Glycal approach to the synthesis of macrolide (-)-A26771B

Article abstract of DOI:10.1039/c4ra17084a

A convergent total synthesis of a 16-membered macrolactone natural product (-)-A26771B 1 starting from 3,4,6-tri-O-acetyl-d-glucal 7 is reported. The Ferrier rearrangement of acetylated glucal 7, cross metathesis between chiral fragments 3 and 4, Yamaguchi macrolactonization and selective oxidation of the allylic alcohol are the key features of the synthesis.

Full text of DOI:10.1039/c4ra17084a

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DOI: 10.1039/C4RA17084A
‘Glycal Approach to the Syntheis of Macrolide (-)-A26771B’
Puli Saidhareddy and Arun K. Shaw*
A convergent total synthesis of a 16-membered macrolactone natural product (-)-A26771B 1
starting from 3,4,6-tri-o-acetyl-D-glucal 7 is reported. The Ferrier rearrangement of acetylated
glucal 7, HWE olefination to get the fragment 3, cross metathesis between chiral fragments 3
and 4, Yamaguchi macrolactonization and selective oxidation of the allylic alcohol are the key
features of the synthesis.

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ARTICLE TYPE
‘Glycal Approach to the Syntheis of Macrolide (-)-A26771B’
Puli Saidhareddy and Arun K. Shaw*
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
5
Abstract: A convergent total synthesis of a 16-membered macrolactone natural product (-)-
A26771B 1 starting from 3,4,6-tri-o-acetyl-D-glucal 7 is reported. The Ferrier rearrangement of
acetylated glucal 7, cross metathesis between chiral frgments 3 and 4, yamaguchi
macrolactonization and selective oxidation of the allylic alcohol are the key features of the
synthesis.
1
0
Introduction
Results and Discussion:
The retrosynthetic analysis of the title macrolide 1
Macrolide antibiotics are safe and effective class
of drugs for the treatment of bacterial infections. Most of
1
is shown in the Scheme 1. It could be synthesized by
esterification of the chiral alcohol 2 with succinic
anhydride. This macrolactone could be obtained from
fragments 3 and 4, as the precursors of cross metathesis
them target the bacterial ribosome by binding reversibly
the 50S subunit in the peptidyl transferase center which
ultimately blocks protein synthesis. The macrolide (-)-
4
5
2
1
2
2
3
5
0
5
0
A26771B was first isolated from the fungus Pencillium
3
(CM) followed by Yamaguchi macrolactonization of the
turbatum by K. H. Michel et al. in 1977 and later its
resulting CM product. The intermediate 3 could be
absolute configuration was established by Kuniaki Tatsuta
4
50 prepared by Wittig olefination of the aldehyde derived
from Swern oxidation of primary alcohol 5 which in turn
could be prepared from peracetylated-D-glucal 7 via the 2,
and his group in 1980. Structurally it possesses γ-oxo-δ-
acyloxy-α,β-unsaturated carboxyl functionality and two
asymmetric centers 5S and 15R. It showed moderate
activity against Gram-positive bacteria, mycoplasma and
3
-dideoxy glucopyranose 6. The synthesis of the fragment
5
4 could be possible by treating (R)-propylene oxide 9 with
the bromide 8. Its preparation could be anticipated from
commercially available 1,5-pentanediol 10.
fungi. Owing to its interesting structural feature as well as
5
5
biological activity, its total synthesis became the
challenging task to synthetic community. More than ten
different synthetic strategies for the title natural product
reported so far include stereoselective, asymmetric, chiron
approach, etc.6 Our ongoing interest in chiron based
chemistry towards the synthesis of biological active natural
7
8
products and recently reported macrolide encouraged us
to design the synthesis of antibacterial macrolide (-)-
A26771B (Figure 1).
Figure 1: Structure of (-)-A26771B (1).
Scheme 1: Retrosynthetic analysis of (-)-A26771B
3
4
5
0
___________________________________
Medicinal and Process Chemistry Division,
CSIR-Central Drug Research Institute (CDRI),
Lucknow-226031.Tel: +91-9415403775;
E-mail: akshaw55@yahoo.com
60
As per the retrosynthesis delineated above, our
approach to the total synthesis of 1 was commenced with
Ferrier rearrangement of the commercially available
peracetylated-D-glucal 7 with benzyl alcohol in the
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9
presence of catalytic amount of InCl
3
to afford 2,3-
chlorochromate (PCC) oxidation of 15 and afterward one
unsaturated pyranoside 11 in 95% yield. Hydrogenation of
carbon Wittig olefination of the resulting aldehyde
the double bond and deprotection of the O-benzyl group at 50 produced 6-Bromo-1-hexene 8 in 81% yield. Its in situ
anomeric position by H
2
in the presence of Pd/C produced
prepared Grignard reagent was treated with (R)-propylene
oxide 9 in the presence of a catalytic amount of CuCN to
deliver the desired (R)-non-8-en-2-ol 4 in 89% yield.
5
0
5
0
5
the hemiacetal 6 in 98% yield. Its deacetylation with
sodium methoxide in MeOH followed by regioselective
protection of the resulting primary OH group with t-
butylchlorodiphenyl silane (TBDPSCl) and imidazole
furnished compound 12 in 92% yield. Its Wittig olefination
with methyltriphenylphosphonium bromide in the presence
of t-BuOK produced the unsaturated alcohol 13 in 60%
yield. However, its yield was increased to 81% when n-
BuLi was used in place of t-BuOK. Acetonide protection
of the two syn-hydroxyl groups with 2,2-dimethoxy
propane (2,2-DMP) in the presence of p-toluenesulfonic
acid (PTSA) and deprotection of silyl protecting group
with tetrabutylammoniumfluoride (TBAF) in THF
afforded primary alcohol 14 in 80% yield over two steps.
The fragment 3, required for ring closing metathesis, was
obtained from alcohol 14 by two step reaction sequences
1
1
2
2
5
5
Scheme 3: Synthesis of Fragment 4
Reagents and conditions: (a) 47% HBr, toluene, 120 ºC, 12 hrs,
8
5%; (b) (i) PCC, molecular sieves 4 Å, CH
(Ph) PCH Br, t-BuOK, dry THF, 0 ºC to RT, 2 h, 81%; (c) Mg,
dry THF, C Br , 5 h, reflux, then (R)-Propyleneoxide, CuCN,
2
Cl2, 0 ºC, 4 h; (ii)
6
0
3
3
H
2 4
2
dry THF, -15 ºC, 4 h, 89%.
