Enantioselective synthesis of macrolactone core of the natural product Sch725674

Article abstract of DOI:10.1016/j.tet.2014.02.008

An enantioselective synthesis of the macrolactone core of natural product Sch725674 was accomplished from furfural. Key reactions in assembly of the macrolactone are the use of furan as a but-2-ene-dione equivalent and ring closing metathesis.

Full text of DOI:10.1016/j.tet.2014.02.008

Accepted Manuscript
Enantioselective Synthesis of Macrolactone Core of the Natural Product Sch725674
Sunil Kumar Sunnam, Kavirayani R. Prasad
PII:
S0040-4020(14)00166-5
10.1016/j.tet.2014.02.008
TET 25257
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 November 2013
Revised Date: 4 February 2014
Accepted Date: 5 February 2014
Please cite this article as: Sunnam SK, Prasad KR, Enantioselective Synthesis of Macrolactone Core of
the Natural Product Sch725674, Tetrahedron (2014), doi: 10.1016/j.tet.2014.02.008.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Enantioselective Synthesis of the
Macrolactone Core of Natural Product
Sch725674
Leave this area blank for abstract info.
Sunil Kumar Sunnam and Kavirayani R. Prasad*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, INDIA

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Enantioselective Synthesis of Macrolactone Core of the Natural Product Sch725674
Sunil Kumar Sunnam and Kavirayani R. Prasad*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, INDIA
FAX: +0091-80-23600529; E-mail: prasad@orgchem.iisc.ernet.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An enantioselective synthesis of the macrolactone core of natural product Sch725674 was
accomplished from furfural. Key reactions in assembly of the macrolactone are the use of furan
as a but-2-ene-dione equivalent and ring closing metathesis.
2014 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Macrolide
Total synthesis
Natural products
Sch725674
1. Introduction
olefin in macrolactone 2 and subsequent deprotection of the silyl
groups. Synthesis of the macrolactone 2 is planned by RCM of
During the investigations on isolation of bio-active natural
products, the group at Schering-Plough Company isolated a 14-
membered macrolactone natural product Sch725674 (1) (fig. 1)
from the culture of Aspergillus sp.1 The natural product 1 consists
of an α, β unsaturated lactone and three free chiral secondary
hydroxy groups in which two are contiguous. While the structure
of Sch725674 was assigned based on extensive NMR
experiments, absolute stereochemistry of the chiral centers was
not assigned. We undertook the total synthesis and assignment of
the stereochemistry of the natural product keeping in mind the
requirement for a general procedure to access all stereoisomers of
the natural product. During the course of our investigations, The
Curran’s group at the University of Pittsburg disclosed the total
synthesis of Sch725674.2 They assigned the stereochemistry of
the natural product as 4R,5S,7R,13R by synthesizing all the
possible diastereomers using an elegant ingenious flourous
tagging technology developed in their group and comparison of
the data with that reported for the natural product. We have been
involved in the total synthesis of macrolides3 and in this article
we disclose our efforts in detail towards the total synthesis of
Sch725674 which culminated in the successful assembly of the
macrolactone core; an analogue of a key intermediate in Curran’s
synthesis.
the ester 3. Formation of the C1-C11 fragment 4, which is the
acid unit of the ester was envisaged by elaboration of the 1,3-diol
6. Oxidative opening of the furan4 in 6 and further oxidation to
the acid with required E-geometry is planned to assemble the C1-
C11 acid fragment, while asymmetric allylation of n-hexanal is
envisaged for the synthesis of the homoallylic alcohol fragment
5.
OP
OP
OH
OP
OP
OH
OP
OP
OH
O
O
O
O
O
O
R
R
R
2
3
1
R = n-C5H11
P = TBS
OP
OP
OP
OH
R
O
HO
O
5
OH OH
4
6
Scheme-1. Retrosynthesis for Sch725674
2. Results and Discussion
OH
5
OH
4
Accordingly, synthesis of the C1-C11fragment 4 began with
the addition of 1-butenylmagnesium bromide to the Weinreb
amide 85 to furnish the silyloxy ketone 9 in 97% yield. Exposure
of 9 to HF·pyridine afforded the hydroxy ketone 10 in 97% yield.
Stereoselective reduction of the keto group in 10 with
tetramethylammoniumtriacetoxy borohydride6gave the 1,3-diol 6
in 97% yield. Protection of both hydroxy groups in 6 as the bis-
silylether 11 was accomplished using standard reaction
conditions in 96% yield. Pivotal oxidation of the furan in 11 with
7
OH
O
O
10
13
Fig 1: Sch 725674 (1)
As depicted in Scheme-1, our approach for the synthesis of
Sch725674 relied on the selective hydrogenation of the C10-C11

2
Tetrahedron
ACCEPTED MANUSCRIPT
NBS proceeded smoothly to afford the keto aldehyde 12 in 76%
yield, which on further oxidation with NaClO2 furnished the acid
13 in 93% yield. Stereoselective reduction of the ketone in 13
under Luche reduction conditions rendered the alcohol 147 in
99% yield which was protected as the TES ether 15 in 97% yield
using TESOTf in presence of 2,6-lutidine (scheme-2).
Scheme-2: Synthesis of the C1-C11 acid fragment of Sch725674
OH
After successfully synthesizing the acid fragment, the required
known homoallylic alcohol 5 was synthesized from n-hexanal
using a procedure described earlier.8 Yamaguchi esterification of
the acid unit 15 with the alcohol 5 produced the ester 16 in 83%
yield. At this stage, selective deprotection of the TES ether in 16
in presence of the TBS ether was effected by using EtOCOCl in
MeOH to afford the allylic alcohol 17 in 54% yield. Mitsunobu
inversion of the alcohol furnished the corresponding p-
nitrobenzoate 18 in 89% yield. Reaction of 18 with K2CO3/
MeOH produced a 1:1 mixture of the required inverted alcohol
and methyl 4-nitrobenzoate as an inseparable mixture. However,
protection of the free alcohol as the TBS ether cleanly furnished
3 (61% yield for two steps), which on reaction with Grubbs’
second generation afforded the macrolactone 29 in excellent yield
(Scheme-3).
OTES
5
HO
2,4,6-trichlorobenzoyl chloride
NEt3, DMAP, Benzene
O
TBSO
15
OTBS
OTES
0
C to rt,5 h, 83%
EtOCOCl, MeOH
O
0
C to rt, 20 min
54%
R
R
O
O
TBSO
OTBS
OTBS
OTBS
16
OH
PPh3, PNBA, DIAD
toluene, rt, 2 h, 89%
O
TBSO
OPNB
17
i) K2CO3, MeOH, rt
ii) TBSOTf, 2,6-lutidine
CH2Cl2
O
R
O
TBSO
18
50 C to rt, 1 h
61% for two steps
OTBS
G-II (cat)
O
2
CH2Cl2, 0.003 M
3 h, 97%
R
O
TBSO
3
OTBS
Scheme-3: Synthesis of the macrolactone 2
After the eventful assembly of the macrolactone core of 1, we
faced an unexpected difficulty in selective hydrogenation of the
active olefin at C10-C11 position in macrolactone 2 in presence
of the unsaturated C2-C3 olefin. Standard hydrogenation with
Pd/C, Pd/BaCO3 and with Pd/CaCO3 produced a mixture of
compounds. In a solitary instance, we could see the formation of

