Convenient strategies for the synthesis of 1,4-phenylene spaced sugars

Article abstract of DOI:10.1016/j.carres.2011.11.005

Two synthetic strategies have been developed for the synthesis of spaced sugars with lipophilic 1,4-phenylene core. A building block combining the usefulness of Weinreb amide functionality and modified Julia olefination reaction has been explored towards this objective. This building block offers complete flexibility in attaching any desired sugar derivative across phenylene spacer via C-C bond formation. The other strategy uses carbohydrate based building blocks for the synthesis of symmetrical as well as unsymmetrical 1,4-phenylene spaced sugars. This is the first report for the synthesis of 1,4-phenylene spaced sugars via C-C bond formation.

Full text of DOI:10.1016/j.carres.2011.11.005

Carbohydrate Research 347 (2012) 55–63
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Convenient strategies for the synthesis of 1,4-phenylene spaced sugars
⇑
Annamalai Senthilmurugan, Indrapal Singh Aidhen
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Two synthetic strategies have been developed for the synthesis of spaced sugars with lipophilic 1,4-
phenylene core. A building block combining the usefulness of Weinreb amide functionality and modified
Julia olefination reaction has been explored towards this objective. This building block offers complete
flexibility in attaching any desired sugar derivative across phenylene spacer via C–C bond formation.
The other strategy uses carbohydrate based building blocks for the synthesis of symmetrical as well as
unsymmetrical 1,4-phenylene spaced sugars. This is the first report for the synthesis of 1,4-phenylene
spaced sugars via C–C bond formation.
Received 9 September 2011
Received in revised form 3 November 2011
Accepted 4 November 2011
Available online 19 November 2011
Keywords:
Spaced sugars
Julia olefination
Sulfones
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
herein describes the first successful synthesis of 1,4-phenylene
spaced sugars 3, through a novel alternative route.
Carbohydrate dimers, wherein two sugar moieties are con-
nected by aromatic ring and one or two acetylenic bonds were
envisioned as an exciting new class of scaffolds.1a,b Incidentally,
Hans Peter Wessel’s search for simplified structural analogues as
heparinoid mimetics at Roche also culminated with compounds
represented by structure 1.1c
2. Results and discussion
Two disconnections envisaged for the synthesis of 3 are delin-
eated in Figure 4. Disconnection I, through synthon A has few
apparent advantages over disconnection II through synthon B.
The former allows assembling of sugar residues on the core, both
as electrophilic and nucleophilic components in the synthetic
scheme. Sequential addition of same or different sugars would fur-
ther enable convenient access to symmetrical and unsymmetrical
Aromatic2 or non-aromatic3 spacers have been linked with cyc-
lic or acyclic sugars through O/N/S atoms or through various func-
tionalities, such as ethers, thioethers, esters, amides, thioamides,
urea, thiourea, carbamates and thiocabamates, (Fig. 1). In our quest
towards spaced sugars with lipophilic cores, as a new functional
material for exploration towards bola-amphipiles or after sulfation
of the free hydroxyls, as heparionoid mimetics, we aimed at biphe-
nyl and phenylene spaced sugars 2 and 3, respectively. Synthesis of
envisaged biphenyl and phenylene spaced sugar poses a challenge,
particularly when the spacer and the sugar residues are linked di-
rectly through C–C bond and not through any linker group or func-
tionality, (Fig. 2).
Sugar
L
L
Sugar
Spacer
Aromatic Spacers :-
Non-aromatic Spacers :-
O
O
O
Recently, we accomplished the synthesis of 4,40-biphenyl
spaced sugars 2 through bis-alkylation of sulfonyl stabilized ben-
zylic carbanion in the building block 4 with sugar derived halides
and subsequent de-sulfonylation.4 However, the strategy failed
when applied to the synthesis of 1,4-phenylene spaced sugars 3
through the corresponding building block 5, (Fig. 2).
It is entropically favored expulsion of phenylsulfinate ion that
precedes the desired alkylation, which mars the success with build-
ing block 5 towards the synthesis of 3 (Fig. 3). The work presented
O
O
O
H
N
N
H
O
O
4
8
O
O
H
N
H
N
MeOOC
COOMe
O
O
L=Linkers groups :-
Ethers, Thioethers, Esters, Amides, thioamides,
Urea, Thiourea, Carbamates, thiocarbamates.
⇑
Corresponding author. Tel.: +91 44 22574219; fax: +91 44 22574202?
E-mail address: isingh@iitm.ac.in (I.S. Aidhen).
Figure 1. General classifications of spaced sugars.
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.11.005

56
A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
NaH, DMF 0 οC, 1 h
NaH, DMF 0 οC, 1 h
7
C
C
SO2Ph
O
O
O
n
81%
67%
O
O
O
O
PhO2S
2
: n = 2
n
3: n = 1
8
9
O
O
4
: n = 2
5: n = 1
Polyhydroxylated
alkyl residues
Z
Z
O
Figure 2. Biphenyl and phenyl spaced sugars through sulfones.
O
O
O
H
O
H
11:
97%
13:
10:
Z = CON(OMe)Me
Z = CHO
Z = CON(OMe)Me
Z = CHO
LAH, THF
0
LAH, THF
οC, 1 h
οC, 1 h
88%
12:
0
C
C
5
Scheme 1. Synthesis of carbohydrate tethered aromatic aldehydes.
3
synthetic scheme, which dictated the choice of these two sulfones
as nucleophilic sugar component. The sulfone 14 could be easily syn-
thesized in three convenient and high yielding steps, starting from
SO2Ph
NaH/DMF
5
SO2Ph
PhO2S
PhO2S
6
known di-isopropylidene protected D-arabino-configured alcohol
15.8 It involved the conversion of the alcohol 15 to the corresponding
bromide 16 with N-bromosuccinimide and triphenylphosphine in
DMF as solvent at 50 °C. Thio-alkylation of commercially available
2-mercaptobenzothiazole 17 with bromide 16 in presence of NaH
in DMF at 0 °C afforded the sulfide 18 in 83% yield. Final oxidation
of sulfide 18 using m-chloroperbenzoic acid furnished the desired
sugar based sulfone 14 as a crystalline solid, Scheme 2. Using the
Figure 3. Fragmentation of carbanion from sulfone 5.
1,4-phenylene spaced sugars, respectively. Disconnection II, rather
simply, demands reaction of sugar based nucleophilic component
with aromatic di-aldehyde as synthetic equivalent for electrophilic
synthon B.
Towards developing a strategy based on disconnection I, build-
ing block 7,5 developed by us, combining usefulness of Weinreb
amide (WA) functionality and modified Julia olefination protocol
lends itself as an elegant synthetic equivalent for the synthon A.
Multi-grams of this can be easily synthesized in four steps starting
from commercially available 4-toluic acid.4 The carbanion from
sulfone 7, generated with sodium hydride in dry DMF at 0 °C was
same protocol, literature known
D
-glucose derived alcohol 199 was
D-xylo-configured sulfone 21 through
conveniently converted to
sulfide 20a.
Julia olefination of the aldehydes 12 and 13 were now at-
tempted with these two sulfones (1.2 equiv), using NaH as a base
in DMF at 0 °C. Knowing well that the aldehydes 12 and 13 used
were E/Z mixture, and Julia olefination had now created an addi-
tional alkene functionality with E/Z possibility, the reaction prod-
uct after removal of the 2-hydroxy benzothiazole with cold 10%
aqueous NaOH wash, was directly subjected to palladium cata-
lysed hydrogenation in ethyl acetate at room temperature for
24 h. To our delight, synthesis of protected 1,4-phenylene spaced
sugars 22a–d could be achieved in good yields (Table 1). Under
the prescribed hydrogenation conditions, the O-benzyl ether pro-
tection on 22d was found to be labile (see compound 22b vs 22d).
