Cross dehydrogenative coupling of sugar enol ethers with terminal alkenes in the synthesis of pseudo-disaccharides, chiral oxadecalins and a conjugated triene

Article abstract of DOI:10.1039/c8ob00168e

An efficient strategy for the synthesis of C-2 and C-3 branched sugar dienes via cross dehydrogenative coupling of sugar enol ethers with terminal alkenes was developed. Both pyran and furan based enol ethers coupled smoothly with electron rich as well as deficient alkene sources yielding sugar dienes with complete E-stereoselectivity. This coupling reaction was applied successfully for the synthesis of orthogonally protected pseudo-C-saccharides as an alternative to olefin metathesis. Substrate scope was further enhanced by reacting exoglycals with methyl acrylate to generate C-5 branched sugars with moderate diastereoselectivity. These diene subunits were reacted with maleic anhydride under [4 + 2] cycloaddition conditions to generate highly functionalised chiral oxadecalin cores. Finally, utilizing this C-C bond formation, a sugar based conjugated triene was synthesized in excellent yield and selectivity.

Full text of DOI:10.1039/c8ob00168e

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Cross dehydrogenative coupling of sugar enol ethers with
terminal alkenes in the synthesis of pseudo disaccharides, chiral
oxadecalins and conjugated triene
Received 00th January 20xx,
Accepted 00th January 20xx
Nazar Hussain,a,b Madhu Babu Tatina,a,b and Debaraj Mukherjeea,b*
DOI: 10.1039/x0xx00000x
An efficient strategy for the synthesis of C-2 and C-3 branched sugar dienes via cross dehydrogenative coupling of sugar
enol ethers with terminal alkenes was developed. Both pyran and furan based enol ethers coupled smoothly with electron
rich as well as deficient alkene sources yielding sugar dienes with complete E-stereoselectivity. This coupling reaction was
applied successfully for the synthesis of orthogonally protected pseudo-C-saccharides as an alternative to olefin
metathesis. Substrate scope was further enhanced by reacting exoglycals with methyl acrylate to generate C-5 branched
sugar with moderate diastereoselectivity. These diene subunits were reacted with maleic anhydride under [4+2]
cycloaddition condition to generate highly functionalised chiral oxadecalin cores. Finally, utilizing this C-C bond formation,
www.rsc.org/
sugar
based
conjugated
triene
was
synthesized
in
excellent
yield
and
selectivity.
stage for several chemical modifications.3b For example
reduction of bridging double bond may lead to C-disaccharide
having methylene3b, or ethylene3c linkage. Synthetically the
major difficulty associated with the synthesis of a pseudo-C-
saccharides is the elaborate building block strategies of two
coupling monosaccharides units. One way of achieving this
type of pseudo-C-disaccharides is via olefin cross metathesis
approach which requires multiple steps with very poor overall
yield and loss of two carbon units in the coupling step.3c Daniel
Werz and his co-workers successfully synthesized Pseudo-C-
disaccharides containing a diene subunit from glycals via Stille
type coupling of 1-stannylglucal and exocyclic bromoolefins.3b
Till date, synthesis of a C-glycosidic bond from glycal mostly
utilizes anomeric carbon atom, whereas C-2/C-3 positions of
sugar is yet to be exploited towards this end. Thus, an
innovative approach for the synthesis of a variety of different
C-pseudodisaccharide linkages by utilizing C-2 position of
glycals would be of high synthetic value.
Introduction
Naturally occurring carbohydrates and their downstream
products represent useful chiral pool intermediates for
enantioselective synthesis of biologically active natural and
non-natural products due to their diversity, multi chiral
architecture, well defined stereochemistry, and high degree of
oxygenation.1 During the last few decades glycals, which are
inexpensive and readily available carbohydrate vinyl ethers
endowed with a plethora of stereo chemical and functional
attributes, have served extensively as ‘‘chiral pool’’ resources
in the total synthesis of a wide range of molecules.2 However,
the scope of glycals as chiral building blocks relies on the
development of convenient strategies dedicated to these
requirements. For example, glycals can be utilized in the
synthesis of both 2-deoxy C-glycosides (using anomeric
carbon) and 2-C-branched sugars (using C-2 position).3a
C-glycosides, in which two monosaccharide units are linked
carbon to carbon instead of an oxygen atom, are highly stable
towards enzymatic hydrolysis and hence can act as
carbohydrate mimics. Pseudo-C-disaccharides bearing double
bond stitching monosaccharide units together are of great
synthetic and biochemical prominence as double bond sets the
a.Academy of Scientific and Innovative Research.
Figure 1. Methods for sugar enol ether based CDC coupling reactions.
b.Indian Institute of Integrative Medicine (CSIR), Jammu-180001.
*Corresponding Author.dmukherjee@iiim.ac.in
.
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Further, 2-C-branched sugars have immense importance in
biological systems, besides acting as a precursor for the
synthesis of natural products and medicinally important
scaffolds.4 Molinaro and Yu have demonstrated very recently
the utilization of 2-C branched sugar based diene in the
synthesis of an important inositol-fused monosaccharide called
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bradyrhizose that is relevant to a Nod-factor-independent mL of dioxane (Table 1, entry 5) is the optimum reaction
nitrogen fixation pathway.5a,5b The advantage of 2-C-branched condition. Further when we use 1 equiv. of pyridine, the
sugars is their propensity to undergo 1,2 annulation which may desired product was obtained in lower yield (Table 1, entry 9).
lead to the synthesis of some biologically important 1- Further, when we changed the Pd source from Pd(OAc)2 to
oxadecalin scaffold, which is a key structural unit found in a PdCl2 or Pd(TFA)2,the desired product was still obtained (Table
wide range of biologically active molecules and natural 1, entry 7, 8) but in lower yields. In summary, we have
products.6 Earlier we have reported7a synthesis of C-2 sugars developed two reaction conditions (A, B) which are equally
via sp2-sp3 bond formation (Figure 1). In the present study we efficient for the coupling reaction but we used the more
wanted to a cross-dehydrogenative coupling (CDC) based economical condition A for the rest of the study.
strategy (Fig 1) for synthesizing ethylene linked C-2 branched After successfully optimizing the reaction condition, we next
sugars including pseudo-C-disaccharides which contain a diene explored the substrate scope of coupling reaction for C-2 and
subunit, and further cyclization with suitable dienophiles for C-3 branched furanoid and pyranoid glycals taking panel of
the generation of densely substituted optically active unactivated and activated terminal alkene sources. In general
oxadecalin and conjugated triene frameworks.
Results and discussion
Table 1: Optimization of reaction condition for direct sp2-sp2 bond
Our approach for the synthesis of the diene subunit started formationa
from sugar enol ethers and a terminal alkene source. The most
common approaches for the synthesis of glycal based dienes
are the coupling of vinyl iodides with activated alkenes and the
application of Wittig reaction on 2-formyl glycals.7b,7c These
methods require an additional step to preactivate the C-2
position of glycals and have limited substrate scope. Due to
Entry Catalyst
Oxidant
(equiv.)
Additive
(equiv.)