Now we embarked upon synthesis of the title molecule by
utilizing the above two fragments (3 and 4). Saponification
of the unsaturated methyl ester 3 with LiOH in acetonitrile
furnished the acid 16. Its Yamaguchi esterfication with the
chiral alcohol 4 afforded the compound 17 in 85% yield.11
Its acetonide deprotection with PTSA followed by
oxidation of the resulting allylic OH to unsaturated
diketone 18 with 2,2,6,6-tetramethyl-1-piperidinyloxy
6
7
7
5
0
5
(scheme 2). First the alcohol 14 was converted into
aldehyde by Swern oxidation. It was used directly without
further purification in HWE (Horner-Wadsworth-Emmons)
olefination with trimethyl phosphanoacetate in the
presence of NaH to obtain (E)-α,β-unsaturated methyl ester
3
in 85% yield over two steps.
(
TEMPO) was more successful compared to its oxidation
with MnO both in terms of yield and reaction time.
Having 18 in our hand, its ring closing metathesis (RCM)
2
st
nd
either in the presence of Grubb’s 1 or 2 generation
catalyst in toluene or DCM was futile (scheme 4).12
Scheme 2: Synthesis of fragment 3
3
0
3 2 2
Reagents and conditions: (a) BnOH, InCl , CH Cl , RT, 10 Min,
9
5%; (b) H2, Pd/C, EtOAc, RT, 2-3 hrs, 98%; (c) NaOMe,
MeOH, RT, 30 Min, then TBDPSCl, Imidazole, DMF, 0 ºC - RT,
4 hrs, 92%; (d) (Ph) PCH Br, n-BuLi, dry THF, -78 ºC to RT, 2
h, 81%; (e) (i) 2,2-Dimethoxypropane, PTSA, Acetone, 30 min,
RT (ii) TBAF, THF, 0 ºC - RT, 3 h, 80%; (f) (i) (COCl) , DMSO,
Et N, dry CH Cl , -78 ºC, 2 h; (ii) (MeO) P(O)CH CO Me, NaH,
dry Toluene, reflux, 3 h, 85%.
2
3
3
Scheme 4: Trials to synthesis of (-)-A26771B
8
0
(a) LiOH, H
trichlorobenzoyl Chloride, Et
i) PTSA, MeOH, RT, 3-4 h; (ii) TEMPO, PTSA, dry DCM, 0 ºC
2
O, Acetonitrile, 24 h, RT, 90%; (b) 2,4,6-
3
5
2
3
N, DMAP, THF, 4, RT, 85%; (c)
3
2
2
2
2
2
(
nd
to RT, 6 h, 72%; (d) Grubb's 2 generation catalyst.
The preparation of C-9 fragment 4, which
contains terminal alkene for the cross metathesis and C2-
OH with the required (R)-configuration for esterification,
was carried out from commercially available 1,5-
pentanediol 10 (Scheme 3). The modified literature10
procedure was followed to obtain the monobromide
derivative 15. According to which, the diol 10 was heated
with 47% HBr solution in toluene at 120 ºC to obtain 5-
bromopentan-1-ol 15 in 85% yield. The pyridinium
8
5
Thus, we changed our strategy as depicted in scheme 5.
Accordingly, first the fragments 3 and 4 were tied up by
cross metathesis in the presence of Grubb’s first generation
catalyst in DCM under reflux conditions to obtain the
required α,β-unsaturated diene ester 19 in 75 % yield
(cis:trans ratio 1:3).13 The saponification of 19 with LiOH
4
0
9
0
4
5
in acetonitrile/H O to form the corresponding acid
2
followed by its Yamaguchi’s esterification with 2,4,6-
2
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trichlorobenzoylchloride, Et
pyridine in toluene successfully furnished the 16
membered cyclized unsaturated ester 20 in 74% yield. 45 2N H
Further, the regioselective reduction of the isolated double
bond with Rosenmund reducing reagent (H /Pd-BaSO
3
N and N, N-Dimethylamino
with a 0.25 mm thickness were used. Visualization of the
spots was done by spraying the plate with CeSO (1% in
SO ) and subsequent charring over hot plate. Silica
gel (60–120 mesh) and silica gel (230-400 mesh) were
used for Column chromatography. All the intermediates
were characterized by NMR, IR, ESI-HRMS and optical
4
2
4
5
2
4
)
afforded 21 in 98% yield. Now, its acetonide functional
group was subjected to acid hydrolysis with PTSA in
rotation. NMR experiments were recorded in CDCl at 25
3
MeOH and subsequent selective oxidation of the resulting 50 ºC. Chemical shift values are given on δ scale with
allylic alcohol functionality by TEMPO in PTSA gave the
compound 2 in 86% yield over two steps.
reference to TMS at 0.00 ppm for proton and carbon. The
reference CDCl
appeared at 77.40 ppm for 13C NMR.
NMR spectra were recorded on Bruker Avance 300 MHz
1
0
3
1
13
spectrometer at 300 MHz ( H) and 75 MHz ( C), 400
1
13
5
6
6
7
5
0
5
0
MHz spectrometer at 400 MHz ( H) and 100 MHz ( C).
Optical rotations were determined on an HORIBA, high
sensitive polarimeter, SEPA-300 using a 1 dm cell at 17
ºC-32 ºC in chloroform and methanol; concentrations
mentioned are in g/100 mL. For IR spectra were recorded
on Perkin–Elmer 881 and FTIR-8210 PC Shimadzu
Spectrophotometers. Mass spectra were recorded on a
JEOL JMS-600H high resolution spectrometer using EI
mode at 70 eV. ESI-HRMS were recorded on a JEOL-
AccuTOF, JMS-T100LC spectrometer.
Scheme 5: Synthesis of target macrolide (-)-A26771B
st
(
(
a) Grubb's 1 gen. catalyst, 4, dry DCM, Reflux, 16 hrs, 75 %;
((2R,3S)-3-acetoxy-6-(benzyloxy)-3,6-dihydro-2H-
pyran-2-yl)methyl acetate (11): To a mixture of tri-O-
acetyl-D-glucal 7 (400 mg, 1.47 mmol) and benzylalcohol
b) LiOH,
H
2
O, Acetonitrile, RT, 24 hrs, then 2,4,6-
N, DMAP, THF, 6 hr, RT, 74%; (c)
, EtOAc, RT, 1 h, 98%; (d) (i) PTSA, MeOH, RT,
-4 h; (ii) TEMPO, PTSA, dry DCM 0 ºC to RT, 6 hrs, 86%; (e)
Succinicanhydride, DMAP, CH Cl , RT, 6 hr, 72%.
1
5
trichlorobenzoyl Chloride, Et
/Pd-BaSO
3
H
3
2
4
(
(
0.2 ml, 1.62 mmol) in dry CH
56 mg, 0.29 mmol) was added at room temperature and
2
Cl
2
(5 ml), anhydrous InCl
3
2
2
the contents were stirred for the 15-20 min. After
completion of the reaction (monitored by TLC), the
reaction mixture was quenched by the addition of aqueous
2
0
Finally esterification of alcohol 2 with succinic anhydride
6
b
under analogues conditions as reported produced the
target molecule (-)-A26771B (1). The boiling point,
specific rotation and NMR data of 1 [mp 122-125 ºC,
NaHCO
3
, extracted with CH
2
Cl
2
(3x25 ml), dried over
2
0
6c,e
anhydrous sodium sulphate, filtered and concentrated. The
[
[α]
α]
D
-12.9 (c 0.10 in MeOH), lit.
m.p:152-155 ºC
2
6
75 residue was subjected to flash column chromatography on
silica gel EtOAc/hexane, 10/90 v/v) to obtain pure
2
3
3
5
0
5
D
-13.5 (c 0.18.in MeOH)] were in excellent
agreement with the reported one.
