Synthesis of threo- and erythro-configured trihydroxy open chain lipophilic ketones as possible anti-mycobacterial agents

Article abstract of DOI:10.1016/j.tetasy.2016.11.008

A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from L- and D-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite C[sbnd]C bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation.

Full text of DOI:10.1016/j.tetasy.2016.11.008

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of threo- and erythro-configured trihydroxy open chain
lipophilic ketones as possible anti-mycobacterial agents
Santosh Ramdas Borkar , Naveen Bokolia , Indrapal Singh Aidhen , Inshad Ali Khan b,
a
b
a,
⇑
⇑
a
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
Clinical Microbiology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from
and -ascorbic acid respectively as the starting material, through the use of Grignard reactions for the
requisite CAC bond formations. The lipophilic ketones were screened against
Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side
chains were found to be moderately active against cell proliferation.
Ó 2016 Elsevier Ltd. All rights reserved.
L-
Received 3 November 2016
Accepted 16 November 2016
Available online xxxx
D
1
. Introduction
Blocking the biosynthetic route for the
L-rhamnose unit from a-
D-glucose-1-phosphate, should therefore constitute a valuable
Tuberculosis is widespread disease caused by the bacillus
Mycobacterium tuberculosis. After acquired immune deficiency syn-
specific target, under the broad realm of targeting cell wall synthe-
sis of M. tuberculosis, in the search for anti-tuberculosis drugs.
McNeil et al. showed that RmlC and RmlD enzymes were essential
drome (AIDS), tuberculosis is the prime cause of deaths by infec-
tious disease worldwide.1
–5
It is well known that the
for the biosynthesis of
growth of M. tuberculosis (Fig. 1).
A few reports on blocking the biosynthetic pathway for
nose unit from -glucose-1-phosphate, in the search for
anti-tuberculosis agents have been initiated by McNeil and
L-rhamnose and thus for the cell wall
2
3,24
mycobacterium has a very unique cell envelope that protects it
from various drugs and harsh conditions.6
–10
Mycobacteria also
L-rham-
become resistance to antibiotic agents over time.11 The first line
drugs for the treatment of tuberculosis targets some important
functions of mycobacteria. Isoniazid inhibits mycolic acid biosyn-
a-D
2
4–30
others.
With this in mind, the open-chain threo/erythro-config-
1
2
13
thesis, rifampin targets RNA synthesis, pyrazinamide disrupt
ured ketones 1 (R = H) and 2 (R = H) were envisaged towards pos-
sibly mimicking substrates 5 and 6 in the biosynthetic pathway
and thereby interrupting cell-wall synthesis in M. tuberculosis
through blocking biosynthesis of L-rhamnose. Due to the fact that
mycobacteria have a waxy cell wall, which makes them highly
impermeable for drug molecules, we further conjectured that long
14
plasma membrane of mycobacteria, ethambutol inhibits arabino-
galactan and lipoarabinomannan biosynthesis.15 The mycobacte-
rial cell wall remains an excellent target for developing new drug
candidates. In that regard, the unique polysaccharides of the
mycobacterial cell wall and their attendant preparative enzymes
are attractive targets for the development of new drugs that might
n n
alkyl chain ketones 1 (R = alkyl, C , n > 4) and 2 (R = alkyl, C , n > 4),
1
6
be highly active and selective for the tuberculosis bacillus. In the
search for new drugs, various enzyme inhibitors have been devel-
because of their enhanced lipophilicity would possibly be more
attractive than ethyl ketones in displaying anti-mycobacterial
activity. The synthesis of these ketones and their evaluation for
anti-mycobacterial activity is reported herein.
1
7a–c
oped in order to target the biosynthesis of mycolic acid,
Pepti-
1
8a–d
19a–e
20a,b
doglycan,
Arabinogalactan,
lipoarabinomannan.
In
addition to this, efforts have been expended to inhibit the biosyn-
2
1
thesis of glycolipids and enzymes which are responsible for lipid
transport in M. tuberculosis.22
-Rhamnosyl residue occupies an
2
2
. Results and discussion
L
important anchoring position as a part of the linker disaccharide,
which connects the arabinogalactan and peptidogalactan layers.
.1. Chemistry
The biosynthesis of
cose-1-phosphate and employs four enzymes, RmlA to RmlD.
L-rhamnose in M. tuberculosis starts from D-glu-
The synthesis of ketones 1 and 2 was planned through the
threo- and erythro-configured building blocks 8 and 9 as valuable
starting points. The use of the Grignard reaction has been made
for the incorporation of different alkyl chains through nucleophilic
⇑
Corresponding authors.
http://dx.doi.org/10.1016/j.tetasy.2016.11.008
957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
0
Please cite this article in press as: Borkar, S. R.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.11.008

2
S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
addition onto the morpholine amide functionality in 8 and 9. The
synthesis of the building blocks was envisaged from the corre-
sponding threonolactone 10 and erythronolactone 11 respectively
The threo-configured morpholine amide 8 was next used for the
addition of various alkyl chains via Grignard reaction. Various alkyl
magnesium bromides [CH (CH ) MgBr; n = 1, 3, 7 and 13] were
3 2 n
(
Fig. 2).
prepared by standard procedures and added onto morpholine
amide 8 at 10–15 °C in THF. The reaction afforded the desired
ketones 15a–d in 64–82% yields (Scheme 2). The alkyl ketones
15a–d were subjected to hydrogenation to remove the benzyl
Lactone 10 was readily accessible in a single step from commer-
cially available
onolactone 10 from
L
1
-ascorbic acid 12. The reported procedure for thre-
3
L-ascorbic acid 12 needed slight modification
and optimization to give 10 in 53% yield. The reaction of threono-
lactone 10 with morpholine at room temperature afforded the tri-
hydroxy-morpholine amide 13, although it had the propensity to
cyclize back to the starting lactone 10, during any isolation
attempt. To circumvent this problem, the in situ formed compound
ether protection to obtain
isopropylidene protection was removed under aqueous acidic con-
ditions using acetic acid/H O to give trihydroxy-ketones 1a–d.
a-hydroxy ketones 16a–d. Finally, the
2
The formation of the desired ketones was confirmed by spectro-
1
scopic methods. For example, the H NMR spectrum of ketone 1d
1
3 was directly subjected to isopropylidene protection, which
enabled the formation of -hydroxy morpholine amide 14 in 71%
yield. Finally the free hydroxy group in amide 14 was protected
as benzyl ether to give the desired threo-configured -benzyloxy
morpholine amide 8 as a yellowish solid in 76% yield (Scheme 1).
showed a peak at 0.85 ppm (t, 3H, J = 7.2 Hz, CH
3
) and broad singlet
a
peak at 1.23 ppm (CH
2
ꢀ 11). This confirmed the presence of an
alkyl chain residue in the molecule. The threo-configuration of
the hydroxyl groups at C-2 and C-3 can be explained by the cou-
pling constants of protons H-2 and H-3. The signal at 4.00 ppm
a
OH
OH
[
+
RmIA]
dTTP
O
O
O
[RmIB]
[NAD]
O
HO
HO
HO
HO
HO
OH
OH
+
OH
O
O
-PPi
O-dTDP
O-dTDP
P
O
4
5
3
O
O
R
HO
OH
[
RmIC]
α-
D
-glucose-1-phosphate
HO
OH
[
RmID]
O
O
O
1 and 2 (R = H, Alkyl)
+
NAD(P)H
dTTP = deoxythymidine triphosphate
dTDP = deoxythymidine diphosphate
erythro/threo
OH
OH
OH
O-dTDP
NAD(P)+
OH
O-dTDP
-
7
6
dTDP-α-
L
-rhamnose
-rhamnose in mycobacteria and our hypothesis.
Figure 1. Biosynthesis of
L
OH
O
OH
O
O
O
O
O
HO
O
HO
O
n
N
N
n
OH
OH
erythro-ketones 2
OBn
O
OBn
O
threo-ketones 1
threo-amide 8
erythro-amide 9
O
O
O
O
HO
OH
HO
OH
10
11
Figure 2. Proposed strategy.
HO
OH
O
HO
O
O
Na CO , H O
O
2
3
2
2
O
morpholine, MeOH
HO
HCl (6N) 6 h,
3%
0 oC to rt, 12 h
N
5
HO
O
OH
HO
OH
O
OH
O
1
2
10
1
3
O
O
O
N
O
NaH, PhCH
2
Br
2,2'-DMP, acetone
N
DMF, 0 oC, 1 h
CuSO
o
4
2 4
, conc. H SO
C to rt, 1 h, 71 %
OBn
O
7
6 %
OH
O
0
8
1
4
Scheme 1. Synthesis of threo-configured building block 8.
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S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
O
O
O
O
O
O
O
CH (CH ) CH MgBr
O
H , Pd/C
O
3
2
n
2
2
N
THF, 10-15 °C, 3h
n
ethanol, rt, 3h
n
OBn
O
OBn
OH
8
15a: n = 1 (82%,
16a: n = 1 (61%),
16b: n = 3 (73%),
16c: n = 7 (65%),
16d: n = 13 (72%)
1
1
1
5b: n = 3 (70%,
5c: n = 7 (79%),
5d: n = 13 (64%)
OH
O
2
AcOH/H O
HO
rt, 24h
n
OH
1
a: n = 1 (90%),
b: n = 3 (60%),
c: n = 7 (69%)
d: n = 13 (82%)
1
1
1
Scheme 2. Synthesis of threo-configured ketones 1a–d.
(
3
dd, J
.74 ppm corresponds to H-3. The H-2 showed coupling with H-3
as well as the hydroxyl proton. The small coupling constant of
.0 Hz (JH2–H3) was expected for the disposition of the H-2 and
1
= 6.4 Hz, J
2
= 2.0 Hz) corresponds to H-2 while the peak at
HRMS spectrum of ketone showed m/z = 339.2520, which repre-
+
sents the molecular ion peak [M+Na] for the formula C18
(calculated mass for the formula is 339.2511).