In contrast to the significance of disconnection I for the conve-
nient access of unsymmetrical 1,4-phenylene spaced sugars, the
availability of sulfones 14 and 21 at hand, along with the commer-
cially available terephthalaldehyde 23, as a synthetic equivalent for
synthon B, encouraged exploring the simplicity of disconnection II
for symmetrical 1,4-phenylene spaced sugars. To begin with, the
carbanion generated from sulfone 14 (2.2 equiv) with NaH as base
in DMF at 0 °C was reacted with 1.0 equiv of terephthalaldehyde
reacted with isopropylidene protected D-glycero- and D-arabino-
configured aldehydes 86 and 9,7 respectively as representatives of
electrophilic sugar component. Clean reaction ensued furnishing
the olefinated WA 10 and 11 in isolated yields of 67% and 81%
respectively after chromatography over silica gel. The obtainment
of E/Z mixture is insignificant as the final objective aims at hydro-
genation of the C–C double bonds; hence compounds 10 and 11
were directly subjected to reduction with lithium aluminium hy-
dride at 0 °C for 1 h. Reduction furnished the requisite aldehydes
12 and 13 in very good yields (Scheme 1). Having successfully teth-
ered glycosyl residues on the phenyl ring through building block 7,
the obtained aldehydes 12 and 13 awaited the second attachment
of glycosyl residue through sugar based nucleophilic counterpart.
Towards this end, we envisaged
D-arabino-configured sulfone 14
and -xylo-configured sulfone 21 as illustrative examples. It was the
ease of availability of starting materials and the convenience of the
D
R2
C
C
C
C
C
C
R1
B
A
3
O
R1
R2
(Electrophilic) = protected sugar aldehydes
(Nucleophilic) = protected sugar sulfone
O
N
O
S
O
BT
7
BT - benzo[d]thiazol-1-yl
Figure 4. Retro synthesis for 1,4-phenylene spaced sugar 3.

A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
57
NBS, PPh3
DMF
m-CPBA, 4 Å MS
CH2Cl2, r.t., 6 h
O
O
O
O
O
O
O O
O
O
O
S
Z
BT
OH
74%
O
O
73%
O
15
14
16:
Z = Br
BTSH (17)
NaH, DMF
r.t., 1 h
83%
18:
Z = SBT
O
S
O
m-CPBA, 4 Å MS
CH2Cl2, r.t., 6 h
NBS, PPh3
DMF
HO
Z
O
O
BT
O
O
O
O
O
70%
75%
O
BnO
BnO
O
BnO
19
21
20:
Z = Br
BTSH (17)
NaH, DMF
r.t., 1 h
80%
20a:
Z = SBT
Scheme 2. Synthesis of sulfones 14 and 21.
Table 1
Reaction of sulfones 14 and 21 with the aldehydes 12 and 13
a) NaH, DMF
0
οC - r.t., 1-2 h
12
(or)
13
14
(or)
21
22a-d
b) Pd/C, H2
ethyl acetate
r.t., 24 h
Entries
Aldehydes
Sulfones
Productsa
Yields (%)
O
O
O
O
O
3
1
14
21
65
O
O
O
O
H
2
2
22a
22b
12
O
O
O
O
3
2
3
62
67
BnO
O
O
O
O
O
O
O
O
3
O
O
14
O
O
O
H
2
O
13
22c
O
O
O
O
3
O
4
21
65
BnO
O
2
O
22d
a
Sulfones, aldehydes and all the final products were confirmed by 1H, 13C NMR and mass spectral analysis.
23. After the initial formation of the carbanion and addition of
terephthalaldehyde, the reaction mixture was allowed to reach
room temperature and stirred for 24 h for completion. Besides
minor amounts of starting material and the anticipated 2-hydroxy
benzothiazole as side product, TLC revealed two new spots with
very close Rf values. After careful silica gel column chromatography
under gravity and gradient elution, compounds corresponding to
these spots were isolated and identified as the mono-olefinated
(E/Z) compound 24 (30%) and the desired bis-olefinated (E/Z) com-
pound 25 (60%). The bis-olefin 25 was subjected to palladium cata-
lysed hydrogenation in ethyl acetate at room temperature for 24 h
to provide the symmetrical 1,4-phenylene spaced sugar 26 as

58
A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
O
O
O
BT
S
O
O
O
14
O
NaH, DMF
O
0 οC - r.t., 24 h
23
O
H
O
O
O
O
O
O
O
O
O
O
O
H
O
O
H
24
25, 60%
, 30%
Pd/C, H2
r. t., 24 h
O
90 %
O
O
O
3
O
O
3
O
26
Scheme 3. Reaction of sulfone 14 with terephthalaldehyde 23.
depicted in Scheme 3. The 1H NMR spectrum of compound 26 dis-
played a sharp singlet at d 7.09 corresponding to the four protons of
the aromatic ring, substantiating the symmetry of the molecule.
Also, there were four conspicuous sharp singlets corresponding to
the methyl groups of the isopropylidene protection at d 1.33,
1.34, 1.36 and 1.37, respectively. The 13C NMR spectrum of the com-
pound 26 displayed conspicuous peaks at d 108.9 and 109.6 corre-
sponding to the quaternary carbons of isopropylidene protections.
Two signals at d 139.7 and 128.4 corresponded to two quaternary
carbons and four methine carbons of the symmetric phenylene
spacer, respectively. The deduced structure for compound 26 was
further confirmed by the HRMS study where the mass of
585.3385 found matched with the calculated mass 585.3403 for
conditions, towards the second olefination reaction with the carb-
anion of sulfone 21. Since, reacting 2.2 equivalents of sulfone 21
with terephthalaldehyde 23 was unfruitful with regard to the for-
mation of compound 28, the equivalence of sulfone in the reaction
was reduced. To our delight, 1.0 equivalent of sulfone 21 reacted
swiftly with terephthalaldehyde 23 in 1 h and afforded mono-olef-
inated product, aldehyde 27 in a 60% yield.
Facile formation, convenient isolation and purification of the
compound 27 was a significant achievement, as it would enable
the successful reaction with same/different sulfones facilitating
the synthesis of symmetrical and unsymmetrical 1,4-phenylene
spaced sugars. Towards this objective, aldehyde 27 was subjected
to olefination reaction independently with sulfones 21 and 14, fol-
lowed by hydrogenation (Scheme 5). The successful obtainment of
symmetrical and unsymmetrical 1,4-phenylene spaced sugars, 29
and 30, respectively, thereby demonstrates the importance of for-
mation and isolation of mono-olefinated product 27 (Scheme 5).
Finally, as an illustration to arrive at fully unprotected 1,4-phe-
nylene spaced sugar, symmetrical di-isopropylidene protected
derivative 26 was subjected to deprotection by treating it with a
mixture of trifluoroacetic acid and water (TFA + H2O) in THF as
C
32H50O8Na [M+Na]+.
Reaction of sulfone 21 (2.2 equiv) with 1.0 equivalent of tereph-
thalaldehyde 23 under the same condition as described for sulfone
14, gave a single new product at Rf 0.3 (20% ethyl acetate/hexanes).
On isolation and characterization, it was found to be only mono-
olefinated compound 27 with 60% yield (Scheme 4). The reaction
furnished no trace of the desired bis-olefinated product 28. This re-
sult indicated the poor reactivity of aldehyde 27 under the reaction
O
O
S
BT
O
O
O
BnO
21
O
NaH, DMF
O
0 οC - r.t., 24 h
23
1.0 eq
H
H
O
OBn
O
O
O
O
O
O
O
O
BnO
BnO
O
H
27
(60%)
28 (0%)
Scheme 4. The reaction of sulfone 21 with terephthalaldehyde 23.

A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
59
O
O
O
O
O
O
O
O
BnO
O
2
2
O
OBn
OBn
3
2
O
O
O
29
(80%)
30
(82%)
2) Pd/C, H2
ethyl acetate,
r.t., 24 h
2) Pd/C, H2
ethyl acetate,
r.t., 24 h
1) NaH, DMF,
21,
1) NaH, DMF,
21,
sulfone
0 οC,- r.t., 1-2 h
sulfone
0 οC,- r.t., 1-2 h
[28]
27
Scheme 5. Synthesis of 1,4-phenylene spaced sugars 29 and 30.