2
2
compound 11 ( 445 mg, 1.40 mmol) in 95% yield; [α]
25.5 (c 0.1, CHCl ); R : 0.42 (1:5, EtOAc/Hexane); IR
Neat): νmax 3015, 2930, 2856, 1722, 1656, 1462, 1253,
D
1
3
f
Conclusion
(
In summary, we have developed here a concise and chiron
approach synthesis to 16-membered macrolide (-)-
A26771B in 13 steps with overall yield of 13.7%. The C4
-
1 1
8
8
9
0
5
0
1122, 1063, 755, 665 cm ; H (400 MHz, CDCl
.29 (m, 5H), 5.76-5.84 (m, 2H), 5.24-5.28 (m, 2H), 5.06
bs, 1H), 4.73 (d, J=12 Hz, 1H), 4.53 (d, J=11.72 Hz, 1H),
3
): δ 7.23-
7
(
(
S) stereo center in the starting material 7 was conserved in
4
3
.15-4.20 (m, 1H), 4.04-4.10 (m, 2H), 2.02 (s, 3H), 2.0 (s,
H); 13C (100 MHz, CDCl
): δ 164.00, 163.50, 130.83,
the final molecule at C5 (S), thus showing the right
selection of starting material was well conceived. This
synthetic approach features a sequence of Ferrier
rearrangement, Swern oxidation, HWE olefination, cross
metathesis and Yamaguchi esterification.
3
122.53, 121.10, 120.99, 86.88, 63.52, 60.33, 58.55, 56.17,
+
4
C
6.64, 14.17, 14.01; ESI-HRMS: m/z [M+Na] calcd for
+
17
H
20
O
6
Na 343.1158, measured 343.1147.
((2R,3S)-3-acetoxy-6-hydroxytetrahydro-2H-pyran-2-
Experimental section:
General:
The Organic solvents were made anhydrous by standard
methods before their use. To monitor the progress of the
reaction silica gel (60F-254) 2.5 × 5 cm TLC plates coated
yl)methyl acetate (6): To the stirred solution of compound
11 (200 mg, 0.625 mmol) dissolved in ethyl acetate (5 mL)
was added 10% Pd/C (50 mg) and the resulting solution
was stirred under hydrogen atmosphere at room
temperature for 6 h. The reaction mixture was filtered
4
0
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through a short pad of celite bed and it was washed with
ethyl acetate (3x4 ml). The combined filtrates were
concentrated in vacuo to afford a clear oil which was
for 1 h at -30 °C. The compound 12 (300 mg, 0.78 mmol)
dissolved in dry THF (8 ml) was added to the above Wittig
salt drop wise at -30 °C and the stirring was continued at
purified by column chromatography (EtOAc/hexane, 22/78 55 the same temperature for 30 min. and afterward at room
v/v) to afford the pure hemiacetal 6 (142 mg, 0.62 mmol) temperature for 3-4 h. After completion of the reaction,
in 98% yield; R : 0.32 (1:2, EtOAc/Hexane); IR (Neat): quenched with the NH Cl and washed with brine solution.
max 3425, 3019, 2931, 1638, 1428, 1217, 1109, 762, 669 The combined organic layers were dried over Na SO and
5
0
5
0
5
0
5
0
5
0
f
4
ν
2
4
-
1 1
cm ; H (400 MHz, CDCl
3
): δ 5.31.5.32 (m, 1H), 4.12-
concentrated under reduced pressure. The silica gel column
4
.25 (m, 3H), 3.69-3.74 (m, 1H), 2.1 (s, 3H), 2.06 (s, 3H), 60 chromatography of the crude residue using EtOAc/hexane
1
3
1
1
2
2
3
3
4
4
5
1.99-2.03 (m, 3H), 1.54-1.67 (m, 1H); C (100 MHz,
CDCl ): 171.23, 170.32, 96.09, 91.16, 75.39, 68.88, 68.17,
7.52, 63.59, 63.54, 31.25, 29.02, 27.13, 23.42, 21.29,
(12.5/87.5 v/v) as an eluent, gave the pure compound 13 in
2
6
3
81% yield; [α]
D
+15.5 (c 0.1, CHCl
3
); R
f
: 0.50 (1:4,
6
2
2
EtOAc/Hexane); IR (Neat): νmax 3520, 3025, 2920, 1541,
+
+
-1 1
1.25, 21.05; ESI-HRMS: m/z [M+H] calcd for C10
H
17
O
6
1427, 1217, 1116, 929, 754 cm ; H (400 MHz, CDCl ): δ
3
33.1025, measured 233.1021.
65 7.58- 7.60 (m, 4H), 7.30-7.37 (m, 6H), 5.69-5.73 (m, 1H),
4.87-4.97 (m, 2H), 3.72-3.74 (m, 2H), 3.62-3.66 (m, 1H),
3.50-3.54 (m, 1H), 2.14-2.18 (m, 1H), 1.95-2.05 (m, 1H),
(5S,6R)-6-((tert-
butyldiphenylsilyloxy)methyl)tetrahydro-2H-pyran-2,5-
diol (12): Sodium methoxide was added in portion to the
stirred solution of compound 6 (500 mg, 2.154 mmol)
1.40-1.49 (m, 2H), 0.99 (s, 9H); 13C (100 MHz, CDCl
138.48, 133.06, 133.00, 130.22, 128.13, 128.11, 115.23,
3
): δ
H
dissolved in MeOH at room temperature till the P of the 70 73.87, 72.49, 64.84, 32.04, 30.28, 27.12, 19.44; ESI-
solution becomes 8-9. The stirring was continued at the
same temperature for 1 hour. After completion, the
reaction mixture was concentrated to evaporate the solvent.
Imidazole (288 mg, 4.24 mmol) and the above crude
HRMS: m/z [M+H]+ calcd for C23
H
33
O
Si+ 385.2199,
3
measured 385.2175.
((4R,5S)-5-(but-3-enyl)-2,2-dimethyl-1,3-dioxolan-4-
yl)methanol (14): To the stirred solution of compound 13
residue (314 mg, 2.12 mmol) were taken in a two necked 75 (100 mg, 0.26 mmol) in acetone was added the catalytic
50 ml round bottom flask containing dry DMF (10 ml),
equipped with a magnetic stir bar and nitrogen inlet.
