First stereoselective total synthesis of triumfettamide

Article abstract of DOI:10.1016/j.tet.2013.08.068

The first total synthesis of triumfettamide (1) is described. The asymmetric syntheses of two highly functionalized units - α-hydroxylated C17 monounsaturated fatty acid unit (2) and C26 phytosphingosine (3) have been accomplished involving Sharpless asym

Full text of DOI:10.1016/j.tet.2013.08.068

Tetrahedron 69 (2013) 9457e9462
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Tetrahedron
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First stereoselective total synthesis of triumfettamide
*
Thongam Joymati Devi, Bishwajit Saikia, Nabin C. Barua
Natural Products Chemistry Division, CSIR-North East Institute of Science & Technology, Jorhat 785006, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 June 2013
Received in revised form 9 August 2013
Accepted 26 August 2013
Available online 3 September 2013
The first total synthesis of triumfettamide (1) is described. The asymmetric syntheses of two highly
functionalized unitsda-hydroxylated C17 monounsaturated fatty acid unit (2) and C26 phytosphingosine
(3) have been accomplished involving Sharpless asymmetric dihydroxylation, Sharpless kinetic resolu-
tion, regioselective epoxide opening, regioselective DIBAL-H reduction of acetal, Wittig olefination as the
key steps. Finally N-acylation of phytosphingosine 3 with (2R,6Z)-2-hydroxy-6-heptadecenoic acid 2
followed by DDQ deprotection of PMB, provided target compound 1.
Keywords:
Triumfetta cordofolia
Sphingolipid
Ó 2013 Elsevier Ltd. All rights reserved.
Phytoceramide
Antimicrobial
Stratum corneum
1. Introduction
death. This class of compounds is composed of phytosphingosine
base1 and fatty acid linked by an amide bond. These are abundant in
Phytoceramides (Fig. 1) are a unique class of secondary metab-
olites, which play essential roles in cell growth, survival and cell
yeast, plants2 and also in mammals.3 They exhibit a wide spectrum
of biological activities.4 One important application of phytocer-
amides is in cosmetic industries as they play important roles in
human stratum corneum.5 They are involved in skin permeability
and antimicrobial barrier homeostatic functions.6
Fatty acid
R1
chain
Triumfettamide 1 (Fig. 1), is a phytoceramide, which was iso-
lated from Triumfetta cordofolia A. RICH,7 a wild shrub, which is
localized in the tropical Africa. This species is used as folk medicine
for the treatment of diahorrea, dysentery and cholera. Its crushed
stems are used to treat wounds and aqueous extracts of its stems
and leaves are also employed as laxative, dystocia etc. We have long
been engaged in the synthesis of bioactive natural products8 having
chiral 2-amino alcohol moiety and in continuation of our research
work on synthesis of naturally occurring bioactive sphingolipids,9
we report herein a concise and convergent synthesis of triumfet-
O
NH OH
Phytosphingosine
HO
R2
OH
R
1 and R2 are aliphatic
carbon chain (saturated
or unsaturated)
HO
tamide
1
involving Sharpless asymmetric dihydroxylation,10
(CH2)8Me
Sharpless kinetic resolution,11 regioselective DIBAL-H reduction of
acetal,12 regioselective epoxide opening13 and Wittig olefination14
as the key steps. To the best of our knowledge, no total synthesis
of 1 has been reported till date.
O
NH
OH
(CH2)21Me
HO
OH
1
2. Results and discussion
2.1. Synthetic approach
Fig. 1. Structure of phytoceramide and triumfettamide (1).
Retrosynthetic analysis of triumfettamide 1 is depicted in
* Corresponding author. E-mail addresses: ncbarua2000@yahoo.co.in, ncbarua12@
rediffmail.com (N.C. Barua).