DMSO
(3)
Solventa Yieldb
%
these prefunctionalization issues, the use of unactivated C-H
bond as a coupling partner for CDC has gained tremendous
interest in contemporary organic synthesis.7d,7e In the
literature there is only two reports one is from our group7a
with unactivated cycloalkenes and another one by Xue-liu8a in
which C-2 position of glycals was coupled with activated
alkenes, but the latter approach suffers from various
drawbacks like requirement of activated alkenes, poor yield
and use of stoichiometric amount of Lewis acid which affects
acid labile protecting groups. Further, most of the reported
research focuses on coupling of C-2 position of pyranose
glycals with alkenes under various reaction conditions, but
there is no report in which C-3 position of furanose sugar is
coupled to generate furanose sugar based dienes. The
importance of C-3 linked furanose sugar lies in the fact that
this sugar can be easily converted to pyranose form and has
immense importance in the synthesis of a wide range of
biologically important molecules.8b Our experience in glycal
chemistry9 and the drawbacks of the reported procedure
prompted us to develop an improved method for the
construction of dienes (C-3 and C-2 branched glycosides). For
this purpose, initially we examined the reaction of furanoid
glycal 1a with methyl acrylate 2a in the presence Pd(OAc)2 (10
mol%) along with AgOAc. Taking DMF/DMSO as solvent, we
obtained the desired product in excellent yield (Table 1, entry
1). In order to replace silver acetate with a cheaper oxidant,
we tested several combinations of copper salts with different
palladium catalysts but in all cases the yield of the desired
product was not satisfactory. However, when we added
pyridine as an additive in place of DMSO along with Pd(OAc)2
and Cu(OAc)2.H2O (Table 1, entry 4) we observed some
improvement in yield of the desired product. By changing the
catalyst loading and oxidant along with solvent, we came to
the conclusion that use of 10 mol% of Pd(OAc)2 along with 3
equiv. of Cu(OAc)2.H2O and 2 equiv. pyridine as an additive in 2
(mol %)
1
2
3
4
5
6
7
8
9
Pd(OAc)2 AgOAc (2)
DMF
86
30
45
65
(10)
Pd(OAc)2 Cu(OAc)2 (3)
(10)
DMSO (3) DMF
Pd(OAc)2 Cu(OAc)2.H2O DMSO (3) DMF
(10) (3)
Pd(OAc)2 Cu(OAc)2.H2O Pyridine
(10) (3) (2)
Pd(OAc)2 Cu(OAc)2.H2O Pyridine
(10) (3) (2)
Pd(OAc)2 Cu(OAc)2.H2O ------------- Dioxane Traces
DMF
Dioxane 91
(10)
(3)
PdCl2
(10)
Cu(OAc)2.H2O Pyridine
Dioxane 30
Dioxane 60
Dioxane 67
(3)
(2)
Pd(TFA)2 Cu(OAc)2.H2O Pyridine
(10) (3) (2)
Pd(OAc)2 Cu(OAc)2.H2O Pyridine
(10) (3) (1)
aReaction conditions
mL of solvent at 80 oC for 24 h. bisolated yields after column
chromatography
: 1a (1 equiv.) and 2a (1.5 equiv.) were taken in 2
.
furanose sugar enol ethers coupled well with various terminal
alkenes and were compatible under the standard reaction
condition, giving the corresponding dienes with complete E
stereochemistry (Scheme 1,3a-3c). E-Stereochemistry of newly
formed olefinic protons of 3a was confirmed by coupling
constant values 7.77 (d, J = 15.7 Hz, 1H), 5.98 (d, J = 15.7 Hz,
1H) which are characteristics of E-olefins. In order to check
whether this condition work well with pyranoid glucals, we
selected styrene or substituted styrenes for coupling with
glucals as this is otherwise not possible with existing methods.
Gratifyingly, we obtained satisfactory results when various
styrenes were checked; obtaining desired products in
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moderate to good yield (Scheme 1, 3d-3g). Activated alkenes apply our CDC condition for the synthesis of theses C-
like acrylates gave the desired product in excellent yield with linkedglycoconjugates in single step with complete atomic
exclusive E-selectivity (Scheme 1, 3h). Ether protected
D-
economy.
glucals react with equal ease under similar set of reaction Towards this endeavor we performed areaction between a
condition (Scheme 1, 3i-j). In order to check the feasibility of
the method, reactions of glycals other than
D-glucal were
tested. A substrate derived from L-rhamnose protected with
benzyl group also afforded the desired product with good yield
(Scheme 1, 3k). It was observed that terminal unactivated
alkene like 1-octene also underwent the coupling reaction only
to afford allylated product (Scheme 1, 3l).
Condition A:
Pd(OAc)2, Cu(OAc)2.H2O
O
O
pyridine,dioxane,80 o
C
GP
R
GP
R
Condition B:
n
n
Pd(OAc)2, AgOAc
DMF/DMSO, 80 o
n=0,1
C
2
3a-3l
1
Scheme 2: Comparison between literature and current methods for
the synthesis of ethylene linked disaccharides
benzyl protected glucal and a furanose based terminal alkene.
Gratifyingly, we obtained the required alkenyl linked pseudo C-
disaccharide with excellent (up to 82%) yield (Scheme 3, 6a).
Scheme 1: Csp2-Csp2 coupling of sugar enol ethers with terminal
alkenes. Reaction conditions: Condition A: (1 equiv.), (1.2 equiv.),
Pd(OAc)2 (0.1 equiv.), Cu(OAc)2.H2O (3 equiv.), pyridine (2 equiv.), in
1
2
o
Dioxane at 80 C for 24 h Condition B :
1 (1 equiv.), 2 (1.2 equiv.),
o
Pd(OAc)2 (0.1 equiv.), AgOAc (2.5 equiv.) in DMF/DMSO at 80 C, for
24 h. All the yields were isolated yields after column chromatography.
Both the reaction condition works equally well for any substrate listed
in scheme 1 and takes 20-24 h to complete.
With this efficient tool for the synthesis of sugar based dienes,
we were curious to see whether this method can be applied
for the synthesis of ethylene linked C-disaccharides. According
to the literature there is only two ways of getting this type of
pseudo C-disaccharides one is via Stille type coupling of 1-
stannylglucal and exocyclic bromoolefins (Scheme 2, a) 3b and
other is olefin cross metathesis approach (Scheme 2, b)3c
which requires multiple steps with very poor overall yield and
loss of two carbon units in the coupling step. We were keen to
Scheme 3: Single step synthesis of ethylene-linked disaccharides using Pd-
catalysis. Reaction conditions - 4 (1 equiv.), 5 (1.2 equiv) Pd(OAc)2 (0.1
equiv.) AgOAc (2.5 equiv.) in 2 mL of DMF: DMSO (20:1) at 80 oC; Yields
refer to products isolated after column chromatography. b 0.2 equiv. of PPh3
was used and takes 30 h to complete.
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Synthesis of pseudodisaccharides were successful with For the present study; we selected Diels Alder approach for
different coupling partners such as furanoid glycals and glucals the generation of oxadecalin core from already synthesized
protected with different protecting groups (Scheme 3, 6b-6f). sugar based dienes. We obtained satisfactory yield when we
Glycals such as acetyl protected D-galactal and L-rhamnal reacted these dienes with maleic anhydride in sealed tube at
generated the ethylene linked pseudo C-disaccharides with 60 oC (Scheme 5, 11, and 12). The basic skeleton of Diels-Alder
1
excellent yield and complete E-selectivity (Scheme 3, 6g-6h). adduct 12 was confirmed through HNMR and 13CNMR. In the
We further utilized C-3-O-allylated furanose sugar as a 1HNMR of 12, there is a shift in the anomeric proton with
terminal alkene partner and obtained four atom linked respect to diene 6g from 6.58 to 4.64, appearance of new
disaccharides (Scheme 3, 6i-6j). peak at 5.72 (d, J = 2.0 Hz, 1H) of olefinic protons at the cost
After getting successful results in the preparation of various of two diene (6g) olefinic protons at 6.16, 5.23 and new peak
dienes with endoglycals, we pursued our efforts to extend this at 2.69 – 2.52 (m, 1H) of allylic proton clearly indicated the
methodology to exoglycals. Towards this, we prepared the formation of Diels- Alder adduct 12. Further 13CNMR also
exoglycal
it with ethyl acrylate under optimized reaction conditions to 169.69, 169.36, 169.20, and 167.27 which confirmed the
obtain the desired diene (Scheme 4) in good yield (60%) as a attachment of maleic anhydride with the pseudo
8 starting from diacetone-D-galactose 7 and coupled indicated six carbonyl carbon peaks at δ 171.19, 170.06,
9
mixture of trans,anti,cis and trans,anti,trans (E,anti,Z:E,anti,E). disaccharides. Finally, stereochemistry of newly formed chiral
as determined from matching the J value of similar conjugated centres of 12 (Figure 2) was determined by 2D NMR. In NOESY
compounds in the literature.9j,9k
spectrum of compound 12, cross peak between H1 and βH6a
confirmed stereochemistry at anomeric proton and strong
cross peaks between H1/H8 explained cofaciality of the
β
β
protons.(See SI for detailed analysis).
