Convenient synthesis of D- and L-xylo-1,2,3,4-alkane tetrols from a D-gluco-configured common building block

Article abstract of DOI:10.1016/j.carres.2012.06.005

D-gluco-Configured building block derived from d-(+)-gluconolactone has served as a common chiral template for the synthesis of enantiopure d- and l-xylo-configured 1,2,3,4-alkane tetrols. This has enabled synthesis of medicinally important guggultetrols and their enantiomers from a common starting point. Wittig and Grignard reactions are the key steps used for the incorporation of lipophilic chain.

Full text of DOI:10.1016/j.carres.2012.06.005

Carbohydrate Research 358 (2012) 23–30
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Convenient synthesis of D- and L-xylo-1,2,3,4-alkane tetrols from a D-gluco-
configured common building block
Santosh Ramdas Borkar, Beedimane Narayana Manjunath, Sivaraman Balasubramaniam,
⇑
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:
D
-gluco-Configured building block derived from
D
-(+)-gluconolactone has served as a common chiral tem-
Received 30 April 2012
Received in revised form 7 June 2012
Accepted 9 June 2012
plate for the synthesis of enantiopure - and
D
L-xylo-configured 1,2,3,4-alkane tetrols. This has enabled
synthesis of medicinally important guggultetrols and their enantiomers from a common starting point.
Wittig and Grignard reactions are the key steps used for the incorporation of lipophilic chain.
Ó 2012 Elsevier Ltd. All rights reserved.
Available online 18 June 2012
Keywords:
Guggultetrols
Wittig olefination
Grignard reaction
Barton–McCombie deoxygenation
1. Introduction
In the building block 3, the terminal isopropylidene protected diol
and the amide functionality are orthogonal.
Guggultetrol-18, 1 and guggultetrol-20, 2 are the major naturally
occurring lipids isolated from the gum resin of the tree Commiphora
mukul, known as Guggulu. It has been used in Ayurveda-the ancient
Indian medicinal system for the treatment of inflammation, rheu-
matoid arthritis, obesity, and disorders of lipid metabolism besides
several other ailments.1 There are only few reports available in the
literature for the synthesis of guggultetrols.2 Baring the recently re-
ported synthesis due to Sudalai,2a which uses Sharpless asymmetric
epoxidation of an allylic alcohol, the other synthetic routes banked
on the starting material from the chiral pool. Prasad in 2007 had
Tethering of alkyl chain on the left hand side through suitable
functional group inter-conversions would furnish the -xylo-
1,2,3,4-alkane tetrol, whereas appending alkyl chain through the
use of amide functionality on the right would enable synthesis of
D
L
-xylo-1,2,3,4-alkane tetrol. Hence syntheses of
D
-xylo-configured,
-xylo-config-
natural guggultetrols, as well as their enantiomers,
L
ured can be realized from the same building block 3 thereby illus-
trating the significance of our new building block 3. (Fig. 1) The
results presented herein constitute first report, wherein a common
building block has enabled access to both natural guggultetrols and
their enantiomers and paves the way for convenient access to any
commenced their synthesis from L
-(+)-tartaric acid derivative,2b
whereas the earlier approaches in 1981 due to Kjer2c and later in
1986 due to Sukhdev2d had made use of pentodialdo-1,4-furano-
D- or L-xylo configured long chain 1,2,3,4-alkane tetrols 4. This fully
demonstrates the built-in versatility of our new building block.
sides and
D-mannitol/D-xylose, respectively, as their starting
material for their synthetic adventure. In a different perspective,
long chain alkane-1,2,3,4-tetrols have also evinced great interests
under carbohydrate based environmentally benign surfactants.3
2. Results and discussion
Syntheses of
D-xylo-1,2,3,4-alkane tetrols were accomplished
Our new open chain D-gluco-configured building block, 2-O-ben-
starting with the 2-O-benzyl-morpholine amide 3 as depicted in
Scheme 1. The selective hydrolysis of the terminal isopropylidene
protection in compound 3 was carried out with zinc nitrate hexahy-
drate in acetonitrile at 50 °C affording the diol 5 in 92% yield. The diol
5 was subjected to oxidative cleavage using sodium periodate in
presence of sodium bicarbonate to furnish the aldehyde 6. Wittig
olefinations of the aldehyde 6 were carried out using different alkyl-
zyl-morpholine amide 34 easily amenable on multi-gram scale as
crystalline solid from inexpensive and commercially available
D
-(+)-d-gluconolactone, presented a unique potential to deliver syn-
thesis of both - and -xylo-configured long chain polyol 4 with judi-
D
L
cious interplay of sequence and mode of long carbon-chain addition.
triphenylphosphonium
bromides
[CH3(CH2)nCH2P+(Ph)3Brꢀ]
namely, butyltriphenylphosphonium bromide5a (n = 2), octyltriphe-
nylphosphonium bromide5b (n = 6), tridecyltriphenylphosphonium
⇑
Corresponding author.
E-mail address: isingh@iitm.ac.in (I.S. Aidhen).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.06.005

24
S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
OH
OH
OH
R1
R2
n
OH OH
OH OH
4
1
(D series: R1 =alkyl; R2 = OH)
L series: R1 = OH; R2 = alkyl
: n = 11, Guggultetrol-18
[(D)-xylo-octadecane-1,2,3,4-tetrol]
2: n = 13, Guggultetrol-20
[(D)-xylo-eicosane-1,2,3,4-tetrol]
Orthogonal
O
O
O
O
N
O
OBn
O
3
M
I
OH
OH
R
R
R
R
O
R
OH
HO
OH OH
(D)-xylo-1,2,3,4-alkane tetrol
OH OH
(L)-xylo-1,2,3,4-alkane tetrol
Figure 1. Common building block 3 for
D- and
L
-xylo-1,2,3,4-alkane tetrols.
O
O
O
O
HO
O
O
b
HO
a
H
N
N
3
O
OBn
6
O
O
O
OBn
5
O
c
O
O
H
H
O
d
N
N
n
H3C(H2C)
n
O
OH
O
O
OBn
8 a d
-
7 a d
-
e
O
O
f
OH
OAc
n
n
O
OH
OH
O
OAc
10 a-d
9 a-d
g
OAc
h
OH
OAc
n
n
OH OH
AcO
OAc
11a-b
12 a-d
1: Guggul tetrol-18 (n =11)
2: Guggul tetrol-20 (n =13)
a
b
c
d
[ : n = 2, : n = 6, : n = 11, : n = 13]
Scheme 1. Synthesis of
D
-xylo-1,2,3,4-alkane tetrols. Reagents and conditions: (a) Zn(NO3)2ꢁ6H2O, CH3CN, 50 °C, 7 h, 92%; (b) CH2CI2, aq NaHCO3 soln, aq NalO4 soln, 0 °C to rt,
2 h; (c) CH3(CH2)nCH2P+(Ph)3Brꢀ, BuLi, THF, 0 °C to rt, 6 h, 50% over two steps; (d) Pd/C, H2, EtOH–AcOH (1:1), rt, 3 h, 75–90%; (e) NaBH4, EtOH, 60 °C, 4 h, 80–90%; (f) Ac2O,
Et3N, DMF, rt, 12 h, 80–90%; (g) CH3COOH–H2O, 80 °C, 6 h, 75–90%; (h) Ac2O, Et3N, DMF, rt, 12 h, 80–90%.

S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
25
bromide5c (n = 11), and pentadecyltriphenylphosphonium bro-
mide5d (n = 13). The alkyltriphenylphosphonium bromides were
prepared by treating the corresponding alkyl bromides with tri-
phenylphosphine in chlorobenzene at 125 °C except for butyltriphe-
nylphosphonium bromide which was formed in toluene at 90 °C.
Reacting alkyltriphenylphosphonium bromide with n-BuLi in THF
as solvent and at 0 °C, produced the corresponding alkylidenetriphe-
nylphosphorane [CH3(CH2)nCH@PPh3 where n = 2, 6, 11 or 13].
