - 7.20 (c = 0.1, CHCl3), (literature [α]25 = -
D
D

max 3022, 2994, 2891, 1742, 1596, 1468, 1317 cm-1. HRMS (ESI): Calcd.
5.6 (c = 1.0, CHCl3)[5d] 1H NMR (CDCl3, 500 MHz) :1.31 (s, 3 H, CH3),
1.43-1.46 (m, 1 H), 1.47 (s, 3 H, CH3), 1.78-1.92 (m, 2 H, CH2), 2.07 (dd,
J = 13.2, 4.0 Hz, 1 H), 2.59-2.64 (m, 1 H), 2.68-2.72 (m, 1 H), 3.87 (s, 3 H,
OCH3), 4.16-4.22 (m, 1 H), 4.71 (t, J = 4.2 Hz, 1 H), 5.11 (s, 2 H, OCH2Ph),
5.82 (d, J = 3.7 Hz, 1 H), 6.65-6.67 (m, 1 H, ArH), 6.75-6.80 (m, 2 H, ArH),
7.26-7.29 (m, 1 H, ArH), 7.35 (t, J = 7.3 Hz, 2 H, ArH), 7.42-7.43 (m, 2 H,
ArH) ppm. 13C NMR (125 MHz, CDCl3) δ : 26.2 (CH3), 26.7 (CH2), 32.1
(CH2), 36.2 (CH2), 39.0 (CH2), 56.0 (OCH3), 71.3 (OCH2), 77.2 (CH), 80.6
(CH), 105.3 (CH), 110.9 (C), 112.4 (CH), 114.4 (CH), 120.2 (CH), 127.3
(CH), 127.8 (CH), 128.6 (CH), 135.1 (C), 137.5 (C), 146.4 (C), 149.6 (C)
ppm. IR (KBr): max 2981, 2891, 1596, 1468, 1317, 1019 cm–1. HRMS
(ESI): Calcd. for C23H28O5Na [M+Na]+: 407.1834; found: 407.1838.
for C15H18O4Na [M+Na]+: 285.1103; found: 285.1098.
General procedure for reduction of aryl ketones: To a solution of the
aryl ketones (11a-f) (1 equiv.) in EtOH (3 mL) 10% Palladium hydroxide
on activated charcoal (20 mol%) was added and the reaction mixture was
stirred for 6 h under hydrogen atmosphere at room temperature. After this
time, the reaction mixture was filtered and the solvent was evaporated
under reduced pressure. The obtained residue was purified by silica gel
column chromatography to obtain the desired products.
Compound (15a): Yield: 83% (0.395 g) from 11a (0.500 g), Rf: 0.45 (1:4,
EtOAc/Hexanes). White solid, Melting point: 46-48 ºC. [α]20D = - 8.90 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) 1.31 (s, 3 H, CH3), 1.42-1.49 (m,
1 H), 1.49 (s, 3 H, CH3), 1.74-1.82 (m, 1 H), 1.89-1.96 (m ,1 H), 2.07 (dd,
J = 13.2, 4.1 Hz, 1 H), 2.57-2.76 (m, 2 H, CH2), 3.77 (s, 3 H, OCH3), 4.17-
4.23 (m, 1 H), 4.71 (t, J = 4.3 Hz, 1 H), 5.82 (d, J = 3.8 Hz, 1 H), 6.82 (d, J
= 8.7 Hz, 2 H, ArH), 7.11 (d, J = 8.7 Hz, 2 H, ArH) ppm. 13C NMR (100
MHz, CDCl3)δ : 26.2 (CH3), 26.7 (CH2), 31.6 (CH2), 36.3 (CH2), 39.0 (CH2),
55.3 (OCH3), 77.3 (CH), 80.7 (CH), 105.3 (CH), 110.9 (C), 113.9 (CH),
129.3 (CH), 133.9 (C), 157.9 (C) ppm. IR (KBr): max 2958, 2862, 1574,
1461, 1317, 1058 cm–1. HRMS (ESI): Calcd. for C16H22O4Na [M+Na]+:
301.1416; found: 301.1388.
Compound (15h): Prepared from benzylation reaction of 15e; Yield: 87%
(0.340 g) from 15e (0.300 g), Rf: 0.46 (1:4, EtOAc/Hexanes). White solid,
Melting point: 46-48 ºC. [α]20D = - 5.96 (c = 0.1, CHCl3), 1H NMR (CDCl3,
500 MHz) :1.31 (s, 3 H, CH3), 1.39-1.48 (m, 1 H), 1.48 (s, 3 H, CH3), 1.72-
1.77 (m, 1 H), 1.84-1.90 (m, 1 H), 2.05 (dd, J = 13.2, 4.1 Hz, 1 H), 2.53-
2.60 (m, 1 H), 2.64-2.72 (m, 1 H), 3.85 (s, 3 H, OCH3), 4.14-4.21 (m, 1 H),
4.69-4.70 (m, 1 H), 5.12 (s, 2 H, OCH2Ph), 5.81 (d, J = 3.8 Hz, 1 H), 6.73-
6.77 (m, 2 H, ArH), 6.81 (d, J = 8.0 Hz, 1 H, ArH), 7.27-7.31 (m, 1 H, ArH),
7.36-7.38 (m, 2 H, ArH),7.43-7.45 (m, 2 H, ArH) ppm. 13C NMR (125 MHz,
CDCl3) δ : 26.2 (CH3), 26.7 (CH2), 32.0 (CH2), 36.2 (CH2), 39.0 (CH2), 56.2
(OCH3), 71.1 (OCH2), 77.2 (CH), 80.7 (CH), 105.3 (CH), 110.9 (C), 112.1
(CH), 114.7 (CH), 121.0 (CH), 127.5 (CH), 127.9 (CH), 128.6 (CH), 134.4
(C), 137.3 (C), 148.0 (C), 148.2 (C) ppm. IR (KBr): max 2981, 2891, 1596,
1468, 1317, 1019 cm–1. HRMS (ESI): Calcd. for C23H28O5Na [M+Na]+:
407.1834; found: 407.1841.