Scheme 4: Coupling of exoglycals with ethyl acrylate. Reaction condition: I)
7 ( 1 equiv.), PPh3 ( 4 equiv. ), Im (4 equiv.), I2 (3.5 equiv.), in toluene at 60 oC
for 3h II) KOtBu (2 equiv.) in DMF rt 1 h III) Condition A: 8 ( 1 equiv.), ethyl
acrylate (1.2 equiv.), Pd(OAc)2 (0.1 equiv.), Cu(OAc)2.H2O (3 equiv.), pyridine
(2 equiv.), PPh3 ( 0.2 equiv. ), in Dioxane at 100 oC for 24 h Condition B : 8 ( 1
equiv.), ethyl acrylate (1.2 equiv.) Pd(OAc)2 (0.1 equiv.), AgOAc (2.5 equiv.),
PPh3 ( 0.2 equiv. ), in DMF/DMSO at 100 oC, for 24 h. Im : Imidazole
Figure 2: Stereo chemical assignment of compound 12 based on NOE
A furanose sugar based triene 15 (Scheme 6) was also
synthesized in four steps by taking diacetone-D-glucose 13
Fused medium sized rings are privileged structures and
attractive targets for synthesis. There are several notable
contributions for the synthesis of oxadecalin cores from
monosaccharides involving ring-closing metathesis,10 Robinson
annulation,11intramolecular aldol condensation,12 radical
cyclization,13 and Diels–Alder cycloaddition14 for the
construction 6,6 and 5,6 bicyclic ring systems. Another
approach for the construction 1-oxabicyclic core is stereo
selective 6-endo-tet cyclization of homoallylic alcohols as
reported from our group15.
(Scheme 6). The importance of this triene lies in the fact that
this type conjugated system present in wide range of natural
products and can be utilized further for the synthesis of
medium to large fused rings attached with sugar moiety.15a,b
Thus diacetone-D-glucose 13 was converted into furanoid
glycal 1a and coupled with methyl acrylate to yield diene 3a
with E- selectivity. Selective deprotection of 5,6-diacetonide
and dehydration yielded the desired triene 15 with 68% overall
yield.
Scheme 6: Synthesis of
a sugar based conjugated triene. Reaction
conditions: i) 13 (3.84 mmol) in DCM, pyridine (15.38 mmol) at 0 oC, triflic
anhydride (5.76 mmol) for 2h. 75% ii) DBU (5.10 mmol) in DMSO overnight
at rt. (quantitative) iii) 1a (2.54mmol), Pd(OAc)2 (0.25 mmol) and
Cu(OAc)2.H2O (7.64 mmol) in 6mL of dioxane, methyl acrylate (3.05 mmol)
and pyridine (5.09 mmol) at 80 oC, 24 h, 78% iv) 3a ( 2.69 mmol) in 70%
ACOH:H2O (10 mL) overnight rt. 87% V) 14 (1.74 mmol) in dry toluene, Im
Scheme 5: Synthesis of oxadecalin cores via Diels-Alder cycloaddition.
Reaction condition: 3g, 6g (1 equiv.), 10 (2 equiv.), 2 mL of ACN in a
sealed tube at 60 oC for 6 h. ACN: Acetonitrile
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(6.99mmol), PPh3 (6.99 mmol) and iodine (6.99 mmol) 60 oC for 3 h. 68%.Im:
Imidazole
B) General procedure for the preparation of compound 6i and
6j.
With 6i as an example: Palladium(ll)acetate (0.036 mmol, 8.19
mg), PPh3 (0.073 mmol, 19 mg) silver acetate (0.91 mmol, 152
mg) and 3-O-allyl 1,2-5,6-diisopropylidene glucofuranose (0.44
mmol, 132 mg) were added to a stirred solution of Tri-O-
Conclusions
The present study describes an efficient method based upon
cross dehydrogenative coupling for the synthesis of C-2
branched sugars having diene subunits from furanoid and
pyranoid glycals under CDC condition. Pseudodisaccharides
were prepared in a single step by utilizing furanose based
terminal alkene as coupling partner.Tolerance of various
protecting groups of sugar enol ethers and the applicability of
a wide array of activated and unactivated alkenes establishes
the mildness of conditions and generality of the method. Sugar
based dienes could be used for the generation of oxadecalin
cores via Diels Alder cyclization.
acetyl-D-glucal (0.36 mmol, 100 mg) in mixture of DMF and
DMSO (2mL, 10:1) at 80 °C under open air condition. After 24h
the mixture was diluted with ethyl acetate (10 mL), filtered,
and washed successively with water (10 mL) and brine (5 mL).
The organic layer was dried and concentrated under reduced
pressure. The residue was purified by flash column
chromatography (Hexane/EtOAc 7:3) to afford the product as
colorless oil (130 mg 59% yield).
C) Procedure for the synthesis of compound 8 and 9:
To a stirred solution of compound 7 (0.76 mmol, 200 mg) in dry
toluene (5 mL) were added imidazole (3.07 mmol, 209 mg) and
triphenylphosphine (3.07 mmol, 806 mg) at 60 oC. After 30
minutes, Iodine (3.07 mmol, 778 mg) was added in portions
maintaining the reaction temperature in between 56-62 oC and
resulting reaction mixture was allowed to stir for further 3h under
reflux. After completion the reaction mixture was cooled to rt and
diluted with 10 mL ethyl acetate, and washed with water (5 mL)
and Na2S2O3. The organic layer was dried, evaporated, and the
residue was purified by flash column chromatography
(Hexane/EtOAc 9:1) to afford the product 6-deoxy-6-iodo-1,
EXPERIMENTAL SECTION
General information
1H and 13C NMR spectra were recorded using 400 and 500 MHz
spectrometers with TMS as internal standard. Chemical shifts
are expressed in parts per million (δ ppm). Silica gel coated
aluminium plates were used for TLC. The products were
purified by column chromatography on silica gel (60-120 mesh)
using petroleum ether–ethyl acetate as the eluent to obtain
the pure products. Exact masses of all products were derived
by using HRMS having QTOF analyzer. Reagents used were
mostly purchased from Sigma Aldrich.
2:3,4-di-O-isopropylidene-α-D-galacto-1,5-pyranose (200 mg,
70% gummy oil). To a solution of the purified iodinated
product in 5 mL of DMF was added slowly KOtBu (1.08 mmol,
121 mg) and the mixture was kept under stirring at rt for 1h.
After completion the reaction mixture was diluted with ethyl
acetate (10 mL), filtered, and washed with water (5 mL). The
organic layer was dried, evaporated, and the residue was
purified by flash column chromatography (Hexane/EtOAc 9:1)
(A) General procedure for the synthesis of compound 3a-3l,
6a-6h
Method A: with 3a as the example: To a solution furanose
glycal (0.41 mmol, 100 mg), palladium(ll)acetate (0.041 mmol,
9.18 mg) and Cu(OAc)2.H2O (1.23 mmol, 247.5 mg) in 3 mL of
dioxane at 80 °C under open air condition, methyl acrylate
(0.49 mmol, 0.44 mL) and pyridine (0.82 mmol, 0.66 mL) were
added. The mixture was allowed to stir at 80 °C for 24 h. After
completion the mixture was diluted with ethyl acetate (2 mL),
filtered, washed with water (5 mL) and finally with brine (5
mL). The organic layer was dried, evaporated, and the residue
was purified by flash column chromatography (Hexane/EtOAc,
9:1) to afford the product as white solid (123 mg 91% yield).
to afford the product
8 as oily liquid (100 mg, 76% yield).
Pd(OAc)2 (0.02 mmol, 9.2 mg), PPh3 (0.2 equiv), AgOAc (1.03
mmol, 171 mg), and ethyl acrylate (0.49 mmol, 53 µL) were
added to a stirred solution of Compound
8 (0.41 mmol, 50 mg)
o
in mixture of 2 mL DMF/DMSO (20:1) at 80 C for 24 h. After
completion the mixture was diluted with ethyl acetate (2 mL),
filtered, and washed successively with water (5 mL) and brine
(5 mL). The organic layer was dried, evaporated, and the
residue was purified by flash column chromatography
(Hexane/EtOAc, 9:1) to afford the product
mg, 60% yield).