OR
4. Experimental section
4.1. General
TFA, H2O(1:1)
THF
RO
OR
OR
3
RO
26
OR
31:
OR
50 οC, 30 min
3
OR
All reactions were carried out in oven dried glasswares. Dry
DMF was prepared by stirring in calcium hydride and kept under
4 Å molecular sieves after downward distillation. Dry THF was pre-
pared by distilling over Na wire. Solvents used for chromatography
were of LR grade and silica gel used was of 100–200 mesh size.
Thin-layer chromatography was performed on aluminium plates
coated with silica gel 60. Visualisation was observed by UV light
irradiation or by dipping into (Hanessian’s stain) a solution of cer-
ium(IV) sulfate (2.5 g) and ammonium molybdate (6.25 g) in 10%
sulfuric acid (250 mL) followed by charring on a hot plate. For ole-
fins, permanganate stain was used (3 g potassium permanganate,
20 g potassium carbonate, 5 mL 5% sodium hydroxide and
300 mL water). For aldehydes, 2,4-DNP stain prepared by dissolv-
ing 6 g of 2,4-dinitrophenylhydrazine in 30 ml of sulfuric acid
and 40 ml of water in 100 ml of 95% ethanol was used. Melting
points were determined in capillaries and were uncorrected. 1H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded
with chloroform-d (CDCl3), DMSO-d6 as the solvent and tetrameth-
ylsilane (TMS) as reference unless otherwise specified. The num-
bering for the spectral assignment (1H chemical shift) for protons
follows the numbering of the carbon atoms in the corresponding
name of the compound. Mass spectra were recorded on a MI-
CRO-Q TOF mass spectrometer by using the ESI technique at
10 eV. Optical rotations were measured with an Autopol IV polar-
imeter at room temperature.
Ac2O, Et3N
DMAP, DMF
CH2Cl2, r.t., 3 h
R =H (98 %)
32
: R = Ac (95%)
Scheme 6. De-protection followed by per-acetylation sequence of 26.
solvent. The octa-hydroxy compound 31 was obtained as a white so-
lid. Its 1H NMR and 13C NMR could be recorded in DMSO-d6. The
presence of a singlet in 1H NMR at d 7.14 for four protons (–CH) of
the phenyl ring, a quaternary signal at d 139.5 and a signal at d
128.1 for four –CH in 13C NMR confirms the symmetrical substitu-
tion. The presence of four broad singlets at d 4.12, 4.23, 4.35 and
4.79 corresponding to 2 protons each confirms 8 hydroxyl groups
in the molecule. The integrity of poorly soluble octa-hydroxy com-
pound could be further established through per-acetylation leading
to the formation of the octa-acetate derivative 32 (Scheme 6). The 1H
NMR spectrum of compound 32 again displayed a sharp singlet at d
7.03 corresponding to the four protons of the aromatic ring, which
proves the symmetry of the molecule. Also, there were a bunch of
very close conspicuous singlets between d 2.03 and 2.07 corre-
sponding to the 24 (–CH3) methyl protons of the acetyl groups pres-
ent. The 13C NMR spectrum of the compound 32 displayed
conspicuous peaks at d 170.7, 170.5, 170.0 and 169.9 corresponding
to the quaternary carbonyl carbons of the acetyl groups; a signal for
two quaternary carbons at d 139.2 and a signal at d 128.4 for the four
methine carbons of the phenylene ring. The deduced structure for
compound 32 was further confirmed by the HRMS study, where
found mass of 761.2997 matched with the calculated mass of
761.2993 for C36H50O16Na, [M+Na]+.
4.2. General procedures
4.2.1. General procedure for the Julia olefination reaction of
sulfones with aldehydes (A)
To a suspension of NaH (1.1 equiv according to sulfone) in anhy-
drous DMF, a solution of sulfone (1.2 equiv) in anhydrous DMF
(4 mL/mmol) was added at 0 °C. The solution turned to reddish or-
ange colour which indicates the formation of carbanion. After
3. Conclusion
A building block combining the usefulness of the Weinreb amide
functionality and Julia olefination reaction has enabled novel and
versatile strategy for 1,4-phenylene spaced sugars, with complete
flexibility in attaching any desired sugar across the phenylene
spacer via C–C bond. Julia reaction of sugar based sulfones has been
equally promising in furnishing symmetrical as well as unsymmet-
rical 1,4-phenylene spaced sugars on reaction with terephthalalde-
hyde as a representative of aromatic di-aldehydes. The concept and
strategy is general and therefore should be applicable to other aro-
matic di-aldehydes. Efforts towards exploring these phenylene
spaced sugars for biological and/or material properties is currently
underway. The results of these studies will be reported elsewhere.
10 min,
a solution of aldehyde (1 equiv) in anhydrous DMF
(2 mL/mmol) was added to the reaction mixture. The disappear-
ance of reddish orange colour was observed. The reaction mixture
was allowed to attain room temperature and maintained for fur-
ther 30 min to 1 h. The course of the reaction was observed by
TLC analysis (Hanessian’s stain). After the consumption of starting
material, the reaction mixture was quenched with water and ex-
tracted with ethyl acetate (3 times). The collected organic layer
was washed with ice-cold 10% NaOH solution (5 ꢀ 15 mL) to get
rid of side product 2-hydroxybenzothiazole. The collected organic
layer was dried over anhydrous Na2SO4, filtered, concentrated

60
A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
and subjected to purification by silica gel column chromatography
or subjected to further reaction according to sulfone.
over anhydrous Na2SO4, filtered, concentrated and subjected to
purification by silica gel column chromatography or subjected to
further reaction according to sulfone.
4.2.2. General procedure for the reduction of Weinreb amide to
aldehyde (B)
4.3. 4-((Benzo[d]thiazol-2-ylsulfonyl)methyl)-N-methoxy-N-
To a suspension of LiAlH4 (0.6 equiv) in anhydrous THF at 0 °C, a
solution of weinreb amide (1.0 equiv) was added dropwise and the
reaction was maintained at 0 °C for another hour. The course of the
reaction was monitored by TLC analysis (Hanessian’s stain as well
as 2,4-DNP stain). After the complete consumption of starting
material, an approximate amount of Na2SO4 was added to the reac-
tion mixture followed by dropwise addition of water to quench the
reaction till the reaction colour changes to white suspension from
grey suspension. The slurry formed can be relaxed with the addi-
tion of DCM. Then the reaction mass was easily filltered through
celite bed and washed thoroughly with DCM. The collected organic
layer was dried over anhydrous Na2SO4, filtered, concentrated and
subjected to purification by silica gel column chromatography.
methylbenzamide (7)5
The building block 7 was prepared according to the literature
procedure.5 Yield: 85–88%. Rf: 0.35 (hexanes/ethyl acetate, 6:4),
colourless crystals, mp: 142–145 °C. IR (CH2Cl2): 1152, 1332,
1469, 1639, 2929, 2972 cmꢁ1 1H NMR [CDCl3, 400 MHz] d 3.32
.
(s, 3H, –NCH3), 3.47 (s, 3H, –OCH3), 4.79 (s, 2H, –SO2CH2BT), 7.33
(d, 2H, J = 8.0 Hz, ArH), 7.56–7.62 (m, 3H, ArH), 7.63–7.69 (m, 1H,
ArH), 7.94 (d, 1H, J = 8.0 Hz, ArH), 8.26 (d, 1H, J = 8.0 Hz, ArH). 13C
NMR [CDCl3, 100 MHz] d 32.6, 59.7, 60.1, 121.3, 124.6, 126.8,
127.2, 127.8, 127.9, 129.8, 133.9, 136.1, 151.6, 164.1, 168.0. HRMS
(ESI): m/z Calcd for C17H16N2O4S2 [M+H]+: 377.0630. Found:
377.0618.