Scheme 1. We envisioned completion of the synthesis of
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.068

9458
T.J. Devi et al. / Tetrahedron 69 (2013) 9457e9462
HO
Wittig olefination of the aldehyde
4 with Wittig salt
(CH2)8Me
(BrꢀPh3PþCH2C19H39) 5 using n-BuLi as base in dry THF at low
temperature furnished the Z-olefin 6 contaminated with its E-iso-
mer in the ratio of 13:1 in 23% overall yield starting from trans-
cinnamaldehyde. Catalytic hydrogenation of compound 6 with 10%
Pd/C in EtOAc15 at room temperature reduced the azide and double
bond as well as deprotected the benzyl groups. This on N-Boc
protection with (Boc)2O, Et3N in DCM16 followed by acetylation of
the diol with Ac2O in pyridine using DMAP17 as catalyst gave the
protected amino diol 7. Phenyl ring cleavage to carboxylic group on
treatment with RuCl3$3H2O, NaIO4, in CH3CN/CCl4/H2O solvent
system18 followed by BH3$Me2S reduction in dry THF19 at room
temperature provided the aminotriol 8. Finally base catalysed
deprotection of two O-Ac of 8 using Et3N in MeOH20 at room
temperature followed by acid catalysed N-Boc deprotection (TFA/
DCM at room temperature)16 furnished the phytosphingosine 3.
O
HO
NH OH
OH
(CH2)21Me
1
NH2 OH
OH
PMBO
C9H19
HO
(CH2)19Me
2
O
OH
3
BocHN
OBn H
O
O
OH
H
Br-Ph3P+CH2(CH2)18Me
PMP
O
5
11
OBn
Wittig olefination
4
Sharpless asymmetric
dihydroxylation
OH
trans-cinnamaldehyde
2.3. Synthesis of (2R,6Z)-2-hydroxy-6-heptadecenoic acid
9
As illustrated in Scheme 3, we began the synthesis of (2R,6Z)-2-
hydroxy-6-heptadecenoic acid by subjecting hex-5-en-1-ol 9 to
Scheme 1. Retrosynthesis of triumfettamide.
Sharpless asymmetric dihydroxylation13 using AD-mix-
a
(and AD-
triumfettamide 1 occurring through N-acylation between C26
phytosphingosine 3 and (2R,6Z)-2-hydroxy-6-heptadecenoic acid
2. The synthesis was designed with several key principles in mind,
mix-
b) to provide the triols 10aeb in 96% yield with 99% ee (as de-
termined by chiral column HPLC) as colourless gum. The triol 10aeb
was protected as benzylidene acetals by reaction with dimethoxy
acetal p-anisaldehyde and catalytic CSA giving compounds 11aeb as
a mixture of two diastereomers (1:1) in 96% yield.21
first we planned creation of chiral hydroxyl group at a-position of
fatty acid 2 occurring through Sharpless asymmetric dihydrox-
ylation10 reaction of commercially available hex-5-en-1-ol 9. The
C-1 carbonyl groups of oxidized products of 11a and 11b would be
elongated through Wittig olefination resulting Z-olefin of the re-
quired hydrocarbon chain. Reductive opening of acetal 12aeb with
DIBAL-H could be used for the formation of terminal primary
alcohol, which in turn would be converted to carboxylic
acid (Scheme 1). The C26 phytosphingosine part could be syn-
thesized from aldehyde 4 through Wittig olefination with phos-
phonium salt 5. Finally aldehyde 4 could be obtained from trans-
cinnamaldehyde.
i
HO
OH
iii
OH
OH
10a
9
HO
OH
ii
iii
OH
10b
O
O
H
O
O
OH
H
C9H19
iv, v
MeO
MeO
vi
2.2. Synthesis of C26 D-ribo-phytosphingosine
12a & 12b
11a & 11b
PMBO
O
vii, viii
Recently we have reported a stereoselective synthetic route to
C18 -ribo-phytospingosine starting from a cheap and commer-
C9H19
PMBO
C9H19
D
OH
cially available trans-cinnamaldehyde.9 Using the same synthetic
route we synthesized the important intermediate aldehyde 4 from
trans-cinnamaldehyde (Scheme 2). At this step different alkyl
chains of varied length can be linked to construct phytosphingo-
sines of different alkyl chain backbones. Here we used C20 phos-
phonium salt to get C26 phytosphingosine 3.