9 as oily liquid (80
Method B: with 3a as the example: To a solution of furanose
glycal (0.41 mmol, 100 mg), in 2mL (10:1) mixture DMF and
DMSO, palladium(ll)acetate (0.041 mmol, 9.18 mg), silver
acetate (1.03 mmol, 171 mg) and methyl acrylate (0.49 mmol,
0.44 mL) were added at 80 °C under open air condition for 24
h. After completion the mixture was diluted with ethyl acetate
(2 mL), filtered, washed with water (5 mL) and finally with
brine (5 mL). The organic layer was dried, evaporated, and the
residue was purified by flash column chromatography
(Hexane/EtOAc 9:1) to afford the product as white solid (116
mg 80% yield).
D) Procedure for the synthesis of compound 11, 12
By taking 11 as the example: Sugar based diene 3g (0.12 mmol, 50
mg) and maleic anhydride 10 (0.25 mmol, 24 mg ) in ACN were
taken in a sealed tube and heated for 6h.The mixture was allowed
to cool at room temperature, diluted with ethyl acetate (5 mL),
washed with water (5 mL) and finally with brine (5 mL). The organic
layer was dried, evaporated, and the residue was purified by flash
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column chromatography (Hexane/EtOAc 7:1) to afford the product
11 as colourless oil (56% yield, 35mg).
E) Procedure for the synthesis of compound 15 from 13.
To a stirred solution of Compound 13 (3.84 mmol, 1g) in 10 mL DCM
o
was added pyridine (15.38 mmol, 1.24 mL) at 0 C. After 5 minutes
triflic anhydride (5.76 mmol, 970 µL) was added and the reaction
mixture was further stirred for 2h. After completion, the mixture
was diluted with DCM (5 mL), washed with water (5 mL) and brine
(5 mL). The organic layer was dried, evaporated, and the residue
was dried over Na2SO4. After super drying the compound over
vacuum pump, the crude compound was used as such for next step
without purification. 3-trifluromethanesulphonate-1,2:3,4-di-O-
isopropylidene-α-D-glucofuranose (2.55 mmol, 1g) was
dissolved in DMSO and DBU (5.10 mmol, 761µL) was added. The
reaction mixture was stirred overnight at rt. The reaction mixture
was diluted with ethyl acetate (50 mL), and washed with brine (50
mL). The organic layer was concentrated, evaporated, and the
residue was dried over Na2SO4 and purified by flash column
chromatography (Hexane/EtOAc 9:1) to get compound 1a as white
solid in quantitative yield (617mg). To a solution of furanose glycal
Following the general procedure (A) 3a was obtained as white
solid (123 mg 91% yield). 1H NMR (500 MHz, CDCl3) δ 7.77 (d, J
= 15.7 Hz, 1H, -C=CH), 6.10 (d, J = 5.3 Hz, 1H, H-1), 5.98 (d, J =
15.7 Hz, 1H, -C=CH), 5.38 (d, J = 5.3 Hz, 1H, H-2), 4.93 (t, J = 6.5
Hz, 1H, H-5), 4.18 (dd, J = 8.4, 6.9 Hz, 1H, H6a), 4.04 (dd, J =
8.5, 6.1 Hz, 1H, H-6b), 3.75 (s, 3H, OMe), 1.49 (s, 3H), 1.47 (s,
3H), 1.41 (s, 3H), 1.39 (s, 3H). 13C NMR (126 MHz, CDCl3)
δ
169.1 (-CO), 161.1 (C-4), 136.3 (-CH=CH), 117.3 (C-3), 115.2 (-
CH=CH), 115.0, 112.4, 107.3 (C-1), 84.1, 68.3, 52.9, 29.2, 29.2,
27.1, 26.9. HRMS (ESI+)
(M+H)+327.1444, found 327.1437.
:
m/z calcd. For C16H23O7
1a (2.54 mmol, 617 mg) in
6 mL of dioxane were added
palladium(II)acetate (0.25 mmol, 56.85 mg) and Cu(OAc)2.H2O (7.64
mmol, 1.5 g) methyl acrylate (3.05 mmol, 275 µL) and pyridine
(5.09 mmol, 411 µL) at 80 °C under open air condition for 24 h.
After completion the reaction mixture was diluted with ethyl
acetate (10 mL), filtered, washed with water (10 mL) and brine (10
mL). The organic layer was dried, evaporated, and the residue was
purified by flash column chromatography (Hexane/EtOAc, 9:1) to
afford the product 3a as white solid (653 mg, 78% yield). The
compound 14 was prepared by dissolving compound 3a (2.69
mmol, 653 mg) in 70% AcOH:H2O (10 mL) and stirring overnight at
rt. After complete conversion of starting material monitored by TLC,
solvent was evaporated and dried over high vacuum pump to
obtain compound 14 (500 mg, 87%) as gummy liquid. This
compound (1.74mmol, 500mg) was dissolved in dry toluene and
warmed to 60 oC. After 5 minutes imidazole (6.99 mmol, 475 mg),
PPh3 (6.99 mmol, 1.83 g) were added and stirred for 30 minutes at
same temperature. Iodine (6.99 mmol, 1.76 g) was added slowly in
slots maintaining the reaction temperature 56-62oC. After complete
addition, the reaction mixture was stirred for further 3h under
reflux. After complete consumption of starting material, the
reaction mixture was cooled to rt, diluted with ethyl acetate
(50mL), filtered, washed with water (20 mL) and sodium
thiosulphate (20 mL). The organic layer was evaporated and the
residue was purified by flash column chromatography
(Hexane/EtOAc 9:1) to afford the desired triene 15 gummy liquid
(300 mg, 68% yield).
Following the general procedure (A) 3b was obtained as white
solid (122 mg 87% yield). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J
= 15.7 Hz, 1H, C=CH), 6.12 (d, J = 5.3 Hz, 1H, H-1), 6.00 (d, J =
15.7 Hz, 1H, C=CH), 5.39 (d, J = 5.3 Hz, 1H, H-2), 4.94 (t, J = 6.6
Hz, 1H, H-5), 4.28 – 4.17 (m, 3H, -OCH2, H-6a), 4.05 (dd, J = 8.4,
6.3 Hz, 1H, H-6b), 1.51 (s, 3H), 1.49 (s, 3H), 1.43 (s, 3H), 1.42 (s,
3H), 1.31 (t, J = 7.1 Hz, 3H).13C NMR (126 MHz, CDCl3) δ 167.2
(-CO), 161.7 (C-4), 134.6 (-CH=CH), 116.4 (C-3), 113.6(-CH=CH),
111.0, 106.0 (C-1), 82.7, 70.2, 66.9, 60.2, 27.8, 25.7, 25.5, 14.3.
HRMS (ESI+): m/z calcd. For C17H25O7 (M+H)+341.1600, found
341.1609.
O
O
O
O
BnO
O
3c, 73%
Following the general procedure (A) 3c was obtained as white
solid (117 mg 73% yield). 1H NMR (400 MHz, CDCl3) δ 7.31 –
7.25 (m, 5H) , 6.53 (d, J = 15.7 Hz, 1H, -C=CH), 5.96 (d, J = 5.4
Hz, 1H, H-1), 5.83 (dt, J = 15.7, 6.0 Hz, 1H, C=CH), 5.31 (d, J =
5.4 Hz, 1H, H-2), 4.79 (t, J = 6.6 Hz, 1H, H-5), 4.08 – 4.02 (m,
3H, -CH2, H-6a), 3.96 (dd, J = 8.3, 6.5 Hz, 1H, H-6b), 1.40 (s, 3H),
1.39 (s, 3H), 1.36 (s, 3H), 1.33 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 153.8 (C-4), 139.7 (C-Olefin), 129.8, 129.2, 129.0,
126.5, 123.6, 116.0 (C-3), 114.3 (C-olefin), 111.9, 106.4 (C-1),
6 | J. Name., 2012, 00, 1-3
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+
85.1, 73.6, 72.2, 71.3, 68.1, 31.2, 29.3, 29.3, 27.3, 27.1. HRMS HRMS (ESI+): m/z calcd. For C22H24NaO9 (M+Na) 455.1318,
(ESI+): m/z calcd. For C22H28NaO6 (M+Na)+411.1784, found found 455.1324.
411.1778.