Addition of THF solution of the aldehyde 6 to the formed alkyl-
idenetriphenylphosphorane at 0 °C and allowing the mixture to stir
for six hours at room temperature furnished the Wittig olefination
product 7a–d in 50% yield over the two steps from diol 5. Wittig
chain extension afforded predominantly the Z-isomer. This infer-
ence was drawn from the H6-olefinic proton appearing in the 1H
NMR spectra of 7b and 7c as doublet of triplets (J = 10.8, 7.2 Hz)
in the range d 5.66–5.71. The olefinated products 7a–d were sub-
jected to palladium catalyzed hydrogenation at atmospheric pres-
sure and room temperature in ethanol–acetic acid mixture (1:1).
These conditions facilitated reduction of the double bond and
hydrogenolysis of the O-benzyl group and furnished the alkyl chain
guggultetrols and their enantiomers. The long alkyl chain incorpo-
ration was achieved by Wittig olefination on the aldehyde and
Grignard addition reaction on to the morpholine amide. The
orthogonal protected building block enabled addition of alkyl
chain. Hence guggultetrols, their enantiomers, other
D- and L-
xylo-1,2,3,4-alkane tetrols are synthesized from common building
block.
4. Experimental section
4.1. General
All reactions were carried out in oven dried glassware’s. Dry
DMF was prepared by stirring with Calcium hydride, downward
distilled, and stored on 4 Å molecular sieves. Dry THF was prepared
by distilling over Na wire. Solvents used for column chromatogra-
phy were LR grade. Magnesium metal was cleaned using 20% HCl
(thrice) followed by washing with distilled water and acetone,
which was dried by keeping it in hot air oven for 12 h at 100 °C.
Thin-layer chromatography was performed on aluminum plates
coated with Silica Gel 60. Visualization was observed by UV light
or by dipping into a solution of cerium (IV) sulfate (2.5 g) and
ammonium molybdate (6.25 g) in 10% sulfuric acid (250 mL)
followed by charring on a hot plate. 1H NMR (400 MHz) and 13C
NMR (100 MHz) spectra were recorded in chloroform-d (CDCl3)
and tetramethylsilane (TMS) as reference. HRMS were recorded
on a MICRO-Q TOF mass spectrometer by using the ESI technique
at 10 eV. IR spectra were recorded on JASCO-FT/IR-4100 spectrom-
eter. Optical rotations were recorded on Autopol IV polarimeter.
tethered
morpholine amide in 8a–d with sodium borohydride afforded the
partially protected -xylo-configured 1,2,3,4-alkane tetrols, 9a–d,
a-hydroxymorpholine amide 8a–d. Facile reduction of the
D
in 80–90% yield. Further confirmation of the obtained diol 9a–d,
was achieved through the di-acetylated derivatives, 10a–d. The
hydrolysis of the internal isopropylidene protection in diols 9a–d
with acetic acid and water at 80 °C afforded the targeted guggulte-
trols 1, 2 and the other analogues 11a,b. Thus syntheses of four D-
xylo-1,2,3,4-alkane tetrols of varied chain lengths have been
achieved. The tetrols 11a,b and guggultetrol 1, 2 were subjected
to peracetylation to obtain the corresponding tetraacetates 12a–
d, respectively, for characterization and thereby confirmation of
obtainment of the tetrols.
4.2. (R)-2-(Benzyloxy)-2-((4S,5R)-5-((R)-1,2-dihydroxyethyl)-
2,2-dimethyl-1,3-dioxolan-4-yl)-1-morpholinoethanone (5)
With successful synthesis of
background, efforts toward the
D
-xylo-configured tetrols in the
Zinc nitrate hexahydrate (17.00 g, 57.0 mmol) was added to the
solution of 2-O-benzyl-morpholine amide (3), (5.00 g, 17.5 mmol)
in 60 mL of acetonitrile. Reaction mixture was heated at 50 °C for
7 h. After complete consumption of starting material, acetonitrile
was evaporated at 40 °C on rotary evaporator. The residue was di-
luted by 100 mL of ethyl acetate. The ethyl acetate layer was
washed with brine (100 mL). Then ethyl acetate layer was kept at
0 °C for 12 h. Ethyl acetate was evaporated and yellow colored gum-
my product was obtained. The crude compound was purified by
column chromatography. Gummy liquid; yield: 92%; Rf 0.16 (ethyl
L
-series started with the aldehyde
6. Simple reduction of this aldehyde 6 in 90% yield and subsequent
benzyl ether protection (60%) furnished the di-O-benzyl protected
morpholine amide 14. The addition of the alkyl carbon chain was
now executed through the use of Grignard reaction on the amide
functionality. Different alkylmagnesium bromides [CH3(CH2)n
CH2MgBr] (Scheme 2), namely, pentadecylmagnesium bromide
(n = 13), tridecylmagnesium bromide (n = 11), and octylmagnesium
bromide (n = 6) were prepared by the standard procedure using the
corresponding alkyl bromides. These alkylmagnesium bromides in
THF solution were now added to the solution of morpholine amide
14 in THF at 10–15 °C. Allowing the reaction mixture to stir for
2.5–3 h at room temperature furnished the corresponding ketones
15a–c in excellent yields 80–82%. No trace of over-addition product
was seen. The conversion of carbonyl group in ketones 15a–c to
methylene group for the targeted synthesis was achieved through
two-step protocol. Ketones 15a–c were reduced to alcohol 16a–c
and subjected to Barton–McCombie deoxygenation6 through thi-
onocarbonate derivatives.
acetate/hexane, 3:2); ½a D23
ꢂ
= +17.71 (c 1.0, CHCl3); IR (neat) mmax
cmꢀ1 3018, 1519, 1420, 1281, 764; 1HNMR (CDCl3/TMS, 500 MHz)
d 1.35, 1.36 (2 ꢃ s, 6H, 2 ꢃ CH3); 2.56 (br s, 4H, D2O exchangeable
protons); 3.44–3.48 (m, 1H); 3.55–3.60 (m, 3H); 3.63–3.67 (m,
3H); 3.72–3.79 (m, 1H); 3.82–3.86 (m, 1H); 4.08 (t, 1H,
J = 7.5 Hz); 4.29 (dd, 1H, J1 = 7.5 Hz, J2 = 5 Hz); 4.47 (d, 1H,
J = 3.5 Hz); 4.50 (d, 1H, J = 11.5 Hz, PhCHaHbO); 4.69 (d, 1H,
J = 11.5 Hz, PhCHaHbO); 7.26–7.37 (m, 5H, Aromatic); 13C NMR
(CDCl3/TMS, 125 MHz) d 26.8, 27.2, 43.0, 46.1, 64.0, 66.8, 72.8,
73.0, 76.8, 76.87, 77.0, 79.0, 79.9, 109.8, 128.2, 128.3, 128.5,
136.5, 168.7; HRMS (ESI) m/z Calcd for C20H29NO7Na [M+Na]+:
418.1842. Found: 418.1839.
The debenzylation in protected alkane-tetrols, 17a–c was ef-
fected with Pd/C/H2 in methanol–acetic acid (1:1) at room temper-
ature. Hydrolysis of the internal isopropylidene protection was
carried out by acetic acid–water (4:1) at 100 °C to obtain ent-2,
ent-1, and 18. These alkane tetrols were subjected to peracetyla-
tion to obtain the corresponding tetraacetates 19a–c for complete
characterization.