TBDPSCl (0.7 ml, 2.54 mmol) was added drop wise to it at
amount of PTSA (24.7 mg, 0.13 mmol) and 2,2-DMP
(0.05 ml, 0.39 mmol). The stirring was continued till the
TLC showed disappearance of the starting material which
took 3-4 hrs .The reaction mixture was then neutralized
-
18 °C and the resulting reaction mixture was stirred for 24
h at the same temperature. After the completion of the 80 with Et
reaction, it was quenched with H O and extracted with
ether (4x5 ml). The combined organic layers were dried
over Na SO and the solvent was removed under reduced
pressure, followed by silica gel column chromatography of
3
N and the solvent was evaporated to obtain the
2
crude light yellow oil which on column chromatography
using EtOAc/Hexane (4/96 v/v) gave the pure acetonide
protected compound in 95% yield.
2
4
TBAF (0.88 ml, 1.0 M solution in THF, 0.88 mmol) was
the resulting residue with EtOAc/hexane (15/85 v/v) as an 85 added drop wise to a stirred solution of above pure
eluent to obtain 12 (753 mg, 1.95 mmol) in 92% yield as a
colorless oil; R : 0.50 (1:4, EtOAc/Hexane); IR (Neat): νmax
compound (250 mg, 0.59 mmol) in THF (10 mL) at 0 °C
and the stirring was continued for 3 h. After disappearance
of the starting material, the reaction mixture was quenched
with water and the organic layer was separated. The
f
-
1
3
1
427, 3015, 2930, 1641, 1427, 1217, 1106, 919, 764 cm ;
H (400 MHz, CDCl ): δ 7.65-7.70 (m, 4H), 7.37-7.46 (m,
3
6
H), 5.17-5.50 (m, 1H), 4.06-4.25 (m, 1H), 3.66-3.96 (m, 90 aqueous layer was extracted with EtOAc (3x5 ml) and the
3H), 1.78-2.13 (m, 4H), 1.07 (s, 3H); 13C (100 MHz,
combined organic layers were dried over Na SO . The
CDCl ): δ 135.81, 130.07, 129.92, 128.00, 127.92, 103.50,
0.07, 77.14, 64.74, 33.82, 29.93, 27.09; ESI-HRMS: m/z
2
4
3
solvent was removed in vacuo and the crude reaction
mixture was purified by silica gel column chromatography
by using EtOAc/hexane (20/80, v/v) as an eluent, to
8
+
+
[M+Na] calcd for C22
H
30NaO Si 409.1811, measured
4
2
6
4
09.1805.
95 furnish the compound 14 in 80% yield; [α]
CHCl ); R : 0.50 (1:4, EtOAc/Hexane); IR (Neat): νmax
3682, 3449, 3018, 2937, 1520, 1216, 760, 671 cm ; H
(400 MHz, CDCl ): δ 5.71-5.79 (m, 1H), 4.91-5.01 (m,
2H), 4.07-4.13 (m, 2H), 3.53-3.56 (m, 2H), 2.18-2.22 (m,
cooled to -78 °C. n-BuLi (0.78 ml, 1.56 mmol, 2 M 100 1H), 2.03-2.11 (m, 2H), 1.46-1.64 (m, 2H), 1.40 (s, 3H),
solution) was added drop wise to the reaction mixture ): δ 137.86, 115.41,
1.29 (s, 3H); 13C (100 MHz, CDCl
under N atmosphere and the resulting mixture was stirred
D
+47.1 (c 0.4,
(2R,3S)-1-(tert-butyldiphenylsilyloxy)hept-6-ene-2,3-
diol (13): Methyltriphenylphosphonium bromide (1.95 g,
5
3
f
-
1
1
.46 mmol) was taken in a oven dried double neck round
3
bottom flask added dry THF (10 ml) and the mixture was
3
2
108.28, 78.09, 76.45, 61.92, 30.82, 28.43, 25.71; ESI-
4
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HRMS: m/z [M+H]+ calcd for C10
H
21
O
3
+
187.1334,
combined organic layers were dried over Na
SO and the
2
4
measured 187.1327.
solvent was removed under reduced pressure. The yellow
crude was subjected to silica gel column chromatography
(
E)-methyl
3-((4R)-5-(but-3-enyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)acrylate (3): A solution of oxalylchloride 55 in EtOAc/hexane (20/80 v/v) to obtain pure compound 15
5
0
5
0
5
0
5
0
5
0
(0.41 ml, 4.83 mmol) dissolved in dry DCM (5 ml) in a 50
ml double necked round bottom flask equipped with a
magnetic stir bar and nitrogen inlet was cooled at -78 °C.
To this solution, DMSO (0.68 ml, 9.66 mmol) was added
(yellow oil) in 85% yield.
6-bromo-1-hexene (8): A solution of 5-Bromopentanol 15
(2 g, 0.012 mmol) in CH
to a suspension of PCC (3.8 g, 0.018 mmol) and 4 Å
Cl (10 ml) at 0ºC. The
2
Cl
2
(10 ml) was added drop wise
drop wise and the stirring was continued for 5 min. The 60 molecular sieves (800 mg) in CH
2
2
1
1
2
2
3
3
4
4
5
alcohol 14 (600 mg, 3.22 mmol) dissolved in DCM was
added drop wise to the above reaction mixture and the
stirring was further continued for 30 min at the same
reaction was stirred vigorously at 0ºC for 3 h, diethyl ether
(6 ml) was then added and the mixture was stirred for an
additional 1 hour. The suspension was filtered over a silica
gel pad (petroleum ether:ethyl acetate, 80:20, 300 mL).
temperature. Afterward, Et N (2.25 ml, 16.1 mmol) was
3
now added drop wise to it and the stirring was continued 65 The solvent was evaporated under reduced pressure to give
till the completion of the reaction. The reaction mixture
was quenched with saturated NH Cl and extracted with
DCM (3x5 ml). The combined organic layers were dried
over Na SO and the solvent was removed under reduced
the corresponding aldehyde that was used immediately in
the next step.
Methyltriphenylphosphonium bromide (29 g, 0.083 mmol)
and potassium tert-butoxide (6.2 g, 0.055 mmol) was taken
4
2
4
pressure. The crude aldehyde was used for the next step 70 in an oven dried two neck RB flask. The mixture was
without further purification.
To a solution of NaH (60% dispersion in mineral oil, 191
mg, 4.77 mmol) in dry THF (5 mL) was added the methyl
cooled to 0 °C and charged the flask with THF (20 ml)
under N atmosphere. The reaction mixture was stirred at
2
the same temperature for 1 hr till the yellow color was
appeared. The crude aldehyde (4.5 g , 0.027 mmol)
2
-(dimethoxyphosphoryl)acetate (1.07 g, 4.77 mmol) at 0
°
C. After stirring at room temperature for 30 min, a 75 dissolved in dry THF (8 ml) was added to the above Wittig
solution of the crude aldehyde in THF (5 mL) obtained
above was added to it and the mixture was further stirred
for another 10 min. It was diluted with saturated solution
salt drop wise at 0 °C . Afterward, the temperature of the
reaction bath was raised to room temperature (25 C).