Following the general procedure (A) 3g was obtained as
colorless oil (103 mg 71% yield). 1H NMR (400 MHz, CDCl3)
δ
Following the general procedure (A) 3d was obtained as
colorless oil (98 mg 71% yield). 1H NMR (400 MHz, CDCl3) 7.31
(m, 4H) 7.21 (m, 1H) 6.81 (s, 1H, H-1) 6.57 (d, J = 16.4 Hz, 1H, -
C=CH) 6.27 (d, J = 16.4 Hz, 1H, -C=CH) 5.77 (d, J = 3.0 Hz, 1H, H-
3) 5.19 (t, J = 3.5 Hz, 1H) 4.52 – 4.42 (m, 2H) 4.27 – 4.17 (m,
1H) 2.13 – 2.08 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 170.5,
170.2, 169.6, 146.4 (C-1), 137.3, 128.6 (–C=CH-), 127.1, 125.9,
124.9, 123.9 (–C=CH-), 110.7 (C-2), 73.7, 67.0, 63.5, 61.3, 20.9,
7.34 – 7.27 (m, 2H), 6.98 (t, J = 8.7 Hz, 2H), 6.80 (s, 1H, H-1),
6.47 (d, J = 16.4 Hz, 1H, -C=CH), 6.22 (d, J = 16.4 Hz, 1H, -C=CH),
5.74 (d, J = 3.0 Hz, 1H, H-3), 5.18 (t, J = 3.5 Hz, 1H), 4.48 (dd, J =
15.7, 5.1 Hz, 2H), 4.21 (dd, J = 6.8, 3.9 Hz, 1H), 2.11 (s, 3H),
2.10 (s, 3H), 2.09 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ
170.4, 170.2, 169.5, 163.2, 160.8, 146.4(C-1), 133.57,
127.4 (-C=CH), 127.3, 123.8, 123.7, 115.6, 115.4, 110.6
(C-2), 99.0, 73.8, 67.0, 63.6, 61.3, 20.8, 20.7.HRMS (ESI+)
:
20.8.
HRMS
(ESI+)
:
m/z
calcd.
for C20H22NaO7
m/z calcd. For C20H21FNaO7 (M+Na)+ 415.1169, found
(M+Na)+397.1258, found 397.1234.
415.1165.
Following the general procedure (A) 3e was obtained as
colorless oil (125 mg 74% yield). 1H NMR (500 MHz, CDCl3)
δ
Following the general procedure (A) 3h was obtained as
colorless oil (108 mg 83% yield). 1H NMR (400 MHz, CDCl3)
7.44 – 7.34 (m, 2H) 7.26 – 7.15 (m, 2H) 6.82 (s, 1H, H-1) 6.55
(d, J = 16.4 Hz, 1H, -C=CH) 6.18 (d, J = 16.3 Hz, 1H, -C=CH) 5.74
(d, J = 3.1 Hz, 1H) 5.17 (t, J = 3.4 Hz, 1H) 4.54 – 4.45 (m, 2H),
4.23 – 4.11 (m, 1H) 2.10 (s, 3H), 2.10 (s, 3H), 2.09 – 2.07 (s,
3H). 13C NMR (126 MHz, CDCl3) 170.5, 170.2, 169.5, 146.9 (C-
1), 136.3, 131.7(-C=CH), 127.4, 124.8, 123.5, 120.7 (–C=CH),
110.5 (C-2), 73.8, 66.9, 63.3, 61.2, 20.9, 20.8, 20.8. HRMS
(ESI+): m/z calcd. For C20H21BrNaO7 (M+Na)+; 475.0368, found
475.0365.
δ
7.14 (d, J = 15.9 Hz, 1H), 6.92 (s, 1H), 5.57 (d, J = 15.8 Hz, 1H),
5.53 (d, J = 2.2 Hz, 1H), 5.10 (t, J = 3.4 Hz, 1H), 4.46 – 4.34 (m,
2H), 4.12 (dd, J = 11.6, 3.9 Hz, 1H), 3.66 (s, 3H), 2.03 (s, 3H),
2.02 (s, 3H), 2.02 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 170.3,
169.9, 169.3, 167.4, 152.2, 141.0, 113.8, 109.3, 74.4, 66.3,
62.7, 61.0, 51.5, 29.6, 20.8, 20.7, 20.7. HRMS (ESI+): m/z calcd.
For C16H20NaO9 (M+Na)+ 379.1005, found 379.1012.
OBn
O
OMe
BnO
OBn
O
3i, 89%
Following the general procedure (A) 3i was obtained as gummy
solid (107 mg 89% yield). 1H NMR (400 MHz, CDCl3) δ 7.48 –
7.15 (m, 16H, (15HOBn, 1H, -C=CH)), 6.94 (s, 1H, H-1), 5.70 (d, J
= 15.7 Hz, 1H, -C=CH), 4.65 (m, 2H), 4.59 – 4.52 (m, 1H), 4.51 –
4.43 (m, 4H), 4.22 – 4.15 (m, 1H), 4.01 (t, J = 3.1 Hz, 1H), 3.78
(dd, J = 10.4, 6.9 Hz, 1H), 3.73 (s, 3H, OMe), 3.66 (dd, J = 10.4,
5.2 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 167.9 (-CO), 152.2 (C-
1), 143.2 (-C=CH), 137.7, 137.4, 137.2, 128.6, 128.5, 128.5,
128.2, 128.1, 128.1, 127.1, 127.8, 127.8, 112.7 (-C=CH), 111.0
Following the general procedure (A) 3f was obtained as
colorless oil (113 mg 71% yield). 1H NMR (500 MHz, CDCl3)
δ
7.34 (m, 2H) 7.04 – 6.95 (m, 2H) 6.81 (s, 1H, H-1) 6.51 (d, J =
16.2 Hz, 1H, -C=CH) 6.23 (d, J = 16.3 Hz, 1H, -C=CH) 5.75 (d, J =
2.9 Hz, 1H), 5.18 (t, J = 3.6 Hz, 1H) 4.50 – 4.43 (m, 2H), 4.21 (m,
1H), 2.29 (s, 3H), 2.11 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H). 13C
NMR (126 MHz, CDCl3) δ 171.9, 171.6, 171.0, 171.0, 151.0,
148.0 (C-1), 144.6, 136.6, 128.2 (-C=CH), 125.6, 125.3, 123.1 (-
C=CH) 112.0 (C-2), 75.2, 68.4, 64.9, 62.7, 22.5, 22.3, 22.3, 22.2.
This journal is © The Royal Society of Chemistry 20xx
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(C-2), 76.5, 73.4, 71.9, 70.8, 69.9, 69.9, 51.4, 31.6, 22.7, 14.2.
+
HRMS (ESI+): m/z calcd. For C31H32NaO6 (M+Na) ; 523.2097,
found 523.2090.
Following the general procedure (A) 6a was obtained as
gummy solid (131 mg 82% yield). 1H NMR (400 MHz, CDCl3)
δ
7.32 (m, 8H), 7.27 (m, 7H), 6.67 (s, 1H, H-1), 6.26 (d, J = 15.9
Hz, 1H, H-7), 5.94 (d, J = 3.8 Hz, 1H, H-12), 5.51 (dd, J = 15.8,
Following the general procedure (A) 3j was obtained as gummy 6.7 Hz, 1H, H-8), 5.16 (d, J = 3.0 Hz, 1H, H-11), 4.80 (dd, J = 6.6,
solid (106 mg 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.38 – 2.5 Hz, 1H), 4.66 (d, J = 1.5 Hz, 1H), 4.54 (d, J = 3.8 Hz, 1H), 4.49
7.26 (m, 14H, 13H-OBN, 1H -C=CH), 7.25 – 7.20 (m, 2H), 6.94 (d, J = 6.3 Hz, 2H), 4.44 (s, 2H), 4.38 – 4.33 (m, 1H), 4.22 (d, J =
(s, 1H, H-1), 5.68 (d, J = 15.7 Hz, 1H, -C=CH) 4.66 (d, J = 5.8 Hz, 2.9 Hz, 1H), 4.00 – 3.95 (m, 1H), 3.78 (dd, J = 10.5, 6.5 Hz, 1H),
2H), 4.57 – 4.44 (m, 5H), 4.19 (s, 1H), 4.15 (m, 2H), 4.02 (t, J = 3.65 (dd, J = 10.6, 4.4 Hz, 1H), 1.93 (s, 3H), 1.54 (s, 3H), 1.33 (s,
3.1 Hz, 1H), 3.78 (dd, J = 10.4, 6.9 Hz, 1H), 3.67 (dd, J = 10.4, 3H). 13C NMR (101 MHz, CDCl3) δ 169.8, 146.7 (C-1), 137.9,
5.2 Hz, 1H), 1.65 (m, 2H), 1.43 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H). 137.8, 131.2 (C-7), 128.5, 128.4, 128.4, 127.1, 127.9, 127.7,
13C NMR (101 MHz, CDCl3) δ 167.5, 152.0 (C-1), 142.8 (-C=CH), 127.7, 116.8 (C-8), 111.9 (C-2), 111.4, 104.4 (C-12), 83.6, 80.3,
137.8, 137.5, 137.3, 128.7, 128.5, 128.4, 128.2, 128.1, 128.0, 77.7, 76.2, 73.4, 72.1, 71.8, 71.1, 69.8, 68.24, 26.7, 26.3,
127.9, 127.8, 127.7, 113.3 (-C=CH), 111.1 (C-2), 76.5, 73.4, 20.7.HRMS (ESI+) :(m/z) calcd. forC38H42NaO9 (M+Na)+
71.9, 70.7, 70.1, 70.0, 68.1, 63.9, 30.9, 19.2, 13.6.HRMS (ESI+)
m/z calcd. For C34H38NaO6 (M+Na) +565.2566, found 565.2571.