4.3. Preparation of the aldehyde (6) and general procedure for
Wittig olefination of the aldehyde
To a solution of the diol 5 (3.00 g, 7.59 mmol) in CH2Cl2 was
added 5% sodium bicarbonate solution (16 mL) and the mixture
was cooled to 0 °C; this was followed by addition of 13% solution
of sodium periodate (2.44 g, 11.38 mmol) in water (19 mL). The
reaction mixture was allowed to warm slowly to room temperature
and was stirred for 2 h. Upon completion of the reaction as
3. Conclusion
A
versatile
D-gluco configured building block, 2-O-benzyl-
morpholine amide is used as chiral template for synthesis of

26
S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
O
O
O
O
a
b
6
HO
N
BnO
O
N
O
OBn
13
O
O
OBn
O
14
O
OH
O
c
d
BnO
nCH3
BnO
nCH3
O
OBn
O
OBn
15a-c
16a-c
e, f
OH
O
g, h
HO
nCH3
BnO
nCH3
OH OH
O
OBn
17a-c
ent-2 (n = 13)
ent-1 (n = 11)
18 (n = 6)
OAc
i
AcO
nCH3
OAc OAc
19 a-c
a: n = 13, b: n = 11, c: n = 6
Scheme 2. Synthesis of L-xylo-1,2,3,4-alkane tetrols. Reagents and conditions: (a) NaBH4, methanol, 0 °C to rt, 30 min, 90%; (b) NaH, PhCH2Br, DMF, 1 h, 0 °C to rt, 60%; (c)
CH3(CH2)nCH2MgBr, THF.10–15 °C, 3 h, 80–82%; (d) NaBH4, methanol, 0 °C to rt, 30 min, 97%; (e) 1,10-thiocarbonyl diimidazole, toulene, 110 °C, 8–10 h, 75–85%; (f) Bu3SnH,
AIBN, toulene, 80 °C, 6–7 h, 55%; (g) H2, Pd/C (10%), methanol–acetic acid (1:1), rt, 5–6 h; (h) acetic acid–H2O (4:1), 100 °C, 12 h; (i) (AcO)2O, Et3N, DMAP, rt, 10–12 h, yield
60% (over three steps).
monitored by thin layer chromatography, the organic layer was
separated and the aqueous layer was saturated with sodium
chloride and then extracted with CH2Cl2 (20 mL ꢃ 3). The combined
organic extract was dried over Na2SO4 and evaporated under re-
duced pressure at room temperature to get crude compound. This
was used in the next step without purification.
acid remaining was removed by azeotropic distillation with tolu-
ene. The crude residue was subjected to silica gel column chroma-
tography to obtain the pure products as syrup in 80–90% yield.
4.4.1. (R)-2-((4R,5R)-2,2-Dimethyl-5-pentyl-1,3-dioxolan-4-yl)-
2-hydroxy-1-morpholinoethanone (8a)
A
solution of the alkyltriphenylphosphonium bromide
Syrupy liquid; yield: 80%; Rf 0.16 (ethyl acetate/hexane, 3:7);
(6.19 mmol) in anhydrous THF (20 mL) was cooled to 0 °C and
n-BuLi (5.78 mmol) was added to it drop wise to obtain a dark red
solution. The reaction mixture was allowed to stir at room temper-
ature for 30 min and this was followed by drop wise addition of a
solution of the aldehyde 6 (1.50 g, 4.13 mmol) in anhydrous THF
(10 mL) at ice cold temperature. The reaction mixture was allowed
to stir at room temperature for 6 h. Upon completion of the reaction
as monitored by thin layer chromatography, the reaction mixture
was treated with saturated solution of ammonium chloride and then
extracted with ethyl acetate (30 mL ꢃ 3). The combined organic ex-
tracts were dried over Na2SO4 and evaporated under reduced pres-
sure. The resulting residue was subjected to silica gel column
chromatography to furnish the olefinated products, 7a–7d as syrup
in 50–55% yield. These were directly subjected to hydrogenation.
½
a 2D5 = +9.99 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 3419, 1643, 1265,
ꢂ
1114; 1HNMR (CDCl3/TMS, 400 MHz) d 0.78–0.88 (m, 3H, CH3CH2);
1.18–1.32 (m, 10H); 1.47–1.54 (m, 4H); 3.43–3.79 (m, 9H); 3.97–
3.98 (m, 2H); 4.38–4.45 (m, 1H, CH2CHCH); 13C NMR (CDCl3/TMS,
100 MHz) d 13.9 (CH3CH2); 22.4 (CH3CH2); 25.6 (CH3CH2CH2);
26.6, 27.3 (C(CH3)2); 29.5, 31.7 (CH2CH2CH); 33.0 (CH2CH2CH);
42.9, 45.9 (CH2NCH2); 66.5 76.7, 77.0, 77.4, 80.8 (CHCHC@O);
108.9 (C(CH3)2); 170.0 (C@O); HRMS (ESI) m/z Calcd for C16H29NO5-
Na [M+Na]+: 338.1943. Found: 338.1953.
4.4.2. (R)-2-((4R,5R)-2,2-Dimethyl-5-nonyl-1,3-dioxolan-4-yl)-
2-hydroxy-1-morpholinoethanone (8b)
Syrupy liquid; yield: 80%; Rf 0.32 (ethyl acetate/hexane, 3:7);
½
a 2D5 = +10.59 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 3419, 1643,
ꢂ
1265, 1114; 1H NMR (CDCl3/TMS, 400 MHz) d 0.79–0.82 (m, 3H,
CH3CH2); 1.14–1.28 (m, 10H, CH3(CH2)5); 1.31, 1.32 (2s, 6H,
C(CH3)2); 1.40–1.60 (m, 6H, (CH2)3CH); 3.38–3.69 (m, 8H, mor-
pholinyl); 3.70–3.72 (m, 1H, CHC@O); 3.95–4.03 (m, 1H, CH2CH);
4.38–4.42 (m, 1H, CHCHC@O); 13C NMR (CDCl3/TMS, 100 MHz) d
14.2 (CH3CH2); 22.7 (CH3CH2); 26.2 (CH3CH2CH2); 26.7, 27.5
(C(CH3)2); 29.4, 29.6, 29.8, 31.9, 33.2 (CH3CH2CH2(CH2)6CH); 43.1,
46.0 (H2CNCH2); 66.5 (CHC@O); 66.8, 76.8, 77.1, 77.2 (H2COCH2);
77.4 (CH2CH); 80.9 (CHCHC@O); 109.1 (C(CH3)2); 170.2 (C@O);
4.4. General procedure for hydrogenation of compounds 7a–d
To a solution of the olefin (1.00 g) in 10 mL of ethanol, were
added, 0.1 mL of acetic acid and 300 mg of 10% Pd/C and the reac-
tion mixture was stirred under hydrogen atmosphere at room tem-
perature for 4 h. Upon completion of the reaction as monitored by
thin layer chromatography, the Pd/C was filtered off over celite and
washed with ethyl acetate (20 mL ꢃ 3); the combined filtrate was
evaporated under reduced pressure and any trace amount of acetic

S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
27
HRMS (ESI) m/z Calcd for C20H37NO5Na [M+Na]+: 394.2569. Found:
(ESI) m/z Calcd for
C
16H28O6Na [M+Na]+: 339.1784. Found:
394.2578.
339.1791.
4.4.3. (R)-2-((4R,5R)-2,2-Dimethyl-5-tetradecyl-1,3-dioxolan-4-
yl)-2-hydroxy-1-morpholinoethanone (8c)
4.5.4. (S)-1-((4S,5R)-2,2-Dimethyl-5-nonyl-1,3-dioxolan-4-
yl)ethane-1,2-diyl diacetate (10b)
Syrupy liquid; yield: 80%; Rf 0.12 (ethyl acetate/hexane, 2:8);
Syrupy liquid; yield: 80%; Rf 0.71 (ethyl acetate/hexane, 3:7);
½
a 2D5
ꢂ
= +6.59 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 3419, 1643, 1265,
½
a 2D5 = +1.19 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1744, 1218, 1060;
ꢂ
1114; 1H NMR (CDCl3/TMS, 400 MHz) d 0.88 (t, 3H, J = 6.4 Hz,
CH3CH2); 1.22–1.34 (m, 22H, CH3(CH2)11); 1.38–1.39 (2s, 6H,
C(CH3)2); 1.59–1.61 (m, 4H); 3.45–3.76 (m, 8H, morpholinyl);
3.73–3.77 (m, 1H, CH2CH); 4.00–4.09 (m, 1H, CH2CHCH); 4.47 (d,
1H, J = 1.6 Hz, CHC@O); 13C NMR (CDCl3/TMS, 100 MHz) d 14.1
(CH3CH2); 22.6, 26.1 (CH3(CH2)2); 26.7, 27.4 (C(CH3)2); 29.3, 29.5,
29.60, 29.67, 29.68, 29.69, 29.72, 31.9, 33.1 (–(CH2)11–CH); 43.0,
45.9 (CH2–N–CH2); 66.35 (OCH2); 76.7, 77.0, 77.1, 77.3, 80.8
(CHC@O); 109.1 (C(CH3)2); 170.1 (C@O); HRMS (ESI) m/z Calcd
for C25H48NO5 [M+H]+: 442.3532. Found: 442.3535.