When the reaction was completed (2 h), the reaction
mixture was quenched with the NH
0
of NaHCO
3
, and extracted with EtOAc. The combined
4
Cl and washed with
organic layers were dried (Na
2
SO ), filtered, and 80 brine solution. The combined organic layers were dried
4
concentrated to give a residue, which was purified by
column chromatography using EtOAc/hexane (3/97, v/v)
as an eluent to afford the unsaturated ester 3 in 85% yield
over Na
2
SO and concentrated under reduced pressure. The
4
silica gel column chromatography of the crude residue
mixture using EtOAc/hexane (0.5/99.5 v/v) as an eluent,
yielded the pure compound 8 in 81% yield; R : 0.80 (Pure
2
6
(over two steps); [α]
D
-42.0 (c 0.3, CHCl
3
); R
f
: 0.71
f
(
1:10, EtOAc/Hexane); IR (Neat): νmax= 3019, 2928, 2854, 85 hexane); IR (Neat): νmax 3020, 2975, 2927, 2855, 1634,
-
1 1
-1
1
1721, 1643, 1215, 758, 669 cm ; H (400 MHz, CDCl
.78 (dd, J =6.15, J =15.67 Hz, 1H), 6.01 (dd, J =1.46,
=15.60 Hz, 1H), 5.69-5.76 (m, 1H), 4.90-5.00 (m, 2H),
.56-4.60 (m, 1H), 4.15-4.20 (m, 1H), 3.68 (s, 3H), 2.02-
.19 (m, 2H), 1.50-1.54 (m, 2H), 1.44 (s, 3H), 1.31 (s, 3H); 90 27.58; ESI-HRMS: m/z [M] calcd for C
3
): δ
849, 757 cm ; H NMR (400MHz, CDCl
(m, 1H), 4.89-4.98 (m, 2H), 3.34 (t, J=6.82 Hz, 2H), 1.99-
2.04 (m, 2H), 1.77-1.84 (m, 2H), 1.44-1.51 (m, 2H); 13
(100 MHz, CDCl ): δ 138.34, 115.22, 33.91, 33.03, 32.39,
3
): δ 5.67-5.77
6
J
4
2
1
1
2
1
2
C
3
+
+
6
H
11Br 162.0044,
3C (100 MHz, CDCl
): δ 166.62, 144.15, 137.80, 122.88,
measured 162.0033.
3
1
2
2
5
15.55, 109.15, 77.78, 77.49, 51.91, 30.59, 30.09, 28.26,
(R)-non-8-en-2-ol (4): A portion of 6-bromo-1-hexene 8
(approx. 50 mg) dissolved in dry THF (10 ml) and
magnesium turnings (178 mg, 7.33 mmol) were taken in a
5.77; ESI-HRMS: m/z [M+H]+ calcd for C13
H
21
O
4
+
41.1440, measured 241.1421.
-bromo-1-pentanol (15): To the stirred solution of 1,5- 95 50 ml two necked round bottom flask, equipped with a
pentanediol 10 (17 g, 0.16 mmol) dissolved in toluene was
added 47% aqueous HBr (0.19 mmol, 10.7 ml) at room
temperature and the mixture was refluxed using Dean stark
apparatus for 4-5 hrs. It was brought to room temperature
and quenched with 1M NaOH at 0 °C. The two layers were 100 bromo-1-hexene 8 (700 mg, 3.66 mmol) in THF (5 ml) to
separated and the organic layer was diluted with EtOAc
and washed thoroughly with water and brine. The
magnetic stir bar, a N inlet and a rubber septum. Two
2
drops of dibromoethane was added to it and the reaction
mixture was refluxed under vigorous stirring followed by
the drop wise addition of the remaining solution of 6-
it., The resulting reaction reaction mixture was continued
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to reflux for another 4 h and afterward the solution was
(E)-((R)-non-8-en-2-yl)
3-((4S,5S)-5-(but-3-enyl)-2,2-
cooled to room temperature.
To another 50 ml two necked round bottom flask equipped
dimethyl-1,3-dioxolan-4-yl)acrylate (17): To a stirred
solution of 16 (350 mg, 1.67 mmol) in THF (7 ml) were
with a magnetic stir bar, a N
2
inlet and a rubber septum, 55 added Et N (0.27 ml, 2 mmol) and 2,4,6-trichlorobenzoyl
3
5
0
5
0
5
0
5
0
5
0
were added (R)-propyleneoxide 9 (0.26 ml, 3.66 mmol)
and CuCN (16.4 mg, 0.183 mmol) in dry THF (15 ml) and
the reaction mixture was cooled to -15 °C. To this stirred
solution, the above freshly prepared Grignard reagent was
added drop wise by using a long needle. After completion 60 (5 ml) and the resulting mixture was heated at reflux for 3
of the addition, the stirring was continued at -15 °C for 4 h
and an additional 2 h at room temperature. After
chloride (0.31 ml, 2 mmol) and the stirring was continued
for 1 h at room temperature. The reaction mixture was now
added to another RB containing a solution of alcohol 4
(300 mg, 2 mmol) and DMAP (1 g, 8.36 mmol) in toluene
1
1
2
2
3
3
4
4
5
h. The reaction mixture was then cooled to room
temperature and quenched with saturated NaHCO
3
completion of the reaction, a saturated solution of NH
4
Cl
solution. The two layers were separated and the aqueous
layer was extracted with EtOAc (3x5 ml). The combined
was added and stirring was continued until a blue aqueous
layer was obtained. The two layers were separated and the 65 organic layers were dried over Na
2
SO , concentrated under
4
aqueous layer was extracted with ether (3x10 ml). The
organic layers were combined, dried over Na SO and
reduced pressure and purified by silica gel column
chromatography using EtOAc/hexane (8/92 v/v) as an
eluent to afford the compound 17 in 85% yield (498 mg,
2
4
evaporated in vacuo. The crude residue was purified by
silica gel column chromatography using EtOAc/hexane
1.42 mmol); R : 0.6 (1:9 EtOAc/Hexane); IR (Neat): νmax
f
-
1
1
(
12/88 v/v) as an eluent to furnish the pure compound 4 in 70 3410, 3019, 2933, 2928, 2860, 1709, 1121, 759 cm ; H
2
1
89% yield (555 mg, 3.26 mmol); [α]
D
-12.1 (c 0.1 in
(400 MHz, CDCl
3
): δ 6.75 (dd, J1=6.38, J2=15.61 Hz,
=15.61 Hz, 1H), 5.67-5.78 (m,
CHCl
433, 3019, 2974, 2928, 2856, 1639, 757 cm ; H NMR
400MHz, CDCl ); δ 5.76-5.86 (m, 1H), 4.91-5.01 (m,
3
); R
f
: 0.55 (1:5 EtOAc/Hexane); IR (Neat): νmax
1H), 5.98 (dd, J =1.51, J
1
2
-1
1
3
2H), 4.84-4.99 (m, 5H), 4.57 (td, J1=1.34, J2=6.36,
J3=12.77 Hz, 1H), 4.15-4.20 (m, 1H), 2.12-2.19 (m, 1H),
(
3
2
H), 3.78-3.79 (m, 1H), 2.01-2.05 (m, 2H), 1.62 (br s, 1H), 75 1.94-2.07 (m, 3H), 1.39-1.55 (m, 9H), 1.24-1.30 (m, 9H),
1
3
13
1.26-1.41 (m, 8H), 1.18 (d, J=6.0 Hz, 3H); C NMR (100
1.16 (d, J=6.20 Hz, 3H). C (100 MHz, CDCl ): δ 165.77,
3
MHz, CDCl
3
) δ 139.49, 114.47, 68.44, 39.70, 29.94, 29.79,
143.30, 139.15, 137.79, 123.90, 115.48, 114.50, 109.06,
77.74, 77.58, 71.43, 36.11, 33.86, 30.53, 30.05, 29.10,
+
2
9.41, 29.25, 26.09; ESI-HRMS: m/z [M+H] calcd for
+
C
9
H19O 143.1436, measured 143.1431.