Compound (15b): Yield: 93% (0.267 g) from 11b (0.300 g), Rf: 0.36 (1:4,
EtOAc/Hexanes). White solid, Melting point: 51-53 ºC. [α]20D = - 7.30 (c =
0.1, CHCl3), 1H NMR (CDCl3, 400 MHz) :1.30 (s, 3 H, CH3), 1.47 (s, 3 H,
CH3), 1.71-1.95 (m, 4 H, 2×CH2), 2.59-2.74 (m, 2 H), 3.84 (s, 3 H, OCH3),
3.85 (s, 3 H, OCH3), 4.15-4.23 (m, 1 H), 4.71 (t, J = 4.2 Hz, 1 H), 5.81 (d,
J = 3.8 Hz, 1 H), 6.71-6.73 (m, 2 H, ArH), 6.76-6.79 (m, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3) δ : 26.2 (CH3), 26.7 (CH2), 32.1 (CH2), 36.3
(CH2), 39.1 (CH2), 55.9 (OCH3), 56.0 (OCH3), 77.2 (CH), 80.7 (CH), 105.3
(CH), 110.9 (C), 111.5 (CH), 112.0 (CH), 120.2 (CH), 134.5 (C), 147.4 (C),
General procedure for the preparation of alkenes 16a-f and17a-e: To
a solution of hemiacetals 10a-f (1 equiv.) in dichloromethane (6 mL/mmol),
was added requisite phosphonium salt (1.1 equiv.) followed by anhydrous
potassium carbonate (2 equiv.) and 18-crown-6 (0.2 equiv.). The reaction
mixture was stirred at 40 oC for 6h (progress was monitored by TLC). The
reaction mixture was diluted with dichloromethane (6 mL), the organic
layer was sequentially washed with water (10 mL) and brine solution (10
149.0 (C) ppm. IR (KBr): max 2974, 2841, 1581, 1491, 1307, 1067 cm–1
.
HRMS (ESI): Calcd. for C17H24O5Na [M+Na]+: 331.1521; found: 331.1537.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801211
European Journal of Organic Chemistry
FULL PAPER
mL) and dried over anhydrous sodium sulfate. Upon condensing the
organic solvent under reduced pressure followed by column
chromatography purification the alkene products 16a-f (from 8f), 17a-e
(from ylides 8a-e) were obtained as E and Z isomers.
130.1 (CH), 131.8 (CH) 133.8 (CH), 135.3 (C), 136.59 (C), 137.4 (C), 146.4
(C), 149.6 (C) ppm. Non-overlapped peaks of minor isomer: 31.3 (CH2),
39.8 (CH2), 43.2 (CH2), 69.0 (CH), 71.7 (CH), 112.40 (CH), 127.5 (CH),
128.5 (CH), 128.8 (CH), 130.9 (CH), 135.2 (C), 136.50 (C) ppm.IR
(CHCl3): max3546, 3064, 2987, 2868, 1571, 1464, 1317, 1015 cm–1
.
HRMS (ESI): Calcd. for C27H30O4Na [M+Na]+: 441.2042; found: 441.2068.
Alkene (16a): Yield: 72% (0.141 g) from 10a (0.150 g), (E:Z= 1:0.5),Rf:
0.61 (1:1, EtOAc/Hexanes). Colorless liquid. 1H NMR (CDCl3, 400 MHz) :
1.70-1.82 (m, 4 H, 2×CH2), 2.60-2.75 (m, 2 H, CH2), 3.09 (bs, 2 H, 2×OH),
3.77 (s, 3 H, OCH3), 3.86-3.95 (m, 1 H), 4.50-4.55 (m, 1 H), 6.21 (dd, J =
15.9, 6.5 Hz, 1 H), 6.57 (d, J = 15.9 Hz, 1 H), 6.80-6.84 (m, 2 H, ArH), 7.10
(t, J = 8.5 Hz, 2 H, ArH), 7.23-7.38 (m, 5 H, ArH) ppm. Non-overlapped
peaks of minor isomer: 4.79-4.85 (m, 1 H), 5.67 (dd, J = 11.6, 9.2 Hz, 1 H),
6.18 (d, J = 6.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3) δ : 30.88 (CH2),
39.99 (CH2), 43.4 (CH2), 55.3 (OCH3), 71.8 (CH), 73.7 (CH), 113.9 (CH),
126.6 (CH), 127.8 (CH), 128.7 (CH), 129.4 (CH), 131.9 (CH) 133.9 (CH),
134.0 (C), 136.6 (C), 157.9 (C) ppm. Non-overlapped peaks of minor
isomer: 30.84 (CH2), 39.93 (CH2), 43.2 (CH2), 69.0 (CH), 71.7 (CH), 127.4
(CH), 128.5 (CH), 128.8 (CH), 130.1 (CH), 130.8 (CH), 133.9 (C), 136.5
Alkene (16e): Yield: 66% (0.121 g) from 10e (0.150 g), (E:Z= 1:0.4),Rf:
0.46 (1:1, EtOAc/Hexanes). Colorless liquid. 1H NMR (CDCl3, 400 MHz)
 : 1.68-1.73 (m, 4 H, 2×CH2), 2.59-2.67 (m, 2 H, CH2), 3.80-3.89 (m, 1 H),
3.85 (s, 3 H, OCH3), 4.48-4.52 (m, 1 H), 5.13 (s, 2 H, OCH2), 6.20 (dd, J =
15.9, 6.5 Hz, 1 H), 6.58 (d, J = 15.9 Hz, 1 H), 6.73-6.75 (m, 2 H, ArH), 6.79-
6.83 (m, 1 H, ArH), 7.24-7.31 (m, 4 H, ArH), 7.32-7.37 (m, 4 H, ArH), 7.41-
7.44 (m, 2 H, ArH) ppm. Non-overlapped peaks of minor isomer: 4.79 (td,
J = 9.2, 2.1 Hz, 1 H), 5.12 (s, 2 H, OCH2), 5.66 (dd, J = 11.6, 9.1 Hz, 1 H),
6.53 (d, J = 11.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.26 (CH2),
39.8 (CH2), 43.4 (CH2), 56.2 (OCH3), 71.1 (OCH2), 71.7 (CH), 73.8 (CH),
112.1 (CH), 114.8 (CH), 121.0 (CH), 126.6 (CH), 127.4 (CH), 127.9 (CH),
128.6 (CH), 128.7 (CH), 130.2 (CH), 131.9 (CH) 134.5 (C), 136.6 (C),
137.4 (C), 148.10 (C) ppm. Non-overlapped peaks of minor isomer: 31.21
(CH2), 39.7 (CH2), 43.3 (CH2), 69.0 (CH2), 71.5 (CH), 128.5 (CH), 128.8
(CH), 131.0 (CH), 133.8 (CH), 134.4 (C), 136.5 (C), 148.16 (C) ppm. IR
(C) ppm. IR (CHCl3): max 3546, 3056, 2991, 2856, 1589, 1468 cm–1
.