1H NMR (CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 7.2 Hz, CH3CH2);
1.24–1.35 (m, 14H, CH3(CH2)7); 1.37, 1.40 (2s, 6H, C(CH3)2);
1.51–1.59 (m, 2H, CH2CH2CH); 2.04, 2.11 (2s, 6H, 2 ꢃ CH3C@O);
3.74–3.76 (m, 1H, CH2CH2CH); 4.14–4.19 (dd, 1H, J1 = 12.0 Hz,
J2 = 8.0 Hz, CHaHbOCOCH3); 4.31–4.35 (dd, 1H, J1 = 12.0 Hz,
J2 = 4.0 Hz, CHaHbOCOCH3); 5.15–5.18 (m, 1H, CHCH2OCOCH3);
13C NMR (CDCl3/TMS, 100 MHz) d 14.2 (CH3CH2); 20.8, 20.9
(2 ꢃ CH3C@O); 22.7 (CH3CH2); 26.0 (CH3CH2CH2); 26.6, 27.5
(C(CH3)2); 29.4, 29.5, 29.7, 29.8, 31.9, 33.0, 63.6 (CH2OCOCH3);
69.3 (CH2CH2CH); 76.8, 77.1, 77.4, 79.4 (CH2CHCH); 109.2
(C(CH3)2); 170.4, 170.7 (2 ꢃ C@O); HRMS (ESI) m/z Calcd for
C20H36O6Na [M+Na]+: 395.2410. Found: 395.2400.
4.5. General procedure for reduction of the
a-hydroxy amides
8a–d to diols 9a–d and diacetylation of the diols 9a–d
4.5.5. (S)-1-((4S,5R)-2,2-Dimethyl-5-tetradecyl-1,3-dioxolan-4-
yl)ethane-1,2-diyl diacetate (10c)
4.5.1. Reduction of the
To a solution of the
a
-hydroxymorpholine amides 8a–d
a
-hydroxy amide 8a–d (0.5 mmol) in 3 mL
Syrupy liquid; yield: 80%; Rf 0.47 (ethyl acetate/hexane, 1:9);
of ethanol, were added two equivalents of sodium borohydride
(0.076 g, 2.0 mmol) and the reaction mixture was stirred at 60 °C
for 4 h. Upon completion of the reaction as monitored by thin layer
chromatography, ethanol was completely evaporated from the
reaction mixture under reduced pressure and at room tempera-
ture. The resulting residue was diluted with 10 mL of water and
neutralized using acetic acid and then extracted with ethyl acetate
(15 mL ꢃ 3). The combined organic extract was concentrated un-
der reduced pressure and the resulting crude material was sub-
jected to silica gel column chromatography to obtain the pure
product in 80–95% yield.
½
a 2D5
ꢂ
= ꢀ1.99 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1744, 1218, 1060;
1H NMR (CDCl3/TMS, 400 MHz) d 0.88 (t, 3H, J = 6.8 Hz, CH3);
1.25–1.33 (m, 24H, CH3(CH2)12); 1.38, 1.40 (2s, 6H, C(CH3)2);
1.54–1.55 (m, 2H); 2.05, 2.12 (2s, 6H, 2 ꢃ CH3C@O); 3.76–3.78
(m, 2H, C-3-H, C-4-H); 4.18–4.20 (dd, 1H, J1 = 9.5 Hz, J2 = 6.0 Hz,
CHaHbOAc); 4.32–4.37 (dd, 1H, J1 = 9.5 Hz, J2 = 2.8 Hz, CHaHbOAc);
5.16–5.22 (m, 1H, CHCH2OAc); 13C NMR (CDCl3/TMS, 100 MHz) d
14.1 (CH3CH2); 22.7, 26.15, 26.67, 27.42, 29.3, 29.5, 29.58, 29.65,
29.67, 29.69, 29.72, 31.9, 33.1, 43.0, 45.9, 66.3, 76.7, 77.0, 77.1,
77.3, 80.80, 109.1 (C(CH3)2); 170.11 (2 ꢃ C@O); HRMS (ESI) m/z
Calcd for C25H46O6Na [M+Na]+: 465.3192. Found: 465.3178.
4.5.2. Diacetylation of the diols (9a–d)
4.5.6. (S)-1-((4S,5R)-5-Hexadecyl-2,2-dimethyl-1,3-dioxolan-4-
yl)ethane-1,2-diyl diacetate (10d)
To a solution of the diol (9a–d), (0.5 mmol) in 2 mL of anhydrous
DMF, were added four equivalents of triethylamine (0.2 mL,
2.0 mmol) under inert atmosphere and the reaction mixture was
cooled to 0 °C. This was followed by drop wise addition of three
equivalents of acetic anhydride (0.15 mL, 1.50 mmol). The reaction
mixture was allowed to stir at room temperature for 8 h. Upon com-
pletion of the reaction as monitored by thin layer chromatography,
the reaction mixture was diluted with 15 mL of ethyl acetate and
washed with saturated sodium bicarbonate solution (10 mL) and
then with water (25 mL). The organic layer was separated, dried
over Na2SO4, and concentrated under reduced pressure to obtain
the crude product which was subjected to silica gel column chro-
matography to obtain the pure product as colorless syrup in 80–
90% yields.
Syrupy liquid; yield: 80%; Rf 0.60 (ethyl acetate/hexane, 1:9);
½
a 2D5
ꢂ
= ꢀ0.99 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 2924, 1749, 1220;
1H NMR (CDCl3/TMS, 400 MHz) d 0.81 (t, 3H, J = 6.4 Hz, CH3CH2);
1.17–1.27 (m, 28H, CH3–(CH2)14); 1.31, 1.32 (2s, 6H, C(CH3)2);
1.44–1.54 (m, 2H, CH2CH); 2.03, 2.10 (2s, 6H, 2 ꢃ CH3C@O);
3.65–3.75 (m, 2H, H-3, H-4); 4.13–4.18 (dd, 1H, J = 7.6 Hz, CHaH-
bOAc); 4.31–4.34 (dd, 1H, J = 4.0 Hz, CHaHbOAc); 5.14–5.18 (m,
1H, CHOAc); 13C NMR (CDCl3/TMS, 100 MHz) d 14.2 (CH3CH2);
20.8, 20.9 (2 ꢃ CH3C@O); 22.8 (CH3CH2); 26.0, 26.6 (C(CH3)2);
27.5, 29.4, 29.6, 29.7, 29.77, 29.8, 29.88, 29.9, 32.04, 33.0, 63.6
(CH2OAc); 69.2 (C-4); 76.8, 77.16, 77.4, 79.5, 109.2, 170.44,
170.74 (2 ꢃ C@O).
4.6. General procedure for preparation of tetraacetates (12a–d)
4.5.3. (S)-1-((4S,5R)-2,2-Dimethyl-5-pentyl-1,3-dioxolan-4-
yl)ethane-1,2-diyl diacetate (10a)
A mixture of the diol 9a–d (0.50 mmol) and 3 mL of acetic acid–
water (8:2) was stirred at 100 °C for 8 h and upon completion of
the reaction as monitored by thin layer chromatography, the reac-
tion mixture was concentrated under reduced pressure and any
remaining acetic acid or water was removed by azeotropic distilla-
tion with toluene (5 mL ꢃ 2). The resulting residue-the crude te-
trol, was then dissolved in anhydrous DMF (3 mL) under inert
atmosphere. To the solution was added 10 equiv of triethylamine
(0.5 mL, 5 mmol) and the reaction mixture was cooled to 0 °C. This
was followed by addition of 8 equiv of acetic anhydride (0.4 mL,
4 mmol) and the reaction mixture was allowed to stir at room tem-
perature for 12 h. Upon completion of the reaction as monitored by
thin layer chromatography, the reaction mixture was diluted with
Syrupy liquid; yield: 80%; Rf 0.47 (ethyl acetate/hexane, 2:8);
½
a 2D5
ꢂ
= ꢀ3.19(c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1744, 1218, 1060;
1H NMR (CDCl3/TMS, 400 MHz) d 0.84 (t, 3H, J = 6.8 Hz, CH3CH2);
1.32–1.37 (m, 6H, CH3(CH2)3); 1.38, 1.39 (2s, 6H, C(CH3)2); 1.41–
1.59 (m, 2H, CH2CH2CH); 2.00, 2.12 (2s, 6H, 2 ꢃ CH3C@O); 3.74–
3.82 (m, 2H, CH–O–C(CH3)2–O–CH); 4.11–4.16 (dd, 1H, J1 = 11.6,
J2 = 7.6 Hz, CHaHbOCOCH3); 4.28–4.32 (dd, 1H, J = 11.6 Hz, 3.6 Hz,
CHaHbOCOCH3); 5.13–5.15 (m, 1H, CHOCOCH3); 13C NMR (CDCl3/
TMS, 100 MHz) d 14.0 (CH3CH2); 20.7, 20.8 (2 ꢃ CH3C@O); 22.5
(CH3CH2); 25.6 (CH3CH2CH2); 26.5, 27.5 (C(CH3)2); 31.8 (CH2CH2
CH); 32.9 (CH2CH2CH); 63.5 (CH2OCOCH3); 69.2 (CH2CH2CH);
76.8, 76.83, 77.1, 77.4, 79.5, 109.1, 170.3, 170.6 (2 ꢃ C@O); HRMS

28
S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
15 mL ethyl acetate and washed with saturated sodium bicarbon-
ate solution (10 mL) and then with water (30 mL). The organic
layer was separated and concentrated under reduced pressure to
obtain the crude product which was subjected to silica gel column
chromatography to obtain the pure product as colorless syrup in
80–90% yields.