4.2.3. General procedure for the synthesis of sulfides (C)
4.4. (S)-4-(2-(2,2-Dimethyl-1,3-dioxolan-4-yl) vinyl)benzalde-
To a stirred solution of 2-mercaptobenzothiazole (1.0 equiv)
hyde (12)
and NaH in anhydrous THF at 0 °C,
a solution of bromide
(1.0 equiv) in anhydrous THF was added dropwise. The course of
the reaction was observed by TLC analysis (Hanessian’s stain). After
the completion of reaction, the reaction mixture was quenched by
adding water to the reaction mixture and it was extracted with
ethyl acetate (3 ꢀ 20 mL). The combined organic layer was washed
with water and brine successively. The collected organic layer was
dried over anhydrous Na2SO4, filtered, concentrated and subjected
to purification by silica gel column chromatography.
By following general procedure B, Weinreb amide 10 was con-
verted to aldehyde 12. Yield: 88%, (E:Z = 1:2). Rf: 0.55 (hexanes/
ethyl acetate, 7:3), viscous liquid. ½a D
ꢂ
+5.843 (c = 5.5, CH2Cl2); IR
(CH2Cl2): 1059, 1213, 1371, 1604, 1698, 2986 cmꢁ1
.
1H NMR
[CDCl3, 400 MHz] d 1.38 (s, 3H, –CH3), 1.47 (s, 3H, –CH3), 3.68–
3.73 (m, 1H, 5-CHaHb and minor E-isomer), 4.14–4.21 (m, 1H, 5-
CHaHb and minor E-isomer), 4.81–4.88 (m, 1H, 4-CH), 5.81–5.86
(dd, 1H, J = 11.6 Hz, 8.8 Hz, –CH@CHAr), 6.74 (d, 1H, J = 11.6,
CH@CHAr), 7.42 (d, 2H, J = 8.0 Hz, ArH), 7.86 (d, 2H, J = 8.0 Hz,
ArH), 10.0 (s, 1H, –CHO). Non-overlapped peaks of minor E-isomer:
d 1.43 (s, 3H, –CH3), 1.48 (s, 3H, –CH3), 4.64–4.74 (m, 1H), 6.30–
6.36 (dd, 1H, J = 15.6 Hz, 6.2 Hz, –CH@CHAr), 6.72 (d, 1H,
J = 16.0 Hz, –CH@CHAr), 7.52 (d, 2H, J = 8.0 Hz, ArH), 7.83 (d, 2H,
J = 8.4 Hz, ArH), 9.9 (s, 1H, –CHO). 13C NMR [CDCl3, 100 MHz] d:
25.8, 26.7 (minor), 26.8, 69.4 (minor), 69.6, 72.1, 76.7 (minor),
110.0, 127.1, 129.3, 129.7, 130.1, 130.6 (minor), 131.8, 131.9,
132.8, 136.0 (minor), 136.1 (minor), 142.2, 191.7. HRMS (ESI):
m/z Calcd for C14H17O3 [M+H]+: 233.1178. Found: 233.1176.
4.2.4. General procedure for the synthesis of sulfones (D)
To a solution of sulfide (1.0 equiv) in anhydrous DCM (20 vol-
umes) at room temperature, crushed 4 Å molecular sieves were
added and stirred for 5 min under N2 atmosphere. Then 3.0 equiv
of m-chloroperbenzoic acid was added slowly for 5 min. The reac-
tion was stirred for another 4 h. The course of reaction was moni-
tored by TLC (Hanessian’s stain). After the completion of the
reaction, the reaction mixture was filtered and the DCM layer
was given a wash with saturated NaHCO3, water and brine succes-
sively. The collected organic layer was dried over anhydrous
Na2SO4, filtered, concentrated and subjected to purification by sil-
ica gel column chromatography.
4.5. 4-(2-((4S,40R,5R)-2,2,20,20-Tetramethyl-[4,40-bi(1,3-diox-olan)]-
5-yl)vinyl)benzaldehyde (13)
4.2.5. General procedure for hydrogenation reaction (E)
By following general procedure B, Weinreb amide 11 was con-
verted to aldehyde 13. Yield: 97%, (E:Z = 4:1). Rf: 0.55 (hexanes/
To the solution of olefins (1.0 equiv) in ethyl acetate (10 vol-
umes), 10 mol % of Pd/C was added and a slight vacuum was applied.
Then the reaction mixture was stirred under H2 balloon for 24 h. The
reaction course was monitored by TLC analysis (KMnO4 staining
agent). After the completion of reaction, the suspension was filtered
through celite bed and washed thoroughly with ethyl acetate. The
combined ethyl acetate layer was evaporated under reduced
pressure and subjected to silica gel column chromatography.
ethyl acetate, 7:3), viscous liquid. ½a D
ꢂ
+8.523 (c = 2, CH2Cl2); IR
(CH2Cl2): 1064, 1166, 1213, 1372, 1603, 1698, 2987 cmꢁ1
.
1H
NMR [CDCl3, 400 MHz] d 1.33 (s, 3H, –CH3), 1.37 (s, 3H, –CH3),
1.44 (s, 3H, –CH3), 1.45 (s, 3H, –CH3), 3.75 (t, 1H, J = 7.6 Hz, 50-
CHaHb), 3.95–3.98 (m, 1H, 50-CHaHb), 4.09–4.19 (m, 2H, 4-CH, 40-
CH), 4.56 (t, 1H, J = 6.4 Hz, 5-CH), 6.38–6.44 (dd, 1H, J = 16.0 Hz,
6.0 Hz, –CHCH@CHAr), 6.78 (d, 1H, J = 16.0 Hz, –CH@CHAr), 7.51
(d, 2H, J = 8.0 Hz, ArH), 7.82 (d, 2H, J = 8.4 Hz, ArH), 9.96 (s,
1H, –CHO). Non-overlapped peaks of minor Z-isomer: d 1.22 (s,
3H, –CH3), 1.38 (s, 3H, –CH3), 3.80 (t, 1H, J = 7.6 Hz, 50-CHaHb),
3.85–3.90 (m, 1H, 50-CHaHb), 4.0–4.9 (m, 2H, 4-CH, 40-CH), 4.65–
4.71 (t, 1H, J = 6.4 Hz, 5-CH), 5.79–5.85 (dd, 1H), 7.58 (d, 2H,
J = 8.0 Hz, ArH), 7.84 (d, 2H, J = 8.0 Hz, ArH), 9.99 (s, 1H, –CHO).
13C NMR [CDCl3, 100 MHz] d 25.2, 26.8, 26.9, 27.0 (minor), 67.3,
75.0 (minor), 76.5 (minor), 76.7, 80.0, 81.4, 81.5 (minor), 109.7
(minor), 109.8, 127.0, 129.5 (minor), 129.6 (minor), 130.1, 130.6,
130.8, 133.0 (minor), 135.4 (minor), 135.5, 142.5 (minor), 142.6,
4.2.6. General procedure for the bis-olefination of
terephthalaldehyde 23 (F)
To a stirred solution of sulfone 14 or 21 (2.2 equiv) in anhydrous
DMF (4 mL/mmol) and NaH at 0 °C, a solution of di-aldehyde 23
(1.0 equiv) in anhydrous DMF (1 mL/mmol) was added and the
reaction mixture was allowed to attain room temperature. The
course of the reaction was observed by TLC analysis (Hanessian’s
stain). After the consumption of starting material, the reaction
mixture was quenched with water and extracted with ethyl ace-
tate (3 times). The collected organic layer was washed with
ice-cold 10% NaOH solution (5 ꢀ 15 mL) to get rid of side product
2-hydroxybenzothiazole. The collected organic layer was dried
191.6, 191.7 (minor). HRMS (ESI): m/z Calcd for
C19H25O5
[M+H]+: 333.1702. Found: 333.1710.