HRMS (ESI): Calcd. for C20H24O3Na [M+Na]+: 335.1623; found: 335.1616.
Alkene (16b): Yield: 69% (0.132 g) from 10b (0.150 g), (E:Z= 1:0.4),Rf:
0.51 (1:1, EtOAc/Hexanes). Pale yellow liquid. 1H NMR (CDCl3, 400
MHz) : 1.78-1.83 (m, 4 H, 2×CH2), 2.64-2.70 (m, 2 H, CH2), 3.84 (s, 3 H,
OCH3), 3.85 (s, 3 H, OCH3), 3.95-4.02 (m, 1 H), 4.52-4.61 (m, 1 H), 6.22
(dd, J = 15.3, 5.0 Hz, 1 H), 6.58 (d, J = 15.8 Hz, 1 H), 6.73-6.79 (m, 3 H,
ArH), 7.24-7.35 (m, 5 H, ArH) ppm. Non-overlapped peaks of minor
isomer: 4.80-4.86 (m, 1 H), 5.68 (t, J = 9.0 Hz, 1 H), 6.53 (d, J = 11.9 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.39 (CH2), 39.9 (CH2), 43.5
(CH2), 55.9 (OCH3), 56.0 (OCH3), 71.8 (CH), 73.7 (CH), 111.4 (CH), 111.8
(CH), 120.2 (CH), 126.5 (CH), 127.8 (CH), 128.4 (CH), 128.6 (CH), 128.8
(CH), 130.1 (CH), 131.9 (CH), 134.6 (CH), 136.59 (C), 147.2 (C), 148.9
(C) ppm. Non-overlapped peaks of minor isomer: 31.35 (CH2), 39.8 (CH2),
43.2 (CH2), 69.0 (CH), 71.7 (CH), 127.4 (CH), 130.8 (CH), 133.8 (CH),
136.50 (C) ppm. IR (CHCl3): max 3546, 3056, 2991, 2856, 1589, 1468,
1304, 1091 cm–1. HRMS (ESI): Calcd. for C21H26O4Na [M+Na]+: 365.1729;
found: 365.1752.
(CHCl3): max3531, 3064, 2987, 2868, 1571, 1464, 1317, 1015 cm–1
.
HRMS (ESI): Calcd. for C27H30O4Na [M+Na]+: 441.2042; found: 441.2020.
Alkene (16f): Yield: 65% (0.132 g) from 10f (0.150 g), (E:Z= 1:0.5), Rf:
0.49 (1:1, EtOAc/Hexanes). White solid, Melting point: 75-77 ºC. 1H NMR
(CDCl3, 400 MHz) : 1.72-1.85 (m, 4 H, 2×CH2), 2.66-2.79 (m, 2 H, CH2),
2.80 (bs, 2 H, 2×OH), 3.88-3.95 (m, 1 H), 4.52 (q, J = 5.8 Hz, 1 H), 6.20
(dd, J = 15.9, 6.5 Hz, 1 H), 6.57 (d, J = 15.9 Hz, 1 H), 7.16-7.20 (m, 5 H,
ArH), 7.31-7.37 (m, 5 H, ArH) ppm. Non-overlapped peaks of minor
isomer: 4.81 (td, J = 9.2, 2.6 Hz, 1 H), 5.66 (dd, J = 11.6, 9.1 Hz, 1 H), 6.51
(d, J = 11.6 Hz, 1 H), 7.23-7.28 (m, 5 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3) δ : 31.8 (CH2), 39.78 (CH2), 43.4 (CH2), 71.8 (CH), 73.7 (CH), 126.0
(CH), 126.6 (CH), 128.5 (CH), 128.7 (CH), 130.2 (CH), 131.9 (CH) 136.6
(C) 142.0 (C) ppm. Non-overlapped peaks of minor isomer: 31.7 (CH2),
39.71 (CH2), 43.2 (CH2), 69.0 (CH), 71.6 (CH), 127.5 (CH), 127.8 (CH),
128.8 (CH), 133.9 (CH), 136.5 (C), 141.9 (C) ppm. IR (KBr): max 3500,
2985, 1600, 1495, 1368, 1078 cm–1. HRMS (ESI): Calcd. for C19H22O2Na
[M+Na]+: 305.1517; found: 305.1533.
Alkene (16c): Yield: 63% (0.118 g) from 10c (0.250 g), (E:Z= 1:0.2),Rf:
0.56 (1:1, EtOAc/Hexanes). Pale yellow liquid. 1H NMR (CDCl3, 400
MHz) : 1.78-1.85 (m, 4 H, 2×CH2), 2.62-2.76 (m, 2 H, CH2), 3.81 (s, 3 H,
OCH3), 3.83 (s, 6 H, 2×OCH3), 3.91-3.99 (m, 1 H), 4.55 (q, J = 6.3 Hz, 1
H), 6.22 (dd, J = 15.8, 6.6 Hz, 1 H), 6.42 (s, 2 H, ArH), 6.58 (d, J = 15.8
Hz, 1 H), 7.28-7.37 (m, 5 H, ArH) ppm. Non-overlapped peaks of minor
isomer: 5.68 (dd, J = 11.6, 9.1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3)
δ : 32.3 (CH2), 39.9 (CH2), 43.4 (CH2), 56.2 (OCH3), 60.9 (OCH3), 71.7
(CH), 73.8 (CH), 105.4 (CH), 126.6 (CH), 128.7 (CH), 132.14 (CH), 132.17
(C), 132.2 (CH), 153.2 (C) ppm. Non-overlapped peaks of minor isomer:
29.8 (CH2), 127.8 (CH), 128.6 (CH), 136.2 (C), 137.9 (C) ppm. IR (CHCl3):
Alkene (17a): Yield: 69% (0.103 g) from 10f (0.100 g), (E:Z= 1:0.66),Rf:
0.60 (1:1, EtOAc/Hexanes). Colorless liquid. 1H NMR (CDCl3, 400 MHz) :
1.73-1.82 (m, 4 H, 2×CH2), 2.67-2.77 (m, 2 H, CH2), 3.79 (s, 3 H, OCH3),
3.89-3.95 (m, 1 H), 4.50 (q, J = 6.0 Hz, 1 H), 6.06 (dd, J = 15.8, 6.7 Hz, 1
H), 6.51 (d, J = 15.8 Hz, 1 H), 6.83-6.87 (m, 2 H, ArH), 7.17-7.23 (m, 4 H,
ArH), 7.24-7.30 (m, 3 H, ArH) ppm. Non-overlapped peaks of minor
isomer: 3.80 (s, 3 H, OCH3), 4.82 (td, J = 9.2, 2.5 Hz, 1 H), 5.57 (dd, J =
11.6, 9.0 Hz, 1 H), 6.45 (d, J = 11.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3) δ : 31.8 (CH2), 39.77 (CH2), 43.5 (CH2), 55.4 (OCH3), 71.77 (CH),
74.0 (CH), 114.1 (CH), 125.9 (CH), 127.8 (CH), 128.5 (CH), 129.3 (C),
129.7 (CH), 129.8 (CH), 130.2 (CH), 142.08 (C), 159.4 (C) ppm. Non-
overlapped peaks of minor isomer: 31.7 (CH2), 39.71 (CH2), 43.3 (CH2),
69.1 (CH), 71.71 (CH), 113.9 (CH), 127.2 (CH), 129.1 (CH), 130.5 (CH),
132.8 (CH), 142.0 (C), 159.0 (C) ppm. IR (CHCl3): max3571, 3056, 2991,
2856, 1589, 1468, 1304 cm–1. HRMS (ESI): Calcd. for C20H24O3Na
[M+Na]+: 335.1623; found: 335.1645.