OH
13a & 13b
2a & 2b
Scheme 3. Synthesis of (2R,6Z)-2-hydroxy-6-heptadecenoic acid. Reagents and con-
ditions: (i) AD-mix- , t-BuOH/H2O (1:1),
, t-BuOH/H2O (1:1), 0 ꢁC, 96%; (ii) AD-mix-
a
b
0
ꢁC, 96%; (iii) p-methoxybenzyl-dimethyl acetal, CSA, DCM, rt, 91%; (iv) DesseMartin
periodinane, NaHCO3, DCM, rt; (v) BrꢀPh3PþCH2(CH2)9Me, n-BuLi, THF, ꢀ45 ꢁC to rt,
89% over two steps; (vi) DIBAL-H, DCM, ꢀ78 ꢁC, 96%; (vii) DesseMartin periodinane,
NaHCO3, DCM, rt; (viii) NaClO2, NaHPO4, t-BuOH, H2O, H2O2, 87% over two steps.
N3
OBn
N3
OBn H
DesseMartin periodinane oxidation22 of the terminal hydroxyl
group of diastereomers 11aeb provided the corresponding
aldehydes, which were subjected to Wittig olefination using
BrꢀPh3PCH2(CH2)9Me in the presence of n-BuLi at ꢀ45 ꢁC to furnish
12aeb in 89% yield with major Z-olefin contaminated with its E-
isomers in the ratio of 12.3:1. Regioselective reduction of acetal
12aeb with DIBAL-H in DCM12 at ꢀ78 ꢁC provided the compound
13aeb in 96% yield. Finally the terminal hydroxyl group of 13aeb
were oxidised to aldehyde using DesseMartin periodinane fol-
lowed by Pinnick oxidation23 (NaClO2, NaHPO4, H2O2, t-BuOH/H2O)
(
Ref. 9
)
i
(CH2)18Me
trans-cinnamaldehyde
Ph
Ph
O
OBn
OBn
Z-6, (E/Z 1:13)
(23.1% overall yield)
4
BocHN
OAc
BocHN
OAc
HO
ii, iii
iv, v
vi
(
)
19
(
)
19
Ph
OAc
OAc
8
7
(79% over two steps)
(84% over three steps)
H2N
OH
HO
(
)
19
to provide the PMB protected a-hydroxyl fatty acids 2aeb.
OH
3
Scheme 2. Synthesis of C20 D-ribo-phytosphingosine. Reagents and conditions: (i)
BrꢀPh3Pþ CH2(CH2)18Me (5), n-BuLi, THF, ꢀ40 ꢁC to rt, 5 h; (ii) 10% Pd/C, H2, EtOAc, rt;
(Boc)2O, Et3N, DCM, rt; (iii) Ac2O, pyridine, DMAP, 2 h,; (iv) NaIO4, RuCl3$H2O, CCl4/
CH3CN/H2O (2:2:3), 0 ꢁC to rt, 8 h; (v) BH3$Me2S, THF, ꢀ78 ꢁC to rt, 6 h; (vi) pyridine,
MeOH, rt, 4 h; TFA, rt, 2.5 h, 95% yield, 98% ee.
2.4. Synthesis of triumfettamide
With phytosphingosine 3, and fatty acids 2aeb in hand, we
performed the N-acylation by first converting the fatty acids 2aeb

T.J. Devi et al. / Tetrahedron 69 (2013) 9457e9462
9459
to their corresponding acid chlorides and then treated with 3 in
presence of base (Scheme 4). Exposure of 2aeb to SOCl2 under
reflux condition24 provided the corresponding acid chlorides
14aeb, which on treatment with amine 3 in THF/NaOAc (aq) 8 M
(1:1) system,16 followed by PMB deprotection with DDQ in DCM/
MeOH25 furnished the target compounds 1aeb in 70% yield over
three steps (Scheme 3). We compared the spectroscopic data
recorded for the synthetic Triumfettamide 1a and 1b with the re-
ported natural product 1. A comparison of the optical rotations
further corroborates this assignment. Natural 1 and synthetic 1a
spectrometer, and CHCl3 was used as the sole solvent unless oth-
erwise indicated. Mass spectra were recorded on WATERS Micro-
mass ZQ 4000 (ESI Probe) spectrometer. Optical rotations were
recorded on PerkineElmer 343 polarimeter. All solvents were dis-
tilled at their boiling point and commercially available chemicals
were used directly without purification. All analytical data were
recorded at Analytical Chemistry Division (CSIR-NEIST, Jorhat-6,
Assam, India).