A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
61
4.6. 2-((2-((4S,40R,5R)-2,2,20,20-Tetramethyl-[4,40-bi(1,3-di-
oxolan)]-5-yl)ethyl)thio)benzo[d] thiazole (18)
(m, 1H), 3.81 (d, 1H, J = 2.80 Hz), 4.21–4.28 (m, 1H), 4.45 (d, 1H,
J = 12.0 Hz, OCHaHbPh), 4.59 (d, 1H, J = 4.0 Hz, 6a-CH), 4.67 (d, 1H,
J = 12.0 Hz, –OCHaHbPh), 5.86 (d, 1H, J = 4.0 Hz, 3a-CH), 7.23–7.34
(m, 5H, –OCH2C5H5), 7.57–7.67 (m, 2H, ArH), 8.01 (d, 1H,
J = 7.60 Hz, ArH), 8.19 (d, 1H, J = 7.6 Hz, ArH). 13C NMR [CDCl3,
100 MHz] d 21.8, 26.2, 26.7, 51.9, 71.7, 77.8, 81.7, 82.1, 104.7,
111.7, 122.5, 125.5, 127.7, 127.9, 128.0, 128.1, 128.6, 136.8,
136.9, 152.7, 165.5. HRMS (ESI): m/z Calcd for C23H26NO6S2
[M+H]+: 476.1202. Found: 476.1226.
By following general procedure C, bromide 16 was converted to
sulfide 18. Yield: 73%. Rf: 0.4 (hexanes/ethyl acetate, 9.2:0.8), col-
ourless gum. ½a D
ꢂ
+9.283 (c = 1, CH2Cl2); IR (CH2Cl2): 1076, 1146,
1266, 1328, 1377, 1470, 2981 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d
1.21 (s, 3H, –CH3), 1.25 (s, 3H, –CH3), 1.29 (s, 3H, –CH3), 1.34 (s,
3H, –CH3), 1.96–2.07 (m, 1H, –CH2CH2S), 2.20–2.30 (m, 1H, –
CH2CH2S), 3.30–3.40 (m, 1H), 3.46–3.54 (m, 1H), 3.53 (t, 1H,
J = 8.0 Hz, 5h-CHaHb), 3.84–3.89 (m, 2H), 3.92–3.99 (m, 3H),
4.00–4.08 (m, 2H), 7.21 (t, 1H, J = 8.0 Hz, ArH), 7.33 (t, 1H,
J = 8.0 Hz, ArH), 7.67 (d, 1H, J = 8.0 Hz, ArH), 7.78 (d, 1H,
J = 8.0 Hz, ArH). 13C NMR [CDCl3, 100 MHz] d 25.2, 26.7, 27.0,
27.3, 30.1, 33.5, 67.8, 79.0, 81.1, 109.4, 121.0, 121.5, 124.2, 126.0,
135.2, 153.3, 166.8. HRMS (ESI): m/z Calcd for C19H26NO4S2
[M+H]+: 396.1303. Found: 396.1316.
4.10. (4S,40R,5R)-5-(3-(4-(2-((S)-2,2-Dimethyl-1,3-dioxolan-4-
yl)ethyl)phenyl)propyl)-2,2,20,20-tetramethyl-4,40-bi(1,3-diox-
olane) (22a)
By following the general procedure A and general procedure E,
compound 12 was converted to 22a. Yield: 65%. Rf: 0.55 (hexanes/
ethyl acetate, 9:1), colourless liquid. ½a D
ꢂ
+1.597 (c = 1, CH2Cl2); IR
(CH2Cl2): 1024, 1086, 1230, 1382, 1440, 2898, 2932 cmꢁ1
.
1H
4.7. 2-((2-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyltetra-
hydrofuro[2,3-d][1,3]dioxol-5-yl) ethyl)thio)benzo[d]thiazole
(20a)
NMR [CDCl3, 400 MHz] d 1.33 (s, 3H, –CH3), 1.34 (s, 3H, –CH3),
1.35 (s, 3H, –CH3), 1.36 (s, 3H, –CH3), 1.37 (s, 3H, –CH3), 1.42 (s,
3H, –CH3), 1.66–2.00 (m, 6H), 2.56–2.80 (m, 4H), 3.49–3.58 (m,
2H), 3.89–3.97 (m, 2H), 3.98–4.04 (m, 2H), 4.06–4.15 (m, 2H),
7.06–7.12 (m, 4H, ArH). 13C NMR [CDCl3, 100 MHz] d 25.3, 25.7,
26.7, 27.0, 27.4, 27.7, 31.6, 33.2, 35.4, 67.7, 69.3, 75.5, 77.2, 80.3,
81.0, 108.7, 109.5, 128.2, 128.5, 138.8, 139.9. HRMS (ESI): m/z
Calcd for C26H40O6 [M+H]+: 449.2903. Found: 449.2912.
By following general procedure C, bromide 20 was converted to
sulfide 20a. Yield: 78%. Rf: 0.4 (hexanes/ethyl acetate, 9.2:0.8), col-
ourless gum. ½a D
ꢂ
ꢁ15.023 (c = 1, CH2Cl2); IR (CH2Cl2): 1051, 1071,
1216, 1254, 1376, 2927, 2987 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d
1.24 (s, 3H, –CH3), 1.40 (s, 3H, –CH3), 2.00–2.30 (m, 2H, –SCH2CH2),
3.18–3.28 (m, 1H, –SCH2CHaHb), 3.36–3.45 (m, 1H, –SCH2CHaHb),
3.78 (d, 1H, J = 2.8 Hz, 6-CH), 4.24–4.31 (m, 1H, 5-CH), 4.42 (d,
1H, J = 11.6 Hz, –OCHaHbPh), 4.55 (d, 1H, J = 3.6 Hz, 6a-CH), 4.62
(d, 1H, J = 12.0 Hz, –OCHaHbPh), 5.85 (d, 1H, J = 3.6 Hz, 3a-CH),
7.15–7.25 (m, 5H, –OCH2Ph; 1H, BT-H), 7.31–7.35 (m, 1H, ArH),
7.66 (d, 1H, J = 8.0 Hz, ArH), 7.77 (d, 1H, J = 8.0 Hz, ArH), 8.19 (d,
1H, J = 7.6 Hz, ArH). 13C NMR [CDCl3, 100 MHz] d 26.2, 26.7, 28.1,
30.3, 71.8, 78.8, 82.0, 82.3, 104.7, 111.5, 120.9, 121.5, 124.1,
126.0, 127.7, 128.0, 135.2, 137.3, 153.3, 166.8. HRMS (ESI): m/z
Calcd for C23H26NO4S2 [M+H]+: 444.1303. Found: 444.1298.
4.11. (3aR,5R,6S,6aR)-6-(Benzyloxy)-5-(3-(4-(2-((S)-2,2-di-
methyl-1, 3-dioxolan-4-yl)ethyl)phenyl)propyl)-2,2-dimethyl
tetrahydrofuro[2,3-d][1,3]dioxole (22b)
By following the general procedure A and general procedure E,
compound 12 was converted to 22b. Yield: 62%. Rf: 0.4 (hexanes/
ethyl acetate, 9:1), colourless liquid. ½a D
ꢂ
ꢁ5.043 (c = 2, CH2Cl2);
IR (CH2Cl2): 1074, 1162, 1215, 1374, 2865, 2930, 2987 cmꢁ1
.
1H
NMR [CDCl3, 400 MHz] d 1.31 (s, 3H, –CH3), 1.36 (s, 3H, –CH3),
1.43 (s, 3H, –CH3), 1.47 (s, 3H, –CH3), 1.66–2.00 (m, 6H), 2.54–
2.78 (m, 4H), 3.52 (t, 1H, J = 7.6 Hz), 3.75 (d, 1H, J = 2.8 Hz), 3.98–
3.44 (m, 1H), 4.06–4.16 (m, 2H), 4.45 (d, 1H, J = 12.0 Hz,
OCHaHbPh), 4.60 (d, 1H, J = 4.0 Hz, 6a-CH), 4.68 (d, 1H, J = 12.0 Hz,
–OCHaHbPh), 5.90 (d, 1H, J = 4.0 Hz, 3a-CH), 7.06 (d, 2H, J = 8.4 Hz,
ArH), 7.29–7.37 (m, 5H, ArH). 13C NMR [CDCl3, 100 MHz] d 25.8,
26.3, 26.8, 27.1, 27.7, 28.0, 31.7, 35.5, 35.6, 69.4, 71.8, 75.5, 80.4,
81.9, 81.9, 82.2, 104.7, 108.8, 111.3, 127.8, 128.0, 128.3, 128.6,
137.7, 138.9, 139.9. HRMS (ESI): m/z Calcd for C30H40O6 Na
[M+Na]+: 519.2723. Found: 519.2727.