36 4
H O Na
2
In order to prepare the erythro-configured building block 9, a
H-3 protons in the threo-configured configuration. The three major
conformations for the ketone 1d were A–C (Fig. 3).
similar synthetic scheme as shown in Scheme 1 was now con-
ducted on D-isoascorbic acid 17 as the starting material. The ery-
Although the overall J value would be the weighted average of
all conformers, conformer A seems to be the major contributing
conformer to the equilibrium, wherein the dihedral angle between
H-2 and H-3 should support the observed low value (J = 2 Hz). The
C NMR spectrum of 1d showed a peak at 213.2 ppm, which con-
firmed the presence of a ketone functionality in the molecule, fur-
thro configured amide 9 also underwent the clean addition of
various alkyl Grignard reagents with the same protection/depro-
tections as described earlier, to afford the erythro-configured
ketones 2a–d (Scheme 3).
1
3
The erythro-configured ketones were confirmed by 1H and 13
C
1
NMR spectra. For example in the H NMR spectrum of 2d, the H-
2 proton appears at 3.84 ppm as a triplet with J = 5.5 Hz while
ther indicating no formation of cyclic hemiketal structure D. The
ROC
H
OH
3
O
1
HO
OH
2
OH
CH
2
OH
R
4
OH
H
OH
H
+
δ
R
O
R
O
O
H
3
OH
3
+
δ
H
+δ
2
H
2
H2
OH
H
O
R
O
4
OH
O
H
3
2
H
H
3
O
OH
OH
1
HO
OH
R
A
B
C
D
o
o
o
dihedral angle = 90
dihedral angle ≅ 60
dihedral angle ≅ 60
3
3
3
J = 0-2 Hz
J = 2-5 Hz
J = 2-5 Hz
Figure 3. Stable conformers of ketone 1d.
HO
HO
Na
2 3 2 2
CO , H O
O
O
O
NaH, PhCH Br
O
O
O
O
O
2
O
O
HCl (6N) 6 h
DMF, 0 oC, 1h
90 %
N
N
HO
OH
HO
OH
OH
18
O
OBn
O
9
1
7
11
O
O
OH
O
O
O
RMgBr, THF
0-15 °C, 3h
H
2
, Pd/C
AcOH/H
2
O
O
O
HO
9
EtOH, rt, 3h
rt, 24h
1
n
n
n
OH
OH
OBn
2
0a: n = 1 (70%),
0b: n = 3 (66%),
0c: n = 7 (72%),
0d: n = 13 (6%)
2a: n = 1 (80%),
2b: n = 3 (70%),
2c: n = 7 (66%),
2d: n = 13 (79%)
1
1
1
1
9a: n = 1 (90%),
9b: n = 3 (95%),
9c: n = 7 (92%),
2
2
2
9d: n = 13 (89%)
Scheme 3. Synthesis of erythro-configured ketones 2a–d.
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4
S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
ROC
H
OH
3
O
1
HO
2
OH
OH
R
R
4
OH
H
CH OH
2
H
+
δ
O
OH
OH
3
O
+δ
R
H
3
H
2
H
2
R
O
+
δ
H
2
4
OH
H
O
2
O
H
O
H3
O
O
H
H
3
1
OH
OH
OH
R
HO
C
A
B
D
dihedral angle = large
dihedral angle = 60
o
C
dihedral angle = 0 oC
3
3
J = 7-11 Hz
J = 2-5 Hz
3
J = 7-11 Hz
Figure 4. Stable conformers of ketone 2d.
the H-3 proton appears at 3.61 ppm as a triplet with J = 5.5 Hz. The
coupling constant between H-2 and H-3 is higher than the threo-
isomer, as presented earlier. This can be rationalized through the
conformer B of 2d (Fig. 4). In this conformation, the dihedral angle
between H-2–H-3 is 60° and favorably matches with the observed
value of J = 5.5 Hz. The other two conformers A and C were
expected to have a much larger coupling constant between the
H-2–H-3 protons. The C and DEPT NMR spectra of 2d showed
the presence of carbonyl functionality at 212.2 ppm, further indi-
cating no formation of cyclic hemiketal structure D. The obtain-
ment of the molecule was confirmed by mass spectroscopy,
NADH/ H+
+
O
N
2
NAD / H O
N
HO
O
O
HO
O
O
resazurin (blue color)
resorufin (pink color)
Figure 5. REMA method (Resazurin Microtiter Assay).
1
3
lipophilic ketones bearing tetradecyl alkyl chain, were found to
be active, in contrast to the corresponding ethyl-ketones 1a and
a respectively. It would be too early to conclude, as to whether
these compounds were responsible for blocking the biosynthesis
of -rhamnose, but the observed activity with these lipophilic
2
which showed a base peak at 339.2499 that corresponds to [M
+
+
Na] (Calcd mass for the formula C18
H
36
O
4
Na is 339.2499).
L
ketones does reflect a possible interference in the growth of their
waxy cell wall and hence disruption of cell proliferation. Further
studies are required for understanding the mechanism for the inhi-
bitory action of these open chain ketones 1d and 2d.
2
.2. Biological assay
After successful synthesis of threo 1a–d and erythro 2a–d-con-
figured trihydroxy-ketones, we next studied their anti-mycobacte-
rial activity. In pharmacology, logP values of new compounds are
necessary because it gives information about the solubility of the
compound in water or a lipophilic environment. For the quantifica-
tion of the lipophilicity of the synthesized threo and erythro
ketones 1a–d and 2a–d, the logP values of these ketones were cal-
culated by ChemBioDraw 14.0 software. The logP values of ketones
3
. Conclusion
The threo- and erythro-configured open chain trihydroxy
ketones 1a–d and 2a–d visualized for possible anti-mycobacterial
activity were readily synthesized through the threo and erythro-
configured morpholine amide based building blocks 8 and 9.
Among the synthesized ketones, as expected, the lipophilic ketones
1
c, 1d and 2d were also evaluated experimentally (Table 1).
According to logP values, it was clear that compounds 1a and 2a
are hydrophilic, whereas 1d and 2d have a lipophilic nature.
In order to determine the minimum inhibitory concentration of
test compounds 1a–d and 2a–d against M. tuberculosis H37Rv
1
d and 2d with a tetradecyl carbon chain were found to be moder-
ately active against M. tuberculosis proliferation, thus confirming
that lipophilic ketones are better compared to ethyl ketones.
(
ATCC 27294), the REMA method (Resazurin Microtiter Assay)
32
was used as described by Polamino et al. (Fig. 5), supplemented
with 0.2% glycerol and 10% ADC (bovine albumin/dextrose/cata-
lase) was prepared.
4. Experimental
4.1. General
The results of this assay are summarized in the Table 1. It was
found that compounds 1d and 2d were active at 16–32
centration. As conjectured, both the threo- and erythro-configured
l
g/mL con-
For reaction purposes and column chromatography, distilled
and dry solvents were used. For column chromatography,
Table 1
Evaluation of logP values and screening of ketones 1a–d and 2a–d against M. tuberculosis cell proliferation
Entry
Compound
LogP (Theoretical)
LogP (Experimental)
MIC in lg/mL
1
2
3
4
5
6
7
8
9
1a
2a
1b
2b
1c
2c
1d
2d
ꢁ1.40
ꢁ1.40
ꢁ0.57
ꢁ0.57
1.10
1.10
3.60
3.60
—
—
—
—
2.39
—
2.34
2.56
—
>64
>64
>64
>64
>64
>64
32
16
>0.06
>0.06
Rifampicin
Isoniazid
3.85 [Drug bank]
ꢁ0.64
1
0
—
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S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
1
00–200 mesh size silica gels were used. All the reactions were fol-
lowed by TLC analysis. This was done using pre-coated ‘MERCK
254’ plates. The spot detection on TLC was done by exposure of
CH
110.0, (CMe
65.8 (OCH CH); 46.1 (NCH
HRMS (ESI): m/z Calcd for C11H19NO Na, [M+Na] : 268.1161, found
5
268.1171.
3
); 1.34 (s, 3H, CH
3
); 13C NMR [CDCl
3
, 100 MHz]: d 169.4 (CO);
2
); 76.3 (CHCO); 67.8 (CH); 66.8 (CH ); 66.6 (CH
3
), 43.0 (NCH ), 26.4 (CH ), 25.3 (CH
2
2
);
);
F
2
2
2
3
+
plate under UV light or dipping in to the solution of Hanessian’s
stain followed by charring on hot plate. High resolution NMR
experiments were recorded on BRUKER AV 400 FT NMR and AV
5
00 FT NMR instrument operating at 400 MHz and 500 MHz
4
.3. Synthesis of 1-morpholino-2-O-benzyl-(3,4-O-isopropy-
respectively using tetramethylsilane (TMS) as the internal stan-
dard. Infra-Red spectra were recorded using JASCO FT/IR spec-
trophotometer. High resolution mass spectra (HRMS) were
recorded on a MICRO Q TOF mass spectrometer using ESI technique
at 10 eV.