3
product 19 arising from the reduction of the required olefin,
however the reaction was non-reproducible. Similar tendencies
were observed in the hydrogenation of a structurally similar
macrolactone 20 by the Curran’s group.10 The Curran’s group
circumvented the problem arose in the partial hydrogenation of
the olefin in a structurally similar lactone 20 containing florous
tagged silicon by using Pd/SrCO3 for the hydrogenation
(Scheme-4). They have elaborated the resultant lactone 21 to the
natural product 1. We believe such a hydrogenation should
provide the required macrolactone which can be elaborated to
Sch725674 (1) using the procedure reported by Curran’s group.
bromobut-1-ene (6.7 mL, 64 mmol) and Mg turnings (2.3 g,
ACCEPTED MANUSCRIPT
95.4 mmol)] dropwise over a period of 1 h, maintaining the
temperature at 0 °C. After the reaction was complete (TLC), it
was quenched by careful addition of sat. NH4Cl solution (20 mL)
at 0 °C. The aqueous layer was extracted with EtOAc (3 ×30 mL)
and the combined organic layer was washed with brine solution
(30 mL). The pale yellow residue obtained after evaporation of
the solvent was purified by silica gel column chromatography
(PE−EtOAc, 98:2) to obtain 9 (9.52 g, 30.9 mmol, 97%) as a
25
colorless oil. [α]D −69.3 (c 1.0, CHCl3) IR (neat): νmax 2956,
2932, 1720, 1216cm−1. 1H NMR (CDCl3): δ (ppm) = 7.33 (d, J =
1.6 Hz, 1H), 6.29 (dd, J = 3.2, 1.8 Hz, 1H), 6.17 ( d, J = 3.2 Hz,
1H), 5.79 (ddt, J = 16.8, 10.2, 6.4 Hz, 1H), 5.21 (dd, J = 8.4, 4.4
Hz, 1H), 5.01 (d, J = 17.2 Hz, 1H), 4.96 (d, J = 10.2 Hz, 1H),
3.05 (dd, J = 15.2, 8.6 Hz, 1H), 2.68 (dd, J = 15.2, 4.4 Hz, 1H),
2.51– 2.55 (m, 2H), 2.29–2.33 (m, 2H), 0.81 (s, 9H), 0.03 (s,
3H), −0.10 (s, 3H). 13C NMR (CDCl3): δ (ppm) = 207.6, 155.8,
141.6, 137.0, 115.2, 110.1, 106.1, 65.0, 49.4, 43.4, 27.3, 25.7 (3
× C), 18.0, −5.1, −5.3. HRMS (ESI): m/z [M + Na]+ calcd for
C17H28O3SiNa: 331.1705; found: 331.1705.
OTBS
OTBS
OTBS
OTBS
Selective
hydrogenation
OTBS
OTBS
O
O
O
O
R
R
2
19
OTIPSF5
OTIPSF5
OTIPSF5
OTIPSF5
(S)-1-(furan-2-yl)-1-hydroxyhept-6-en-3-one (10): To
a
solution of 9 (0.84g, 2.72 mmol) in THF (3 mL), pyridine (0.5
mL, 6.2 mmol) and HF Pyridine complex (70% w/v, 0.5 mL) was
added dropwise at 0 °C, and was stirred at rt for 1 h. After the
reaction was complete (TLC), solid NaHCO3 (0.5 g) was
introduced into the reaction mixture portionwise until the
effervescences ceased. The contents were filtered through a short
pad of celite and the solvent was evaporated to obtain a pale
yellow oil which was purified by silica gel column
chromatography (PE−EtOAc, 9:1) to obtain 10 (0.51 g, 97%) as a
H2
OTIPS
O
OTIPS
1
Pd/ SrCO3
O
O
O
reported by
Curran's group
see ref. 2
R
R
20
21
Scheme -4: Synthesis of 1 reported by Curran’s group
25
3. Conclusions
colorless oil. [α]D −32.1 (c 1.0, CHCl3). IR (neat): νmax 3447,
1715, 1406, 1011, 740 cm−1. H NMR (CDCl3): δ (ppm) = 7.35
1
In conclusion, enantioselective synthesis of the macrolactone
core of Sch725674 is accomplished from furfural. Pivotal steps in
the synthetic sequence include the assembly of the required acid
unit by elaboration of a chiral furyl carbinol and ring closing
metathesis (RCM) to construct the macrolactone. The
macrolactone is structurally similar to that reported by the
Curran’s group which was elaborated to the natural product.
(d, J = 2.4 Hz, 1H), 6.32 (dd, J = 3.2, 2.0 Hz, 1H), 6.25 (d, J =
3.2 Hz, 1H), 5.79 (ddt, J = 16.8, 10.2, 6.4 Hz, 1H), 5.17–5.23 (m,
1H), 5.03 (d, J = 18.4 Hz, 1H), 4.99 (d, J = 11.2 Hz, 1H), 3.34 (s,
1H), 3.03 (dd, J = 17.2, 8.8 Hz, 1H), 2.88 (dd, J = 17.2, 3.2 Hz,
1H), 2.56 (t, J = 7.2 Hz, 2H), 2.34 (dd, J = 13.8, 6.8 Hz, 2H). 13C
NMR (CDCl3): δ (ppm) = 209.8, 154.8, 142.1, 136.6, 115.5,
110.2, 106.2, 63.7, 47.2, 42.5, 27.3. HRMS (ESI): m/z [M + Na]+
calcd for C11H14O3Na: 217.0841; found: 217.0841.
4. Experimental section
(1S,3R)-1-(furan-2-yl)hept-6-ene-1,3-diol
(6):
General Procedures: Unless stated otherwise, all reagents were
purchased from commercial sources and were used without
additional purification. All reactions were performed under an
inert atmosphere unless noted otherwise. THF was freshly
distilled over Na-benzophenone ketyl. Petroleum ether (PE)
refers to the fraction boiling in the 60–80 °C range. Column
chromatography was performed on silica gel (Acme grade, 100–
200 mesh). TLC plates (Merck pre-coated silica gel 60 F254
plates) were made visual with UV light, in an iodine chamber, or
with phosphomolybdic acid spray. Melting points were recorded
Tetramethylammonium triacetoxyborohydride (2.7 g, 10.3 mmol)
was added to a mixture of acetonitrile/acetic acid (2:1, 15 mL) at
0 °C and stirred at rt for 0.5 h. The mixture was cooled to −30 °C
and a solution of 10 (1.0 g, 5.15 mmol) in acetonitrile/acetic acid
(2:1, 15 mL) was added dropwise to the reaction mixture. The
reaction mixture was allowed to warm upto −20 °C and was
stirred for additional 6 h. After the reaction was complete (TLC),
it was quenched by addition of sat. sodium potassium tartrate
solution (5 mL) and with sat. NaHCO3 solution (15 mL). The
aqueous layer was extracted with EtOAc (10 mL × 3), the
combined organic layer was washed with brine (10 mL), dried
over Na2SO4. Evaporation of the solvent gave a pale yellow oil
which on purification by silica gel column chromatography
(PE−EtOAc, 2:1) afforded 6 (0.99 g, 97%) as a colorless oil.
using
a Buchi M-560 melting point apparatus and are
uncorrected. IR spectra were recorded on a Perkin-Elmer
1
spectrophotometer. H (400 MHz) and 13C (100 MHz) NMR
spectra were recorded on a Bruker 400 MHz spectrometer using
CDCl3 or CD3OD as the solvent. High-resolution mass
spectrometry (HRMS) was performed using a Waters Micromass
Q-TOF operating in the ESI mode. Optical rotations were
measured on a Rudolph Autopol IV polarimeter at 25 °C. β-
Silyloxy amide 8 was synthesized according to the procedure
described earlier5 by us.
25
[α]D −34.0 (c 1.1, CHCl3). IR (neat): νmax 3378, 2924, 1642,
1
1445, 914, 738 cm−1. H NMR (CDCl3): δ (ppm) = 7.37 (d, J =
2.0 Hz, 1H), 6.33 (dd, J = 3.2, 2.0 Hz, 1H), 6.25 (d, J = 3.2 Hz,
1H), 5.81 (ddt, J = 16.8, 10.0, 6.8 Hz, 1H), 5.02–5.07 (m, 2H),
4.97 (d, J = 10.2 Hz, 1H), 3.92–3.98 (m, 1H), 3.52 (bs, 1H), 2.80
(bs, 1H), 2.11–2.31 (m, 2H), 1.99–2.02 (m, 1H), 1.87–1.90 (m,
1H), 1.56–1.61 (m, 2H). 13C NMR (CDCl3): δ (ppm) = 156.6,
141.8, 138.2, 114.9, 110.1, 105.6, 68.6, 65.3, 41.0, 36.3, 29.9.
HRMS (ESI): m/z [M + Na]+ calcd for C11H16O3Na: 219.0997;
found: 217.0999.
(S)-1-((tert-butyldimethylsilyl)oxy)-1-(furan-2-yl)hept-6-en-3-
one (9): To an ice-cold solution of 8 (10.0 g, 31.8 mmol) in dry
THF (30 mL) was added 4-butenylmagnesiumbromide (64 mL of
1 M solution in THF, 64 mmol) [freshly prepared from 4-