4.8. 2-((2-((4S,40R,5R)-2,2,20,20-Tetramethyl-[4,40-bi(1,3-di-
oxolan)]-5-yl)ethyl)sulfonyl)benzo[d]thiazole (14)
By following general procedure D, sulfide 18 was oxidized to sul-
fone 14. Yield: 73%. Rf: 0.4 (hexanes/ethyl acetate, 7:3), colourless
crystals, mp: 90 °C. ½a D
ꢂ
+10.978 (c = 1, CH2Cl2); IR (CH2Cl2): 1076,
1146, 1266, 1328, 1377, 1470, 2981 cmꢁ1
.
1H NMR [CDCl3,
400 MHz] d 1.25 (s, 3H, –CH3), 1.28 (s, 3H, –CH3), 1.29 (s, 3H, –
CH3), 1.32 (s, 3H, –CH3), 2.08–2.20 (m, 1H, –CHCH2CH2), 2.31–2.43
(m, 1H, –CHCH2CH2), 3.50 (t, 1H, J = 7.6 Hz, 5h-CHaHb), 3.60–3.83
(m, 2H), 3.87–4.01 (m, 3H), 4.08–4.11 (dd, 1H, J = 8.0 Hz, 5.6 Hz),
7.59 (t, 1H, J = 7.2 Hz, ArH), 7.64 (d, 1H, J = 7.6 Hz, ArH), 8.01 (d,
1H, J = 7.6 Hz, ArH), 8.21 (d, 1H, J = 8.0 Hz, ArH).13C NMR [CDCl3,
100 MHz] d 25.2, 26.6, 26.7, 27.0, 27.2, 51.9, 67.9, 77.0, 78.3, 81.2,
109.7, 109.8, 122.4, 125.5, 128.1, 136.8, 152.8, 165.6. HRMS (ESI):
m/z Calcd for C19H26NO6S2 [M+H]+: 428.1202. Found: 428.1203.
4.12. (4S,40R,5R)-2,2,20,20-Tetramethyl-5-(3-(4-(2-((4R,40R,5S)-
2,2,20,20-tetramethyl-[4,40-bi(1,3-dioxolan)]-5-yl)ethyl)phen-
yl)propyl)-4,40-bi(1,3-dioxolane) (22c)
By following the general procedure A and general procedure E,
compound 13 was converted to 22c. Yield: 67%. Rf: 0.5 (hexanes/
ethyl acetate, 9:1), colourless gum. ½a D
ꢂ
+11.597 (c = 3, CH2Cl2); IR
(CH2Cl2): 1066, 1086, 1215, 1253, 1374, 2928, 2980 cmꢁ1
.
1H
4.9. 2-((2-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyltetra-
hydrofuro[2,3-d][1,3]dioxol-5-yl) ethyl)sulfonyl)benzo[d]thi-
azole (21)
NMR [CDCl3, 400 MHz] d 1.33 (s, 3H, –CH3), 1.34 (s, 6H, 2 ꢀ –
CH3), 1.36 (s, 3H, –CH3), 1.37 (s, 6H, 2 ꢀ –CH3), 1.39 (s, 3H, –CH3),
1.42 (s, 3H, –CH3), 1.50–1.90 (m, 10H), 2.00–2.10 (m, 2H), 2.60–
2.74 (m, 3H), 2.77–2.87 (m, 1H), 3.50–3.65 (m, 2H), 3.89–3.98
(m, 4H), 3.98–4.50 (m, 2H), 4.08–4.15 (m, 2H), 7.08–7.15 (m, 4H,
ArH). 13C NMR [CDCl3, 100 MHz] d 25.4, 26.8, 26.9, 27.1, 27.2,
27.5, 27.54, 27.8, 31.8, 32.0, 33.3, 35.5, 35.6, 67.8 (2 ꢀ –CH2O),
77.2, 77.4, 80.0, 80.4, 81.1, 81.2, 108.9, 109.0, 109.6, 109.7, 128.4,
128.5, 139.3, 139.8. HRMS (ESI): m/z Calcd for C31H49O8 [M+H]+:
549.3348. Found: 549.3356.
By following general procedure D, sulfide 20a was oxidised to
sulfone 21. Yield: 75%. Rf: 0.3 (hexanes/ethyl acetate, 4:1), colour-
less gum. ½a D
ꢂ
ꢁ16.855 (c = 0.9, CH2Cl2); IR (CH2Cl2): 1071, 1216,
1254, 1376, 2927, 2987 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d 1.29
(s, 3H, –CH3), 1.42 (s, 3H, –CH3), 2.14–2.25 (m, 1H, –CHCHaHbCH2),
2.30–2.42 (m, 1H, –CHCHaHbCH2), 3.47–3.57 (m, 1H), 3.64–3.74

62
A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
4.13. (3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyl-5-(3-(4-(2-
((4S,40R,5R)-2,2,20,20-tetramethyl-[4,40-bi(1,3-dioxolan)]-5-yl)
ethyl)phenyl)propyl)tetrahydrofuro[2,3-d][1,3]dioxole (22d)
in THF (1 mL) and stirred at 50 °C for 30 min. The product octa-
hydroxy compound started to precipitate out in few minutes. After
the staring material was consumed, the solvents were evaporated
and co-evaporated with toluene to the product as white solid.
Yield: 98% (70 mg). Insoluble white solid, mp: 182–184 °C. IR
By following the general procedure A and general procedure E,
compound 13 was converted to 22d. Yield:65%. Rf: 0.3 (hexanes/ethyl
(neat): 738, 1213, 1465, 3057, 3111 cmꢁ1 1H NMR [DMSO-d6,
.
acetate, 9:1), colourless liquid. ½a D
ꢂ
ꢁ0.998 (c = 0.8, CH2Cl2); IR
400 MHz] d 1.40–1.80 (m, 8H), 2.55–2.65 (m, 4H), 3.17 (d, 2H,
J = 7.2 Hz), 3.30–3.56 (m, 4H), 3.58–3.67 (m, 2H), 3.68–3.78 (m,
2H), 4.12 (br s, 2H, 2 ꢀ OH), 4.23 (br s, 2H, 2 ꢀ OH), 4.35 (br s,
2H, 2 ꢀ OH), 4.79 (br s, 2H, 2 ꢀ OH), 7.14 (s, 4H, ArH). 13C NMR
[DMSO-d6, 100 MHz] d 27.1, 33.1, 34.9, 63.7, 69.1, 71.7, 73.0,
128.1, 139.5.
(CH2Cl2): 1066, 1147, 1214, 1325, 1375, 2924, 2985 cmꢁ1
.
1H NMR
[CDCl3, 400 MHz] d 1.29 (s, 3H, –CH3), 1.33 (s, 3H, –CH3), 1.36 (s, 3H,
–CH3), 1.38 (s, 3H, –CH3), 1.41 (s, 3H, –CH3), 1.45 (s, 3H, –CH3), 1.47
(s, 3H, –CH3),1.60–2.10 (m, 6H), 2.60–2.85 (m, 4H), 3.59 (t, 1H,
J = 7.6 Hz), 3.91–3.98 (m, 2H), 3.98–4.05 (m, 2H), 4.07–4.14 (m, 2H),
4.48 (d, 1H, J = 3.2 Hz, 6a-CH), 5.86 (d, 1H, J = 2.8 Hz, 3a-CH), 7.09 (d,
1H, J = 8.0 Hz, ArH), 7.09 (d, 2H, J = 8.0 Hz, ArH), 7.12 (d, 2H,
J = 7.6 Hz, ArH). 13C NMR [CDCl3, 100 MHz] d 25.4, 26.2, 26.7, 26.8,
27.1, 27.2, 27.5, 27.9, 31.8, 35.5, 35.6, 67.7, 75.5, 77.2, 79.9, 80.3,
81.2, 85.3, 104.3, 109.0, 109.7, 111.5, 128.5, 139.5. HRMS (ESI): m/z
Calcd for C28H42O8Na [M+Na]+: 529.2777. Found: 529.2776.