4.7. (R)-2-(Benzyloxy)-2-((4S,5R)-5-(hydroxymethyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)-1-morpholinoethanone (13)
To a solution of aldehyde (6), (5.34 mmol) in 15 mL of methanol,
sodium borohydride (0.22 g, 5.87 mmol) was added in fractions at
0 °C. Reaction mixture was stirred for 30 min. After complete con-
sumption of starting material as monitored by thin layer chroma-
tography, methanol was evaporated on rotary evaporator. To the
reaction residue 10 mL saturated solution of ammonium chloride
was added. Product was extracted by CH2Cl2 (20 mL ꢃ 3) and dried
over Na2SO4. Organic layer was evaporated to obtain crude product
which was purified by column chromatography. Syrupy liquid;
4.6.1. (2S,3S,4R)-Nonane-1,2,3,4-tetrayl tetraacetate (12a)
Syrupy liquid; yield: 80%; Rf 0.35 (ethyl acetate/hexane, 2:8);
½
a 2D5 = +1.19 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1743, 1214, 733;
ꢂ
1H NMR (CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 6.8 Hz, CH3CH2);
1.20–1.34 (m, 6H, CH3(CH2)3); 1.50–1.57 (m, 2H, CH2CH); 2.04,
2.07, 2.08 (4s, 12H, 4 ꢃ CH3C@O); 3.93–3.98 (dd, 1H, J1 = 12.4 Hz,
J2 = 5.6 Hz, CHaHbOCOCH3); 4.33–4.37 (dd, 1H, J1 = 12.4 Hz,
J2 = 3.6 Hz, CHaHbOCOCH3); 5.07–5.12 (m, 1H, CH2CH2CH); 5.23–
5.29 (m, 2H, CH2CH2CHCH); 13C NMR (CDCl3/TMS, 100 MHz) d
13.9 (CH3CH2); 20.6, 20.7, 20.8, 21.0 (4 ꢃ CH3C@O); 22.4, 24.6,
30.5, 31.4 (CH3(CH2)4); 62.1 (CH2OCOCH3); 69.6 (CH2CH2CH);
71.3, 71.4 (CHCHCH2OCOCH3); 76.8, 77.1, 77.4, 170.08, 170.12,
170.45, 170.50 (2 ꢃ C@O) HRMS (ESI) m/z Calcd for C17H28O8Na
[M+Na]+: 383.1682. Found: 383.1687.
yield: 90%; Rf 0.20 (ethyl acetate/hexane, 2:3); ½a D23
ꢂ
= +31.72 (c 1.0
CHCl3) IR (liquid film) mmax cmꢀ1 3685, 3028, 1518, 1423, 1219,
928, 752; 1H NMR (CDCl3/TMS, 400 MHz) d 1.41, 1.43 (2 ꢃ s, 6H,
2 ꢃ CH3); 2.55 (br s, 1H, OH); 3.49–3.87 (m, 10H); 4.23(br s, 2H);
4.35 (br s, 1H); 4.54 (d, 1H, J = 12 Hz, PhCHaHb); 4.73 (d, 1H,
J = 12 Hz, PhCHaHb); 7.29–7.40 (m, 5H, Ar-H); 13C NMR (CDCl3/
TMS, 100 MHz) d 26.8, 27.1 (2 ꢃ CH3); 42.8, 46.0 (2 ꢃ N–CH2);
62.0, 66.9, 72.55, 76.7, 77.07, 77.3, 77.4, 77.5, 79.0, 109.5, 128.1,
128.2, 128.5, 136.6, (Aromatic); 167.9 (CO); HRMS (ESI) m/z Calcd
for C19H28NO6 [M+H]+: 366.1917. Found: 366.1907.
4.8. (R)-2-(Benzyloxy)-2-((4S,5R)-5-((benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)-1-morpholinoethanone (14)
4.6.2. (2S,3S,4R)-Tridecane-1,2,3,4-tetrayl tetraacetate (12b)
Syrupy liquid; yield: 70%; Rf 0.62 (ethyl acetate/hexane, 3:7);
½
a 2D5
ꢂ
= ꢀ0.99 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1743, 1214, 733;
1H NMR (CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 6.8 Hz, CH3CH2);
1.17–1.40 (m, 14H, CH3(CH2)8); 1.51 (m, 2H); 2.04, 2.06, 2.062,
2.09 (4s, 12H, 4 ꢃ CH3C@O); 3.93–3.98 (dd, 1H, J1 = 12.4 Hz,
J2 = 5.6 Hz, CHaHbOCOCH3); 4.33–4.37 (dd, 1H, J2 = 12.4 Hz,
J2 = 3.6 Hz, CHaHbOCOCH3); 4.99–5.10 (m, 1H, CHCH2OCOCH3);
A solution of morpholine amide (13), (2.00 g, 5.47 mmol) in 3 mL
of DMF was added to a solution of sodium hydride (0.144 g,
6.02 mmol) in 7 mL of DMF at 0 °C. After 10 min benzyl bromide
(0.71 mL, 6.02 mmol) was added drop wise. Reaction mixture was
stirred at 0 °C to room temperature for 1 h. After complete consump-
tion of starting material as revealed by thin layer chromatography,
reaction mixture was quenched by addition of 5 mL saturated solu-
tion of ammonium chloride. Product was extracted by 80 mL of ethyl
acetate. The organic layer was washed by water and dried over
Na2SO4. The organic layer was evaporated on rotary evaporator to
furnish crude product. The product was purified by column chroma-
tography. Syrupy liquid; yield: 70%; Rf 0.40 (ethyl acetate/hexane,
5.18–5.28 (m, 2H); 13C NMR (CDCl3/TMS, 100 MHz)
d 14.0
(CH3CH2); 20.6, 20.7, 20.8, 21.0 (4 ꢃ CH3C@O); 22.4, 22.7, 24.6,
24.9, 29.3, 29.4, 29.5, 30.5 (CH3(CH2)8); 31.4, 31.9, 62.1, 69.6,
71.3, 71.4, 76.8, 77.1, 77.4, 170.08, 170.12, 170.45, 170.50
(4 ꢃ C@O); HRMS (ESI) m/z Calcd for
C
21H36O8Na [M+Na]+:
439.2308. Found: 439.2306.
2:3); ½a 2D3
ꢂ
= +19.12 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 3018, 2399,
4.6.3. (2S,3S,4R)-Octadecane-1,2,3,4-tetrayl tetraacetate (12c)
Syrupy liquid; yield: 70%; Rf 0.20 (ethyl acetate/hexane, 1:9);
1628, 1522, 1431, 1215, 768; 1H NMR (CDCl3/TMS, 400 MHz) d
1.31, 1.32 (2 ꢃ s, 6H, 2 ꢃ CH3); 3.30–3.32 (m, 1H); 3.43–3.59 (m,
7H); 3.67 (d, 1H, J = 12.8 Hz); 3.84(d, 1H, J = 12.8 Hz); 4.09 (dd, 1H,
J1 = 3.6 Hz, J2 = 8 Hz); 4.19 (d, 1H, J = 4 Hz); 4.22–4.26 (m, 1H);
4.39 (d, 1H, J = 11.6 Hz, PhCHaHb); 4.46 (s, 2H, PhCH2); 4.58 (d, 1H,
J = 11.6 Hz, PhCHaHb); 7.18–7.26 (m, 10H, Ar-H); 13C NMR (CDCl3/
TMS, 100 MHz) d 26.8, 27.1 (2 ꢃ CH3); 42.9, 45.9 (2 ꢃ N-CH2); 66.9
(CH2OH); 70.22, 72.68, 73.5, 76.0, 76.8, 77.1, 77.4, 78.2, 80.0, 109.8
(CMe2); 127.6, 127.7, 128.0, 128.1, 128.3, 128.4, 128.5, 128.6,
136.8, 137.9 (Aromatic); 168.1 (CO); HRMS (ESI) m/z Calcd for
½
a 2D5 = +1.3(c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1743, 1214, 733; 1H
ꢂ
NMR (CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 5.6 Hz, CH3CH2);
1.24–1.30 (m, 24H, CH3-(CH2)12); 1.30–1.90 (m, 2H), 2.04, 2.05,
2.081, 2.084 (4s, 12H, 4 ꢃ CH3CO); 3.95–4.01 (m, 1H, CHaHbOAc);
4.37–4.39 (m, 1H, CH2CH2CH); 5.06–5.12 (m, 1H, H-2); 5.25–5.26
(m, 2H); 13C NMR (CDCl3/TMS, 100 MHz) d 14.2 (CH3); 20.7, 20.8,
20.9, 21.0 (4 ꢃ CH3C@O); 22.8, 25.0, 26.3, 29.4, 29.5, 29.6, 29.75,
29.79, 29.82, 30.7, 32.0, 62.1, 69.7, 71.3, 71.5, 76.8, 77.1, 77.4,
170.1, 170.2, 170.5, 170.6 (4 ꢃ C@O); HRMS (ESI) m/z Calcd for
26H34NO6 [M+H]+: 456.2386. Found: 456.2385.
C
26H46O8 [M+Na]+: 509.3090. Found: 509.3104.
C
4.9. General procedure for the addition of Grignard reagents on
to the morpholine amide 14
4.6.4. (2S,3S,4R)-Icosane-1,2,3,4-tetrayl tetraacetate (12d)
Syrupy liquid; yield: 70%; Rf 0.20 (ethyl acetate/hexane, 1:9);
½
a 2D5 = +0.99 (c 1.0, CHCl3); IR (neat) mmax cmꢀ1 1743, 1214, 733;
ꢂ
1H NMR (CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 6.0 Hz, CH3CH2);
1.20–1.31 (m, 28H, CH3(CH2)14); 1.40–1.60 (m, 2H, CH2); 2.04,
2.07, 2.09 (4s, 12H, 4 ꢃ CH3C@O); 3.94–3.98 (dd, 1H, J1 = 12.4 Hz,
J2 = 5.6 Hz, CHaHbOAc); 4.34–4.40 (dd, 1H, J1 = 13.6 Hz, J2 = 2.8 Hz,
CHaHbOAc); 5.06–5.13 (m, 1H, H-4); 5.22–5.30 (m, 2H, H-2, H-3);
13C NMR (CDCl3/TMS, 100 MHz) d 14.2 (CH3CH2); 20.72, 20.79,
20.8, 21.05(4 ꢃ CH3C@O); 22.8, 25.0, 29.3, 29.4, 29.6, 29.73, 29.77,
29.80, 30.6, 32.0 (CH3(CH2)15); 62.1 (CH2OAc); 69.7 (C-4); 71.3,
71.5 (C-2, C-3); 76.8, 77.1, 77.3, 77.4 170.1, 170.2, 170.5, 170.6
(4 ꢃ CH3C@O); HRMS (ESI) m/z Calcd for C28H50O8Na [M+Na]+:
537.3403. Found: 537.3416.
To a solution of morpholine amide (14), (1.960 g, 4.3 mmol) in
4 mL of dry THF,
a solution of alkylmagnesium bromide
(12.9 mmol) in dry THF (10 mL), was added under inert atmo-
sphere at 10–15 °C and reaction mixture was stirred for 3 h at
15 °C to room temperature. Thin layer chromatography revealed
the complete consumption of starting material. Subsequent hydro-
lysis was achieved by the cautious addition of saturated ammo-
nium chloride solution. Aqueous layer was extracted with ethyl
acetate (100 mL). Organic extract was washed with water, dried
over Na2SO4, and evaporated to get crude product. This was puri-
fied by column chromatography to get the desired ketone.

S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
29
4.9.1. (R)-1-(Benzyloxy)-1-((4S,5R)-5-((benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl) heptadecane-2-one (15a)
Gummy liquid; yield: 80%; Rf 0.60 (ethyl acetate/hexane, 2:3);
evaporated to obtain yellow colored gummy compound. Product
was purified by column chromatography.
½
a 2D3
ꢂ
= +18.76 (c 1.5, CHCl3); IR(liquid film) mmax cmꢀ1 2922, 2854,
4.10.1. (4R,5R)-4-((S)-1-(Benzyloxy)heptadecyl-5-((benzyloxy)
methyl)-2,2-dimethyl-1,3-dioxolane (17a)
1719, 1457, 1219; 1H NMR (CDCl3/TMS, 400 MHz) d 0.9 (t, 3H,
J = 6.4 Hz, CH2CH3); 1.30 (m, 24H, CH3(CH2)12); 1.41 (s, 3H, CCH3);
1.46 (s, 3H, CCH3); 1.52 (m, 2H, COCH2CH2); 2.60 (m, 2H, COCH2);
3.56 (two dd, 2H, J1 = 10 Hz, J2 = 5.2 Hz, BnOCH2); 3.38 (d, 1H,
J = 3.2 Hz, BnOCH); 4.12 (dd, 1H, J1 = 8 Hz, J2 = 3.2 Hz, C2-H); 4.30
(ddd, 1H, J1 = 8 Hz, J2 = 4.8 Hz, J3 = 2.8 Hz, C3-H); 4.47 (d, 1H,
J = 12 Hz, OCH2Ph); 4.56 (s, 2H, OCH2Ph); 4.70 (d, 1H, J = 12 Hz,
OCH2Ph); 7.35 (m, 10H); 13C NMR (CDCl3/TMS, 100 MHz) d 14.2,
22.8, 26.8, 27.2, 29.2, 29.4, 29.5, 29.6, 29.8, 32.0, 39.7, 70.3, 73.5,
73.6, 75.4, 76.8, 77.1, 77.4, 79.2, 83.3, 109.9, 127.8, 128.1, 128.6,
137.2, 138.0, 211.9; HRMS (ESI) m/z Calcd for C37H57O5 [M+H]+:
581.4206. Found: 581.4185.
Yellow colored gummy liquid; yield: 49% (over three steps); Rf
0.46 (ethyl acetate/hexane, 1:9); ½a D23
ꢂ
= +2.39 (c 1,CHCl3); IR (liquid
film) m
max cmꢀ1 2924, 2851, 2797, 1719, 1593, 1458, 1088, 742; 1H
NMR (CDCl3/TMS, 400 MHz) d 0.77–0.81 (m, 3H, CH3); 1.18 (br,
28H, CH3(CH2)14); 1.33 (s, 3H, CH3); 1.35 (s, 3H, CH3); 1.45–1.46
(m, 2H, BnOCHCH2); 3.37–3.46 (two dd, 2H, J1 = 8 Hz, J2 = 4 Hz,
BnOCH2); 3.50 (dt, 1H, J1 = 12 Hz, J2 = 4 Hz, BnOCH); 3.88 (dd, 1H,
J1 = 8 Hz, J2 = 4.4 Hz, CHCHCH); 4.05–4.06 (m, 1H, CH2COCH);
4.47 (s, 2H, PhCH2); 4.51 (two d, 2H, J = 12 Hz, PhCH2); 7.16–7.23
(m, 10H, ArH);13C NMR (CDCl3/TMS, 100 MHz) d 14.1, 22.7, 25.9,
27.14, 27.17, 29.4, 29.6, 29.72, 29.76, 30.6, 31.9, 71.0, 72.7, 73.5,
76.4, 77.1, 77.4, 78.4, 79.3, 109.0, 127.5, 127.6, 127.7, 128.0,
128.3, 138.1, 138.6; HRMS (ESI) m/z Calcd for C37H59O4 [M+H]+:
567.4413. Found: 567.4423.
4.9.2. (R)-1-(Benzyloxy)-1-((4S,5R)-5-((benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl) pentadecane-2-one (15b)
Yellow colored gummy liquid; yield: 70%; Rf 0.65 (ethyl acetate/
hexane, 2:3); ½a D23
ꢂ
= +30.14 (c 1, CHCl3); IR(liquid film) mmax cmꢀ1
4.10.2. (4R,5R)-4-((Benzyloxy)methyl-5-((5)-1-benzyloxy)
pentadecyl-2,2dimethyl-1,3dioxolane (17b)
2924, 2855, 2360, 1594, 1459, 1089; 1H NMR (CDCl3/TMS,
400 MHz)
d
0.92 (t, 3H, J = 7.2 Hz, CH2CH3); 1.30 (br, 20H,
Yellow colored gummy liquid; yield: 53% (over three steps); Rf
CH3(CH2)10); 1.41 (s, 3H, CH3); 1.46 (s, 3H, CH3); 1.57 (m, 2H,
COCH2CH2); 2.6 (m, COCH2); 3.55 (two dd, 2H, J1 = 8 Hz, J2 = 4 Hz,
BnOCH2); 3.86 (d, 1H, J = 2.8 Hz, BnOCH); 4.12 (dd, 1H, J1 = 8 Hz,
J2 = 3.2 Hz); 4.28–4.35 (m, 1H, CH2CHCH); 4.48 (d, 1H, J = 12 Hz,
PhCHaHbO); 4.56 (s, 2H, PhCH2O); 4.71 (d, 1H, J = 12 Hz, PhCHaHbO);
7.30–7.40 (m, 10H, ArH); 13C NMR (CDCl3/TMS, 100 MHz) d 14.1,
22.7, 22.8, 26.7, 27.1, 29.1, 29.3, 29.4, 29.5, 29.6, 29.7, 31.9, 39.6,
70.3, 73.4, 73.5, 75.3, 76.7, 77.0, 77.3, 79.1, 83.2, 109.0, 127.7,
128.0, 128.4, 128.5, 137.1, 137.9, 211.8; HRMS (ESI) m/z Calcd for
0.44 (ethyl acetate/hexane, 1:9); ½a D23
ꢂ
= +1.59 (c 1, CHCl3); IR (liquid
film) mmax cmꢀ1 2925, 2853, 1741, 1596, 1458, 1372, 1250, 1091,
741; 1H NMR (CDCl3/TMS, 400 MHz) d 0.80 (t, 3H, J = 5.2 Hz, CH3);
1.18 (br, 24H, Ch3(CH2)12); 1.34 (s, 3H, CH3); 1.36 (s, 3H, CH3);
1.45–1.46 (m, 2H, BnOCHCH2); 3.38–3.43 (two dd, 2H, J1 = 8 Hz,
J2 = 4 Hz, BnOCH2); 3.48 (ddd, 1H, J1 = 16.4 Hz, J2 = 10.4 Hz,
J3 = 5.6 Hz, BnOCH); 3.89 (dd, 1H, J1 = 6.8 Hz, J2 = 4.4 Hz, CHCHCH);
4.06–4.08 (m, 1H, BnOCH2COCH); 4.49 (s, 2H, PhCH2); 4.50 (d, 1H,
J = 12.8 Hz, PhCHaHb); 4.54 (d, 1H, J = 12.4 Hz, PhHaHb); 7.18–7.25
(m, 10H, ArH); 13C NMR (CDCl3/TMS, 100 MHz) d 14.1, 22.7, 25.3,
25.9, 27.11, 27.14, 29.3, 29.61, 29.68, 29.7, 29.8, 30.6, 30.9, 31.9,
71.0, 71.70, 71.8, 72.7, 73.4, 73.5, 76.4, 76.7, 77.0, 77.3, 78.4, 79.3,
80.68, 109.1, 127.5, 127.63, 127.67, 127.7, 127.9, 128.0, 128.3,
128.4, 128.5, 137.9, 138.12, 138.5; HRMS (ESI) m/z Calcd for
C
35H52O5Na [M+Na]+ : 575.3712. Found: 575.3723.
4.9.3. (R)-1-(Benzyloxy)-1-((4S,5R)-5-((benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)decane-2-one (15c)
Yellow colored gummy liquid; yield: 82%; Rf 0.5 (ethyl acetate/
hexane, 2:3); ½a D23
ꢂ
= +16.76 (c 0.5, CHCl3); IR (liquid film)
m
max cmꢀ1
C
35H55O4 [M+H]+: 539.4100. Found: 539.4098.
2929, 2858, 1739, 1601, 1456, 1374, 1243, 1048, 851; 1H NMR
(CDCl3/TMS, 400 MHz) d 0.80 (t, 3H, J = 6.8 Hz CH2CH3); 1.18 (br,
10H, CH3(CH2)5); 1.29 (s, 3H, CH3); 1.34 (s, 3H, CH3); 1.45–1.49
(m, 2H, COCH2CH2); 2.4–2.5 (m, 2H, COCH2); 3.41–3.48 (two dd,
2H, J1 = 10 Hz, J2 = 4.8 Hz, BnOCH2); 3.76 (d, 1H, J = 3 Hz, BnOCH);
4.00 (dd, 1H, J1 = 8 Hz, J2 = 3.2 Hz); 4.19 (ddd, 1H, J1 = 8 Hz,
J2 = 4.8 Hz, J3 = 2 Hz, CH2CHCH); 4.36 (d, 1H, J = 12 Hz, PhCHaHbO);
4.44 (s, 2H, PhCH2O); 4.58 (d, 1H, J = 12 Hz, PhCHaHb); 7.18–7.25
(m, 10H, ArH); 13C NMR (CDCl3/TMS, 100 MHz) d 14.2, 22.8, 22.9,
26.8, 27.2, 29.3, 29.5, 31.9, 39.8, 70.4, 73.5, 73.7, 75.4, 76.8, 77.1,
77.4, 79.3, 83.4, 109.9, 127.8, 128.1, 128.5, 128.6, 137.2, 138.0,
211.9; HRMS (ESI) m/z Calcd for C30H42O5Na [M+Na]+: 505.2930.
Found: 505.2923.
4.10.3. (4R,5R)-4-((S)-1-(Benzyloxy)decyl-5-
((benzyloxy)methyl)-2,2-dimethyl-1,3-dioxolane (17c)
Yellow colored gummy liquid; yield: 54% (over three steps); Rf
0.38 (ethyl acetate/hexane, 1:1); ½a D23
ꢂ
= +4.79 (c 1, CHCl3); IR (li-
quid film) mmax cmꢀ1 2925, 2855, 1594, 1372, 1251, 1089, 739;
1H NMR (CDCl3/TMS, 400 MHz) d 0.81 (t, 3H, J = 6.8 Hz, CH3);
1.17 (br, 14H, CH3(CH2)7);1.34 (s, 3H, CH3); 1.36 (s, 3H, CH3);
1.43–1.49 (m, 2H, BnOCHCH2); 3.37–3.41 (two dd, 2H, J1 = 7.2 Hz,
J2 = 4.8 Hz, BnOCH2); 3.48 (ddd, 1H, J1 = 6 Hz, J2 = 10.4 Hz,
J3 = 14 Hz, BnOCH); 3.89 (dd, 1H, J1 = 8 Hz, J2 = 4.4 Hz, CHCHCH);
4.07 (ddd, 1H, J1 = 5.6 Hz, J2 = J3 = 3.6 Hz, BnOCH2COCH); 4.49 (s,
2H, PhCH2); 4.51 (d, 1H, J = 12.8 Hz, PhCHaHb); 4.54 (d, 1H,
J = 11.6 Hz, PhHaHb); 7.18–7.27 (m, 10H, ArH); 13C NMR (CDCl3/
TMS, 100 MHz) d 14.2, 22.8, 26.0, 27.2, 29.4, 29.7, 29.8, 30.7,
32.0, 71.1, 72.8, 73.6, 76.5, 76.8, 77.1, 77.4, 77.6, 78.6, 79.4,
109.3, 127.6, 127.75, 127.79, 128.1, 128.42, 128.48, 138.2, 138.7;
HRMS (ESI) m/z Calcd for C30H44O4Na [M+Na]+: 491.3137. Found:
491.3135.