lidene)- -threonamide 8
L
A
solution of
a-hydroxy-morpholine amide 14 (6.88 g,
1
9.9 mmol) in 25 mL of DMF was added to a suspension of sodium
hydride (0.520 g, 21.8 mmol) in 20 mL of DMF at 0 °C. Benzyl bro-
mide (2.65 mL, 21.8 mmol) was then added dropwise. The reaction
mixture was then stirred for 1 h. After completion of the reaction, a
4
.2. Synthesis of 1-morpholino-(3,4-O-isopropylidene)-
L-threon-
amide 14
1
0 mL saturated solution of ammonium chloride was added to the
reaction mixture and the organic compound was extracted by
20 mL of ethyl acetate (40 mL ꢀ 3). The organic layer was washed
SO . The organic layer
L
-Ascorbic acid 12 (14.00 g) was dissolved in 200 mL of water
and then allowed cooled to 0 °C. To this cold solution, Na CO
17.00 g) was added in small portions over a period of 10 min with
continuous stirring. The resulting solution was then stirred for
0 min at 0 °C. Next, H (27 mL) was added dropwise over a per-
1
2
3
with water (30 mL ꢀ 3) and dried over Na
2
4
(
was evaporated on a rotary evaporator to furnish a crude product,
which was purified by column chromatography using ethyl acet-
ate/hexanes mixture (2:3). Nature: White crystalline solid; mp:
3
2 2
O
iod of 10 min after which the resulting reaction mixture was stir-
red at 0 °C for 30 min. The flask was then immersed in a water
bath at 50–55 °C and stirring was continued for 45 min to obtain
pale yellow solution. At this point, activated carbon (3.0–4.0 g)
was added to the reaction mixture to decompose the excess perox-
ide while maintaining the water bath temperature up to 60 °C. The
reaction mixture was then stirred for 30–45 min at 65–70 °C. The
hot mixture was filtered on a Celite pad and the filter cake was
washed with 100–150 mL water. The combined filtrate was acidi-
fied to pH 1 by the cautious addition of 6 M HCl at 0 °C. The reac-
tion mixture was then allowed to warm up to room temperature
and stirred for 1 h. The acidic solution was concentrated by using
rotary evaporator at 50 °C. After the complete removal of water,
the residue was dried at 55 °C under reduced pressure. It is essen-
tial that all of the moisture be removed at this point and a constant
weight was abstained. To the residue, 50 mL of ethyl acetate were
added and heated at 70 °C for 5 min, after which the ethyl acetate
was then filtered. This process was repeated for 4–5 times to
extract the organic compound. The combined filtrate was then con-
centrated to give a crude lactone as gummy compound 10 (5.60 g).
7
4–76 °C; Yield: 76%; TLC (R
f
): 0.62 (Ethyl acetate/Hexane, 2:3);
); IR (neat) max: 3020 (CAH), 1641
C@O), 1476 (ArAH), 1215 (CAO) cm
00 MHz]: d 7.28–7.37 (m, 5H, Aromatic), 4.70 (d, 1H, J = 11.6 Hz,
OCH Ph); 4.57 (d, 1H, J = 11.6 Hz, OCH Ph); 4.50 (q, 1H,
J = 6.8 Hz, CH CHCH); 4.21 (d, 1H, J = 5.6 Hz, CHCHCO); 4.08 (dd,
H, J = 8.8 Hz, J = 6.8 Hz, CH CH); 3.84 (dd, 1H, J = 8.4 Hz,
= 6.8 Hz, CH CH); 3.72–3.77 (m, 2H); 3.62–3.70 (m, 2H);
.51–3.61 (m, 3H); 3.43–3.51 (m, 1H); 1.35, 1.41 (2 ꢀ s, 6H,
23
[a
]
D
= +11.4 (c 1.0, CHCl
3
m
ꢁ1
1
(
4
;
3
HNMR [CDCl ,
a
H
b
a b
H
2
1
1
2
a
H
b
1
J
2
a b
H
3
2
1
13
ꢀ CH
28.6 (CH); 128.2 (CH); 109.9 (CMe
Ph); 67.0 (2 ꢀ OACH ); 66.2 (OACH
2 ꢀ NACH ); 25.4, 26.5 (2 ꢀ CH ); HRMS (ESI): m/z Calcd for C18
Na, [M+Na] , 358.1630 found 358.1621.
3
); CNMR [CDCl
3
, 100 MHz]: d 168.2 (CO); 137.1 (C);
); 79.5 (CH); 76.1 (CH); 72.1
); 42.8, 46.1
2
(
(
OCH
2
2
2
2
3
-
+
H
25NO
5
4
.4. General procedure for the synthesis of ketones 15a–d
To a solution of morpholine amide 8, (1.000 mmol) in 4 mL of
dry THF, a solution of alkyl magnesium bromide (3.000 mmol,
equiv) in dry THF (2 mL), was added under an inert atmosphere
3
The
purification.
To a solution of
10 mL), morpholine (1.48 mL, 2 equiv) was added dropwise and
L-threonolactone 10 was used in the next step without further
at 10–15 °C and the mixture was stirred for 3 h at 15 °C to room
temperature. TLC revealed the complete consumption of starting
material. Subsequent hydrolysis was achieved by the cautious
addition of saturated ammonium chloride solution. The aqueous
layer was extracted with ethyl acetate, washed with water, dried
over Na SO and concentrated to get crude product. This was puri-
2 4
fied by column chromatography using Ethyl acetate/Hexanes mix-
ture, to get the desired ketone 15a–d.
L
-threonolactone 10 (1.00 g) in methanol
(
the reaction mixture was stirred for 12 h at room temperature.
After the total consumption of the starting material, the methanol
was evaporated on rotary evaporator. Excess morpholine was
removed by azeotropic distillation with toluene. The residue was
dissolved in dry acetone (20 mL) and cooled to 0 °C. To this solu-
0
tion, 2 2-dimethoxy propane (4.2 mL) was added followed by
anhydrous CuSO
dropwise until effervescence ceased after which the reaction mix-
ture was stirred for 1 h. The reaction mixture was then filtered
4
powder (2.70 g). Next, conc. H
2
SO
4
was added
4.4.1. 1-Ethyl-2-O-benzyl-(3,4-O-isopropylidene)-
L
-threose 15a
): 0.46
); IR (Thin
mmax: 3021 (CAH); 1714 (C@O); 1524 (Ar, C@C); 1215
Nature: Yellow solid; mp: 40–42 °C; Yield: 82%; TLC (R
f
2
3
(Ethyl acetate/Hexane, 1:9); [
film)
(CAO) cm ; H NMR [CDCl
matic); 4.70 (d, 1H, J = 11.6 Hz, OCH
J = 11.6 Hz, OCH Ph); 4.30 (dd, 1H, J = 12.0 Hz, J
CHCH); 4.00 (dd, 1H, J = 8.4 Hz, J = 6.8 Hz, CH
1H, J = 8.8 Hz, J = 6.8 Hz, CH CH); 3.83 (d, 1H, J = 5.2 Hz); 2.66
(dddd, 1H, J = J = 18.8 Hz, J = J = 7.2 Hz, CH CH ); 2.57 (dddd,
1H, J = J = 18.8 Hz, J = J CH ); 1.42 (s, 3H, CCH
CH ); 1.34 (s, 3H, CCH CH ); 1.02 (t, 3H, J = 6.4 Hz, CH
NMR [CDCl , 100 MHz]: d 211.9 (CO); 137.3 (C); 128.6 (CH);
128.1 (CH); 109.7 (C(CH ); 84.5 (CH CH); 76.3 (CHCHCO); 73.6
(CH Ph); 65.8 (CH CH); 33.2 (COCH CH ); 26.3 (CH ); 25.5 (CH );
D 3
a] = +37.0 (c 1.0, CHCl
through a Celite pad to remove CuSO
4
. The residue was washed
ꢁ
1 1
with ethyl acetate (60 mL). The combined filtrate was then neutral-
ized by triethylamine (2–2.5 mL) and the solvents were evaporated
to give a crude compound, which was purified by column chro-
matography using ethyl acetate/Hexanes mixture (1:1). Nature:
3
, 400 MHz]: d 7.29–7.36 (m, 5H, Aro-
Ph); 4.58 (d, 1H,
= 6.8 Hz, CH
CH); 3.84 (dd,
a
H
b
a
H
b
1
2
2
-
1
2
a b
H
Gummy compound; Yield: 71%; TLC (R
f
): 0.15 (Ethyl acetate/Hex-
); IR (Thin film) max: 3019
NMR [CDCl
00 MHz]: d 4.44–4.47 (m, 1H, CHCHCO); 4.33 (td, 1H, J = 6.8 Hz,
= 4.4 Hz, CH CHCH); 4.07 (dd, 1H, J = 8.8 Hz, J = 6.8 Hz, CH
CH); 3.89 (dd, 1H, J = 8.4 Hz, J = 6.8 Hz, CH CH); 3.63–3.79 (m,
H, Morpholinyl); 3.39–3.48 (m, 3H, Morpholinyl) 1.39 (s, 3H,
1
2
a
H
b
2
3
ane, 1:1); [
(
a
]
D
= ꢁ10.95 (c 1.0, CHCl
3
m
1
2
3
4
a
H
b
3
ꢁ1
1
CAH), 1643 (C@O), 1215 (CAO) cm
;
H
3
,
1
2
3
4
= 7.2 Hz, CH
H
a b
3
3
-
C
1
3
4
1
3
3
3
2
CH
3
);
J
2
2
1
2
H
a b
-
3
H
b
3
)
2
2
1
2
a
5
2
2
2
3
3
3
Please cite this article in press as: Borkar, S. R.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.11.008

6
S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
7
3
.09 (CH
01.1416, found 301.1420.
2
CH
3
); HRMS (ESI): m/z Calcd for C16
H
22
O
4
Na, [M+Na]+:
orated to obtain a crude compound, which was purified by column
chromatography using ethyl acetate-hexanes mixture (1:4) to
obtain alcohol in 61–73% yield.