4.17. (2R,20R,3S,30S,4R,40R)-7,70-(1,4-Phenylene)-bis(heptane-
1,2,3,4-tetrayl tetraacetate) (32)
To the octa-hydroxy compound 29 (0.070 g, 0.174 mmol) in
CHCl3 (2 mL), two drops of DMF were added to facilitate solubility,
and then acetic anhydride (0.27 mL, 16 equiv, 2.786 mmol) was
added. And a corresponding amount of triethylamine (0.387 mL,
16 equiv, 2.786 mmol) was added and a catalytic amount of
dimethylaminopyridine (10%) was added. The reaction mixture
was stirred overnight. After the completion of the reaction, the
reaction mixture was diluted with CHCl3 and was washed with
water. The crude product was purified by silica gel column chro-
matography. Yield: 95% (0.116 g). Rf: 0.8 (only hexanes), white so-
4.14. 4-(3-((4S,40R,5R)-2,2,20,20-Tetramethyl-[4,40-bi(1,3-diox-
olan)]-5-yl)prop-1-en-1-yl)benzaldehyde (24)
By following the general procedure F, sulfone 14 was reacted
with di-aldehyde 23. One of the products obtained was 24,
mono-olefinated aldehyde 24. Yield: 30%, (E:Z = 0.6:1). Rf: 0.3 (hex-
ane/ethyl acetate, 8:2), viscous liquid. ½a D
ꢂ
+9.182 (c = 2, CH2Cl2); IR
(CH2Cl2): 1068, 1160, 1213, 1375, 1602, 1698, 2987 cmꢁ1. 1H NMR
[CDCl3, 400 MHz] d 1.24 (s, 3H, –CH3+minor), 1.29 (s, 3H, –CH3+mi-
nor), 1.33 (s, 3H, –CH3, minor), 1.36 (s, 3H, –CH3), 1.39 (s, 3H, –
CH3), 2.49–2.57 (m, 1H, minor), 2.58–2.68 (m, 1H), 2.72–2.88 (m,
1H+minor), 3.56 (t, 1H, J = 7.6 Hz), 3.61 (t, 1H, J = 7.6 Hz, minor),
3.87–4.60 (m, 3H+minor), 5.95–6.04 (dt, 1H, J = 11.6 Hz, 7.2 Hz,
olefinH), 6.48–6.53 (m, 1H+minor), 6.58 (d, 1H, J = 11.6 Hz, ole-
finH), 7.47 (d, 2H, J = 8.0 Hz, ArH), 7.48 (d, 2H, J = 8.0 Hz, minor,
ArH), 7.79 (d, 2H, J = 8.0 Hz, ArH), 7.82 (d, 2H, J = 8.0 Hz, ArH),
9.94 (s, 1H, CHO, minor), 9.97 (s, 1H, CHO).13C NMR [CDCl3,
100 MHz] d 25.3, 25.36 (minor), 26.6, 26.8 (minor), 27.0, 27.1 (min-
or), 27.3, 27.39 (minor), 32.5, 36.9 (minor), 67.9, 77.3 (minor),
77.37, 79.8 (minor), 79.9, 80.6 (minor), 80.7, 109.3 (minor),
109.38, 109.71, 109.78 (minor), 126.6, 129.4, 129.7, 130.0, 130.2,
130.3 (minor), 130.8, 131.5, 134.8, 135.2 (minor), 143.6 (minor),
143.7, 191.7 (minor), 191.8. HRMS (ESI): m/z Calcd for C20H26O5Na
[M+Na]+: 369.1678. Found: 369.1669.
lid, mp: 90–92 °C. ½a D
ꢂ
+14.970 (c = 0.4, CH2Cl2); IR (CH2Cl2): 1071,
1219, 1373, 1745, 2926 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d 1.45–
1.63 (m, 8H), 2.0–2.01 (m, 24H), 2.53 (t, 4H, J = 6.8 Hz, 2 ꢀ –CH2Ar),
4.08–4.12 (dd, 2H, J = 12.4 Hz, 5.2 Hz, –CHaHbCH(O)), 4.20 (d, 2H,
J = 12.4 Hz–CHaHbCH(O)), 5.05–5.13 (m, 2H), 5.14–5.22 (m, 2H),
5.26 (d, 2H, J = 8.4 Hz, –CH(O)), 7.03 (s, 4H, ArH). 13C NMR [CDCl3,
100 MHz] d 26.7, 26.8, 26.9, 20.4, 35.2, 62.0, 68.4, 70.3, 70.4,
18.4, 139.2, 169.9, 170.0, 170.5, 170.7. HRMS (ESI): m/z Calcd for
C
36H50O16Na [M+Na]+: 761.2997. Found: 761.2993.
4.18. 4-(3-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyltetra-
hydrofuro[2,3-d][1,3]dioxol-5-yl) prop-1-en-1-yl)benzaldehy-
de (27)
By following the general procedure F, sulfone 14 was reacted
with di-aldehyde 23. The product obtained was 24, mono-olefinated
aldehyde 27. Yield: 60%, (E:Z = 1:3). Rf: 0.3 (hexanes/ethyl acetate,
8:2), viscous liquid. ½a D
ꢂ
ꢁ42.215 (c = 2, CH2Cl2); IR (CH2Cl2): 1018,
4.15. 1,4-Bis(3-((4S,40R,5R)-2,2,20,20-tetramethyl-[4,40-bi(1,3-
1076, 1165, 1213, 1378, 1603, 1696, 2989 cmꢁ1
.
1H NMR [CDCl3,
dioxolan)]-5-yl)propyl)benzene (26)
400 MHz] d 1.36 (s, 3H, –CH3), 1.53(s, 3H, –CH3), 2.60–2.88 (m, 2H,
C@CCH2), 3.87(s, 1H), 3.89 (s, 1H, minor), 4.13–4.21 (m, 1H, minor),
4.27–4.35 (m, 1H), 4.44 (d, 1H, J = 12.0 Hz, –OCHaHbPh), 4.53 (d, 1H,
J = 12.0 Hz, –OCHaHbPh), 4.68 (m, 2H), 4.79 (m, 1H, minor), 5.80–
5.90 (m, 1H), 5.96 (d, 1H, J = 2.8 Hz, 3a-CH), 5.99 (d, 1H, J = 2.8 Hz,
3a-CH, minor), 6.54 (d, 1H, J = 2.8 Hz, OlefinH, minor), 6.57 (d, 1H,
J = 12.4 Hz, OlefinH), 7.23–7.43 (m, 5H, ArH), 7.48 (d, 1H,
By following the general procedure F, sulfone 14 was reacted
with di-aldehyde 23. One of the products isolated was bis-olefin
25 which was subsequently converted to 26 by hydrogenation using
the general procedure E. Yield: 90%. Rf: 0.3 (hexanes/ethyl acetate,
8:2), viscous liquid. ½a D
ꢂ
+11.643 (c = 3, CH2Cl2); IR (CH2Cl2): 1066,
1215, 1253, 1374, 2930, 2986 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d
J = 7.6 Hz, ArH), 7.83 (d, 1H, J = 7.6 Hz, ArH), 10.0 (s, 1H, –CHO). 13
C
1.33 (s, 3H, –CH3), 1.34 (s, 3H, –CH3), 1.36 (s, 3H, –CH3), 1.37 (s,
3H, –CH3), 1.55–1.88 (m, 2H), 2.57–2.66 (m, 4H), 3.54 (t, 1H,
J = 7.6 Hz, 50-CH), 3.89–3.96 (m, 4H), 3.97–4.40 (m, 2H), 4.07–4.14
(dd, 2H, J = 8.0 Hz, 6.0 Hz, 4-CH), 7.08 (s, 4H, ArH). 13C NMR [CDCl3,
100 MHz] d 25.4, 26.8, 27.1, 27.5, 27.9, 33.3, 35.5, 67.8, 80.4, 81.1,
108.9, 109.6, 128.4, 139.7. HRMS (ESI): m/z Calcd for C32H50O8Na
[M+Na]+: 585.3403. Found: 585.3385.