4.2. Chemical procedures and characterisation data
show optical rotations [
a
]
20 ꢀ7.36 (c 0.095, C5H5N)7 and [
a
]
D
20 ꢀ6.1
D
(c 0.108, C5H5N), which is almost identical, while the isomer 1bhas
4.2.1. Preparation of phosphonium salt 5. In a round bottom flask,
fitted with a condenser was taken Ph3P (0.723 g, 2.76 mmol) and
heated until it melted (85 ꢁC) under N2 atmosphere. Then bro-
moeicosane (1 g, 2.76 mmol) was added and stirred for 24 h at the
same temperature. The salt was washed with Hexane under
refluxed condition to remove the left over Ph3P. Then the solvent
was removed under vacuum and dried to get white powdery solid
(1.4 g, 2.20 mmol, mp 76e79 ꢁC, 80% yield).
20
[
a]
þ1.7 (c 0.112, C5H5N).
D
PMBO
(CH2)8Me
O
OH
2a & 2b
i
4.2.2. Compound 6. To a stirred solution of Wittig salt 5 (0.542 g,
0.870 mmol) in dry THF (10 mL) at ꢀ15 ꢁC was added dropwise
a 1.6 M solution of n-BuLi in Hexane (0.54 mL, 0.870 mmol) and
continued to stir for 20 min. Then crude aldehyde 4 (0.290 mmol)
was added and continued stirring for 15 min at the same temper-
ature. The mixture was allowed to attain at room temperature and
stirred for 4 h. The reaction was quenched with saturated aqueous
NH4Cl solution and extracted with ether. The combined organic
extracts were washed with water, brine and dried. Evaporation of
the solvent gave a residue, which was purified by column chro-
matography (2% EtOAc/Hexane) to give 6 (0.126 g, 0.185 mmol, 64%
over two steps) as a colourless oil; Elemental analysis calcd. Found:
C, 79.40; H, 9.58; N, 6.21. C45H65N3O2 requires C, 79.48; H, 9.63; N,
NH2 OH
PMBO
O
(CH2)8Me
(CH2)21Me
Cl
OH OH
14a & 14b
3
i, ii
HO
HO
(CH2)8Me
(CH2)8Me
O
NH
OH
O
NH
OH
HO
HO
(CH2)21Me
(CH2)21Me
6.18; O, 4.17; Rf (5% EtOAc/Hexane) 0.70; [a]
20 þ21.4 (c 1.09, CHCl3);
OH
OH
D
IR nmax (film) 2924, 2852, 2102, 1456, 772 cmꢀ1; 1H NMR (300 MHz
1a
1b
CDCl3) d 7.56e7.14 (15H, m, aromatics), 5.50e5.48 (2H, m, CH]CH),
4.61e4.55 (4H, m, benzyl protons), 4.31 (1H, d, J¼10.3 Hz, CHN3),
4.12e4.10 (1H, m, 2CH), 3.92e3.90 (1H, m, 3CH), 2.13e2.10 (1H, m,
4CH), 2.03e1.98 (3H, m, 4CH & 7CH2), 1.23e1.03 (34H, m, (CH2)17),
Scheme 4. Synthesis of triumfettamide through N-acylation of C26 D-ribo-phytos-
phingosine with fatty acid. Reagents and conditions: (i) SOCl2, reflux, 90 min; (ii)
NaOAc (aq), THF, 2 h, rt; (iii) DDQ, DCMeMeOH, 2 h, rt.
0.89 (3H, t, J¼6.3 Hz, CH3); 13C NMR (75 MHz, CDCl3)
d 139.6, 136.8,
3. Conclusions
130.9,129.0,128.8,127.4,125.6, 84.3, 74.4, 73.0, 58.8, 33.3, 30.5, 30.1,
29.9, 29.8, 29.6, 27.1, 23.1, 14.0; MS (ESI, positive ion): m/z (%)¼679.1
(100) [Mþ].