4
.4.2. 1-Butyl-2-O-benzyl-(3,4-O-isopropylidene)-
Nature: Gummy liquid; Yield: 70%; TLC (R ): 0.44 (Ethyl acetate/
); IR (Thin film) max: 3020
L-threose 15b
f
4
.5.1. 1-Ethyl-(3,4-O-isopropylidene)-
L
-threose 16a
): 0.48 (Ethyl
); IR (Thin film)
2
3
Hexane, 1:9); [
a
]
D
= +42.5 (c 1.0, CHCl
3
m
Nature: Gummy compound; Yield: 61%; TLC (R
f
CAH); 1713 (C@O); 1520 (Ar, C@C); 1215 (CAO) cm ; 1H NMR
ꢁ
1
(
[
23
acetate/Hexane, 1:4); [
max: 3020 (CAH); 1708 (C@O); 1218 (CAO) cm ; H NMR [CDCl
00 MHz]: d 4.44 (td, 1H, J = 6.8 Hz, J = 2.8 Hz); 4.07–4.11 (m,
H); 4.00 (td, 1H, J = 6.8 Hz, J = 1.2 Hz); 3.48 (d, 1H, J = 5.6 Hz);
a]
D
= ꢁ33.8 (c 1.0, CHCl
3
CDCl
3
, 400 MHz]: d 7.29–7.36 (m, 5H, Aromatic); 4.70 (d, 1H,
Ph); 4.58 (d, 1H, J = 12.0 Hz, OCH Ph); 4.30
= 12.4 Hz, = 5.6 Hz, OCH CHCH); 4.00 (dd, 1H,
= 6.8 Hz, CH CH); 3.83 (dd, 1H, = 8.4 Hz,
CH); 3.81 (d, 1H, J = 5.6 Hz, CHCHCO); 2.50–2.63
); 1.48–1.57 (m, 2H, CH ); 1.42 (s, 3H, CH ); 1.33 (s,
); 1.26–1.31 (m, 2H, CH ); 0.88 (t, 3H, J = 7.2 Hz, CH CH );
C NMR [CDCl , 100 MHz]: d 211.5 (CO); 137.3 (C); 128.6 (CH);
28.1 (CH); 109.7 (C(CH ); 84.5 (CHCHCO); 76.4 (CH CH); 73.6
Ph); 65.8 (CH CH); 39.6 (COCH CH );
); 26.3, 25.4 (2 ꢀ CH
5.0 (CH CH ); 22.3 (CH CH ); 13.9 (CH CH ); HRMS (ESI): m/z
Na, [M+Na] : 329.1729, found 329.1741.
ꢁ1 1
m
3
,
J = 12.0 Hz, OCH
dd, 1H,
= 8.8 Hz,
= 6.8 Hz, CH
m, 2H, CH
H
a b
a b
H
4
2
2
2
1
1
2
(
J
1
J
2
2
1
2
J
J
1
J
2
a
H
b
J
1
.68 (ddd, 1H, J
.51 (ddd, 1H, J
.37 (s, 3H, CCH
= 7.6 Hz, J = 1.2 Hz, CH
10.0 (CO); 109.9 (C(CH
CH); 32.0 (COCH CH
1
= 18.0 Hz, J
2
= 14.8 Hz, J
3
= 7.2 Hz, CH
= 7.2 Hz, CH
CH
); C NMR [CDCl
); 75.9 (CH CH), 75.8 (CHCHCO); 65.7
); 26.0 (CH ); 25.4 (CH ); 7.4 (CH CH );
HRMS (ESI): m/z Calcd for C Na, [M+Na] : 211.0946, found
a
H
b
2
CH );
2
a b
H
= 18.0 Hz, J
= 14.4 Hz, J
a b
H
2
CH );
1
2
3
(
2
2
3
3
CH
3
); 1.32 (s, 3H, CCH
3
3
); 0.90 (td, 3H,
, 100 MHz]: d
3
H, CH
3
2
2
3
13
J
1
2
2
CH
3
3
1
3
3
2
3
)
2
2
1
(
2
3
)
2
2
(CH
2
2
3
3
3
2
3
OCH
2
2
2
3
3
+
9
16 4
H O
2
2
2
3
+
2
3
2
11.0955.
26 4
Calcd for C18H O
4
.5.2. 1-(n-Butyl)-(3,4-O-isopropylidene)-
L
-threose 16b
): 0.31 (Ethyl
); IR (Thin film)
4
1
.4.3. 1-(n-Octyl)-2-O-benzyl-(3,4-O-isopropylidene)-
5c
Nature: Gummy compound; Yield: 79%; TLC (R
L-threose
Nature: Gummy compound; Yield: 73%; TLC (R
f
23
acetate/Hexane, 1:9); [
a]
D
= ꢁ21.1 (c 1.0, CHCl
3
ꢁ1 1
f
): 0.72 (Ethyl
); IR (Thin film)
max: 3020 (CAH);1708 (C@O); 1524 (Ar, C@C); 1218 (CAO)
mmax: 3020 (CAH); 1716 (C@O); 1215 (CAO) cm ; H NMR [CDCl ,
3
23
D 3
acetate/Hexane, 1:4); [a] = +37.0 (c 1.0, CHCl
m
4
2
00 MHz]: d 4.45 (td, 1H, J
H); 4.00 (dd, 1H, = 8.4 Hz,
= 8.0 Hz, J = 6.8 Hz, CH
= 8.0 Hz, = 6.8 Hz, CH
CH ); 1.30–1.34 (m, 5H, CCH
.90 (t, 3H, J = 7.6 Hz, CH
09.5 (CO); 109.9 (C(CH
CH); 38.4 (COCH CH
2.3 (CH ); 13.9 (CH CH ); HRMS (ESI): m/z Calcd for C11
1
= 6.8 Hz, J
= 7.2 Hz); 2.64 (ddd, 1H,
CH ); 2.51 (ddd, 1H,
CH ); 1.58–1.65 (m,
CH , CH );
, 100 MHz]: d
CH), 75.7 (CHCHCO); 65.7
); 25.5 (CH ); 25.4 (CH );
Na,
2
= 2.4 Hz); 4.08–4.11 (m,
J
1
J
2
ꢁ
1 1
cm
;
H NMR [CDCl
3
, 400 MHz]: d 7.26–7.36 (m, 5H, Aromatic);
Ph); 4.58 (d, 1H, J = 9.6 Hz, OCH
= 10.0 Hz, J = 5.6 Hz, CH CHCH); 4.00 (dd, 1H,
= 5.2 Hz, CH CH); 3.83 (dd, 1H, = 6.8 Hz,
CH); 3.80 (d, 1H, J = 4.4 Hz); 2.52–2.63 (m, 2H,
); 1.53–1.56 (m, 2H, COCH CH ); 1.42 (s, 3H, CCH CH );
); 1.20–1.30 (br, 10H, 5 ꢀ CH ); 0.87 (t, 3H,
, 100 MHz]: d 211.5 (CO);
); 84.6 (CH CH),
CH); 39.9 (COCH CH );
); 29.2 (CH ); 26.3 (CH ); 25.4
); 14.2 (CH CH ); HRMS (ESI): m/z
Na, [M+Na] : 385.2355, found 385.2343.
J
J
1
= 17.2 Hz, J
= 17.2 Hz,
2
2
3
a
H
b
2
4.70 (d, 1H, J = 10.4 Hz, OCH
Ph); 4.30 (dd, 1H, J
a
H
b
a b
H -
1
J
J
3
a
H
b
2
1
2
2
2
0
2
H); 1.37 (s, 3H, CCH
3
3
3
3
2
J
J
1
= 6.8 Hz,
= 5.2 Hz, CH
J
2
a
H
b
J
1
13
2
CH
); 76.0 (CH
); 26.0 (CH
3 3
); C NMR [CDCl
2
a b
H
3
)
2
2
COCH
.34 (m, 3H, CCH
J = 5.2 Hz, CH CH
2
2
2
3
3
(CH
2
2
3
3
2
3
1
3
CH
3
1
2
2
2
2
3
20
H O
4
3
2
3
); C NMR [CDCl
3
[
M+Na] : 239.1259, found 239.1259.
+
1
7
3
37.3 (C); 128.6 (CH); 128.1 (CH); 109.7 (C(CH
6.4 (CHCHCO); 73.6 (CH Ph); 65.8 (CH
1.9 (CH ); 29.4 (CH ); 29.3 (CH
); 23.0 (CH ); 22.7 (CH
Calcd for C22
3
)
2
2
2
2
2
3
4
.5.3. 1-(n-Octyl)-(3,4-O-isopropylidene)-
L
-threose 16c
): 0.12 (Ethyl
); IR (Thin film)
2
2
2
2
3
Nature: Gummy compound; Yield: 65%; TLC (R
f
(CH
3
2
2
2
3
2
3
+
acetate/Hexane 1:9); [
a]
D
= ꢁ23.0 (c 1.0, CHCl
3
1 1
34 4
H O
ꢁ
m
max: 3021 (CAH); 1716 (C@O); 1216 (CAO) cm ; H NMR [CDCl
00 MHz]: d 4.39–4.43 (td, 1H, J = 6.8 Hz, J = 2.4 Hz); 4.04 (dd,
H, J = 8.0 Hz, J = 6.8 Hz); 3.95 (dd, 1H, J = 8.4 Hz, J = 7.2 Hz);
.54 (d, 1H, J = 5.6 Hz); 2.58 (dt, 1H, J = 16.8 Hz, J = 7.6 Hz, CH
); 2.46 (dt, 1H, J = 17.2 Hz, J = 7.2 Hz, CH CH ); 1.56–1.58
m, 2H); 1.32 (s, 3H, CCH CH ); 1.27 (s, 3H, CCH CH ); 1.20–1.24
(m, 10H, CH ); 0.81 (t, 3H, J = 6.8 Hz, CH ); C NMR [CDCl
00 MHz]: d 209.5 (CO); 109.8 (C(CH ); 75.9 (CH CH), 75.6
CHCHCO); 65.6 (CH CH); 38.6 (COCH CH ); 31.8 (CH ); 29.3
CH ); 29.1 (CH ); 29.0 (CH ); 25.9 (CH ); 25.3 (CH ); 23.3 (CH );
2.6 (CH ); 14.0 (CH CH ); HRMS (ESI): m/z Calcd for C15
M+Na] : 273.2066, found 273.2084.