4.10. General procedure for deoxygenation of the alcohols
16a–c
To a solution of alcohol (16a–c), (0.70 mmol) in toluene (8 mL),
1,10-thiocarbonyldiimidazole (1.26 mmol) was added. Reaction
mixture was subjected to reflux at 110 °C for 6–7 h. After complete
consumption of starting material, toluene was evaporated to
obtain crude product. The product was purified by column
chromatography.
4.11. General procedure for debenzylation and isopropylidene
deprotection of 17a–c
To a solution of thionocarbonate (0.30 mmol) in toluene (5 mL),
Bu3SnH (0.13 mL, 0.45 mmol) was added. Then a pinch of AIBN
was added to the reaction mixture. The reaction mixture was heated
at 80 °C for 8–9 h. After completion of reaction toluene was
To a solution of 1,4-dibenzyloxy tetrol (17a–c), (0.159 mmol) in
4 mL methanol–acetic acid (1:1), 10% Pd/C (0.046 mmol) was
added to the reaction mixture in H2 gas atmosphere. Reaction
mixture was stirred for 8 h. Thin layer chromatography revealed

30
S. R. Borkar et al. / Carbohydrate Research 358 (2012) 23–30
complete consumption of starting material. Then Pd/C was filtered
off over celite. The residue was washed with ethyl acetate. Com-
bined organic layer was collected and evaporated to obtain yellow
colored gummy product. Product used in next step without purifi-
cation. Similar results were observed with palladium hydroxide.
A solution of 1,4-diol (0.129 mmol) in 2 mL acetic acid–water
(4:1) was refluxed at 100 °C for 14 h. Thin layer chromatography
showed complete consumption of starting material. Then acetic
acid was evaporated by azeotropic distillation with toluene. Then
saturated solution of sodium bicarbonate (2 mL) was added to
the reaction residue and product was extracted in ethyl acetate.
Crude compound was used in next step without purification.
20.9, 21.0, 22.8, 25.0, 29.4, 29.5, 29.6, 29.7, 30.7, 32.0, 62.1, 69.7,
71.3, 71.5, 76.8, 77.1, 77.4, 170.2, 170.5; HRMS (ESI) m/z Calcd for
C
26H46O8Na [M+Na]+: 509.3090. Found: 509.3106.
4.12.3. (2R,3R,4S)-Trideane-1,2,3,4tetrayl tetra acetate (19c)
Yellow colored gummy liquid; Yield 60% (over three steps); Rf
0.56 (ethyl acetate/hexane, 1:1); ½a D23
= ꢀ1.59 (c 1, CHCl3); IR(li-
ꢂ
quid film) mmax cmꢀ1 2925, 2857, 1742, 1437, 1371, 1220, 1027,
953, 768; 1H NMR(CDCl3/TMS, 400 MHz) d 0.86 (t, 3H, J = 6.4 Hz,
CH3); 1.17 (br s, 14H, CH3(CH2)7); 1.48–1.51 (m, 2H, AcOCHCH2);
2.02 (s, 3H, OCOCH3); 2.05 (two s merge, 6H, OCOCH3); 2.07 (s,
3H, OCOCH3); 3.96 (dd, 1H, J1 = 5.2 Hz, J2 = 1.6 Hz, AcOCHaHb);
4.34 (dd, 1H, J1 = 5.6 Hz, J2 = 2.4 Hz, AcOCHaHb); 5.05–5.06 (m,
1H, AcOCHCH2); 5.21–5.24 (m, 2H, AcOCHCH); 13C NMR (CDCl3/
TMS, 400 MHz) d 14.1, 20.6, 20.7, 20.8, 20.9, 22.7, 24.7, 24.9,
29.3, 29.4, 29.5, 30.6, 31.9, 36.7, 62.1, 69.7, 71.3, 71.5, 76.8, 77.1,
77.4, 170.14, 170.17, 170.51, 170.57; HRMS (ESI) m/z Calcd for
4.12. General procedure for preparation of 1,2,3,4-tetraacetate
19a–c
To
a solution of alkane-1,2,3,4-tetrol ent-2, ent-1, or 18
(0.201 mmol) in CH2Cl2 (2 mL), acetic anhydride (0.15 mL,
1.612 mmol) was added. Then triethylamine (0.22 mL, 1.612 mmol)
was added. A pinch of DMAP was added and reaction mixture was
stirred at room temperature for 12 h. After consumption of starting
material as revealed by thin layer chromatography, reaction mix-
ture was quenched by adding 10 mL of water and product was ex-
tracted in CH2Cl2 (10 mL ꢃ 3). Yellow gummy product was
obtained. Product was purified by column chromatography.
C
21H36O8Na [M+Na]+: 439.2308. Found: 439.2299.
Acknowledgements
The authors thank DST New Delhi for funding toward the
400 MHz NMR spectrometer to the Department of Chemistry, IIT-
Madras under the IRPHA scheme and ESI-MS facility under FIST
program. Board of Research in Nuclear Sciences (BRNS) is acknowl-
edged for funding of project 2008/37/21/BRNS. Santosh Borkar is
thankful to IIT-Madras for HTRA fellowship.
4.12.1. (2R,3R,4S)-Icosane-1,2,3,4tetrayl tetra acetate (19a)
Yellow colored gummy liquid; Yield 58% (over three steps); Rf
0.46 (ethyl acetate/hexane, 1:1); ½a D23
= ꢀ1.39 (c 1, CHCl3); IR (liquid
ꢂ
Supplementary data
film) mmax cmꢀ1 2923, 2853, 1745, 1371, 1223, 1025; 1H NMR
(CDCl3/TMS, 400 MHz) d 0.87 (t, 3H, J = 6 Hz, CH3); 1.24 (br s, 28H,
CH3(CH2)14); 1.47–1.60 (m, 2H, AcOCHCH2); 2.04 (s, 3H, OCOCH3);
2.07 (two s merge, 6H, OCOCH3); 2.09 (s, 3H, OCOCH3); 3.96 (dd,
1H, J1 = 12.4 Hz, J2 = 4.4 Hz, AcOCHaHb); 4.35 (dd, 1H, J1 = 12.4 Hz,
J2 = 2.8 Hz, AcOCHaHb); 5.07–5.08 (m, 1H, AcOCHCH2); 5.23–5.25
(m, 2H, AcOCHCH); 13C NMR (CDCl3/TMS, 100 MHz) d 14.1, 20.6,
20.7, 20.9, 22.7, 23.3, 24.6, 24.9, 29.0, 29.2, 29.3, 29.5, 29.6, 29.7,
30.5, 31.9, 36.6, 62.0, 69.6, 71.2, 71.4, 76.7, 77.0, 77.3, 170.06,
170.1, 170.43, 170.49; HRMS (ESI) m/z Calcd for C28H50O8Na
[M+Na]+: 537.3403. Found: 537.3402.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2012.
06.005.
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4.12.2. (2R,3R,4S)-Octadeane-1,2,3,4tetrayl tetra acetate (19b)
Yellow colored liquid; Yield 56% (over three steps); Rf0.58 (ethyl
acetate/hexane, 1:1); ½a D23
= ꢀ3.59 (c 1, CHCl3); IR(liquid film) mmax
ꢂ
cmꢀ1 2924, 2854, 1745, 1371, 1214, 1026; 1H NMR (CDCl3/TMS,
400 MHz) d 0.81 (t, 3H, J = 7.2 Hz, CH3); 1.17 (br s, 22H, CH3(CH2)11);
1.34–1.60 (m, 4H); 1.95 (s, 3H, OCOCH3); 1.962 (two s merge, 6H,
OCOCH3); 1.968 (s, 3H, OCOCH3); 3.89 (dd, 1H, J1 = 12 Hz,
J2 = 5.2 Hz, AcOCHaHb); 4.30 (dd, 1H, J1 = 12 Hz, J2 = 3.2 Hz, AcO-
CHaHb); 5.00–5.02 (m, 1H, AcOCHCH2); 5.16–5.21 (m, 2H,
AcOCHCH); 13C NMR (CDCl3/TMS, 100 MHz) d 14.2, 20.7, 20.8,