A concise and convergent synthetic route for the synthesis of
triumfettamide has been developed. The synthesis of novel
chiral
a-hydroxy fatty acid fragment was accomplished using
4.2.3. Compound 7. To a solution of E/Z-6 (0.110 g, 0.161 mmol) in
ethyl acetate (8 mL) was added 10% Pd/C (30 mg) and stirred under
hydrogen for 6 h. After completing the reaction, it was filtered and
the filtrate was evaporated to give a residue, which was used di-
rectly in the subsequent reaction without further purification. To
the stirred solution of the crude amine in DCM (6 mL) were added
Et3N (0.024 g, 0.241 mmol) and di-tert-butyldicarbonate (0.042 g,
0.193 mmol) successively at room temperature and continued to
stir for 5 h. Then the reaction mixture was diluted with DCM and
washed with saturated aqueous NH4Cl and separated the organic
phase. The organic layer was dried and concentrated in vacuo to
give the crude product. To the above crude product in pyridine
(1.5 mL) were added DMAP (catalytic amount) and acetic anhydride
(0.15 mL, 0.805 mmol) successively at room temperature and stir-
red for 3 h under N2 atmosphere. After completing the reaction, ice-
cooled 6 N HCl solution was added to the reaction mixture at 0 ꢁC
and extracted with ethyl acetate. The combined organic extracts
were washed with saturated aqueous NaHCO3 solution, water and
then brine. Then it was dried and evaporated to give a residue,
which was purified by flash chromatography to compound 7
(0.089 g, 0.136 mmol, 84% over three steps) as colourless oil; Ele-
mental analysis calcd. Found: C, 72.74; H, 10.50; N, 2.09. C40H69NO6
Sharpless asymmetric dihydroxylation and regioselective DIBAL-H
reduction of acetal. Wittig olefination was successfully applied to
introduce aliphatic alkyl chains. The overall yield of the target
compounds 1a and the isomer 1b are 6.5% and 6.1% starting from
commercially available and inexpensive trans-cinnamaldehyde and
hex-5-en-1-ol.
4. Experimental section
4.1. General
The following solvents and reagents were dried prior to use:
CH2Cl2 (from P2O5), Et2O, and THF (freshly distilled from sodium/
benzophenone). Analytical thin layer chromatography (TLC) was
performed using Merck silica gel 60 F254 precoated plates. Flash
chromatography (CombiFlash) was performed with Merck silica gel
(230e400 mesh), column chromatography was performed with
Merck silica gel (100e200 mesh) Moisture sensitive reactions were
conducted under a dry nitrogen and argon atmosphere. NMR
spectroscopic data were obtained with Bruker DPX-300 NMR ma-
chine. IR spectra were recorded on a PerkineElmer 1640 FT-IR

9460
T.J. Devi et al. / Tetrahedron 69 (2013) 9457e9462
requires C, 72.79; H, 10.54; N, 2.12; O, 14.55; Rf (5% EtOAc/Hexane)
Evaporation of the solvent gave a residue, which was purified by
column chromatography to give triol, 10a (0.385 g, 2.87 mmol, 96%)
as a colourless gum; Elemental analysis calcd. Found: C, 53.68; H,
20
0.68; [
2875, 1744, 1713, 1221, 1169, 758, 701 cmꢀ1
CDCl3) 7.33e7.21 (5H, m, aromatic), 5.35 (2H, m, NH & CHOAc
a
]
þ27.3 (c 1.12, CHCl3); IR nmax (film) 3351, 2965, 2935,
D
;
1H NMR (300 MHz
d
10.50. C6H14O3 requires C, 53.71; H, 10.52; O, 35.77; Rf (EtOAc/
20
protons), 5.12 (1H, m, CHNHAc), 4.95 (1H, m, CHOAc), 1.87 (6H, br s,
CH3CO),1.66e1.60 (2H, m, CH2), 1.41 (9H, s, C(CH3)3), 1.26 (40H, br s,
(CH2)20), 0.91 (3H, t, J¼7.5 Hz, CH3); 13C NMR (75 MHz, CDCl3)
MeOH, 9:1) 0.16; [
a
]
ꢀ8.2 (c 1.08, MeOH); IR nmax (film) (KBr)
D
3388, 2935, 2861, 1642, 1372, 1056, 772; 1H NMR (300 MHz CD3OD)
3.61 (2H, m, 1CH2), 3.46 (2H, m, 6CH2), 3.33 (1H, m, 2CH), 1.92 (2H,
br s, OH), 1.41e1.31 (4H, m, CH2), 1.19 (2H, m, CH2); 13C NMR
d
d
171.1, 169.9, 154.9, 138.7, 128.4, 127.6, 127.1, 79.9, 74.7, 72.2, 54.3,
32.8, 31.9, 30.6, 29.6, 29.5, 29.4, 29.3, 28.7, 28.3, 28.1, 22.6, 20.8,
(75 MHz, CD3OD) d 76.8, 71.6, 64.0, 33.5, 32.9, 20.7; MS (ESI, positive
20.6, 18.3, 14.0; MS (ESI, positive ion): m/z (%)¼659.0 (100) [Mþ].
ion): m/z (%)¼134.0 (100) [Mþ].