4
Tetrahedron
ACCEPTED MANUSCRIPT
(1S,3R)-1,3-bis((tert-butyldimethylsilyl)oxy)-1-(furan-2-
Hz, 1H), 4.96 (d, J = 10.2 Hz, 1H), 4.36 (t, J = 6.0 Hz, 1H), 3.83
yl)hept-6-en (11): To a solution of the diol 6 (0.24 g, 1.22 mmol)
in CH2Cl2 (5 mL) was added TBDMSCl (0.9 g, 6.0 mmol),
imidazole (0.49 g, 7.2 mmol) and 4-(dimethylamino)pyridine
(0.73 g, 6.0 mmol). The reaction mixture was refluxed for 6 h,
and after the reaction was complete (TLC), it was poured into
water (10 mL). The aqueous layer was extracted with Et2O (10
mL × 3). The combined organic layer was washed with brine (10
mL), dried over Na2SO4 and the solvent was evaporated to obtain
a yellow oil which on purification by silica gel column
chromatography (PE−EtOAc, 99:1) to yield 11 (0.5 g, 96%) as a
(quin, J = 5.6 Hz, 1H), 2.07 (ABq, J = 14.4, 6.8 Hz, 2H), 1.76–
1.82 (m, 2H), 1.57–1.64 (m, 2H), 0.91 (s, 9H), 0.88 (s, 9H), 0.07
(s, 3H), 0.06 (s, 3H), 0.05 (s, 3H), 0.03 (s, 3H). 13C NMR
(CDCl3): δ (ppm) = 200.1, 169.8, 138.2, 137.2, 130.6, 114.7,
76.0, 68.8, 42.0, 36.7, 29.2, 25.8 (3 × C), 25.7 (3 × C), 18.0 (2 ×
C), –3.9, –4.2, –4.5, –4.8. HRMS (ESI): m/z [M + Na]+ calcd for
C23H44O5Si2Na: 479.2625; found: 479.2628.
(4S,5S,7R,E)-5,7-bis((tert-butyldimethylsilyl)oxy)-4-
hydroxyundeca-2,10-dienoic acid (14): CeCl3·7H2O (0.25g,
0.68 mmol) was added to a solution of 13 (0.2 g, 0.45 mmol) in
MeOH (5 mL) at rt and the reaction mixture was stirred for 0.5 h
at room temperature. The reaction mixture was cooled to –78 °C
and NaBH4 (0.03 g, 0.81 mmol) was added slowly portion wise.
The mixture was stirred for an additional 0.5 h at the same
temperature and then quenched by careful addition of water (2
mL). Most of the solvent was evaporated off and water (10 mL)
was added to the white solid thus obtained. The aqueous layer
was extracted with EtOAc (3 × 10 mL). The combined organic
layer was washed with brine (10 mL), dried over anhydrous
Na2SO4 and the solvent was evaporated off to give a colorless oil.
This crude oil was subjected to silica gel column chromatography
(PE–EtOAc, 4:1) to afford secoacid 14 (0.2 g, 99%) as a
25
colorless oil. [α]D −31.6 (c 1.0, CHCl3). IR (neat): νmax 2956,
2930, 1255, 1078, 836, 774 cm−1. H NMR (CDCl3): δ (ppm) =
1
7.36 (d, J = 1.6 Hz, 1H), 6.300 (dd, J = 3.2, 2.8 Hz, 1H), 6.16 (d,
J = 2.8 Hz, 1H), 5.81 (ddt, J = 16.8, 10.0, 6.6 Hz, 1H), 5.00 (d, J
= 16.8 Hz, 1H), 4.94 (d, J = 10.2 Hz, 1H), 4.80 (dd, J = 8.0, 5.2
Hz, 1H), 3.83 (t, J = 6.0 Hz, 1H), 2.04–2.11 (m, 3H), 1.86–1.87
(m, 1H), 1.50–1.55 (m, 2H), 0.89 (s, 9H), 0.85 (s, 9H), 0.07 (s,
3H), 0.04 (s, 3H), 0.02 (s, 3H), –0.20 (s, 3H). 13C NMR (CDCl3):
δ (ppm) = 156.9, 141.3, 138.7, 114.3, 110.0, 106.2, 68.8, 65.2,
44.4, 36.8, 29.2, 25.9 (3 × C), 25.8 (3 × C), 18.1 (2 × C), –4.1, –
4.3, –4.8, –5.0. HRMS (ESI): m/z [M + Na]+ calcd for
C23H44O3Si2Na: 447.2727; found: 447.2729.
(5S,7R,E)-5,7-bis((tert-butyldimethylsilyl)oxy)-4-oxoundeca-
2,10-dienal (12): To a stirred suspension of 11 (0.19 g, 0.45
mmol) and NaHCO3 (0.075 g, 0.89 mmol) in acetone/H2O (9:1, 4
mL) at –20 °C was added N-bromosuccinimide (0.095 g, 0.54
mmol) portion wise and was stirred at the same temperature for
0.5 h. Furan (0.16 mL, 2.23 mmol) was introduced into the
reaction mixture at –20 °C to quench the excess NBS and was
stirred for additional 0.5 h. Pyridine (0.04 mL) was added to the
mixture and was stirred at rt for additional 2 h. The reaction
mixture was then poured into pH-7.5 buffer (5 mL) and the
aqueous layer was washed with EtOAc (5 mL × 3). The
combined organic layer was washed with brine, dried over
Na2SO4 and the solvent was evaporated to obtain a yellow color
oil which on purification by silica gel column chromatography
(PE−EtOAc, 99:1) furnished 12 (0.15 g, 76%) as a colorless oil.
25
colorless oil. [α]D −10.0 (c 1.5, CHCl3). IR (neat): νmax 3420,
2957, 2928, 1715, 1260, 835 cm−1. H NMR (CDCl3): δ (ppm) =
1
7.07 (dd, J = 15.6, 3.6 Hz, 1H), 6.14 (dd, J = 15.6, 1.6 Hz, 1H),
5.79 (ddt, J = 17.2, 10.2, 6.4 Hz, 1H), 5.01 (d, J = 17.2 Hz, 1H),
4.96 (d, J = 10.2 Hz, 1H), 4.26 (s, 1H), 3.78–3.86 (m, 2H), 2.05–