3
,
4
2
3
CH
(
1
2
4
.4.4. 1-(n-Tetradecyl)-2-O-benzyl-(3,4-O-isopropylidene)-L-
1
2
1
2
threose 15d
1
2
a b
H -
f
Nature: Yellow solid; mp: 39–41 °C; Yield: 64%; TLC (R ): 0.52
23
2
1
2
a
H
b
2
(
Ethyl acetate/Hexane, 1:9); [
film) max: 3020 (CAH); 1713 (C@O); 1523 (Ar, C@C); 1216
CAO) cm
matic); 4.71 (d, 1H, J = 11.6 Hz); 4.58 (d, 1H, J = 11.6 Hz); 4.30
dd, 1H, = 12.0 Hz, = 6.4 Hz); 4.00 (dd, 1H, = 8.8 Hz,
= 6.8 Hz); 3.83 (dd, 1H, J = 8.4 Hz, J = 6.4 Hz); 3.80 (d, 1H,
J = 5.6 Hz); 2.49–2.64 (m, 2H); 1.47–1.57 (m, 2H); 1.42 (s, 3H,
CCH CH ); 1.34 (m, 3H, CCH CH ); 1.20–1.30 (m, 22H); 0.88 (t,
H, J = 6.4 Hz, CH ); C NMR [CDCl , 100 MHz]: d 211.5 (CO);
37.4 (C); 128.6 (CH); 128.1 (CH); 109.7 (C(CH ); 84.6 (CH CH),
6.5 (CHCHCO); 73.6 (CH Ph); 65.8 (CH CH); 39.9 (COCH CH );
2.0 (CH ); 29.8 (CH ); 29.79 (CH ); 29.75 (CH ); 29.6 (CH ); 29.5
); 29.4 (CH ); 29.3 (CH ); 26.4 (CH ); 25.5 (CH ); 23.0 (CH );
2.8 (CH ); 14.2 (CH CH ); HRMS (ESI): m/z Calcd for C28 Na,
D 3
a] = +31.15 (c 1.0, CHCl ); IR (Thin
3
3
3
3
m
1
3
ꢁ1
1
2
2
CH
3
3
,
(
3
; H NMR [CDCl , 400 MHz]: d 7.26–7.36 (m, 5H, Aro-
1
(
(
2
[
3
)
2
2
2
2
3
2
(
J
1
J
2
J
2
2
2
2
3
3
2
J
2
1
2
2
2
3
29 4
H O ,
+
3
3
3
3
13
3
1
7
3
2
CH
3
3
3
)
2
2
4.5.4. 1-(n-Tetradecyl)-(3,4-O-isopropylidene)-
L
-threose 16d
): 0.61
); IR (Thin
Nature: Yellow solid; mp = 54–56 °C; Yield: 72%; TLC (R
f
2
2
2
3
2
3
(Ethyl acetate/Hexane, 1:4); [
a
]
D
= ꢁ17.6 (c 1.0, CHCl
3
2
2
2
2
2
ꢁ
1 1
(CH
2
2
2
3
3
2
film)
m
max: 3021 (CAH); 1716 (C@O); 1216 (CAO) cm
, 400 MHz]: d 4.45 (td, 1H, J = 6.8 Hz, J = 2.8 Hz); 4.08–
= 8.0 Hz, J = 6.8 Hz); 2.64 (dt, 1H,
CH ); 2.51 (dt, 1H, J = 17.2 Hz,
); 1.60–1.66 (m, 2H); 1.38 (s, 3H, CCH CH );
); 1.20–1.29 (m, 22H); 0.87 (t, 3H, J = 6.4 Hz,
); C NMR [CDCl , 100 MHz]: d 209.5 (CO); 110.0 (C
); 76.0 (CH CH); 75.7 (CHCHCO); 65.8 (CH CH); 38.7
(COCH CH ); 32.0 (CH ); 29.8 (CH ); 29.79 (CH ); 29.74 (CH );
29.6 (CH ); 29.5 (CH ); 29.3 (CH ); 26.0 (CH ); 25.4 (CH ); 23.5
(CH ); 22.8 (CH ); 14.2 (CH CH ); HRMS (ESI): m/z Calcd for C21
Na, [M+Na] : 379.2824, found 379.2813.
; H NMR
2
2
2
3
H
46
O
4
[CDCl
3
1
2
+
[
M+Na] : 469.3294, found 469.3283.
4.12 (m, 2H); 4.01 (dd, 1H, J
1
2
J
J
1
= 17.6 Hz, J
= 7.2 Hz, CH
2
= 7.6 Hz, CH
CH
CH
a
H
b
2
1
4
.5. General procedure for the synthesis of ketones 16a–d
2
a
H
b
2
3
3
1
.33 (s, 3H, CCH
3
3
1
3
To a solution of ketone 15a–d (1.481 mmol) in 4.4 mL of etha-
nol, Pd/C (10%) (0.007 mmol) was added and the reaction mixture
was stirred in H gas atmosphere. After 3–4 h, TLC revealed the
complete consumption of the starting material. The reaction mix-
ture was then filtered over Celite. The residue was washed with
ethyl acetate. The combined organic layer was collected and evap-
CH
(CH
2
CH
3
3
3
)
2
2
2
2
2
3
2
2
2
2
2
2
2
3
3
2
2
2
3
-
+
40 4
H O
Please cite this article in press as: Borkar, S. R.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.11.008

S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
7
4
.6. General procedure for the hydrolysis of isopropylidene
3.30 (m, 1H, CH
2H, COCH CH
); 1.18–1.30 (br, 22H, 11 ꢀ CH
a
H
b
CH, merged with HOD peak); 2.44–2.56 (m,
protection towards the synthesis of ketones 1a–d
2
2
, merged with DMSO base peak); 1.40–1.50 (m, 2H,
); 0.85 (t, 3H, J = 6.4 Hz, CH
, 100 MHz]: d 213.2 (CO); 76.6 (CHCHCO);
CH); 61.9 (CH CH); 38.3 (O@CCH ); 31.2 (CH ); 29.0
); 28.98 (CH ); 29.91 (CH ); 28.66 (CH ); 28.62 (CH ); 22.6
); 22.0 (CH ); 13.9 (CH CH ); HRMS (ESI): m/z Calcd for C18
Na, [M+Na] : 339.2511, found 339.2520.
For the synthesis of erythro-configured ketones, similar proce-
CH
CH
2
2
2
-
1
3
a-Hydroxy ketone 16 (1.000 mmol) was dissolved in the mix-
3
); C NMR [DMSO-d
6
ture of acetic acid/H O (4 mL, 3:1) and the reaction mixture was
2
72.5 (CH
2
2
2
2
stirred for 12–14 h at room temperature. Progress of the reaction
was monitored by TLC. After complete consumption of starting
material, acetic acid was evaporated. Further, traces of acetic acid
and water was evaporated by azeotropic distillation with toluene
(CH
(CH
H O
36 4
2
2
2
2
2
2
2
2
3
-
+
(
3 mL ꢀ 3) to get gummy residue. This residue was washed with
dures were followed by using
material.
D-isoascorbic acid as starting
hexanes (5 mL ꢀ 2) to remove non-polar impurities which offered
pure compound.
4
.7. Synthesis of 1-morpholino-2-O-benzyl-(3,4-O-isopropy-
4
.6.1. 1-Ethyl-
Nature: Gummy compound; Yield: 90%; TLC (R
L-threose 1a
lidene)- -erythronamide 9
D
f
): 0.42 (MeOH/
= ꢁ33.0 (c 0.5, MeOH); IR (Thin film)
2
3
Ethyl acetate, 0.5:9.5); [a]
D
ꢁ1
1
m
[
3
max: 3022 (CAH); 1713 (C@O); 1213 (CAO) cm
(CD SO, 500 MHz]: d 4.86 (br, 1H, OH); 4.62 (br, 2H, OH);
.90–4.10 (m, 1H, CHCHCO); 3.73 (br, 1H, CH CHCH); 3.40–3.43
CH); 3.30–3.32 (m, 1H, CH CH, merged with
, merged with DMSO base
;
H NMR
4
1
.7.1. 1-Morpholino-(3,4-O-isopropylidene)-D-erythronamide
8
3 2
)
2
Nature: White crystalline solid; mp 80–82 °C; Yield: 70%; TLC
(
m, 1H, CH
HOD peak); 2.50–2.64 (m, 2H, COCH
peak); 0.91 (t, 3H, J = 7.5 Hz, CH
a
H
b
a
H
b
25
(R
f
): 0.23 (Ethyl acetate/Hexane, 2:3); [
IR (Thin film) max: 3430 (CAH); 1650 (C@O); 1247 (CAO) cm ; H
, 400 MHz]: d 4.29 (m, 1H); 4.16 (m, 1H); 3.93–4.01 (m,
a]
D
= ꢁ23.35 (c 1.0, CHCl
3
);
2
CH
2
ꢁ1 1
m
13
2
CH
3
);
C
NMR [CD
CH); 61.9 (CH
); HRMS (ESI): m/z Calcd for
6 13 4
H O , [M+H] : 149.0814, found 149.0813.
3 2
) SO,
NMR [CDCl
3
1
25 MHz]: d 213.9 (CO); 76.6 (CHCHCO); 72.6 (CH
2
2
-
2
2
1
6
H); 3.88 (d, J = 13.2 Hz, 1H); 3.60–3.69 (m, 6H); 3.39–3.48 (m,
CH); 31.6 (O@CCH ); 7.21 (CH CH
C
2
2
3
13
H); 1.29, 1.38 (2 ꢀ s, 6H, CH
3
); C NMR [CDCl
3
, 100 MHz]: d
CH);
); 24.8
+
2 2
71.1 (CO); 110.0, (CMe ); 77.5 (CHCO); 68.9 (CH); 67.8 (CH
6.7 (OCH
) 26.2 (CH
46.1341, found 246.1338.