4.2.4. Compound 8. To
a
solution of compound
7
(80 mg,
4.2.7. Compound 10b. Compound 10b was synthesized following
the procedure described for the synthesis of compound 10a using
0.121 mmol) in CCl4/CH3CN/H2O (2:2:3) (1.5 mL) was added NaIO4
(310 mg, 1.45 mmol) slowly at 0 ꢁC. After stirring for 30 min at 0 ꢁC,
RuCl3$3H2O (0.05 equiv) was added and the temperature was
raised to room temperature and continued stirring for overnight.
The reaction mixture was filtered and washed the solid with DCM
three times. The combined filtrate was dried and concentrated in
vacuum to give carboxylic acid residue, which was used directly in
the subsequent step without further purification. To a stirred so-
lution of the crude organic acid in dry THF (1.5 mL) was added
BH3$Me2S (0.04 mL, 0.181 mmol) at ꢀ78 ꢁC and continued to stir for
10 min at the same temperature. Then it was allowed to attain at
20 ꢁC and stirred for 2 h under inert atmosphere. The reaction was
quenched with methanol and the resulting mixture was concen-
trated in vacuum giving a residue, which was purified by flash
chromatography to give 8, as a colourless oil, (58 mg, 0.095 mmol,
79% over two steps); Elemental analysis calcd. Found: C, 68.45; H,
AD-mix-b as the catalyst. Colourless gum; (0.380 g, 2.84 mmol,
96%); Elemental analysis calcd. Found: C, 53.67; H, 10.55. C6H14O3
requires C, 53.71; H, 10.52; O, 35.77; Rf (EtOAc/MeOH, 9:1) 0.16;
20
[a
]
þ8.0 (c 1.03, MeOH); IR nmax (film) (KBr) 3387, 2935, 2862,
D
1642, 1372, 1056, 771; 1H NMR (300 MHz CD3OD)
d 3.61 (2H, m,
1CH2), 3.46 (2H, m, 6CH2), 3.32 (1H, m, 2CH), 1.96 (2H, br s, OH),
1.39e1.32 (4H, m, CH2), 1.18 (2H, m, CH2); 13C NMR (75 MHz,
CD3OD) d 76.8, 71.6, 64.1, 33.5, 32.9, 21.0; MS (ESI, positive ion): m/z
(%)¼134.0 (100) [Mþ].
4.2.8. Compound 11a. To a stirred solution of triol (10a) (0.350 g,
2.60 mmol) in DCM (10 mL) were added CSA (0.025 g) and p-
methoxybenzyldimethyl acetal (0.56 mL, 3.9 mmol) successively at
room temperature and continued to stir for 3 h. Then triethyl amine
was added to the reaction mixture and stirred for 10 min. Evapo-
ration of the solvent under reduced pressure gave a residue, which
11.05; N, 2.24. C35H67NO7 requires C, 68.48; H, 11.00; N, 2.28; O,
20
18.24; Rf (30% EtOAc/Hexane) 0.40; [
a
]
þ17.1 (c 1.06, CHCl3); IR
was purified by column chromatography to give a 1:1 di-
D
nmax (film) 3384 (br), 2924, 1746, 1713, 1019, 702 cmꢀ1
;
1H NMR
astereomeric mixture of 11a (0.596 g, 2.36 mmol, 91%) as colourless
oil; Elemental analysis calcd. Found: C, 66.63; H, 7.94. C14H20O4
requires C, 66.65; H, 7.99; O, 25.37; Rf (EtOAc/Hexane, 3:7) 0.4; IR
nmax (film) 3418, 2938, 2866, 1615, 1518, 1249, 1075, 1033, 830; 1H
(300 MHz CDCl3) 5.24 (1H, br s, NH), 5.11 (1H, m, 3CH), 5.03 (1H,
d
m, 4CH), 4.98 (1H, m, 2CH), 3.75 (1H, m, 1CHa), 3.56 (1H, m, 1CHb),