2.10 (m, 2H), 1.86–1.93 (m, 1H), 1.55–1.60 (m, 3H), 0.89 (s,
9H), 0.87 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H), 0.04 (s, 3H), 0.03 (s,
3H). 13C NMR (CDCl3): δ (ppm) = 171.2, 151.5, 138.1, 120.9,
114.8, 73.1, 72.2, 69.9, 41.2, 36.9, 29.2, 25.8 (3 × C), 25.7 (3 ×
C), 18.0, 17.9, –4.0, –4.1, –4.3, –4.5. HRMS (ESI): m/z [M +
Na]+ calcd for C23H46O5Si2Na: 481.2781; found: 481.2784.
(4S,5S,7R,E)-5,7-bis((tert-butyldimethylsilyl)oxy)-4-
((triethylsilyl)oxy)undeca-2,10-dienoic acid (15): To a solution
of 14 (0.19 g, 0.414 mmol) and 2,6-lutidine (0.28 mL, 2.5 mmol)
in CH2Cl2 (5 mL) was added TESOTf (0.28 mL, 1.24 mmol) at –
50 °C. The mixture was allowed to warm up to room temperature
and was stirred at this temperature. After the reaction was
complete (TLC), it was quenched by addition of sat. aq NaHCO3
solution (5 mL). The reaction mixture is acidified with 1N HCl
till is slightly acidic, and was extracted with EtOAc (3 × 10 mL).
The combined organic layer was washed with brine (5 mL), dried
over Na2SO4 and the solvent was evaporated off to give a
colorless oil. Purification by silica gel column chromatography
(PE–EtOAc, 4:1) afforded acid 15 (0.23 g, 0.4 mmol, 97%) as a
25
[α]D −4.2 (c 0.5, CHCl3). IR (neat): νmax 2956, 2932, 1703,
1698, 1446, 1256, 1110, 837 cm−1. H NMR (CDCl3): δ (ppm) =
1
9.77 (d, J = 7.6 Hz, 1H), 7.28 (d, J = 16.2 Hz, 1H), 6.93 (dd, J =
16.1, 7.6 Hz, 1H), 5.79 (ddt, J = 16.6, 10.2, 6.4 Hz, 1H), 5.01 (d,
J = 17.2 Hz, 1H), 4.96 (d, J = 10.2 Hz, 1H), 4.39 (t, J = 6.8 Hz,
1H), 3.83 (quin, J = 6.0 Hz, 1H), 2.04–2.08 (m, 2H), 1.78–1.82
(m, 2H), 1.59–1.63 (m, 2H), 0.91 (s, 9H), 0.88 (s, 9H), 0.08 (s,
3H), 0.06 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H). 13C NMR (CDCl3): δ
(ppm) = 200.2, 192.9, 140.7, 138.3, 138.1, 114.8, 76.0, 68.8,
42.2, 36.6, 29.2, 25.8 (3 × C), 25.7 (3 × C), 18.2, 18.1, –3.9, –4.3,
–4.5, –4.6. HRMS (ESI): m/z [M + Na]+ calcd for C23H44O4Si2 +
CH3OH + Na: 495.2938; found: 495.2939.
(5S,7R,E)-5,7-bis((tert-butyldimethylsilyl)oxy)-4-oxoundeca-
2,10-dienoic acid (13): A solution of NaClO2 (0.075 g, 0.85
mmol) in H2O (1 mL) was added to a solution of 12 (0.25 g, 0.57
mmol) 2-methylbut-2-ene (0.26 mL, 2.26 mmol) in
tBuOH/phosphate buffer pH 3.5 (2:1, 3 mL) at 10 °C. After
stirring at rt for 1 h, the reaction mixture was diluted with H2O (5
mL) and was acidified with 1 N aq. HCl solution (2 mL). The
aqueous layer was extracted with EtOAc (3 × 5 mL) and the
combined organic layer was washed with brine (10 mL) and
dried over Na2SO4. The solvent was evaporated off to afford a
pale yellow oil, which on purification by silica gel column
chromatography (PE–EtOAc, 9:1), gave acid 13 (0.24 g, 0.52
1
colorless oil. The H NMR spectrum of the compound showed a
diastereomeric mixture of 86:14. [α]D25 −31.5 (c 1.35, CHCl3). IR
(neat): νmax 3493, 2956, 2884, 1703, 1255, 835, 774 cm−1. H
1
NMR (CDCl3): δ (ppm) = 7.24 (dd, J = 15.6, 3.2 Hz, 1Hmaj), 7.06
(dd, J = 15.6, 5.6 Hz, 0.16Hmin), 6.08 (dd, J = 15.6, 1.6 Hz,
1Hmaj), 5.98 (d, J = 15.6 Hz, 0.16Hmin), 5.79 (ddt, J = 17.2, 13.2,
6.4 Hz, 1.16Hmaj+min), 4.99 (d, J = 17.2 Hz, 1.16Hmaj+min), 4.36 (s,
1Hmaj), 4.14 (d, J = 6.8 Hz, 0.16Hmin), 3.80–3.87 (m,
2.32Hmaj+min), 1.99–2.11 (m, 2.32Hmaj+min), 1.68–1.73 (m,
1.16Hmaj+min), 1.48–1.58 (m, 1.16Hmaj+min), 1.26–1.30 (m,
2.32Hmaj+min), 0.96 (t, J = 7.9 Hz, 10.4Hmaj+min), 0.90 (s,
10.4Hmaj+min), 0.87 (s, 10.4Hmaj+min), 0.61 (q, J = 7.8 Hz,
7Hmaj+min), 0.04–0.10 (m, 13.9Hmaj+min). 13C NMR (CDCl3): δ
(ppm) = 171.5, 150.6, 138.7, 120.6, 114.2, 74.5, 72.6, 69.4, 40.1,
37.2, 26.0(3 × C), 25.8 (3 × C), 22.6, 18.1, 17.9, 6.8 (3 × C), 4.8
(3 × C), –3.9, –4.0, –4.1, –4.4 (Minor isomer was not observed in
13C NMR spectrum). HRMS (ESI): m/z [M + Na]+ calcd for
C29H60O5Si3Na: 595.3646; found: 595.3647.
25
mmol, 93%) as a pale yellow oil. [α]D −5.5 (c 1.0, CHCl3). IR
1
(neat): νmax 3419, 2955, 2931, 1709, 1257, 837 cm−1. H NMR
(CDCl3): δ (ppm) = 7.51 (d, J = 15.6 Hz, 1H), 6.80 (d, J = 15.6
Hz, 1H), 5.79 (ddt, J = 17.0, 10.2, 6.4 Hz, 1H), 5.01 (d, J = 17.2