:
665.2727, found 665.2732.
Following the general procedure (A) 6b was obtained as
gummy white solid (165 mg 81% yield). 1H NMR (400 MHz,
CDCl3) δ 6.69 (d, J = 15.7 Hz, 1H, H-7), 6.01 (d, J = 5.4 Hz, 1H, H-
1), 5.96 (d, J = 3.8 Hz, 1H, H-9), 5.66 (dd, J = 15.8, 6.4 Hz, 1H, H-
8), 5.31 (d, J = 5.4 Hz, 1H, H-2), 5.22 (d, J = 3.0 Hz, 1H), 4.85 (m,
2H), 4.57 (d, J = 3.8 Hz, 1H), 4.11 (dd, J = 8.3, 6.8 Hz, 1H), 4.01
(dd, J = 8.3, 6.5 Hz, 1H), 2.05 (s, 3H), 1.53 (s, 3H), 1.46 (s, 3H),
1.45 (s, 3H), 1.39 (s, 3H), 1.39 (s, 3H) 1.33 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 169.6, 153.3 (C-4), 123.6 (C-7), 120.5 (C-3),
114.3 (C-8), 112.9, 112.0, 110.5, 104.1 (C-1), 104.5 (C-9), 83.6,
80.1, 77.5, 69.8, 66.6, 27.9, 27.8, 26.7, 26.2, 25.8, 25.7, 20.7.
HRMS (ESI+): m/z calcd. forC23H32NaO10 (M+Na)+491.1823,
found 491.1818.
Following the general procedure (A) 3k was obtained as
gummy white solid (115 mg 90% yield). 1H NMR (400 MHz,
CDCl3) δ 7.32 – 7.15 (m, 11H, 10H–OBn, 1H-C=CH), 6.82 (s, 1H,
H-1) 5.66 (d, J = 15.7 Hz, 1H, -C=CH), 4.58 (s, 2H), 4.42 (s, 2H),
4.33 (m, 1H), 4.16 (d, J = 1.5 Hz, H), 3.63 (s, 3H, OMe), 1.31 (d, J
= 6.9 Hz, 3H, CH3 ). 13C NMR (126 MHz, CDCl3) δ 168.0, 152.5
(C-1), 143.4 (-C=CH), 137.6, 128.6, 128.5, 128.1, 127.9, 127.9,
112.5 (-C=CH), 110.1 (C-2), 74.1, 72.0, 71.2, 70.4, 51.3, 16.7.
+
HRMS (ESI+): m/z calcd. For C24H26NaO5 (M+Na) 417.1678,
found 417.1674.
Following the general procedure (A) 3l was obtained as
colorless oil (114 mg 81% yield). 1H NMR (400 MHz, CDCl3)
δ
6.30 (s, 1H, C-1), 5.46 (d, J = 5.5 Hz, 1H), 5.42 (m, 1H), 5.29 (m,
1H), 5.17 (dd, J = 7.4, 5.4 Hz, 1H), 4.38 (dd, J = 12.0, 5.8 Hz, 1H),
4.23 – 4.14 (m, 2H), 2.58 (d, J = 6.6 Hz, 2H), 2.09 (s, 3H), 2.06
(s, 3H), 2.05 (s, 3H), 1.97 (m, 2H), 1.36 – 1.26 (m, 6H), 0.88 (t, J
= 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3): δ 170.6, 170.5,
169.7, 141.6, 133.3, 126.0, 109.8, 73.5, 68.3, 68.1, 61.5, 32.4,
31.6, 31.4, 22.5, 20.8, 20.7, 14.0. HRMS (ESI+): m/z calcd.
forC20H30NaO7 (M+Na)+ 405.1889, found 405.1893.
Following the general procedure (A) 6c was obtained as
gummy solid (150 mg 78% yield). 1H NMR (400 MHz, CDCl3)
δ
6.68 (s, 1H, H-1), 6.20 (d, J = 16.0 Hz, 1H, H-7), 5.92 (d, J = 3.8
Hz, 1H, H-12), 5.55 (d, J = 3.1 Hz, 1H, H-11), 5.22 (dd, J = 16.0,
6.3 Hz, 1H, H-8), 5.16 (d, J = 2.8 Hz, 1H, H-3), 5.10 (t, J = 3.7 Hz,
1H), 4.74 (dd, J = 6.2, 2.4 Hz, 1H), 4.55 (d, J = 3.8 Hz, 1H), 4.45 –
8 | J. Name., 2012, 00, 1-3
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4.36 (m, 2H), 4.19 – 4.06 (m, 1H), 2.09 – 2.07 (s, 9H), 2.04 (s,
3H), 1.51 (s, 3H), 1.31 (s, 5H). 13C NMR (101 MHz, CDCl3)
δ
170.4, 170.3, 169.6, 169.5, 146.9 (C-1), 129.1 (C-7), 117.6 (C-8),
111.1, 109.8 (C-2), 104.4 (C-12), 83.5, 79.8, 73.8, 67.1, 63.6,
61.1, 29.7, 26.7, 26.2, 20.8, 20.7, 20.6. HRMS (ESI+): m/z calcd.
For C23H30NaO12 (M+Na)+521.1635, found 521.1639.
Following the general procedure (A) 6f was obtained as
gummy liquid (149 mg 73% yield). 1H NMR (400 MHz, CDCl3)
δ
6.58 (s, 1H, H-1), 6.20 (d, J = 15.9 Hz, 1H, H-7), 5.91 (d, J = 3.8
Hz, 1H, H-12), 5.71 (dd, J = 15.9, 7.6 Hz, 1H,H-8), 4.62 (dd, J =
7.6, 2.9 Hz, 1H), 4.55 (d, J = 3.9 Hz, 1H), 4.24 – 4.15 (m, 1H),
4.06 (d, J = 3.7 Hz, 1H), 3.74 (m, 1H), 3.70 (m, 3H), 3.68 – 3.59
(m, 4H), 3.58 – 3.49 (m, 4H), 1.50 (s, 3H), 1.32 (s, 3H), 1.24 –
1.16 (m, 12H).13C NMR (101 MHz, CDCl3) δ 145.1 (C-1), 130.8
(C-7), 118.6 (C-8), 111.1, 111.3 (C-2), 104.7 (C-1), 84.5, 83.2,
81.9, 72.4, 72.3, 68.7, 66.8, 66.2, 65.1, 63.2, 26.8, 26.3, 15.6,
15.5, 15.2, 15.1. HRMS (ESI+): m/z calcd. for C23H38NaO8
(M+Na)+ 465.2464, found 465.2466.