max3449, 3038, 2985, 2847, 1540, 1460, 1304, 1084 cm–1. HRMS (ESI):
Calcd. for C22H28O5Na [M+Na]+: 395.1834; found: 395.1831.
Alkene (16d): Yield: 79% (0.144 g) from 10d (0.250 g), (E:Z= 1:0.4),Rf:
0.43 (1:1, EtOAc/Hexanes). Colorless liquid. 1H NMR (CDCl3, 500 MHz) :
1.72-1.82 (m, 4 H, 2×CH2), 2.59-2.73 (m, 2 H, CH2), 3.14 (bs, 2 H, 2×OH),
3.86 (s, 3 H, OCH3), 3.91-3.96 (m, 1 H), 4.52 (q, J = 6.2 Hz, 1 H), 5.10 (s,
2 H, OCH2), 6.20 (dd, J = 15.9, 6.6 Hz, 1 H), 6.57 (d, J = 15.9 Hz, 1 H),
6.63-6.67 (m, 1 H, ArH), 6.74 (dd, J = 8.5, 1.7 Hz, 1 H, ArH), 6.77-6.80 (m,
1 H, ArH), 7.23-7.36 (m, 8 H, ArH), 7.41-7.43 (m, 2 H, ArH) ppm. Non-
overlapped peaks of minor isomer: 3.84 (s, 3 H, OCH3), 4.82 (td, J = 9.5,
2.6 Hz, 1 H), 5.66 (dd, J = 11.6, 9.1 Hz, 1 H), 6.51 (d, J = 11.6 Hz, 1 H)
ppm. 13C NMR (125 MHz, CDCl3) δ : 31.4 (CH2), 39.9 (CH2), 43.3 (CH2),
56.0 (OCH3), 71.3 (OCH2), 71.8 (CH), 73.8 (CH), 112.44 (CH), 114.3 (CH),
120.3 (CH), 126.6 (CH), 127.3 (CH), 127.8 (CH), 128.6 (CH), 128.7 (CH),
Alkene (17b): Yield: 67% (0.110 g) from 10f (0.100 g), (E:Z= 1:0.4),Rf:
0.51 (1:1, EtOAc/Hexanes). Pale yellow liquid. 1H NMR (CDCl3, 400
MHz) : 1.77-1.85 (m, 4 H, 2×CH2), 2.67-2.78 (m, 2 H, CH2), 3.10 (bs, 2 H,
2×OH), 3.871 (s, 3 H, OCH3), 3.88 (s, 3 H, OCH3), 3.93-3.97 (m, 1 H),
4.49-4.54 (m, 1 H), 6.08 (dd, J = 15.8, 6.7 Hz, 1 H), 6.51 (d, J = 15.8 Hz,
1 H), 6.81 (t, J = 8.4 Hz, 1 H, ArH), 6.84-6.89 (m, 2 H, ArH), 7.18-7.21 (m,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801211
European Journal of Organic Chemistry
FULL PAPER
3 H, ArH), 7.25-7.28 (m, 2 H, ArH) ppm. Non-overlapped peaks of minor
isomer: 3.83 (s, 3 H, OCH3), 3.876 (s, 3 H, OCH3), 4.84 (td, J = 9.1, 2.5
Hz, 1 H), 5.59 (dd, J = 11.6, 9.0 Hz, 1 H), 6.45 (d, J = 11.6 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3) δ : 31.8 (CH2), 39.7 (CH2), 43.4 (CH2), 55.9
(OCH3), 56.0 (OCH3), 71.8 (CH), 73.9 (CH), 108.9 (CH), 111.2 (CH), 119.9
(CH), 125.9 (CH), 129.6 (C), 129.9 (CH), 130.0 (CH), 142.0 (C), 148.5 (C)
149.0 (C) 149.1 (C) ppm. Non-overlapped peaks of minor isomer: 31.7
(CH2), 69.1 (CH), 71.7 (CH), 111.0 (CH), 112.0 (CH), 121.5 (CH), 129.4
(C), 130.8 (CH), 132.5 (CH), 141.9 (C) ppm. IR (CHCl3): max3541, 3056,
2991, 2856, 1589, 1468, 1304, 1091 cm–1. HRMS (ESI): Calcd. for
C21H26O4Na [M+Na]+: 365.1729; found: 365.1700.
136.6 (C), 148.17 (C) ppm. IR (CHCl3): max3532, 3064, 2987, 2868, 1571,
1464, 1317, 1015 cm–1. HRMS (ESI): Calcd. for C27H30O4Na [M+Na]+:
441.2042; found: 441.2053.
General procedure for reduction of alkenes 16a-f and17a-e: To a
solution of E and Z isomers of 16a-f or 17a-e (1.0 equiv) in ethyl acetate
(10 mL/mmol) was added 10% Pd-C (20 mg). Hydrogenation was carried
out at 1 atmospheric pressure of molecular hydrogen (balloon pressure) at
room temperature for 5-6h (monitored by TLC). The reaction mixture was
filtered through short pad of celite and washed thoroughly with ethyl
acetate. The filtrate was condensed under reduced pressure to obtain a
crude mass which was then purified by column chromatography.