28.97, 28.25, 25.74, 25.43, 20.18; ESI-HRMS: m/z
80 [M+H]+ calcd for
351.2530.
C
21
H
35
O
4
+
351.2535, measured
(
E)-3-((4R,5S)-5-(but-3-enyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)acrylic acid (16): To a stirred solution of
compound 3 (400 mg, 1.65 mmol) dissolved in acetonitrile
(S,E)-((R)-non-8-en-2-yl)
5-hydroxy-4-oxonona-2,8-
(10 ml) was added LiOH (159 mg, 6.65 mmol) and small
dienoate (18): To the stirred solution of compound 17 (65
mg, 0.185 mmol) in MeOH was added PTSA (18 mg, 0.09
amount of water (3 ml) at room temperature and stirring
was continued at the same temperature for overnight. After 85 mmol) and stirring was continued for 3-4 hrs. After
completion of the reaction, the reaction mixture was completion of the reaction, the reaction mixture was
acidified with NH Cl and extracted with ether. The organic neutralized with NEt and concentrated under vacuum. The
layers were dried over Na SO , filtered and concentrated
under reduced vacuum. The crude residue was purified by
4
3
2
4
crude product was diluted with EtOAc, wash with the
water and the aqueous layer was extracted with EtOAc
column chromatography in EtOAc-Hexane (38/62 v/v) as 90 (3x5 ml). The combined organic layers were concentrated
an eluent furnishing acid 16 (339 mg, 1.48 mmol) in 90%
in rotavapour.
2
3
yield; [α]
D
+3.5 (c 0.1 in CHCl
3
); R
f
: 0.43 (1:1,
PTSA (61 mg, 0.32 mmol) was added to the above crude
diol (50 mg, 0.16 mmol) dissolved in dry DCM followed
by addition of TEMPO (50 mg, 0.32 mmol) at 0 °C. After
EtOAc/Hexane); IR (Neat): νmax 3440, 3010, 2925, 2845,
-
1
1
1
6
705, 1645, 1205, 758, 669 cm ; H (400 MHz, CDCl
3
): δ
.95 (dd, J =5.88, J =15.56 Hz, 1H), 6.07-6.11 (m, 1H), 95 being stirred for 6 hrs at room temperature, the solvent was
1
2
5.75-5.83 (m, 1H), 4.97-5.07 (m, 2H), 4.67-4.70 (m, 1H),
evaporated and the resulting residue was purified by
column chromatography to obtain the pure compound 18
4
1
3
1
.24-4.29 (m, 1H), 2.21-2.25 (m, 1H), 2.04-2.13 (m, 1H),
.55-1.61 (m, 1H), 1.52 (s, 3H), 1.46-1.50 (m, 1H), 1.38 (s,
in 72% over two steps. R
f
: 0.65 (1:8 EtOAc/Hexane); IR
H). 13C (100 MHz, CDCl
): δ 170.97, 146.54, 137.72,
22.48, 115.64, 109.30, 77.78, 77.35, 30.57, 30.13, 29.93, 100 757 cm ; H (400 MHz, CDCl
(Neat): νmax 3390, 3138, 2928, 2856, 1720, 1706, 1639,
3
-
1
1
3
): δ 7.13(d, J=15.79 Hz,
+
+
28.22, 25.74. ESI-HRMS: m/z [M+H] calcd for C12
H
19
O
4
1H), 6.76 (d, J=15.79 Hz, 1H), 5.67-5.80 (m, 2H), 4.85-
4.99 (m, 5H), 4.36-4.40 (m, 1H), 3.28 (d, J=5.06 Hz, 1H),
2
27.1283, measured 227.1292.
6
|
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Page 8 of 10
2
1
.07-2.24 (m, 2H), 1.84-2.0 (m, 2H), 1.49-1.59 (m, 6H),
3.66-3.73 (m, 4H), 1.90-2.10 (m, 1H), 1.44 (s, 3H), 1.30 (s,
3H), 1.19-1.22 (m, 10H), 1.12 (d, J=6.05 Hz, 3H); C (100
1
3
13
.25-1.33 (m, 4H), 1.21 (d, J=6.32 Hz, 3H). C (100 MHz,
): δ 200.99, 165.01, 139.26, 137.45, 134.57, 133.80,
16.43, 114.75, 75.98, 73.20, 36.13, 34.01, 33.25, 30.08, 55 108.67, 81.48, 78.25, 35.75, 32.32, 31.60, 30.09, 29.87,
CDCl
1
3
MHz, CDCl ): δ 165.90, 143.67, 132.67, 125.64, 124.04,
3
5
0
5
0
5
0
5
0
5
0
29.42, 29.22, 29.10, 25.56, 20.24; ESI-HRMS: m/z
29.75, 28.60, 28.51, 27.84, 27.41, 27.09, 26.71, 25.84,
+
+
+
[
3
(
M+H] calcd for
09.2055.
2E)-methyl
C
18
H
29
O
4
309.2066, measured
23.96, 23.08, 20.84; ESI-HRMS: m/z [M+H] calcd for
+
C
19
H
31
O
4
323.2222, measured 323.2214.