2
), 66.8 (OACH
2
); 43.1 (NCH
); HRMS (ESI): m/z Calcd for C11H20NO
2
); 46.1 (NACH
, [M+H] :
2
4
.6.2. 1-(n-Butyl)-
Nature: Gummy compound; Yield: 60%; TLC (R
L-threose 1b
+
(CH
3
3
5
f
): 0.55 (MeOH/
= ꢁ25.1 (c 0.8, MeOH); IR (Thin film)
2
2
3
Ethyl acetate, 0.5:9.5); [a]
D
ꢁ1
1
m
[
2
max: 3022 (CAH), 1713 (C@O), 1213 (CAO) cm
DMSO-d , 400 MHz]: d 4.80 (d, 1H, J = 6.8 Hz, OH); 4.57–4.60 (m,
H, OH); 4.01 (dd, 1H, J = 6.4 Hz, J = 2.0 Hz, CHCHCO); 3.72–3.77
CHCH); 3.39–3.45 (ddd, 1H, J = 10.4 Hz, J = 7.2 Hz,
= 6.4 Hz, CH CH); 3.20–3.30 (m, 1H, CH CH, merged with
HOD peak); 2.44–2.56 (m, 2H, COCH CH , merged with DMSO base
peak); 1.44 (quin, 2H, J = 7.2 Hz, CH CH CH ); 1.25 (sex, 2H,
J = 7.6 Hz, CH CH CH ); 0.85 (t, 3H, J = 7.2 Hz, CH
DMSO-d , 100 MHz]: d 213.3 (CO); 76.7 (CHCHCO); 72.5 (CH
CH); 37.9 (O@CCH ); 24.8 (CH ); 21.7 (CH ); 13.7 (CH
); HRMS (ESI): m/z Calcd for C
;
H NMR
4
.7.2. 1-Morpholino-2-O-benzyl-(3,4-O-isopropylidene)-D-erythro-
6
namide 9
1
2
Nature: White crystalline solid; mp 78–80 °C; Yield: 90%; TLC
(
m, 1H, CH
2
1
2
2
5
(R
f
): 0.29 (Ethyl acetate/Hexane, 2:3); [
a]
D
= +38.3 (c 1.0, CHCl
3
);
;
J
3
a
H
b
a b
H
ꢁ
1
IR (Thin film) max: 3020 (CAH); 1648 (C@O); 1220 (CAO) cm
m
2
2
1
3
H NMR [CDCl , 400 MHz]: d 7.30–7.38 (m, 5H, Aromatic); 4.62
2
2
3
1
3
(d, 1H, J = 12.0 Hz, OCH H Ph); 4.50 (d, 1H, J = 12.0 Hz, OCH H Ph);
CH
3
); C NMR
CH);
a
b
a
b
2
2
3
2
4
4
.37 (q, 1H, J = 6.4 Hz, CH
.15 (dd, 1H, J
2
CHCH); 4.21 (d, 1H, J = 6.8 Hz, CHCHCO);
= 6.8 Hz, CHCH ); 3.96 (dd, 1H,
[
6
CH
6
2
= 8.8 Hz, J
2
a b
H
1.9 (CH
2
2
2
2
2
-
1
+
J = 8.8 Hz, J = 6.0 Hz, CHCH H ); 3.43 (m, 1H); 3.35–3.78 (m, 7H,
H
8 16
O
4
Na, [M+Na] : 199.0937,
1
2
a
b
3
1
3
Morpholinyl); 1.32 (s, 3H, CH
3
3 3
); 1.39 (s, 3H, CH ); C NMR [CDCl ,
found 199.0946.
1
(
(
00 MHz]: d 168.2 (CO); 137.0 (C); 128.7 (CH); 128.37 (CH); 128.34
CH); 109.8 (CMe ); 77.3 (CHCO); 76.1 CH); 72.8 (OCH Ph); 67.2
CH CH); 66.8 (OCH ), 67.0 (OACH ); 46.1 (NCH ) 42.7 (NACH );
4
.6.3. 1-(n-Octyl)-
Nature: Yellow solid; mp: 75–77 °C; Yield: 69%; TLC (R
L-threose 1c
2
2
f
): 0.60
= ꢁ23.6 (c 0.9, MeOH); IR (Thin film)
2
2
2
2
2
2
3
3 3 26 5
24.9 (CH ); 26.5 (CH ); HRMS (ESI): m/z Calcd for C18H NO , [M
+H] : 336.1810, found 336.1803.
(
MeOH/DCM, 05:9.5); [
a]
D
+
ꢁ1
1
m
max: 3022 (CAH); 1713 (C@O); 1216 (CAO) cm
, 500 MHz]: d 4.81 (d, 1H, J = 6.5 Hz, OH); 4.57 (d, 2H,
J = 6.5 Hz, OH); 4.00 (dd, 1H, J = 6.5 Hz, J = 2.0 Hz, CHCHCO);
CHCH); 3.39–3.44 (m, 1H, CH CH); 3.29–
CH, merged with HOD peak); 2.50–2.60 (m,
, merged with DMSO base peak); 1.40–1.50 (m, 2H,
); 1.18–1.30 (br, 10H, 5 ꢀ CH ); 0.85 (t, 3H, J = 6.5 Hz, CH CH );
C NMR [DMSO-d , 125 MHz]: d 213.3 (CO); 76.7 (CHCHCO); 72.5
CH CH); 61.9 (CH
8.6 (CH ); 28.5 (CH
HRMS (ESI): m/z Calcd for C12
;
H NMR
[
DMSO-d
6
1
2
4.8. Characterisation of ketones 16a–d
3
3
2
.72–3.76 (m, 1H, CH
.32 (m, 1H, CH
H, COCH CH
2
a b
H
a
H
b
4.8.1. 1-Ethyl-2-O-benzyl-(3,4-O-isopropylidene)-D-erythrose
19a
2
2
CH
2
2
2
3
Nature: Gummy liquid; Yield: 90%; TLC (R ): 0.66 (Ethyl acet-
f
1
3
23
6
ate/Hexane, 1:4); [
a]
D
= +43.4 (c 1.0, CHCl ); IR (Thin film)
3
m
max
:
3018 (CAH); 1715 (C@O); 1522 (Ar, C@C); 1214 (CAO) cm ; 1
ꢁ
1
H
(
2
2
2
CH); 38.2 (O@CCH
2
); 31.2 (CH
2
); 28.8 (CH
CH
2
);
);
2
2
); 22.7 (CH ); 22.0 (CH
2
2
); 13.9 (CH
2
3
NMR [CDCl , 400 MHz]: d 7.30–7.23 (m, 5H, Aromatic); 4.48 (q,
2H, J = 11.6 Hz, OCH Ph); 4.22 (q, 1H, J = 6.0 Hz, CH CHCH); 3.96
3
+
H
24
O
4
Na, [M+Na] : 255.1572, found
2
2
2
55.1573.
a b
(dd, 1H, J1 = 8.4 Hz, J2 = 6.4 Hz, CH H CH); 3.83 (dd, 1H,
J
1
2 a b
= 8.8 Hz, J = 6.0 Hz, CH H CH); 3.79 (d, 1H, J = 6.4 Hz, CHCHCO);
4
.6.4. 1-(n-Tetradecyl)-L-threose 1d
2.62–2.41 (m, 2H, CH CH ); 1.40 (s, 3H, CH ); 1.32 (s, 3H, CH );
0.96 (t, 3H, J = 7.2 Hz, CH CH ); CNMR [CDCl , 100 MHz]: d
2 3 3
2
3
3
3
1
3
Nature: Yellow solid; mp: 78–80 °C; Yield: 82%; TLC (R
f
): 0.43
2
3
(
Ethyl acetate/Hexane, 7:3); [
a]
D
= ꢁ27.1 (c 0.6, MeOH); IR (Thin
210.9 (CO); 137.1 (C); 128.6 (CH); 128.26 (CH); 128.2 (CH);
109.9 (C(CH ) ); 84.3 (CHCHCO); 76.1 (CH CH); 73.3 OCH Ph);
ꢁ
1 1
film)
m
max: 3015 (CAH); 1713 (C@O); 1214 (CAO) cm
, 400 MHz]: d 4.79 (d, 1H, J = 6.8 Hz, OH); 4.57 (d, 2H,
J = 6.4 Hz, OH); 4.00 (dd, 1H, J = 6.4 Hz, J = 2.0 Hz, CHCHCO);
.60–3.80 (m, 1H, CH CHCH); 3.39–3.45 (m, 1H, CH CH); 3.20–
; H NMR
3
2
2
2
[
DMSO-d
6
2 2 3 3 3 2
66.6 (CH CH); 33.0 (CH CH ); 25.3 (CH ); 26.6 (CH ); 7.1 (CH -
+
1
2
CH ); HRMS (ESI): m/z Calcd for C16H22O Na, [M+Na] : 301.1416,
3
4
3
2
a
H
b
found 301.1430.
Please cite this article in press as: Borkar, S. R.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.11.008

8
S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
4
1
.8.2. 1-(n-Butyl)-2-O-benzyl-(3,4-O-isopropylidene)-
9b
D
-erythrose
J
2
= 5.2 Hz); 3.10–3.40 (br s, 1H, OH); 2.78–2.88 (m, 1H, CH
CH ); 2.54–2.58 (m, 1H, CH CH ); 1.47 (s, 3H, CH ); 1.33 (s,
3H, CH ); 1.12–1.07 (m, 3H, CH CH , 100 MHz]:
d 211.8 (CO); 110.32 (C(CH ); 76.88 (CHCHCO); 76.4 (CH CH);
67.4 (CH CH); 33.7 (CH CH ); 26.8 (CH ); 25.3 (CH ); 7.39 (CH
CH ); HRMS (ESI): m/z Calcd for C
found 211.0950.