5
Preparation of (R)-non-1-en-4-ol (5): Ti(OiPr)4 (0.45 mL) was
Ethyl chloroformate (26 µL, 0.28 mmol) was added to an ice-
ACCEPTED MANUSCRIPT
added to a stirring solution of TiCl4 (0.05 mL) in CH2Cl2 (10 mL)
at 0 °C. The solution was allowed to warm up to room
temperature and was stirred at rt for 1 h. Ag2O (0.23 g, 1.0 mmol)
was added to the reaction mixture and the stirring was continued
for further 5 h under exclusion of light. The mixture was then
diluted with CH2Cl2 (20 mL) and (S)-BINOL (0.57 g, 1.99 mmol)
was added and the stirring was continued for additional 2 h. The
cold solution of 16 (0.05 g, 0.071 mmol) in MeOH (4 mL) and
was stirred at room temperature. After ~20 min, TLC indicated
the completion of the reaction. Solid NaHCO3 (20 mg) was
introduced into the reaction mixture, stirred for 5 mins, and was
filtered through a short pad of celite. The solvent was evaporated
off and the crude residue thus obtained was purified by silica gel
column chromatography (PE–EtOAc, 97:3) to afford the alcohol
25
catalyst thus prepared was cooled to −10 °C, hexanal (1.0 g, 9.98
mmol) and allyltributyltin (3.4 mL, 10.98 mmol) were added
sequentially. The temperature was raised to 0 °C and the reaction
was stirred for 24 h at the same temperature. After the reaction
was complete (TLC), sat. NaHCO3 solution (100 mL) was added
to the reaction mixture and was stirred vigorously. The aqueous
layer was extracted with Et2O (3 × 30 mL) and the combined
organic layer was washed with brine, dried over Na2SO4 and the
solvent was evaporated in vacuo to obtain orange red oil which
was purified by silica gel column chromatography (PE–EtOAc,
99:1) to afford homoallylic alcohol 5 (1.35 g, 9.14 mmol, 92%)
as a colorless oil. The enantiomeric purity of the alcohol 5 was
determined by HPLC analysis of its 4-nitrobenzoate ester as
17 (0.016 g, 0.038 mmol, 54%) as a colorless oil. [α]D −8.0 (c
0.35, CHCl3). IR (neat): νmax 3492, 2932, 1718, 1462, 1255, 774
cm−1. H NMR (CDCl3): δ (ppm) = 6.93 (dd, J = 15.6, 3.6 Hz,
1
1H), 6.11 (d, J = 1.6 Hz, 1H), 6.07 (d, J = 1.6 Hz, 1H), 5.70–5.84
(m, 2H), 4.95–5.08 (m, 5H), 4.22 (t, J = 2.4 Hz, 1H), 3.78–3.82
(m, 2H), 2.57 (d, J = 8.8 Hz, 1H), 2.33 (t, J = 6.4 Hz, 2H), 2.05–
2.11(m, 2H), 1.88–1.95 (m, 1H), 1.58 (bs, 2H), 1.26 (bs, 8H),
0.89 (s, 12H), 0.86 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H), 0.08 (s,
3H), 0.07 (s, 3H). 13C NMR (CDCl3): δ (ppm) = 165.9, 148.7,
138.2, 133.7, 121.8, 117.5, 114.7, 73.2, 73.0, 72.2, 69.7, 41.3,
38.6, 36.8, 33.5, 31.6, 29.2, 25.8 (3 × C), 25.7 (3 × C), 24.9, 22.5,
18.0, 17.9, 13.9, –4.0, –4.1, –4.2, –4.5. HRMS (ESI): m/z [M +
Na]+ calcd for C32H62O5Si2Na: 605.4033; found: 605.4038.
25
25
described by Feng et al. [α]D +9.0 (c 1.0, CHCl3), Lit.8 [α]D
(4R,5S,7R,E)-5,7-bis((tert-butyldimethylsilyl)oxy)-1-((R)-non-
+9.0 (c 1.0, CHCl3). IR (neat): νmax 3493, 2956, 1475, 1150 cm−1.
1H NMR (CDCl3): δ (ppm) = 5.83 (ddd, J = 17.2, 9.6, 7.6 Hz,
1H), 5.13 (d, J = 17.2 Hz, 1H), 5.13 (d, J = 11.6 Hz, 1H), 3.64
(dt, J = 7.2, 4.4 Hz, 1H), 2.27–2.33 (m, 1H), 2.10–2.17 (m, 1H),
1.70 (bs, 1H), 1.45 (bs, 1H), 1.30 (bs, 5H), 0.89 (t, J = 6.8 Hz,
3H). 13C NMR (CDCl3): δ (ppm) = 135.2, 118.3, 70.9, 42.2, 36.7,
31.8, 25.6, 22.8, 14.3. HRMS (ESI): m/z [M + Na]+ calcd for
C9H18ONa: 165.1255; found: 165.1253.
1-en-4-yloxy)-1-oxoundeca-2,10-dien-4-yl
4-nitrobenzoate
(18): Diisopropylazodicarboxylate (72 µL, 0.37 mmol) was
added to a solution of alcohol 17 (0.072 g, 0.123 mmol), PPh3
(0.097 g, 0.37 mmol) and 4-nitrobenzoic acid (0.062 g, 0.37
mmol) in toluene (0.6 mL) at 0 °C and was allowed to stir at
room temperature for 2 h. The solvent was evaporated off and the
crude residue thus obtained was purified by silica gel column
chromatography (PE–EtOAc, 99:1) afforded the ester 18 (0.08 g,
25
(4S,5S,7R,E)-(R)-non-1-en-4-yl
5,7-bis((tert-
0.11 mmol, 89%) as a pale yellow oil. [α]D +20.1(c 0.75,
CHCl3). IR (neat): νmax 2955, 2930, 1728, 1266, 1116, 837 cm−1.
1H NMR (CDCl3): δ (ppm) = 8.32 (d, J = 8.8 Hz, 2H), 8.23 (d, J