3-((4R,5S)-5-((R)-9-hydroxydec-3-enyl)-
(3aR,8R,17aS,E)-2,2,8-trimethyl-
2
,2-dimethyl-1,3-dioxolan-4-yl)acrylate (19): A solution 60 9,10,11,12,13,14,15,16,17,17a-decahydro-3aH-
1
1
2
2
3
3
4
4
5
of -unsaturated ester 3 and alcohol 4 in dry DCM was
added to a oven dried two neck RB flask, fitted one side
with condenser and other side stopper, containing Grubb’s
1st generation catalyst and the reaction mixture was heated
[1,3]dioxolo[4,5-e][1]oxacyclohexadecin-6(8H)-one (21):
To the stirred solution of compound 20 (50 mg, 0.109
mmol) dissolved in ethyl acetate (5 mL) was added 5% Pd
on BaSO (15 mg) and the resulting solution was stirred
4
to reflux in an inert atmosphere for 6 to 8 hrs. After 65 under hydrogen atmosphere at room temperature for 1 h.
completion of the reaction, the solvent was evaporated and
the crude was subjected to column chromatography to
obtain the pure compound 19 (both cis-trans isomer 1:3
from HPLC and NMR) in 75% yields; ESI-HRMS: m/z
The reaction mixture was filtered through a short pad of
celite bed and it was washed after filtration with ethyl
acetate (4 ml) for 2-3 times. The combined filtrates were
concentrated in vacuo to afford a clear oil which was
+
+
[
M+H] calcd for
341.2351.
3aR,4E,8R,17aS)-2,2,8-trimethyl-
,9,10,11,12,13,17,17a-octahydro-3aH-[1,3]dioxolo[4,5-
e][1]oxacyclohexadecin-6(16H)-one (20): To a stirred
solution of compound 19 (70 mg, 0.21 mmol) dissolved in 75 (400MHz, CDCl
C
19
H
33
O
5
341.2328, measured 70 subjected to column chromatography (EtOAc/hexane, 6/94
v/v) to give the pure compound 21 in 98% yield (49.2 mg,
2
2
(
8
0.11 mmol); [α]
D
+8.2 (c 0.1 in CHCl
3
); R : 0.43 (1:9,
f
EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722,
-1
1
1656, 1462, 1253, 1122, 1063, 755, 665 cm ; H NMR
) δ 6.83 (dd, J =8.32, J =15.8 Hz, 1H),
=1.4, J =15.6 Hz, 1H), 4.64-4.68 (m, 1H), 4.23-
3
1
2
acetonitrile (5 ml) was added LiOH (25 mg, 1.03 mmol)
and a small amount of water (2 ml) at room temperature
and stirring was continued at the same temperature for
overnight. After completion of the reaction, the reaction
6.06 (dd, J
1
2
4.28 (m, 1H), 4.05-4.11 (m, 1H), 2.02-2.30 (m, 4H), 1.54-
1.53-1.64 (m, 8H), 1.29-1.47 (m, 10H), 1.25 (d, J=6.28 Hz,
1
3
3H); C NMR (75 MHz, CDCl ) δ 165.97, 145.06, 123.44,
3
mixture was quenched with saturated NH
with ether (5x5 ml). The combined organic layers were
dried over Na SO , filtered and concentrated.
To a stirred solution of above crude compound (50 mg,
4
Cl and extracted 80 109.44, 75.14, 73.73, 71.57, 36.08, 32.44, 30.08, 28.70,
28.16, 27.95, 27.62, 27.50, 26.78, 24.67, 23.97, 20.84;
ESI-HRMS: m/z [M+Na]+ calcd for
C
H46NaO
+
2
4
26
8
325.2379, measured 325.2360.
(6S,16R,E)-6-hydroxy-16-methyloxacyclohexadec-3-
0
0
.153 mmol) in THF (7 ml) were added Et
.183 mmol) and 2,4,6-trichlorobenzoyl chloride (0.02 ml, 85 ene-2,5-dione (2): To the stirred solution of compound 21
3
N (0.02 ml,
0.183 mmol). Its stirring was continued for 1 h at room
temperature. The reaction mixture was now added to a
solution of DMAP (95 mg, 0.765 mmol) in toluene (5 ml)
and the resulting mixture was reflux for 3 h. After
(30 mg, 0.092 mmol) in THF was added PTSA (9 mg,
0.046 mmol) at room temperature and continued the
stirring for 3 hrs. After completion of the reaction
(monitored by TLC), it was neutralized with triethylamine
completion of the reaction, it was then cooled to room 90 and the entire solution was concentrated under vacuum.
temperature and quenched with saturated NaHCO
3
To the above crude product (15 mg, 0.053 mmol) in dry
DCM (5 ml) was added PTSA (17 mg, 0.11 mmol) and
TEMPO (17 mg, 0.11mmol) at 0 °C. After stirring for 6
hrs at room temperature, the solvent was evaporated and
solution. The two layers were separated and the aqueous
layer was extracted with EtOAc (3x5 ml). The combined
organic layers were dried over Na
2
SO , concentrated under
4
reduced pressure and purified by silica gel column 95 the resulting residue was purified by column
chromatography using EtOAc/hexane (8/92 v/v) as an
chromatography to obtain a pure white solid 2 in 86%
2
6
eluent to afford the compound 20 in 74% yield (284 mg,
yield over two steps. [α]
D
+21.8 (c 0.1, CHCl
3
); R : 0.50
f
2
6
0
.58 mmol); [α]
D
-11.8 (c 0.1, CHCl
3
); R : 0.50 (1:4,
f
(1:4, EtOAc/Hexane); IR (Neat): νmax 3449, 3018, 2937,
-
1
1
EtOAc/Hexane); IR (Neat): νmax 3682, 3449, 3018, 2937,
1702, 1690, 1520, 1205, 758, 669 cm ; H (400 MHz,
): δ 7.23 (d, J=15.76 Hz, 1H), 6.87 (d, J=15.8 Hz,
-1 1
1
520, 1205, 758, 669 cm ; H (400 MHz, CDCl
(dd, J =6.17, J =15.62 Hz, 1H), 6.01 (d, J=15.62 Hz, 1H),
.25-5.99 (m, 2H), 4.56-4.58 (m, 1H), 4.15-4.19 (m, 1H),
3
): δ 6.78 100 CDCl
3
1H), 4.98-5.14 (m, 1H), 4.47-4.51 (m, 1H), 3.38 (d, J=5.32
Hz, 1H), 2.31-2.31 (m, 2H), 1.95-2.03 (m, 1H), 1.62-1.71
1
2
5
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DOI: 10.1039/C4RA17084A
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RSC Advances
(
m, 6H), 1.29-1.44 (m, 13 H); 13C (100 MHz, CDCl
): δ 50 company): Antibiotic lactones. U.S. Patent 1975, 3, 883,
3
2
3
00.95, 164.97, 137.41, 134.53, 75.94, 73.16, 36.10, 33.95,
3.73, 29.68, 29.39, 29.36, 29.02, 28.88, 25.36, 20.84;
561.
[6] (a) S. chatterjee, A. Sharma, S. Chattopadhyay, RSC
Adv., 2014, 4, 42697-42705; (b) C. RajiReddy, D. Suman,
N. N. Rao, Synlett, 2012, 23, 272-274; (c) J. Gebauer, S
+
+
ESI-HRMS: m/z [M+H] calcd for C16
measured 283.1920.