Alkene (17c): Yield: 71% (0.126 g) from 10f (0.100 g), (E:Z= 1:0.8),Rf:
0.39 (1:1, EtOAc/Hexanes). Colorless liquid. 1H NMR (CDCl3, 400 MHz) :
1.69-1.83 (m, 4 H, 2×CH2), 2.64-2.77 (m, 2 H, CH2), 3.01 (bs, 2 H, 2×OH),
3.81 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 3.89-3.96
(m, 1 H), 4.54 (d, J = 5.7 Hz, 1 H), 4.85 (t, J = 9.0 Hz, 1 H), 6.13 (dd, J =
15.9, 5.6 Hz, 1 H), 6.54 (m, 2 H, ArH), 7.19-7.27 (m, 5 H, ArH) ppm. Non-
overlapped peaks of minor isomer: 4.09-4.24 (m, 1 H), 5.63 (t, J = 9.5 Hz,
1 H), 6.46 (d, J = 13.9 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.8
(CH2), 39.8 (CH2), 43.4 (CH2), 56.2 (OCH3), 61.0 (OCH3), 69.1 (CH), 71.8
(CH), 73.7 (CH), 103.7 (CH), 126.05 (CH), 128.51 (CH), 128.54 (CH),
128.6 (CH), 130.1 (CH), 131.2 (CH), 131.4 (CH), 132.3 (C), 133.4 (CH),
141.7 (C), 153.4 (C) ppm. Non-overlapped peaks of minor isomer: 31.7
(CH2), 39.9 (CH2), 43.5 (CH2), 71.7 (CH), 106.1 (CH), 126.09 (CH), 132.1
(C), 141.9 (C), 153.1 (C) ppm. IR (CHCl3): max 3557, 3056, 2991, 2856,
1589, 1468, 1304, 1091 cm–1. HRMS (ESI): Calcd. for C22H28O5Na
[M+Na]+: 395.1834; found: 395.1810.
(3R,5S)-1-(4-methoxyphenyl)-7-phenylheptane-3,5-diol (5a): Yield:
86% (0.069 g) from 16a (0.080 g), Rf: 0.45 (1:1, EtOAc/Hexanes). White
solid, Melting point: 72-73 ºC. [α]37 = + 3.72 (c = 1.0, CHCl3), 1H NMR
D
(CDCl3, 500 MHz) : 1.47-1.51 (m, 2 H, CH2), 1.63-1.76 (m, 4 H, 2×CH2),
2.60-2.72 (m, 4 H, 2×CH2), 3.59-3.64 (m, 1 H), 3.78-3.84 (m, 1 H), 3.79 (s,
3 H, OCH3), 6.84 (d, J = 8.4 Hz, 2 H, ArH), 7.12 (d, J = 8.4 Hz, 2 H, ArH),
7.17-7.20 (m, 3 H, ArH), 7.27-7.30 (m, 2 H, ArH) ppm. 13C NMR (125 MHz,
CDCl3) δ : 31.1 (CH2), 31.6 (CH2), 35.9 (CH2), 37.4 (CH2), 39.3 (CH2), 55.3
(OCH3), 71.3 (2×CH), 113.8 (2×CH), 125.7 (CH), 128.3 (CH), 128.4 (CH),
129.3 (CH), 134.2 (C), 142.6 (C), 157.7 (C) ppm. IR (KBr): max3412, 2968,
2856, 1600, 1468, 1068 cm–1. HRMS (ESI): Calcd. for C20H26O3K [M+K]+:
353.1519; found: 353.1531.
(3R,5S)-1-(3,4-dimethoxyphenyl)-7-phenylheptane-3,5-diol (5b): Yield:
78% (0.062 g) from 16b (0.080 g), Rf: 0.41 (1:1, EtOAc/Hexanes). White
solid, Melting point: 85-87 ºC. [α]35 = − 7.20 (c = 1.0, CHCl3), 1H NMR
D
Alkene (17d): Yield: 64% (0.128 g) from 10f (0.100 g), (E:Z= 1:0.8), Rf:
0.43 (1:1, EtOAc/Hexanes). White solid, Melting point: 58-60 ºC. 1H NMR
(CDCl3, 400 MHz) : 1.72-1.82 (m, 4 H, 2×CH2), 2.69-2.77 (m, 2 H, CH2),
3.72-3.73 (m, 1 H), 3.87 (s, 3 H, OCH3), 3.90-3.94 (m, 1 H), 4.49 (q, J =
6.1 Hz, 1 H), 5.13 (s, 2 H, OCH2), 6.06 (dd, J = 15.8, 6.7 Hz, 1 H), 6.48 (d,
J = 15.4 Hz, 1 H), 6.81-6.82 (m, 1 H, ArH), 6.93-6.94 (m, 1 H, ArH), 7.24-
7.29 (m, 4 H, ArH), 7.33-7.38 (m, 4 H, ArH), 7.40-7.43 (m, 2 H, ArH) ppm.
Non-overlapped peaks of minor isomer: 3.82 (s, 3 H, OCH3), 4.82 (td, J =
9.1, 2.4 Hz, 1 H), 5.14 (s, 2 H, OCH2), 5.57 (dd, J = 11.6, 8.9 Hz, 1 H), 6.42
(d, J = 11.6 Hz, 1 H), 6.75-6.78 (m, 1 H, ArH), 6.84-6.87 (m, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3) δ : 31.78 (CH2), 39.7 (CH2), 43.4 (CH2), 56.0
(OCH3), 66.9 (CH), 71.08 (CH), 71.75 (CH), 73.8 (CH), 112.5 (CH), 113.9
(CH), 119.7 (CH), 127.3 (CH), 128.6 (CH), 130.1 (CH), 132.6 (CH), 137.0
(C), 142.0 (C), 148.3 (C) 149.7 (C) ppm. Non-overlapped peaks of minor
isomer: 31.72 (CH2), 43.3 (CH2), 69.0 (CH), 71.04 (CH), 71.69 (CH), 113.7
(CH), 121.4 (CH), 125.9 (CH), 127.1 (CH), 127.9 (CH), 128.5 (CH), 129.9
(C), 130.0 (CH), 130.7 (CH), 141.9 (C), 147.6 (C), 149.3 (C) ppm. IR
(CDCl3, 400 MHz) : 1.56-1.62 (m, 2 H, CH2), 1.71-1.83 (m, 4 H, 2×CH2),
2.61-2.76 (m, 4 H, 2×CH2), 3.84 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 3.87-