1.96 (6H, s, CH3CO), 1.56 (2H, m, 5CH2), 1.37 (9H, s, C(CH3)3), 1.25
(40H, br s, (CH2)20), 0.87 (3H, t, J¼7.5 Hz, CH3); 13C NMR (75 MHz,
NMR (300 MHz CDCl3)
d
7.39 (2H, d, J¼8.1 Hz, aromatic), 6.92 (2H, d,
CDCl3)
d
171.1, 169.6, 154.9, 79.7, 74.5, 71.9, 65.3, 50.1, 32.8, 31.9,
J¼8.7 Hz, aromatic), 5.86 (0.5H, s, benzylidene acetal proton), 5.75
(0.5H, s, benzylidene acetal proton), 4.27e4.18 (2H, m, CH2), 4.11
(1H, m, CH), 3.81 (3H, s, CH3O), 3.71e3.60 (2H, m, CH2), 1.76e1.48
30.5, 29.7, 29.5, 29.4, 29.1, 28.7, 28.5, 28.3, 28.1, 22.5, 20.8, 20.6, 18.5,
14.1; MS (ESI, positive ion): m/z (%)¼613.0 (100) [Mþ].
(6H, m, CH2); 13C NMR (75 MHz, CDCl3)
d 160.4, 160.2, 130.4, 129.8,
4.2.5. Compound 3. To a solution of 8 (0.080 g, 0.130 mmol) in
methanol (1.5 mL) was added Et3N (0.065 g, 0.650 mmol) at room
temperature and continued to stir for 3.5 h. Then the solvent was
removed under vacuo to give a residue. To the residue dissolved in
DCM (1.5 mL) was added TFA (1 mL) at 0 ꢁC and stirred at room
temperature for 45 min. The reaction mixture was concentrated
under vacuum and the residue was dissolved in methanol followed
by evaporation under vacuum. This process was repeated to remove
excess TFA. The crude product was purified by flash chromatogra-
phy to furnish 3 (0.052 g, 0.122 mmol, 94%) as white solid; Ele-
mental analysis calcd. Found: C, 72.60; H, 12.86; N, 3.21. C26H55NO3
requires C, 72.67; H, 12.90; N, 3.26; O, 11.17; Rf (MeOH/EtOAc/
128.7, 127.8, 113.7, 113.4, 108.5, 103.8, 102.9, 76.3, 76.0, 62.2, 55.5,
55.2, 33.1, 33.0, 32.4, 32.2, 22.0, 21.7; MS (ESI, positive ion): m/z
(%)¼252.0 (100) [Mþ].
4.2.9. Compound 11b. Compound 11b was synthesized following
the procedure described for the synthesis of compound 11a. Col-
ourless oil; (0.602 g, 2.39 mmol, 92%); Elemental analysis calcd.
Found: C, 66.60; H, 7.93. C14H20O4 requires C, 66.65; H, 7.99; O,
25.37; Rf (EtOAc/Hexane, 3:7) 0.4; IR nmax (film) 3418, 2938, 2866,
1615, 1518, 1249, 1075, 1033, 830; 1H NMR (300 MHz CDCl3)
d 7.39
(2H, d, J¼8.1 Hz, aromatic), 6.92 (2H, d, J¼8.7 Hz, aromatic), 5.87
(0.5H, s, benzylidene proton), 5.76 (0.5H, s, benzylidene proton),
4.27e4.18 (2H, m, CH2), 4.11 (1H, m, CH), 3.81 (3H, s, CH3O),
3.71e3.60 (2H, m, CH2), 1.76e1.48 (6H, m, CH2); 13C NMR (75 MHz,
Hexane,1:10:10) 0.30; [
a
]
20 þ5.8 (c 1.05, C5H5N); mp 106 ꢁC; IR nmax
D
(film) (KBr) 3319 (br), 2918, 2850, 1051 cmꢀ1
;
1H NMR (300 MHz
CD3OD)
d
3.75 (1H, dd, J¼10.6, 4.2 Hz,1CHa), 3.57 (1H, m,1CHb), 3.51
CDCl3) d 160.4, 160.2, 130.4, 129.8, 128.7, 127.8, 113.7, 113.4, 108.5,
(1H, m, 4CH), 3.33e3.30 (1H, m, 3CH), 3.02e2.97 (1H, m, 2CH), 1.73
(1H, m, 5CHa), 1.60 (1H, m, 5CHb), 1.33e1.51 {40H, m, (CH2)20}, 0.90
103.8, 102.9, 76.3, 76.0, 62.2, 55.5, 55.2, 33.1, 33.0, 32.4, 32.2, 22.0,
21.7; MS (ESI, positive ion): m/z (%)¼252.0 (100) [Mþ].