H
27
O
4
283.1909,
5
0
5
0
(
0
-)-A26771B (1): A solution of above macrolide 2 (15 mg, 55 .Blechert,. J. Org. Chem., 2006, 71, 2021-2025; (d) W.
.053 mmol), succinic anhydride (10.6 mg, 0.106 mmol),
Lee, H. J. Shin, S. Chang, Tetrahedron: Asymmetry, 2001,
12, 29-31; (e) Y. Kobayashi, H. Okui, J. Org. Chem. 2000,
65, 612-615; (f) M. Nagarajan, Tetrahedron Lett., 1999,
40, 1207-1210; (g) S. C. Sinha, A. Sinha-Bagchi, E.
60 Keinan, J. Org. Chem., 1993, 58, 7789-7796; (h) G.
Quinkert, F. Kueber, W. Knauf, M. Wacker, U. Koch,
H.Becker, H. P. Nestler, G. Durner, G. Zimmermann, J. W.
Bats, E. Egert, Helv. Chim. Acta., 1991, 74, 1853-1923; (i)
B. M. Trost, S. J. Brickner, J. Am. Chem. Soc., 1983, 105,
and DMAP (12.7 mg, 0.106 mmol) in CH Cl (3 mL) was
stirred for 24 h at room temperature. Evaporation of the
solvent followed by the purification of the crude product
by flash chromatography (SiO
afforded 10 mg (72%) of the title macrolide 1 as a white
solid: [α]
MeOH/CH
1742, 1703, 1381, 1300, 1196, 1158, 669 cm ; H (400
2
2
1
1
2
2
; 5% MeOH/CH
2
Cl
2
)
2
6
D
-12.4 (c 0.05, MeOH); R
f
. 0.21 (5%
2
Cl
2
); IR (Neat): νmax 3150, 3019, 2938, 2855,
-
1
1
MHz, CDCl
3
) δ 7.23 (d, J=15.8, 1H), 6.87 (d, J=15.8, 1H), 65 568-575; (j) T. Fujisawa, N. Okada, M. Takeuchi, T. Sato,
5
4
6
.14 (d, J=1.6 Hz 1H), 4.98-5.01 (m, 1H), 2.72-2.79 (m,
Chem. Lett., 1983, 1271-1272; (k) K. Tatsuta, Y.
Amemiya, Y. Kanemura, M. Kinoshita, Bull. Chem. Soc.
Jpn., 1982, 55, 3248-3253; (l) M. Asaoka, M. Abe, T.
Mukuta, H. Takei, Chem. Lett., 1982, 215-218; (m) M.
H), 2.22-2.31 (m, 2H), 1.95-2.03 (m, 1H), 1.54-1.71 (m,
13
H), 1.42-1.44 (m, 13H); C (100 MHz, CDCl ) δ 200.99,
3
178.02, 171.02, 165.01, 139.26, 133.80, 75.98, 73.20,
4
2
C
9.13, 36.13, 34.01, 33.25, 30.08, 29.42, 29.22, 29.10, 70 Asaoka, N. Yanagida, H. Takei, Tetrahedron Lett., 1980,
+
5.56, 20.24. ESI-HRMS: m/z [M+Na] calcd for
21, 4611-4614.
+
20
H
31
O
7
383.2070, measured 383.2075.
[7] (a) P. Ghosal, S. Ajay, S. Meena, S. Sinha, Tetrahedron
Assymetry, 2013, 24, 903-908; (b) P. Ghosal, A. K. Shaw,
J. Org. Chem., 2012, 77, 7627-7632; (c) P. Pal, A. K.
Shaw, Tetrahedron, 2011, 67, 4036-4047; (d) V. Kumar, P.
Das, P. Ghosal, A. K. Shaw, Tetrahedron, 2011, 67, 4539-
Acknowledgement
7
8
8
9
9
5
0
5
0
5
2
3
3
5
0
5
We are thankful to SAIF, CDRI, for providing spectral
data. P.S. thanks the CSIR, New Delhi for awarding Senior
Research Fellowship and Mr. A. K. Pandey for technical
assistance. CDRI Manuscript No. 329/2014/AKS
4
546; (e) P. Ghosal, D. Sharma, B. Kumar, S. Meena, S.
Sinha, A. K. Shaw, Org. Biomol. Chem., 2011, 9, 7372-
383; (f) P. Ghosal, A. K. Shaw, Tetrahedron Lett., 2010,
7
51, 4140-4142; (g) P. Ghosal, V. Kumar, A. K. Shaw,
Carbohydrate Research, 2010, 345, 41-44; (h) P. Ghosal,
V. Kumar, A. K. Shaw, Tetrahedron, 2010, 66, 7504-7509;
Notes and References
[1] (a) For recent reviews, see: S. Omura, Macrolide
Antibiotics. Chemistry, Biology, and Practice, 2nd ed.;
Academic Press Inc.: 2002; (b) J. M. Blondeau, Expert
Opin. Pharmacother, 2002, 3, 1131–1151; (c) J. M.
Blondeau, E. DeCarolis, K. L. Metzer, G. T. Hansen,
Expert Opin. Invest. Drugs, 2002, 11, 189–215.
(
7
i) V. Kumar, A. K. Shaw, J. Org. Chem., 2008, 73, 7526-
531; (j) L. V. R. Reddy, G. N. Swamy, A. K. Shaw,
Tetrahedron: Asymmetry, 2008, 19, 1372-1375; (k) L. V.
R. Reddy, P. V. Reddy, A. K. Shaw, Tetrahedron:
Asymmetry, 2007, 18, 542-546.
[
2] (a) A. S. Mankin,. Curr. Opin. Microbiol., 2008, 11,
[
4
8] P. Saidhareddy, S. Ajay, A. K. Shaw, RSC Adv., 2014,
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4
1
14−421; (b) C. M. T. Spahn, C. D. Prescott, J. Mol. Med.,
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Babu, K. K. Balasubramanian, Tetrahedron Lett., 2000, 41,
4
0
Venkata, T. Paul, G. Sandelin, C. DeBrosse, D. Klepacki,
M. C. Small, A. D. MacKerell, Jr., R. B. Andrade. ACS
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1
271–1274.
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4
5
[
5] (a) K. H. Michel, M. O. Chaney, N. D. Jones, M. M.
[
11] (a) I. Shiina, M. Kubota, H. Oshiumi and M.
Hoehn, R. Nagarajan, J. Antibiotics, 1974, 27, 57-64; (b)
K. H. Michel, M. M. Hoehn (Assigned to Eli Lilly and
Hashizume, J. Org. Chem., 2004, 69, 1822–1830; (b) J.
8
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DOI: 10.1039/C4RA17084A
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Page 10 of 10
Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi,
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13] In order to improve its yield, the cross metathesis
[
3
5
[
between 3 and 4 was carried out in the presence of Grubb’s
nd
2
generation catalyst to afford 19. Unfortunately it was
isolated with low yield (49 %) along with considering
amount of dimer of the side chain.
1
0
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 9