3.91 (m, 2 H, 2×CH), 6.71-6.73 (m, 2 H, ArH), 6.78 (d, J = 8.6 Hz, 1 H,
ArH), 7.18-7.20 (m, 3 H, ArH), 7.25-7.30 (m, 2 H, ArH) ppm. 13C NMR (100
MHz, CDCl3) δ : 31.4 (CH2), 31.7 (CH2), 39.8 (CH2), 40.0 (CH2), 43.1 (CH2),
55.9 (OCH3), 56.0 (OCH3), 72.5 (2×CH), 111.4 (CH), 111.8 (CH), 120.2
(CH), 126.0 (CH), 128.51 (CH), 128.57 (CH) 134.5 (C), 141.9 (C), 147.3
(C), 149.0 (C) ppm. IR (KBr): max3541, 2987, 2864, 1547, 1423, 1059 cm–
1. HRMS (ESI): Calcd. for C21H29O4 [M+H]+: 345.2066; found: 345.2072.
(3S,5R)-1-phenyl-7-(2,3,4-trimethoxyphenyl)heptane-3,5-diol
(5c):Yield: 73% (0.058 g) from 16c (0.080 g), Rf: 0.35 (1:1,
EtOAc/Hexanes). White solid, Melting point: 71-73 ºC. [α]37D = − 3.14 (c =
1.0, CHCl3), 1H NMR (CDCl3, 400 MHz) : 1.49-1.54 (m, 2 H, CH2), 1.62-
1.75 (m, 4 H, 2×CH2), 2.51-2.69 (m, 4 H, 2×CH2), 3.70 (s, 3 H, OCH3), 3.74
(s, 6 H, 2×OCH3), 3.75-3.80 (m, 2 H, 2×CH), 6.33 (s, 2 H, ArH), 7.09-7.11
(m, 3 H, ArH), 7.16-7.20 (m, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3)
δ : 31.7 (CH2), 32.2 (CH2), 39.92 (CH2), 39.96 (CH2), 43.0 (CH2), 56.1
(2×OCH3), 60.9 (OCH3), 72.4 (CH), 72.5 (CH), 105.4 (CH), 126.0 (CH),
128.4 (CH), 128.5 (CH), 136.2 (C), 137.8 (C), 141.8 (C), 153.2 (C) ppm.
IR (KBr): max 3524, 2961, 2872, 1562, 1464, 1041 cm–1. HRMS (ESI):
Calcd. for C22H30O5Na [M+Na]+: 397.1991; found: 397.2007.
(CHCl3): max 3551, 3064, 2987, 2868, 1571, 1464, 1317, 1015 cm–1
.
HRMS (ESI): Calcd. for C27H30O4Na [M+Na]+: 441.2042; found: 441.2037.
Alkene (17e): Yield: 61% (0.122 g) from 10f (0.100 g), (E:Z= 1:0.45),Rf:
0.51 (1:1, EtOAc/Hexanes). White solid, Melting point: 58-60 ºC. 1H NMR
(CDCl3, 400 MHz) : 1.67-1.73 (m, 4 H, 2×CH2), 2.58-2.64 (m, 2 H, CH2),
3.83-3.91 (m, 1 H), 3.85 (s, 3 H, OCH3), 4.48-4.52 (m, 1 H), 5.16 (s, 2 H,
OCH2), 6.22 (dd, J = 15.9, 6.5 Hz, 1 H), 6.59 (d, J = 15.9 Hz, 1 H), 6.74-
6.77 (m, 2 H, ArH), 6.79-6.85 (m, 1 H, ArH), 7.24-7.33 (m, 4 H, ArH), 7.33-
7.39 (m, 4 H, ArH), 7.43-7.47 (m, 2 H, ArH) ppm. Non-overlapped peaks
of minor isomer: 4.76 (td, J = 9.2, 2.1 Hz, 1 H), 5.14 (s, 2 H, OCH2), 5.68
(dd, J = 11.6, 9.1 Hz, 1 H), 6.55 (d, J = 11.6 Hz, 1 H) ppm. 13C NMR (100
MHz, CDCl3) δ : 31.28 (CH2), 39.9 (CH2), 43.6 (CH2), 56.3 (OCH3), 71.4
(OCH2), 71.7 (CH), 73.9 (CH), 112.3 (CH), 114.8 (CH), 121.0 (CH), 126.7
(CH), 127.5 (CH), 127.8 (CH), 128.7 (CH), 128.5 (CH), 130.3 (CH), 131.8
(CH) 134.7 (C), 136.5 (C), 137.3 (C), 148.14 (C) ppm. Non-overlapped
peaks of minor isomer: 31.23 (CH2), 39.6 (CH2), 43.9 (CH2), 69.1 (CH2),
71.6 (CH), 128.9 (CH), 129.0 (CH), 131.4 (CH), 133.6 (CH), 134.5 (C),
(3R,5S)-1-(4-hydroxy-3-methoxyphenyl)-7-phenylheptane-3,5-diol
(5d): Yield: 76% (0.061 g) from 16d (0.080 g), Rf: 0.45 (1:1,
EtOAc/Hexanes). Pale yellow solid, Melting point: 70-72 ºC. [α]37D = − 6.46
(c = 0.5, EtOH), 1H NMR (CDCl3, 500 MHz) : 1.72-1.81 (m, 6 H, 3×CH2),
2.57-2.77 (m, 4 H, 2×CH2), 3.15 (bs, 1 H, OH), 3.85 (s, 3 H, OCH3), 3.86-
3.89 (m, 2 H, 2×CH), 5.59 (bs, 1 H, OH), 6.66-6.69 (m, 2 H, ArH), 6.82 (d,
J = 7.9 Hz, 1 H, ArH), 7.12-7.20 (m, 3 H, ArH), 7.25-7.29 (m, 2 H, ArH)
ppm. 13C NMR (125 MHz, CDCl3) δ : 31.4 (CH2), 31.7 (CH2), 39.8 (CH2),
40.1 (CH2), 43.0 (CH2), 55.9 (OCH3), 72.5 (2×CH), 111.1 (CH), 114.4 (CH),
120.9 (CH), 126.0 (CH), 128.52 (CH), 128.57 (CH), 133.8 (C), 141.9 (C),
143.8 (C), 146.5 (C) ppm. IR (KBr): max 3412, 2968, 2856, 1600, 1468,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801211
European Journal of Organic Chemistry
FULL PAPER
1041 cm–1. HRMS (ESI): Calcd. for C20H27O4 [M+H]+: 331.1909; found:
331.1903.