a b
H -
3
a
H
b
3
3
1
3
Nature: Gummy liquid; Yield: 95%; TLC (R
f
): 0.64 (Ethyl acetate/
3
2
3 3
); CNMR [CDCl
2
3
Hexane, 1:4); [
a]
D
3
= +38.9 (c 1.0, CHCl ); IR (Thin film) max: 3021
m
3
)
2
2
CAH); 1715 (C@O); 1521 (Ar, C@C); 1215 (CAO) cm 1; 1HNMR
ꢁ
(
[
2
2
3
3
3
2
-
+
CDCl
3
, 400 MHz]: d 7.28–7.19 (m, 5H, Aromatic); 4.47 (ABq, 2H,
Ph); 4.20 (q, 1H, J = 6.4 Hz, CH CHCH) (dd, 1H,
= 6.4 Hz, CH CH); 3.81 (dd, 1H, = 6.0 Hz,
CH); 3.77 (d, 1H, J = 6.4 Hz, CHCHCO); 2.54 (dt,
= 7.2 Hz, CH CH ); 2.41 (dt, 1H, J = 17.2 Hz,
CH ); 1.45 (quint, 2H, J = 7.6 Hz, J = 2.4 Hz, CH
); 1.32 (s, 3H, CH ); 1.17–1.26 (m, 5H, CH CH , CH ); 0.81 (t, 3H,
, 100 MHz]: d 210.3 (CO); 137.1
C); 128.53 (CH); 128.50 (CH); 128.2 (CH); 128.1 (CH); 109.7 (C
CH ); 84.2 (CHCHCO); 75.9 (CH CH); 73.2 (OCH Ph); 66.5 (CH
CH ); 26.5 (CH ); 25.2 (CH ); 24.9 (CH CH ); 22.3
); 13.8 (CH CH ); HRMS (ESI): m/z Calcd for C18 Na,
3
9 16 4
H O Na, [M+Na] : 211.0946,
J = 11.6 Hz, OCH
2
2
J
1
= 8.4 Hz,
= 5.6 Hz, CH
= 18.0 Hz, J
= 7.6 Hz, CH
CH
J = 7.2 Hz, CH
J
2
a
H
b
J
1
J
2
a
H
b
4.9.2. 1-(n-Butyl)-(3,4-O-isopropylidene)-
D-erythrose 20b
1
H, J
1
2
H
a b
2
1
Nature: Yellow solid; mp: 41–43 °C; Yield: 66%; TLC (R
f
): 0.42
3
); IR (Thin
2
3
J
2
a
H
b
2
1
2
2
-
(Ethyl acetate/Hexane, 1:4); [
a]
D
= ꢁ120.0 (c 1.0, CHCl
ꢁ1
1
2
3
2
2
3
film)
m
max: 3025 (CAH); 1704 (C@O); 1218 (CAO) cm
, 400 MHz]: d 4.04–4.08 (m, 2H); 4.00 (dd, 1H, J
= 11.6 Hz, J = 5.6 Hz); 3.40–3.60 (br
= 17.6 Hz, J = 7.2 Hz, CH CH ); 2.53
= 7.2 Hz, CH CH ); 1.57 (quin, 2H,
); 1.46 (s, 3H, CCH CH ); 1.25–1.35 (m, 5H,
); 0.81 (t, 3H, J = 7.6 Hz, CH CH
00 MHz]: d 211.5 (CO); 110.2 (C(CH ); 76.8 (CHCHCO); 76.4
(CH CH); 67.3 (CH CH); 39.9 (COCH CH ); 26.7 (CH ); 25.5 (CH );
25.3 (CH CH ); 22.3 (CH CH ); 13.8 (CH CH ); HRMS (ESI): m/z
Calcd for C11 Na, [M+Na] : 239.1259, found 239.1265.
;
HNMR
1
3
2
CH
3
); CNMR [CDCl
3
[CDCl
3
1
= 9.2 Hz,
(
(
J
2
= 5.6 Hz); 3.88 (dd, 1H, J
s, 1H, OH); 2.75 (dt, 1H, J
(dt, 1H, = 17.6 Hz,
J = 7.2 Hz, CH CH CH
CCH CH , CH
1
2
3
)
2
2
2
2
-
1
2
a
H
b
2
CH); 39.2 (COCH
2
3
3
3
2
2
J
1
J
2
a
H
b
2
(CH
2
CH
3
+
2
3
H
26
O
4
2
2
2
3
3
13
[
M+Na] : 329.1729, found 329.1725.
3
3
2
2
3 3
); CNMR [CDCl ,
1
3 2
)
4
1
.8.3. 1-(n-Octyl)-2-O-benzyl-(3,4-O-isopropylidene)-
D
-erythrose
2
2
2
3
3
3
9c
2
2
2
3
+
2
3
Nature: Gummy liquid; Yield: 92%; TLC (R
f
): 0.56 (Ethyl acetate/
20 4
H O
2
3
Hexane, 1:9); [
a]
D
3
= +31.9 (c 1.0, CHCl ); IR (Thin film) max: 3021
m
CAH); 1714 (C@O); 1521 (Ar, C@C); 1215 (CAO) cm 1; 1HNMR
ꢁ
4.9.3. 1-(n-Octyl)-(3,4-O-isopropylidene)-
D-erythrose 20c
(
[
CDCl
3
, 400 MHz]: d 7.31–7.35 (m, 5H, Aromatic); 4.56 (ABq, 2H,
Ph); 4.28 (ABq, 1H, J = 6.4 Hz, CH CHCH); 4.03
= 8.4 Hz, = 6.4 Hz, CH CH); 3.89 (dd, 1H,
= 5.6 Hz, CH CH); 3.85 (d, 1H, J = 6.4 Hz, CHCHCO);
.60 (dt, 1H, J = 18.4 Hz, J
= 18.4 Hz, J = 7.6 Hz, CH
H, CH ), 1.32 (s, 3H, CH
Nature: Yellow solid; mp: 40–41 °C; Yield: 72%; TLC (R
f
): 0.40
3
); IR (Thin
2
3
J = 11.6 Hz, OCH
dd, 1H,
= 8.4 Hz, J
2
1
2
(Ethyl acetate/Hexane, 1:4); [
film)
[CDCl
a
]
D
= ꢁ84.9 (c 1.0, CHCl
ꢁ1
1
(
J
1
J
2
a
H
b
m
3
max: 3021 (CAH); 1708 (C@O); 1218 (CAO) cm
, 400 MHz]: d 4.07–4.10 (m, 2H); 4.02 (dd, 1H, J
= 13.6 Hz, J = 6.0 Hz); 2.76 (dt, 1H,
CH ); 2.53 (dt, 1H, J = 17.6 Hz,
); 1.57 (m, 2H); 1.47 (s, 3H, CCH CH ); 1.34
); 1.25–1.30 (m, 10H, 5 ꢀ CH ); 0.86 (t, 3H,
, 100 MHz]: d 211.5 (CO);
CH); 67.2 (CH CH);
); 29.26 (CH ); 29.21
); 22.7 (CH ); 14.1 (CH
;
HNMR
J
1
2
a
H
b
1
= 8.8 Hz,
2
1
2
= 7.2 Hz, CH
CH ); 1.52–1.53 (m, 2H); 1.40 (s,
CH ), 0.87 (t, 3H,
, 100 MHz]: d 210.6 (CO);
37.2 (C); 128.56 (CH); 128.3 (CH); 128.2 (CH); 109.9 (C(CH );
4.4 (CHCHCO); 76.0 (CH CH); 73.4 (OCH Ph); 66.6 (CH CH);
9.6 (COCH CH ); 29.4 (CH ); 29.2 (CH ); 29.1 (CH ); 26.6 (CH );
5.3 (CH ); 23.0 (CH ); 22.6 (CH ); 14.2 (CH CH ); HRMS (ESI):
Na, [M+Na] : 385.2355, found 385.2368.
a
H
b
2
CH ); 2.49 (dt, 1H,
J
2
J
1
J
2
= 5.2 Hz); 3.89 (dd, 1H, J
= 17.6 Hz, J = 7.6 Hz, CH
= 7.2 Hz, CH CH
CH
1
2
J
1
2
a
H
b
2
2
a
H
b
2
1
3
3
3
); 1.26 (br s, 10H, CH
CNMR [CDCl
2
2
a
H
b
2
3
3
1
3
J = 7.2 Hz, CH
2
CH
3
);
3
(s, 3H, CCH
J = 6.8 Hz, CH
110.3 (C(CH
40.3 (COCH
(CH ); 26.7 (CH
CH ); HRMS (ESI): m/z Calcd for C15
found 295.1879.