= 8.8 Hz, 2H), 6.98 (dd, J = 15.6, 5.6 Hz, 1H), 6.03 (d, J = 15.6
Hz, 1H), 5.70–5.86 (m, 2H), 5.66 (t, J = 1.6 Hz, 1H), 4.96–5.08
(m, 5H), 4.13 (bs, 1H), 3.84 (t, J = 5.6 Hz, 1H), 2.29–2.37 (m,
2H), 2.10 (ABq, J = 14.4, 6.8 Hz, 2H), 1.70 (t, J = 6.0 Hz, 2H),
1.53–1.64 (m, 2H), 1.26 (bs, 8H), 0.88 (s, 12H), 0.85 (s, 9H),
0.13 (s, 3H), 0.07 (s, 3H), 0.05 (s, 3H), –0.01 (s, 3H). 13C NMR
(CDCl3): δ (ppm) = 165.1, 163.7, 150.6 (2 × C), 140.8, 138.2,
135.2 (2 × C), 133.5, 130.8, 124.4, 123.6, 117.7, 114.7, 77.7,
73.9, 71.2, 69.3, 41.6, 38.5, 36.9, 33.5, 31.6, 29.2, 25.8 (3 × C),
25.7 (3 × C), 24.9, 22.5, 18.0, 17.9, 13.9, –3.6, –4.0, –4.2, –4.3.
HRMS (ESI): m/z [M + Na]+ calcd for C39H65NO8Si2Na:
754.4146; found: 754.4146.
butyldimethylsilyl)oxy)-4-((triethylsilyl)oxy)undeca-2,10-
dienoate (16): To a solution of 15 (0.475 g, 0.83 mmol) in
benzene (5 mL) was added NEt3 (0.58 mL) and 2,4,6-
trichlorobenzoyl chloride (0.15 mL, 0.96 mmol) at 0 ° C and was
stirred at rt for 0.5 h. After the formation of mixed anhydride
(TLC), the solution was cooled to 0 °C and a solution of 4-
(dimethylamino)pyridine (0.5 g, 4.1 mmol) and alcohol 5 (0.14 g,
1.0 mmol) was introduced dropwise in to the reaction mixture.
The reaction mixture was warmed to room temperature and was
stirred for additional 5 h. After the completion of the reaction
(TLC), it was quenched by addition of sat. NaHCO3 solution (10
mL) and the aqueous layer was washed with EtOAc (3 × 10 mL).
The combined organic layer was washed with brine (5 mL), dried
over Na2SO4 and the solvent was evaporated off to give a pale
yellow oil. Purification of the residue by silica gel column
chromatography (PE–EtOAc, 99:1) afforded ester 16 (0.47 g,
0.674 mmol, 83%) as a colorless oil. [α]D25 −21.0 (c 0.8, CHCl3).
IR (neat): νmax 2957, 2932, 1741, 1571, 1273, 1119, 917, 857
(4R,5S,7R,E)-(R)-non-1-en-4-yl
4,5,7-tris((tert-
butyldimethylsilyl)oxy)undeca-2,10-dienoate (3): To a stirred
solution of 18 (0.08 g, 0.11 mmol) in MeOH (3 mL), was added
K2CO3 (0.03 g, 0.22 mmol) and stirred at room temperature for
0.5 h. After completion of the reaction (TLC), it was filtered
through a short pad of celite and the solvent was evaporated off.
The crude residue thus obtained was purified by silica gel column
chromatography (PE–EtOAc, 99:1) to afford a 1:1 inseparable
mixture of the inverted alcohol and methyl 4-nitrobenzoate as
judged by the 1H NMR spectrum.
To a stirred solution of the mixture obtained above (0.054 g) was
added 2,6-lutidine (32 µL, 0.28 mmol) and TBSOTf (26 µL, 0.14
mmol) at –50 °C. The mixture was allowed to warm to room
temperature and was stirred at room temperature for 1 h. The
reaction mixture was poured into sat. aqueous NaHCO3 solution
(5 mL) and the aqueous layer was extracted with Et2O (3 × 5
mL). The combined organic layer was washed with brine (5 mL),
dried over Na2SO4. The residue obtained after evaporation of
solvent was purified by silica gel column chromatography (PE–
EtOAc, 99:1) to afford the ester 3 (0.047 g, 61% for two steps) as
1
cm−1. H NMR (CDCl3): δ (ppm) = 7.10 (dd, J = 15.6, 3.2 Hz,
1Hmaj), 6.91(dd, J = 15.6, 6.0 Hz, 0.16Hmin), 6.05 (d, J = 1.6 Hz,
1Hmaj), 6.01 (d, J = 1.6 Hz, 0.16Hmin), 5.70–5.94 (m,
2.32Hmaj+min), 4.91–5.08 (m, 5.8Hmaj+min), 4.33 (s, 1Hmaj), 4.08 (d,
J = 4.8 Hz, 0.16Hmin), 3.75–3.85 (m, 2.32Hmaj+min), 2.31–3.36 (m,
2.32H maj+min), 1.67–1.73 (m, 1.16Hmaj+min), 1.45–1.60 (m,
3.48Hmaj+min), 1.28 (s, 9.28Hmaj+min), 0.63–0.98 (m, 34.8Hmaj+min),
0.57–0.62 (m, 6.9Hmaj+min), 0.03–0.09 (m, 13.9Hmaj+min). 13C NMR
(CDCl3): δ (ppm) = 166.1, 147.5, 138.8, 133.8, 121.6, 117.5,
114.2, 74.5, 73.2, 72.6, 69.4, 40.1, 38.6, 37.1, 33.6, 31.6, 29.4,
26.0 (2 × C), 25.9 (2 × C), 25.8 (2 × C), 24.9, 22.5, 18.0, 17.9,
13.9, 6.8 (3 × C), 4.8 (3 × C), –3.9 (2 × C), –4.0 (2 × C) (Minor
isomer was not observed in 13C NMR spectrum). HRMS (ESI):
m/z [M + Na]+ calcd for C38H76O5Si3Na: 719.4898; found:
719.4899.
(4S,5S,7R,E)-(R)-non-1-en-4-yl
5,7-bis((tert-
butyldimethylsilyl)oxy)-4-hydroxyundeca-2,10-dienoate (17):