141.8 (C), 153.2 (C) ppm. IR (KBr): max3524, 2961, 2872, 1562, 1464,
1041 cm–1. HRMS (ESI): Calcd. for C22H31O5 [M+H]+: 375.2171; found:
375.2159.
(3R,5S)-1-(3-hydroxy-4-methoxyphenyl)-7-phenylheptane-3,5-diol
(5e): Yield: 72% (0.058 g) from 16e (0.080 g), Rf: 0.45 (1:1,
EtOAc/Hexanes). Pale yellow solid, Melting point: 68-70 ºC. [α]36D = − 3.43
(c = 1.0, CHCl3), 1H NMR (CDCl3, 400 MHz) : 1.53-1.62 (m, 2 H, CH2),
1.71-1.79 (m, 4 H, 2×CH2), 2.59-2.73 (m, 4 H, 2×CH2), 3.64-3.75 (m, 2 H,
2×CH), 3.84 (s, 3 H, OCH3), 5.77 (bs, 1 H, OH), 6.65 (d, J = 8.1 Hz, 1 H,
ArH), 6.74-6.77 (m, 2 H, ArH), 7.16-7.19 (m, 3 H, ArH), 7.25-7.29 (m, 2 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.1 (CH2), 31.7 (CH2), 39.82
(CH2), 39.85 (CH2), 43.0 (CH2), 56.1 (OCH3), 72.4 (2×CH), 110.9 (CH),
114.8 (CH), 119.8 (CH), 125.9 (CH), 128.5 (CH), 135.2 (C), 142.0 (C),
144.9 (C), 145.6 (C) ppm. IR (KBr): max 3467, 2991, 2873, 1574, 1451,
1027 cm–1. HRMS (ESI): Calcd. for C20H27O4 [M+H]+: 331.1909; found:
331.1906.
(3S,5R)-1-(4-hydroxy-3-methoxyphenyl)-7-phenylheptane-3,5-diol
(9d): Yield: 81% (0.073 g) from 17d (0.090 g), Rf: 0.45 (1:1,
EtOAc/Hexanes). Pale yellow solid, Melting point: 69-71 ºC. [α]25D = + 6.45
(c = 0.5, EtOH), 1H NMR (CDCl3, 400 MHz) : 1.54-1.64 (m, 2 H, CH2),
1.70-1.82 (m, 4 H, 2×CH2), 2.57-2.79 (m, 4 H, 2×CH2), 3.10 (bs, 1 H, OH),
3.44 (bs, 1 H, OH), 3.65-3.74 (m, 1 H, CH), 3.85 (s, 3 H, OCH3), 3.87-3.89
(m, 1 H, CH), 5.58 (bs, 1 H, OH), 6.66-6.69 (m, 2 H, ArH), 6.82 (d, J = 7.9
Hz, 1 H, ArH), 7.18-7.20 (m, 3 H, ArH), 7.25-7.29 (m, 2 H, ArH) ppm. 13
C
NMR (100 MHz, CDCl3)δ : 31.5 (CH2), 31.7 (CH2), 39.8 (CH2), 40.1 (CH2),
43.2 (CH2), 55.9 (OCH3), 72.4 (2×CH), 111.5 (CH), 114.4 (CH), 120.9 (CH),
126.0 (CH), 127.2 (CH), 128.52 (CH), 128.57 (CH), 128.7 (CH), 130.0 (CH),
133.8 (C), 141.9 (C), 143.8 (C), 146.6 (C) ppm. IR (KBr): max 3412, 2968,
2856, 1600, 1468, 1041 cm–1. HRMS (ESI): Calcd. for C20H27O4 [M+H]+:
331.1909; found: 331.1892.
(3R,5S)-1,7-diphenylheptane-3,5-diol (5f): Yield: 81% (0.080 g) from 16f
(0.100 g), Rf: 0.51 (1:1, EtOAc/Hexanes). White solid, Melting point: 81-82
ºC. [α]25D = 0 (c = 1.0, CHCl3), 1H NMR (CDCl3, 400 MHz) : 1.55-1.67 (m,
2 H, CH2), 1.75-1.84 (m, 4 H, 2×CH2), 2.64-2.81 (m, 4 H, 2×CH2), 3.15-
3.55 (bs, 2 H, 2×OH), 3.89-3.91 (m, 2 H, 2×CH), 7.19-7.22 (m, 6 H, ArH),
7.27-7.31 (m, 4 H, ArH) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.7 (2×CH2),
39.8 (2×CH2), 43.1 (CH2), 72.4 (2×CH), 126.0 (CH), 128.53 (CH), 128.57
(CH) 141.9 (C) ppm. IR (KBr): max 3352, 2928, 2891, 1549, 1468, 1068
(3S,5R)-1-(3-hydroxy-4-methoxyphenyl)-7-phenylheptane-3,5-diol
(9e): Yield: 63% (0.063 g) from 17e (0.100 g), Rf: 0.45 (1:1,
EtOAc/Hexanes). Pale yellow solid, Melting point: 67-69 ºC. [α]25D = + 3.46
(c = 1.0, CHCl3), 1H NMR (CDCl3, 400 MHz) : 1.52-1.62 (m, 2 H, CH2),
1.71-1.81 (m, 4 H, 2×CH2), 2.57-2.77 (m, 4 H, 2×CH2), 3.23 (bs, 1 H, OH),
3.44 (bs, 1 H, OH), 3.84 (s, 3 H, OCH3), 3.85-3.88 (m, 2 H, 2×CH), 5.78
(bs, 1 H, OH), 6.65 (dd, J = 8.1, 2.0 Hz, 1 H, ArH), 6.74-6.77 (m, 2 H, ArH),
7.15-7.19 (m, 3 H, ArH), 7.25-7.29 (m, 2 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3) δ : 31.1 (CH2), 31.7 (CH2), 39.82 (CH2), 39.85 (CH2), 43.0 (CH2),
56.1 (OCH3), 72.4 (2×CH), 110.9 (CH), 114.8 (CH), 119.8 (CH), 125.9
(CH), 127.2 (CH), 128.5 (CH), 135.2 (C), 142.0 (C), 145.0 (C), 145.6 (C)
ppm. IR (KBr): max 3467, 2991, 2873, 1574, 1451, 1027 cm–1. HRMS
(ESI): Calcd. for C20H26O4Na [M+Na]+: 353.1729; found: 353.1721.