3
3
2
1
3
1
8
3
2
3
)
2
2
CH
3
);
CNMR [CDCl
3
2
2
2
3
)
2
); 76.8 (CHCHCO); 76.3 (CH
CH ); 31.8 (CH ); 29.4 (CH
); 25.3 (CH ); 23.4 (CH
2
2
2
3
2
2
2
3
2
3
2
2
2
3
2
2
+
2
3
2
3
3
2
2
2
-
+
m/z Calcd for C22
H
34
O
4
3
28 4
H O Na, [M+Na] : 295.1885,
4
.8.4. 1-(n-Tetradecyl)-2-O-benzyl-(3,4-O-isopropylidene)-D-
erythrose 19d
4.9.4. 1-(n-Tetradecyl)-(3,4-O-isopropylidene)-
D
-erythrose 20d
): 0.58
); IR (Thin
Nature: Gummy compound; Yield: 89%; TLC (R
f
): 0.46 (Ethyl
); IR (Thin film)
max: 3020 (CAH); 1701 (C@O); 1522 (Ar, C@C); 1215 (CAO)
Nature: Yellow solid; mp: 60–62 °C; Yield: 61%; TLC (R
f
2
3
23
acetate/Hexane, 1:9); [
a
]
D
= +39.2 (c 1.0, CHCl
3
(Ethyl acetate/Hexane, 1:4); [
a
]
D
= ꢁ63.7 (c 1.0, CHCl
3
ꢁ
1
1
m
film)
m
max: 3020 (CAH); 1701 (C@O); 1216 (CAO) cm
, 400 MHz]: d 4.07–4.11 (m, 2H); 4.03 (dd, 1H, J
= 8.0 Hz, J = 6.4 Hz, J = 5.2 Hz, CH
CHCH); 3.43 (d, 1H, J = 5.2 Hz); 2.77 (dt, 1H, = 17.6 Hz,
= 7.2 Hz, CH CH ); 2.54 (dt, 1H, J = 17.2 Hz, J = 7.2 Hz, CH
); 1.56–1.64 (m, 2H); 1.49 (s, 3H, CCH CH ); 1.35 (s, 3H, CCH
); 1.20–1.30 (m, 22H, 11 ꢀ CH
;
HNMR
ꢁ
1
1
cm
;
HNMR [CDCl
3
, 400 MHz]: d 7.28–7.37 (m, 5H, Aromatic);
[CDCl
3
1
= 8.8 Hz,
4
.59 (d, 1H, J = 11.6 Hz); 4.53 (d, 1H, J = 11.6 Hz); 4.29 (dd, 1H,
= 12.0 Hz, J = 6.4 Hz); 4.03 (dd, 1H, J = 8.4 Hz, J = 6.4 Hz);
.89 (dd, 1H, J = 8.4 Hz, J = 5.6 Hz); 3.85 (d, 1H, J = 6.4 Hz); 2.59
= 18.0 Hz, = 7.6 Hz, COCH CH ); 2.49 (dt, 1H,
= 18.0 Hz, J = 7.6 Hz, COCH CH ); 1.50–1.60 (m, 2H, CH );
.40 (s, 3H, CCH CH ); 1.32 (m, 3H, CCH ); 1.20–1.30 (m,
2H, 11 ꢀ CH ); 0.88 (t, 3H, J = 6.8 Hz, CH
J
2
= 5.6 Hz); 3.90 (ddd, 1H, J
1
2
3
2
-
J
1
2
1
2
J
1
3
1
2
J
2
a
H
b
2
1
2
a
H
b
-
-
(
dt, 1H,
J
1
J
2
a
H
b
2
CH
CH
CH
2
3
2
3
3
3
J
1
2
a
H
b
2
2
2
); 0.87 (t, 3H, J = 6.8 Hz,
, 100 MHz]: d 211.5 (CO); 110.3 (C
CH), 76.5 (CHCHCO); 67.4 (CH CH); 40.3 (COCH
); 29.83 (CH ); 29.8 (CH ); 29.7 (CH ); 29.6 (CH
), 29.3 (CH ); 26.8 (CH ); 25.4 (CH ); 23.5 (CH
); 14.2 (CH CH ); HRMS (ESI): m/z Calcd for C21
1
3
1
2
1
1
3
3
3
CH
3
CH
); 76.8 (CH
); 32.0 (CH
29.5 (CH
(CH
3
);
CNMR [CDCl
3
1
3
2
2
CH
3
); CNMR [CDCl
3
,
(CH
CH
3
)
2
2
2
2
-
00 MHz]: d 210.5 (CO); 137.2 (C); 128.6 (CH); 128.28 (CH);
28.25 (CH); 109.9 (C(CH ); 84.4 (CH CH), 76.1 (CHCHCO); 73.4
CH); 39.6 (COCH CH ); 32.0 (CH ); 29.84
); 29.7 (CH ); 29.6 (CH ); 29.56 (CH ); 29.50
); 26.6 (CH ); 25.3 (CH ); 23.0 (CH ); 22.8 (CH );
); HRMS (ESI): m/z Calcd for C28
3
2
2
2
2
2
);
3
)
2
2
2
2
3
3
2
4
); 22.8
Na, [M
(
(
(
CH
CH
CH
2
Ph); 66.6 (CH
2
); 29.81 (CH
2
); 29.3 (CH
CH
2
2
3
2
2
2
3
H
40
O
+
2
2
2
2
+Na] : 379.2824, found 379.2802.
2
3
3
2
2
+
1
4.2 (CH
2
3
H
46
O
4
Na, [M+Na] :
4.10. Characterisation of ketones 2a–d
4
69.3294, found 469.3293.
4
.10.1. 1-(Ethyl)-D-erythrose 2a
4
4
.9. Characterisation of ketones 20a–d
.9.1. 1-(Ethyl)-(3,4-O-isopropylidene)-
Nature: Gummy liquid; Yield: 80%; TLC (R
f
): 0.23 (MeOH/DCM,
= ꢁ14.5 (c 1.0, MeOH); IR (Thin film) max: 3018 (CAH);
HNMR [DMSO-d , 400 MHz]: d
2
3
1
:9); [
a]
D
m
ꢁ1
1
D
-erythrose 20a
1705 (C@O); 1222 (CAO) cm
;
6
Nature: Yellow solid; mp: 43–45 °C; Yield: 70%; TLC (R
f
): 0.43
5.31 (d, 1H, J = 5.2 Hz, OH); 4.82 (d, 1H, J = 5.6 Hz, OH); 4.49 (d,
1H, J = 4.8 Hz, OH); 3.87 (d, 1H, J = 5.2 Hz); 3.60–3.63 (m, 1H);
23
(
Ethyl acetate/Hexane, 1:4); [
a
]
D
= ꢁ96.5 (c 1.0, CHCl
3
); IR (Thin
;
ꢁ
1
1
film)
m
max: 3021 (CAH); 1706 (C@O); 1214 (CAO) cm
HNMR
3.38 (br, 2H); 2.48–2.60 (m, 2H, CH
2
CH
3
); 0.84–0.90 (m, 3H, CH
2
-
1
3
[
3
CDCl , 400 MHz]: d 4.02–4.08 (m, 3H); 3.89 (dd, 1H, J
1
= 11.6 Hz,
CH
3
);
CNMR [DMSO-d
6
,
100 MHz]: d
212.8 (C@O); 77.4
Please cite this article in press as: Borkar, S. R.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.11.008

S. R. Borkar et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
9
(
CHCHCO); 73.6 (CH
CH ); HRMS (ESI): m/z Calcd for C
found 171.0626.
2
CH); 62.0 (CH
2
CH); 31.7 (CH
H O Na, [M+Na] : 171.0633,
6 12 4
2
CH
3
); 7.2 (CH
2
-
prepared 0.01% resazurin solution (Acros, Morris Plains, NJ, USA)
was added to each well and the plates to be re-incubated at
37 °C for 24 h. Minimum Inhibitory concentration (MIC) was
defined as the lowest concentration of the drug that prevented
the change in color of media. The dye resazurin used in this assay
has a blue color, which when it undergoes irreversible reduction to
resorufin, turns pink. In biological systems, resazurin is reduced to
resorufin by NADPH dehydrogenase or NADH dehydrogenase. If
there is no change in the blue color, this indicates that there is
no growth. While the concentration at which cellular growth is
there, enzymatic activity changes the resazurin into resorufin,
which is pink in color and demonstrates active growth in wells.
So the concentration range up to which there is no color change
is regarded as MIC. The results of this assay is summarized in the
Table 1. The change in color of growth control well to pink indi-
cated the proper growth of the isolate and no change in color of
sterile control well indicates absence of contaminants.
+
3
4
.10.2. 1-(n-Butyl)-D-erythrose 2b
Nature: Gummy liquid; Yield: 70%; TLC (R
f
): 0.30 (MeOH/DCM,
= ꢁ36.6 (c 1.0, MeOH); IR (Thin film) max: 3018 (CAH);
HNMR [DMSO-d , 400 MHz]: d
.29 (d, 1H, J = 5.2 Hz, OH); 4.80 (d, 1H, J = 6.0 Hz, OH); 4.48 (t,
H, J = 5.6 Hz, OH); 3.85 (t, 1H, J = 5.6 Hz); 3.61 (quin, 1H,
2
3
1
1
5
1
:9); [
a]
D
m
ꢁ
1
1
709 (C@O); 1218 (CAO) cm
;
6
1
J = 5.6 Hz); 3.44 (quin, 1H, J = 5.6 Hz); 3.34 (br, 1H); 2.45–2.62
m, 2H, O@CCH CH ); 1.38–1.44 (m, 2H, CH ); 1.21–1.28 (m, 2H,
CH ); 0.85 (t, 3H, J = 7.6 Hz, CH
00 MHz]: d 212.3 (CO); 77.4 (CHCHCO); 73.5 (CH
CH); 38.0 (COCH CH ); 24.8 (CH CH ); 21.7 (CH CH
CH ); HRMS (ESI): m/z Calcd for C
found 199.0956.
(
2
2
2
1
3
2
2
CH
3
);
6
CNMR [DMSO-d ,
1
2
CH); 62.0 (CH
); 13.8 (CH
2
-
-
2
3
2
2
2
3
2
+
3
8 16 4
H O Na, [M+Na] : 199.0946,
4
.10.3. 1-(n-Octyl)-
D
-erythrose 2c
Acknowledgements
Nature: Yellowish Solid; mp: 45–47 °C; Yield: 66%; TLC (R
f
):
= ꢁ25.0 (c 1.0, MeOH); IR (Thin film)
23
0
m
.40 (MeOH/DCM, 1:9); [
a
]
D
The authors thank DST New Delhi for funding toward the
400 MHz and 500 MHz NMR spectrometer to the Department of
Chemistry, IIT Madras under the IRPHA scheme. S.R.B. is thankful
to IIT-Madras for HTRA fellowship.
ꢁ1 1
max 3021 (CAH); 1708 (C@O); 1218 (CAO) cm ; HNMR [DMSO-
d
6
, 400 MHz]: d 5.28 (d, 1H, J = 5.2 Hz, OH); 4.79 (d, 1H, J = 5.2 Hz,
OH); 4.47 (t, 1H, J = 5.2 Hz, OH); 3.84 (m, 1H); 3.58–3.62 (dd, 1H,
J
J
1
= 10.8 Hz, J
= 5.2 Hz, CH
); 1.39–1.43 (m, 2H, CH
2
= 5.6 Hz, CH
CH); 3.29–3.35 (m, 1H); 2.43–2.61 (m, 2H,
); 1.23 (br s, 10H, 5 ꢀ CH ); 0.85
); CNMR [DMSO-d , 100 MHz]: d 212.2
CO); 77.4 (CHCHCO); 73.5 (CH CH); 62.0 (CH CH); 38.3 (O@CCH );
1.2 (CH ); 28.9 (CH ); 28.6 (CH ); 22.6 (CH ); 22.0 (CH ); 13.9
CH CH ); HRMS (ESI): m/z Calcd for Na, [M+Na] :
55.1572, found 255.1559.
a b 1
H CH); 3.41–3.45 (dd, 1H, J = 10.8 Hz,
2
a b
H
A. Supplementary data
O@CCH
(
(
3
(
2
2
2
2
13
t, 3H, J = 6.4 Hz, CH
2
CH
3
6
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.11.
2
2
2
2
2
2
2
2
0
08.
+
2
3
12 24 4
C H O
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.10.4. 1-(n-Tetradecyl)-
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