6
Tetrahedron
ACCEPTED MANUSCRIPT
25
References and notes
a colorless oil. [α]D −2.9 (c 1.0, CHCl ). IR (neat): ν 2956,
3
max
2931, 1716, 1256 cm−1. 1H NMR (CDCl3): δ (ppm) = 6.90 (dd, J
= 15.6, 5.6 Hz, 1H), 5.93 (d, J = 15.6 Hz, 1H), 5.70–5.84 (m,
2H), 4.90–5.08 (m, 5H), 4.14 (t, J = 1.6 Hz, 1H), 3.84–3.87 (m,
1H), 3.78–3.81 (m, 1H), 2.33 (bs, 2H), 2.03–2.08 (m, 2H), 1.54–
1.58 (m, 4H), 1.27 (bs, 8H), 0.86–0.92 (m, 30H), 0.09 (s, 3H),
0.08 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H), 0.05 (s, 3H), 0.03 (s, 3H).
13C NMR (CDCl3): δ (ppm) = 165.9, 147.4, 138.5, 133.7, 122.3,
117.5, 114.5, 77.0, 74.1, 73.3, 69.4, 42.1, 38.6, 37.3, 33.5, 31.6,
29.2, 26.0 (3 × C), 25.9 (2 × C), 25.8 (2 × C), 25.7 (2 × C), 24.9,
22.5, 18.3, 18.2, 18.0, 13.9, –3.5, –3.6, –3.9, –4.0, –4.4, –4.6.
HRMS (ESI): m/z [M + Na]+ calcd for C38H76O5Si3Na: 719.4898;
found: 719.4896.
part of the work was presented by S.K.S at the J-NOST meeting
held at the Indian Institute of Science Education research (IISER),
Mohali, India, December 15-18, 2011.
1. Yang, S, W.; Chan, T. M.; Terracciano, J.; Loebenberg, D.; Patel,
M.; Chu, M. J. Antibiot. 2005, 58, 535.
2. Moretti, J. D.; Wang, X.; Curran, D. P. J. Am. Chem. Soc. 2012,
134, 7963.
3. a) Pawar, A. B.; Prasad, K. R. Chem. Eur. J. 2012, 18, 15202 . b)
Prasad, K. R.; Revu, O. Synthesis 2012, 44, 2243. c) Prasad, K.
R.; Gutala, P. Tetrahedron 2011, 67, 4514. d) Prasad, K. R.;
Gandi, V. R. Tetrahedron: Asymmetry 2011, 22, 499. e) Prasad, K.
R.; Penchalaih, K. Tetrahedron, 2011, 67, 4268. f) Prasad, K. R.;
Gandi, V.R.; Nidhiry, J. E.; Bhat, K. S.; Synthesis. 2010, 15, 2521.
4. For seminal work of Kobayashi’s group on oxidative ring opening
of furan to the corresponding but-2-ene-1,4-dione see: a)
Kobayashi, Y.; Watatani, K.; Kikori, Y.; Mizojiri, R. Tetrahedron
Lett. 1996, 37, 6125. b) Kobayashi, Y.; Nakano, M.; Kumar, G.
B.; Kishihara, K. J. Org. Chem. 1998, 63, 7505. c) Kobayashi, Y.;
Matsuumi, M. J. Org. Chem. 2000, 65, 7221. d) Kobayashi, Y.;
Kumar, G. B.; Kurachi, T.; Acharya, H. P.; Yamazaki, T.;
Kitazume, T. J. Org. Chem. 2001, 66, 2011. For our work on the
oxidative opening of furan in natural product synthesis see: e)
Prasad, K. R.; Pawar, A. B. Org. Lett. 2011, 13, 4252. f) Sunnam,
S. K.; Prasad, K. R. Synthesis 2013, 45, 1991.
(3E,5R,6S,8R,14R)-5,6,8-tris((tert-butyldimethylsilyl)oxy)-14-
pentyloxacyclotetradeca-3,11-dien-2-one (2): To
a stirred
solution of 3 (0.016 g, 0.023 mmol) in CH2Cl2 (7.5 mL) was
added Grubbs’ second generation catalyst (2 mg, 0.0023 mmol)
and was heated to reflux for 3 h. After the reaction was complete
(TLC), the solvent was evaporated off and the crude residue thus
obtained was purified by silica gel column chromatography (PE–
EtOAc, 99:1) to afford the macrolactone 2 (0.015 g, 97%) as a
25
colorless oil. [α]D +36.2 (c 0.8, CHCl3). IR (neat): νmax 2958,
2942, 1715, 1262, 832 cm−1. H NMR (CDCl3): δ (ppm) = 6.79
1
5. Prasad, K. R.; Revu, O. J. Org. Chem. in press
6. Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc.
1988, 110, 3560-3578.
(dd, J = 15.6, 4.4 Hz, 1H), 5.96 (dd, J = 15.6, 1.6 Hz, 1H), 5.30–
5.34 (m, 2H), 4.98 (tdd, J = 8.0, 4.8, 2.8 Hz, 1H), 4.46 (d, J = 2.4
Hz, 1H), 3.72–3.77 (m, 1H), 2.31–2.38 (m, 2H), 2.21–2.25 (m,
1H), 1.95–2.08 (m, 1H), 1.87–1.91(m, 1H), 1.63–1.72 (m, 1H),
1.50–1.56 (m, 1H), 1.25–1.55 (m, 9H), 0.86–0.94 (m, 30H), 0.13
(s, 3H), 0.12 (s, 3H), 0.11 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H), 0.06
(s, 3H). 13C NMR (CDCl3): δ (ppm) = 166.8, 148.4, 133.3, 126.1,
120.8, 77.7, 73.2, 73.0, 65.5, 42.9, 38.8, 35.3, 34.2, 31.6, 27.4,
26.0 (3 × C), 25.9 (3 × C), 25.8 (3 × C), 25.3, 22.5, 18.4, 18.2,
18.1, 13.9, –3.3, –4.4, –4.6, –4.7, –4.8, –5.0. HRMS (ESI): m/z
[M + Na]+ calcd for C36H72O5Si3Na: 691.4585; found: 691.4588.
7.
Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226. The
diastereomeric ratio of the product alcohol is inconclusive from
NMR at this stage. However, a diastereomeric ratio of 84:16 was
observed in 1H NMR spectrum when 14 was converted to 15
which was also a non-separable mixture. This diastereomeric
mixture was used as such in the next step. Separation of the major
diasteromer 17 was accomplished in the TES deprotection of 16 in
54% yield.
8. a) Das, B.; Laxminarayana, K.; Krishnaiah, M.; Kumar, D. N.
Helv. Chic. Acta 2009, 92, 1840. b) Feng, J. P.; Shi, Z, F.; Zhang,
J, T.; Qi, X, L.; Cao, X. P. J. Org. Chem. 2008, 73, 6873.
1
9. Although, H NMR spectrum of 2 exhibited a single isomer, we
were unable to ascertain the configuration at the newly formed
C10-C11 olefin in the metathesis reaction. However E/Z ratio of
the C10-C11 olefin is of no consequence as hydrogenation of the
olefin is the next step in the synthetic sequence.
Acknowledgments
10. Moretti, J. D. PhD thesis, University of Pittsburg, 2010. Wang, X.
PhD thesis, University of Pittsburg, 2009.
We thank the Department of Science and Technology (DST),
New Delhi for funding. K. R. P is a Swarnajayanthi fellow of
DST, New Delhi. K. R. P. thanks Prof. Dennis Curran of the
University of Pittsburg for providing a copy of the theses of Drs.
J. D. Moretti and X. Wang.
Supplementary Material
1
Copies of H NMR and 13C NMR spectra for all the new
compounds synthesized are provided.