.
cm–1 HRMS (ESI): Calcd. for C19H25O2 [M+H]+: 285.1855; found:
285.1840.
(3S,5R)-1-(4-methoxyphenyl)-7-phenylheptane-3,5-diol (9a): Yield:
68% (0.061 g) from 17a (0.090 g), Rf: 0.45 (2:3, EtOAc/Hexanes). White
solid, Melting point: 72-74 ºC. [α]37 = − 3.72 (c = 1.0, CHCl3), 1H NMR
D
(CDCl3, 400 MHz) : 1.55-1.61 (m, 2 H, CH2), 1.71-1.82 (m, 4 H, 2×CH2),
2.61-2.76 (m, 4 H, 2×CH2), 3.05 (bs, 1 H, OH), 3.78 (s, 3 H, OCH3), 3.83-
3.87 (m, 2 H, 2×CH), 6.83 (d, J = 8.6 Hz, 2 H, ArH), 7.11 (d, J = 8.6 Hz, 2
H, ArH), 7.17-7.20 (m, 3 H, ArH), 7.25-7.30 (m, 2 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3) δ : 30.8 (CH2), 31.8 (CH2), 39.8 (CH2), 40.0 (CH2), 43.1
(CH2), 55.3 (OCH3), 72.4 (2×CH), 114.0 (CH), 126.0 (CH), 128.54 (CH),
128.57 (CH), 133.9 (C), 141.9 (C), 157.9 (C) ppm. IR (KBr): max 3412,
2968, 2856, 1600, 1468, 1068 cm–1. HRMS (ESI): Calcd. for C20H26O3K
[M+K]+: 353.1519; found: 353.1529.
The percentage cell viability was calculated using the following
equation.Cell viability (%) = Test sample optical density/Control sample
optical density × 100.
Supporting Information (see also the footnote on the first page of this
article): 1H and 13C NMR and HRMS spectra of the compounds.
(3S,5R)-1-(3,4-dimethoxyphenyl)-7-phenylheptane-3,5-diol (9b): Yield:
71% (0.057 g) from 17b (0.080 g), Rf: 0.41 (2:3, EtOAc/Hexanes). White
Acknowledgements
solid, Melting point: 85-87 ºC. [α]35 = + 7.21 (c = 1.0, CHCl3), 1H NMR
D
The authors thank the Department of Science and Technology
(DST), New Delhi, for funding towards the 400 MHz NMR
spectrometer to the Department of Chemistry, Indian Institute of
Technology Madras (IIT-Madras), under Intensification of
Research in High Priority Areas (IRPHA) scheme and ESI-MS
facility under Fund for Improvement of Science & Technology
Infrastructure (FIST) program. The Board of Research in Nuclear
Sciences (BRNS) is acknowledged for funding of project-2013.
The Council of Scientific & Industrial Research (CSIR) New Delhi
is also acknowledged for funding of the project in 2015.
(CDCl3, 400 MHz) : 1.56-1.64 (m, 2 H, CH2), 1.76-1.82 (m, 4 H, 2×CH2),
2.61-2.75 (m, 4 H, 2×CH2), 3.38-3.66 (m, 2 H, 2×CH), 3.85 (s, 6 H,
2×OCH3), 3.93 (bs, 1 H, OH), 6.72-6.79 (m, 2 H, ArH), 7.18-7.28 (m, 6 H,
ArH) ppm. 13C NMR (100 MHz, CDCl3) δ : 31.4 (CH2), 31.7 (CH2), 39.8
(CH2), 40.0 (CH2), 43.0 (CH2), 55.9 (OCH3), 56.0 (OCH3), 72.5 (2×CH),
111.4 (CH), 111.8 (CH), 120.2 (CH), 126.0 (CH), 128.51 (CH), 128.57 (CH),
134.5 (C), 141.9 (C), 147.3 (C), 149.0 (C) ppm. IR (KBr): max3541, 2987,
2864, 1547, 1423, 1059 cm–1. HRMS (ESI): Calcd. for C21H29O4 [M+H]+:
345.2066; found: 345.2091.
(3R,5S)-1-phenyl-7-(3,4,5-trimethoxyphenyl)heptane-3,5-diol
(9c):Yield: 73% (0.051 g) from 17c (0.070 g), Rf: 0.35 (1:1,
EtOAc/Hexanes). White solid, Melting point: 70-72 ºC. [α]37D = + 3.16 (c =
1.0, CHCl3), 1H NMR (CDCl3, 400 MHz) : 1.57-1.65 (m, 2 H, CH2), 1.75-
1.81 (m, 4 H, 2×CH2), 2.62-2.76 (m, 4 H, 2×CH2), 3.23 (bs, 2 H, 2×OH),
3.81 (s, 3 H, OCH3), 3.83 (s, 6 H, 2×OCH3), 3.85-3.91 (m, 2 H, 2×CH),
6.41 (s, 2 H, ArH), 7.16-7.20 (m, 3 H, ArH), 7.26-7.30 (m, 2 H, ArH) ppm.
13C NMR (100 MHz, CDCl3) δ : 31.7 (CH2), 32.2 (CH2), 39.91 (CH2), 39.95
(CH2), 43.0 (CH2), 56.1 (2×OCH3), 60.9 (OCH3), 72.4 (CH), 72.5 (CH),
105.4 (CH), 126.0 (CH), 128.4 (CH), 128.5 (CH), 136.2 (C), 137.8 (C),
Keywords: Diarylheptanoids • Alkylation • Anions • Cytotoxic
activity • Yashabushidiol A
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Layout 2:
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Synthesis of Diarylheptanoids
Kasireddy Sudarshan, Govindaraj
Perumal, Indrapal Singh Aidhen,*
Mukesh Doble*
1– 10
A new route for the synthesis of unsymmetrical linear diarylheptanoids 1 and their
enantiomers 2 via a common electrophilic intermediate 3 is presented using acyl
anion chemistry and Wittig olefination. The cytotoxic activity of all the synthesized
linear diarylheptanoids is tested.
Synthesis of Unsymmetrical Linear
Diarylheptanoids and their
Enantiomers and Antiproliferative
Activity Studies
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