Following the general procedure (A) 6d was obtained as
gummy liquid (161 mg 77% yield). 1H NMR (400 MHz, CDCl3)
δ
6.56 (s, 1H, H-1), 6.20 (d, J = 15.8 Hz, 1H, H-7), 5.92 (d, J = 3.8
Hz, 1H, H-12), 5.51 (dd, J = 15.8, 6.7 Hz, 1H, H-8), 5.15 (d, J =
2.9 Hz, 1H, H-11), 4.77 (dd, J = 6.6, 2.7 Hz, 1H), 4.53 (d, J = 3.8
Hz, 1H), 4.19 (d, J = 5.3 Hz, 1H), 4.01 (d, J = 3.8 Hz, 1H), 3.75 –
3.48 (m, 9H), 2.04 (s, 3H), 1.51 (s, 3H), 1.30 (s, 3H), 1.20 (m,
9H). 13C NMR (101 MHz, CDCl3) δ 169.7, 146.4 (C-1), 131.3 (C-
7), 116.6 (C-8), 111.8 (C-2), 111.8, 104.4 (C-12), 83.6, 80.3,
77.7, 76.5, 72.4, 72.0, 68.5, 66.8, 66.0, 62.9, 26.7, 26.2, 20.6,
15.5, 15.5, 15.1. HRMS (ESI+): m/z calcd. forC23H36NaO9
(M+Na)+479.2257, found 479.2251.
Following the general procedure (A) 6g was obtained as
gummy liquid (149 mg 77% yield). 1H NMR (400 MHz, CDCl3)
δ
6.58 (s, 1H, H-1), 6.16 (d, J = 15.9 Hz, 1H, H-7), 5.90 (d, J = 3.8
Hz, 1H, H-12), 5.80 (d, J = 4.3 Hz, 1H, H-3), 5.37 (t, J = 4.2 Hz,
1H), 5.23 (dd, J = 16.0, 6.4 Hz, 1H, H-8), 5.14 (d, J = 2.9 Hz, 1H,
H-11), 4.72 (dd, J = 6.4, 2.4 Hz, 1H), 4.53 (d, J = 3.8 Hz, 1H),
4.42 (m, 1H), 4.38 – 4.32 (m, 1H), 4.24 (m, 1H), 2.08 (s, 3H),
2.07 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 1.49 (s, 3H), 1.29 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 170.6, 170.6, 169.5, 169.5, 146.5
(C-1), 128.5 (C-7), 117.9 (C-8), 111.1, 110.5 (C-2), 104.4 (C-12),
83.5, 72.1, 65.4, 61.8, 61.4, 26.7, 26.2, 20.8, 20.6, 20.6, 20.5.
HRMS (ESI+): m/z calcd. for C23H30NaO12 (M+Na)+ 521.1635,
found 521.1643
Following the general procedure (A) 6e was obtained as
gummy solid (124 mg 79% yield). 1H NMR (400 MHz, CDCl3)
δ
7.35 – 7.28 (m, 10H), 7.26 (dd, J = 7.2, 2.2 Hz, 5H), 6.66 (s, 1H,
H-1), 6.25 (d, J = 15.9 Hz, 1H, H-7), 5.92 (d, J = 3.8 Hz, 1H, H-
12), 5.73 (dd, J = 15.9, 7.6 Hz, 1H, H-8), 4.65 (m, 2H), 4.54 (m,
2H), 4.48 (m, 3H), 4.36 (dd, J = 6.4, 4.2 Hz, 1H), 4.27 (d, J = 2.8
Hz, 1H), 3.96 (t, J = 4.0 Hz, 1H), 3.80 – 3.64 (m, 4H), 3.57 (dd, J
= 9.4, 7.0 Hz, 1H), 3.50 – 3.42 (m, 1H), 1.52 (s, 3H), 1.33 (s, 3H),
1.12 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 146.2 (C-
1), 138.1, 138.0, 137.9, 130.6 (C-7), 128.6, 128.5, 128.5, 128.4,
128.4, 128.3, 128.0, 127.9, 127.9, 127.8, 127.7, 127.7, 127.6,
118.8 (C-8), 111.7, 111.3 (C-2), 104.7 (C-12), 84.4, 83.3, 81.8,
76.2, 73.4, 72.1, 71.1, 71.4, 70.2, 68.4, 66.2, 26.9, 26.3, 15.2.
HRMS (ESI+): m/z calcd. for C38H44NaO8 (M+Na)+651.2934,
found 651.2939.
Following the general procedure (A) 6h was obtained as
gummy liquid (140 mg 63% yield). 1H NMR (400 MHz, CDCl3)
δ
6.68 (s, 1H, H-1), 6.24 (d, J = 15.9 Hz, 1H, H-7), 5.90 (d, J = 3.8
Hz, 1H, H-12), 5.61 (d, J = 2.8 Hz, 1H, H-3), 5.30 (dd, J = 15.9,
8.0 Hz, 1H, H-8), 5.14 (d, J = 2.8 Hz, 1H, H-11), 4.92 (t, J = 3.7
Hz, 1H), 4.70 (dd, J = 8.0, 2.7 Hz, 1H), 4.52 (d, J = 3.8 Hz, 1H),
4.28 (m, 1H), 2.08 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 1.52 (s, 3H),
1.35 (d, J = 6.9 Hz, 3H), 1.30 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 170.1, 169.7, 169.7, 147.1 (C-1), 132.2 (C-7), 115.9 (C-8),
111.9, 109.1 (C-2), 104.3 (C-12), 83.7, 80.4, 72.4, 70.9, 63.9,
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26.7, 26.2, 20.9, 20.8, 20.6, 16.2. HRMS (ESI+): m/z calcd. for Following the general procedure (C)
Journal Name
9
was obtained as oily
C21H28NaO10 (M+Na)+ 463.1580, found 463.1573
liquid (80 mg 60% yield). 1H NMR (400 MHz, CDCl3) δ 7.69
(dd, J = 15.6, 11.3 Hz, 1H, Hb, E,E), 7.57 (dd, J = 15.1,
12.2 Hz, 1H, Hb, E,Z), 6.02 (d, J = 12.2 Hz, 1H, Hc, E,Z),
5.87 (dd, J = 15.4, 11.9 Hz, 2H, Ha, E,E), Hc (E,E), 5.76 –
5.71 (m, 2H, Ha, E,E)), 5.66 (d, J = 3.7 Hz, 1H), 5.12 (d, J =
7.3 Hz, 1H), 4.63 (ddd, J = 11.3, 7.2, 2.2 Hz, 2H), 4.56 (d, J
= 7.1 Hz, 1H), 4.34 (dd, J = 3.6, 2.5 Hz, 1H), 4.28 (dd, J =
3.3, 2.1 Hz, 1H), 4.24 – 4.16 (m, 4H), 1.47 (s, 6H), 1.42 (s,
3H), 1.40 (s, 3H), 1.38 (s, 3H), 1.35 (m, 5H), 1.30 – 1.27
(m, 5H). 13C NMR (101 MHz, CDCl3) δ 167.0 (CO), 167.0
(CO), 154.1, 152.1, 138.1, 137.5, 120.7, 120.6, 115.2,
112.9, 111.0, 110.9, 110.5, 110.2, 97.6, 97.6, 73.5, 72.70,
72.1, 70.9, 70.5, 66.9, 60.3, 60.2, 26.9, 26.7, 26.5, 26.4,
25.6, 24.6, 24.5, 14.3. HRMS (ESI+): m/z calcd. for C17H25O7
(M+H)+ 341.1600, found 341.1595
OAc
O
O
O
O
AcO
O
OAc
O
O
6i,
59%
Following the general procedure (B) 6i was obtained as
colorless liquid (125 mg 59% yield). 1H NMR (400 MHz, CDCl3)
δ 6.67 (s, 1H, H-1), 6.09 (d, J = 16.1 Hz, 1H, H-7), 5.86 (d, J = 3.7
Hz, 1H, H-12), 5.60 (d, J = 3.2 Hz, 1H, H-3), 5.42 (dt, J = 15.9, 5.8
Hz, 1H, H-8), 5.13 (t, J = 3.6 Hz, 1H), 4.52 (d, J = 3.7 Hz, 1H),
4.47 – 4.38 (m, 2H), 4.35 – 4.26 (m, 1H), 4.17 (dd, J = 11.1, 3.4
Hz, 1H), 4.15 – 4.09 (m, 3H), 4.09 – 4.05 (m, 1H), 3.99 (dd, J =
8.6, 5.7 Hz, 1H), 3.92 (d, J = 2.9 Hz, 1H), 2.09 (s, 3H), 2.08 (s,
3H), 2.07 (s, 3H), 1.49 (s, 4H), 1.42 (s, 4H), 1.35 (s, 4H), 1.31 (s,
4H).13C NMR (101 MHz, CDCl3) δ 170.4, 170.1, 169.5, 146.4 (C-
1), 127.9 (C-7), 121.3 (C-8), 111.8, 109.7 (C-2), 109.0, 105.2 (C-
12), 82.8, 81.3, 81.2, 73.7, 72.5, 70.9, 67.3, 67.1, 63.9, 61.2,
26.8, 26.3, 25.5, 25.4 20.8, 20.7, 20.7. HRMS (ESI+): m/z calcd.