NMR [CDCl3, 100 MHz] d 26.2, 26.7, 27.8, 71.7 (minor), 71.8, 79.7
(minor), 79.7 (minor), 79.9, 81.7 (minor), 81.8, 82.1 (minor), 82.2,
81.8, 82.1 (minor), 82.2, 104.8, 111.5, 126.6 (minor), 127.6, 127.9,
128.0 (minor), 128.4, 128.6 (minor), 129.3, 129.7, 129.9, 130.1
(minor), 130.7, 131.4 (minor), 134.7, 137.4, 143.5, 191.7 (minor),
191.8. HRMS (ESI): m/z Calcd for C24H26O5Na [M+Na]+: 417.1678.
Found: 417.1667.
4.16. (2R,20R,3S,30S,4R,40R)-7,70-(1,4-Phenylene)-bis(heptanes-
1,2,3,4-tetraol) (31)
4.19. 1,4-bis(3-((3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyl-
tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propyl)benzene (29)
A mixture of trifluroaceticacid and water (1:1, 1 + 1 mL) was
To a suspension of NaH (1.1 equiv according to sulfone) in anhy-
added to a solution of the tetraacetonide 26 (0.100 g, 0.178 mmol)
drous DMF, a solution of sulfone 21 (1.0 equiv) in anhydrous DMF

A. Senthilmurugan, I. S. Aidhen / Carbohydrate Research 347 (2012) 55–63
63
(4 mL/mmol) was added at 0 °C. The solution turned to reddish or-
ange colour which indicates the formation of carbanion. After
10 min, a solution of aldehyde 24 (1.0 equiv) in anhydrous DMF
(2 mL/mmol) was added to the reaction mixture. The disappearance
of reddish orange colour was observed. The reaction mixture was al-
lowed to attain room temperature and maintained for further 1 h.
The course of the reaction was observed by TLC analysis (Hanes-
sian’s stain and 2,4-DNP solution). After the consumption of starting
material, the reaction mixture was quenched with water and ex-
tracted with ethyl acetate (3 times). The collected organic layer
was washed with ice-cold 10% NaOH solution (5 ꢀ 15 mL) to get
rid of side product 2-hydroxybenzothiazole. The collected organic
layer was dried over anhydrous Na2SO4, filtered, concentrated and
subjected to hydrogenation by following the general procedure E
to furnish 29. Yield: 80%. Rf: 0.3 (hexanes/ethyl acetate, 8:2). viscous
OCHaHbPh, furo ring), 5.90 (d, 2H, J = 4.0 Hz, 3a-CH, furo ring),
7.05 (d, 2H, J = 8.0 Hz, –CH2C6H4CH2–), 7.08 (d, 2H, J = 8.0 Hz, –
CH2C6H4CH2–), 7.27–7.37 (m, 5H, –OCH2C6H5, furo ring). 13C
NMR [CDCl3, 100 MHz] d 25.4, 26.3, 26.8, 27.1, 27.5, 27.7, 27.8,
20.0, 33.3, 35.5, 35.6, 67.8, 71.8, 77.3, 80.4, 80.5, 81.2, 82.0, 82.3,
104.7, 108.9, 109.6, 111.3, 127.8, 128.0, 128.4, 128.45, 128.5,
137.7, 139.6, 139.7. HRMS (ESI): m/z Calcd for
C36H50O8Na
[M+Na]+: 633.3403. Found: 633.3404.
Acknowledgement
The authors thank the DST New Delhi for funding towards the
400 MHz NMR spectrometer to the Department of Chemistry, IIT-
Madras under the IRPHA scheme and ESI-MS facility under the
FIST programme. Funding from CSIR, Project No.: 01(1971)/05/
EMR-II is gratefully acknowledged. Senthilmurugan A. is thankful
to IIT-Madras for HTRA fellowship and initial support from the
CSIR project.
liquid. ½a D
ꢂ
+37.147 (c = 3.6, CH2Cl2). IR (CH2Cl2): 1017, 1076, 1165,
1215, 1374, 2929, 2989 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d 1.32 (s,
6H, 2 ꢀ CH3), 1.48 (s, 6H, 2 ꢀ CH3), 1.50–1.60 (m, 2H), 1.67–1.86
(m, 6H), 2.57–2.64 (m, 4H, –CH2C6H4), 3.76 (d, 2H, J = 2.8 Hz, 5-
CH), 4.11–4.16 (m, 2H, 6-CH), 4.46 (d, 2H, J = 12.0 Hz, –OCHaHbPh),
4.61 (d, 2H, J = 4.0 Hz, 6a-CH), 4.68 (d, 2H, J = 12.0 Hz, –OCHaHbPh),
5.91 (d, 2H, J = 3.6 Hz, 3a-CH), 7.04 (s, 4H, –CH2C6H4CH2–), 7.27–
7.37 (m, 10H, –OCH2C6H5). 13C NMR [CDCl3, 100 MHz] d 26.3, 26.7,
27.7, 28.0, 35.6, 71.8, 80.4, 82.0, 82.3, 104.7, 111.3, 127.8, 128.0,
128.4, 128.5, 137.7, 139.6. HRMS (ESI): m/z Calcd for C40H50O8Na
[M+Na]+: 681.3403. Found: 681.3398.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2011.11.005.
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4.20. (3aR,5R,6S,6aR)-6-(Benzyloxy)-2,2-dimethyl-5-(3-(4-(3-
((4S,40R,5R)-2,2,20,20-tetramethyl-[4, 40-bi(1,3-dioxolan)]-5-yl)
propyl)phenyl)propyl)tetrahydrofuro[2,3-d][1,3]dioxole (30)
To a suspension of NaH (1.1 equiv according to sulfone) in anhy-
drous DMF, a solution of sulfone 14 (1.0 equiv) in anhydrous DMF
(4 mL/mmol) was added at 0 °C. The solution turned to reddish or-
ange colour which indicates the formation of carbanion. After
10 min, a solution of aldehyde 24 (1.0 equiv) in anhydrous DMF
(2 mL/mmol) was added to the reaction mixture. The disappear-
ance of reddish orange colour was observed. The reaction mixture
was allowed to attain room temperature and maintained for fur-
ther 1 h. The course of the reaction was observed by TLC analysis
(Hanessian’s stain and 2,4-DNP solution). After the consumption
of starting material, the reaction mixture was quenched with water
and extracted with ethyl acetate (3 times). The collected organic
layer was washed with ice-cold 10% NaOH solution (5 ꢀ 15 mL)
to get rid of side product 2-hydroxybenzothiazole. The collected
organic layer was dried over anhydrous Na2SO4, filtered, concen-
trated and subjected to hydrogenation by following the general
procedure E to furnish 30. Yield: 82%. Rf: 0.3 (hexanes/ethyl
acetate, 8:2), viscous liquid. ½a D
ꢂ
ꢁ13.561 (c = 3.4, CH2Cl2); IR
(CH2Cl2): 1017, 1075, 1214, 1260, 1376, 2864, 2930, 2986 cmꢁ1
.
1H NMR [CDCl3, 400 MHz] d 1.31 (s, 3H, –CH3, furo ring), 1.33
(s, 3H, –CH3), 1.34 (s, 3H, –CH3), 1.37 (s, 3H, –CH3), 1.38 (s, 3H, –
CH3), 1.48 (s, 3H, –CH3, furo ring), 1.51–1.65 (m, 2H), 1.67–1.86
(m, 6H, 3 ꢀ CH2), 2.55–2.67 (m, 4H, –OCHaHb Ar), 3.55 (t, 1H,
J = 8.0 Hz), 3.76 (d, 2H, J = 3.2 Hz, 5-CH-furo ring), 3.90–3.97
(m, 2H, arabino-H), 3.98–4.45 (m, 1H, arabino-H), 4.08–4.16 (m,
2H, arabino-H), 4.46 (d, 2H, J = 12.0 Hz, –OCHaHbPh, furo ring),
4.60 (d, 2H, J = 3.6 Hz, 6a-CH, furo ring), 4.68 (d, 2H, J = 12.0 Hz, –
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