ACCEPTED MANUSCRIPT
1H NMR spectrum of compound 9
13C NMR spectrum of compound 9
1

ACCEPTED MANUSCRIPT
1H NMR spectrum of compound 10
13C NMR spectrum of compound 10
2

ACCEPTED MANUSCRIPT
O
OH OH
1H NMR spectrum of compound 6
O
OH OH
13C NMR spectrum of compound 6
3

ACCEPTED MANUSCRIPT
1H NMR spectrum of compound 11
13C NMR spectrum of compound 11
4

ACCEPTED MANUSCRIPT
O
H
O
TBSO
OTBS
1H NMR spectrum of compound 12
O
H
O
TBSO
OTBS
13C NMR spectrum of compound 12
5

ACCEPTED MANUSCRIPT
O
HO
O
TBSO
OTBS
1H NMR spectrum of compound 13
O
HO
O
TBSO
OTBS
13C NMR spectrum of compound 13
6

ACCEPTED MANUSCRIPT
OH
HO
O
TBSO
OTBS
1H NMR spectrum of compound 14
OH
HO
O
TBSO
OTBS
13C NMR spectrum of compound 14
7

ACCEPTED MANUSCRIPT
OTES
HO
O
TBSO
OTBS
1H NMR spectrum of compound 15
OTES
HO
O
TBSO
OTBS
13C NMR spectrum of compound 15
8

ACCEPTED MANUSCRIPT
1H NMR spectrum of compound 5
13C NMR spectrum of compound 5
9

ACCEPTED MANUSCRIPT
OTBS
OTES
OTBS
O
O
1H NMR spectrum of compound 16
OTBS
OTES
OTBS
O
O
13C NMR spectrum of compound 16
10

ACCEPTED MANUSCRIPT
OTBS
OH
OTBS
O
O
1H NMR spectrum of compound 17
OTBS
OH
OTBS
O
O
13C NMR spectrum of compound 17
11

ACCEPTED MANUSCRIPT
OTBS
OPNB
OTBS
O
O
1H NMR spectrum of compound 18
OTBS
OPNB
OTBS
O
O
13C NMR spectrum of compound 18
12

ACCEPTED MANUSCRIPT
OTBS
OH
OTBS
O
O
1H NMR spectrum of compound obtained by reaction of 18 with K2CO3/MeOH
OTBS
OH
OTBS
O
O
13C NMR spectrum of compound obtained by reaction of 18 with K2CO3/MeOH
13

ACCEPTED MANUSCRIPT
OTBS
OTBS
OTBS
O
O
1H NMR spectrum of compound 3
OTBS
OTBS
OTBS
O
O
13C NMR spectrum of compound 3
14

ACCEPTED MANUSCRIPT
OTBS
OTBS
OTBS
O
O
1H NMR spectrum of compound 2
OTBS
OTBS
OTBS
O
O
13C NMR spectrum of compound 2
15