for C27H38NaO13 (M+Na)+ 593.2210, found 593.2219
O
O
O
Following the general procedure (D) 11 was obtained as oily
liquid (35 mg 56% yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (m,
2H), 7.08 (m, 2H), 6.34 (s, 1H), 5.54 (d, J = 4.9 = 4. Hz, 1H), 4.92
(m, 1H), 4.89 – 4.84 (m, 1H), 4.25 – 4.17 (m, 1H), 4.04 (m, 1H),
3.75 (m, 1H), 3.58 (m, 1H), 2.13 (s, 3H), 2.12 (s, 6H). 13C NMR
(101 MHz, CDCl3) δ 171.1, 169.7, 169.3, 168.6, 167.4, 132.6,
130.5, 130.4, 130.4, 115.7, 115.5, 74.5, 71.1, 69.1, 63.4, 60.3,
45.1, 44.7, 38.5, 29.7, 20.1, 20.8, 20.8. HRMS (ESI+): m/z calcd.
for C24H23FNaO10 (M+Na)+ 513.1173, found 513.1168.
O
AcO
O
OAc
O
O
6j,
63%
Following the general procedure (B) 6j was obtained as
colorless liquid (154 mg 63% yield). 1H NMR (400 MHz, CDCl3)
δ 6.66 (s, 1H, H-1), 6.07 (d, J = 16.0 Hz, 1H, H-7), 5.93 (d, J = 3.6
Hz, 1H, H-3), 5.86 (d, J = 3.6 Hz, 1H, H-11), 5.58 (d, J = 3.3 Hz,
1H), 5.36 (dt, J = 15.9, 6.0 Hz, 1H), 4.96 (t, J = 4.0 Hz, 1H), 4.51
(dd, J = 8.5, 3.7 Hz, 1H), 4.33 – 4.25 (m, 2H), 4.18 – 4.12 (m,
1H), 4.11 – 4.03 (m, 2H), 4.01 – 3.95 (m, 1H), 3.93 (d, J = 3.0 Hz,
1H), 2.07 (s, 3H), 2.06 (s, 3H), 1.48 (s, 3H), 1.43 (s, 3H), 1.41 (s,
3H), 1.35 (s, 3H), 1.30 (d, J = 4.3 Hz, 3H).13C NMR (101 MHz,
CDCl3) δ 170.3, 169.8, 147.0 (C-1), 128.7 (C-7), 120.7 (C-8),
111.8, 111.8, 109.6 (C-2), 109.2, 108.1, 105.3, 105.3 (C-12),
85.1, 82.9, 81.3, 81.2, 80.1, 75.2, 73.5, 72.5, 72.3, 71.3, 71.2,
67.7, 67.3, 64.9, 26.3, 26.2, 25.4, 25.2, 20.9, 20.8, 16.2. HRMS
(ESI+): m/z calcd. for C25H36NaO11 (M+Na)+ 535.2155, found
535.2147
Following the general procedure (D) 12 was obtained as white
gummy solid (37 mg 62% yield). 1H NMR (400 MHz, CDCl3)
δ
5.90 (d, J = 3.6 Hz, 1H), 5.72 (d, J = 2.0 Hz, 1H), 5.54 (s, 1H),
5.44 (dd, J = 5.4, 3.0 Hz, 1H), 5.40 (d, J = 2.7 Hz, 1H), 5.06 (dd, J
= 11.1, 2.7 Hz, 1H), 4.74 (dd, J = 11.9, 9.0 Hz, 1H), 4.62 (dd, J =
8.1, 1.6 Hz, 1H), 4.56 (d, J = 3.6 Hz, 1H), 4.45 – 4.39 (m, 1H),
3.91 (dd, J = 12.0, 4.9 Hz, 1H), 3.74 – 3.64 (m, 2H), 2.69 – 2.52
(m, 1H), 2.09 (s, 3H), 2.04 (s, 6H), 2.01 (s, 3H), 1.58 (s, 3H), 1.33
(s, 6H).13C NMR (101 MHz, CDCl3) δ 171.2, 170.1, 169.7, 169.4,
169.2, 167.3, 134.4, 123.2, 113.1, 104.5, 83.5, 75.5, 73.1, 69.5,
67.6, 64.2, 59.2, 44.6, 40.7, 33.3, 31.9, 26.8, 26.7, 20.8, 20.8,
20.6, 20.5. HRMS (ESI+): m/z calcd. for C27H32NaO15 (M+Na)+
619.1639, found 619.1647.
10 | J. Name., 2012, 00, 1-3
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ARTICLE
Mukherjee, S. K. Yousuf, and S. C. Taneja, Org. Lett., 2008, 10, 4831; (g) S. K.
Yousuf, S. C. Taneja, and D. Mukherjee, J. Org. Chem., 2010, 75, 3097. (h) A. K.
Kusunuru, M. Tatina, S. K. Yousuf, D. Mukherjee, Chem. Commun., 2013, 49
,
10154-10156. (i) M. Tatina, A. K Kusunuru, S. K. Yousuf, D. Mukherjee, Chem.
Commun., 2013, 49, 11409-11411. (j) R. Pathak, A. K. Shaw, A. P. Bhaduri,
Tetrahedron., 2002, 58, 3535-3541. (k) M. Tatina, A. K Kusunuru, S. K. Yousuf,
D. Mukherjee, Eur. J. Org. Chem., 2014, 7333–7338
10 (a) D. J.Holt, W. D. Barker, P. R Jenkins, D. L Davies, J. Garratt J. Fawcett, D. R.
Russell, and S. Ghosh, Angew. Chem., Int. Ed., 1998, 37, 3298–3300; (b) D. J.
Holt, W. D. Barker, P. R. Jenkins, J. Org. Chem., 2000, 65, 482–493.
Following the general procedure (E) 15 was obtained as oily
liquid (300 mg 68% yield). 1H NMR (400 MHz, CDCl3) δ 7.56
(dd, J = 15.5, 0.6 Hz, 1H), 6.59 (dd, J = 17.1, 11.0 Hz, 1H), 6.14
(d, J = 5.3 Hz, 1H), 6.01 (d, J = 15.5 Hz, 1H), 5.94 (dd, J = 17.1,
1.4 Hz, 1H), 5.59 (dd, J = 11.0, 1.4 Hz, 1H), 5.42 (d, J = 5.2 Hz,
1H), 3.76 (s, 3H), 1.47 (s, 3H), 1.34 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 167.7, 158.0, 134.3, 122.8, 121.1, 115.6, 113.6, 113.4,
105.3, 82.5, 51.4, 27.8, 27.5. HRMS (ESI+): m/z calcd. for
C13H16NaO5 (M+Na)+ 275.0895, found 275.0890.
11 R. V Bonnert, and P. R. Jenkins, J. Chem. Soc. Chem. Commun., 1987, 6–7.
12 A. J. Wood, P. R. Jenkins, J. Fawcett, and D. R. Russell, J. Chem. Soc., Chem.
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15 R. L. Mallkharjuna, and D. Mukherjee, Rsc. Advances., 2014, 4, 37908-37913
16 (a) B. Munhyung, H. P. So, K. Yun, k. L. Sang, Jongheon, S.; Joo-won, O. Dong-
Chan, Drugs., 2017, 15, 38; (b) W. Dan, and G. Shuanhu, Org. Chem.
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The authors are thankful to DST-India (EMR-2016-004710) for
funding. Nazar Hussain thanks UGC New Delhi for a senior
research fellowship. IIIM Publication No. IIIM/2147/2017.
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