(3H, t, J¼7.0 Hz, CH3); 13C NMR (75 MHz, CD3OD)
d 76.4, 74.3, 65.5,
54.6, 33.6, 33.0, 31.1, 30.0, 29.9, 29.7, 29.6, 27.3, 26.9, 23.2, 14.0; MS
4.2.10. Compound 12a. To a stirred solution of alcohol 11a (0.150 g,
0.594 mmol) in DCM (6 mL) were added NaHCO3 (0.499 g,
5.94 mmol) and 15% DesseMartin periodinane solution in DCM
(2.4 mL, 0.891 mmol) at room temperature and continued to stir for
2 h. Then the reaction was quenched with saturated Na2S2O5 and
saturated NaHCO3 aqueous solution and extracted with DCM. The
combined organic extracts were dried and evaporated to give the
aldehyde, which was used for the next step without further puri-
fication. BrꢀPh3PþCH2(CH2)9Me (0.886 g, 1.78 mmol) was dissolved
(ESI, positive ion): m/z (%)¼429.0 (100) [Mþ].
4.2.6. Compound 10a. To a stirred solution of AD-mix-a (4.2 g) in
20 mL of 1:1 t-BuOH/H2O at 0 ꢁC was added hex-5-en-1-ol (0.300 g,
2.99 mmol) and continued to stir for 16 h at the same temperature.
Solid sodium metabisulfite (2.5 g) was added to quench the re-
action and allowed to attain at room temperature and stirred for
1 h. Then the mixture was extracted with ethyl acetate and dried.

T.J. Devi et al. / Tetrahedron 69 (2013) 9457e9462
9461
20
in THF (15 mL) and to it 1.6 M solution of nBuLi in Hexane (1.2 mL,
1.78 mmol) was added at ꢀ15 ꢁC and stirred for 30 min at the same
temperature and then the above crude aldehyde in THF (2 mL) was
added at ꢀ45 ꢁC and stirred for 3 h at room temperature. After
completing the reaction saturated aqueous NH4Cl solution was
added and extracted with diethyl ether. The combined organic
extracts were washed with water, brine and dried. Evaporation of
the solvent gave a residue, which was purified by column chro-
matography to give the compound 12a (0.205 g, 0.528 mmol, 89%)
as colourless oil in the ratio of 1:1 diastereomeric mixture; Ele-
mental analysis calcd. Found: C, 77.23; H, 10.32. C25H40O3 requires
C, 77.27; H, 10.38; O, 12.35; Rf (EtOAc/Hexane 1:9) 0.56; IR nmax
(film) 3003, 2925, 2854, 1615, 1517, 1081, 827; 1H NMR (300 MHz
12.29; Rf (EtOAc/Hexane 1:4) 0.41; [
a
]
ꢀ9.1 (c 1.02, CHCl3); IR
D
nmax (film) 3420, 3003, 2925, 2854, 1613, 1514, 1464, 1248, 1038,
771; 1H NMR (300 MHz CDCl3)
d
7.30 (2H, d, J¼8.1 Hz, aromatic),
6.92 (2H, d, J¼8.7 Hz, aromatic), 5.40e5.34 (2H, m, CH]CH), 4.58
(1H, d, J¼11.1 Hz, benzyl proton), 4.48 (1H, d, J¼11.4 Hz, benzyl
proton), 3.80 (3H, s, CH3O), 3.68 (1H, m, CH), 3.51e3.48 (2H, m,
CH2), 2.05e1.97 (6H, m, CH2), 1.60 (4H, m, CH2), 1.26 (14H, br s,
(CH2)7), 0.90 (3H, t, J¼6.3 Hz, CH3); 13C NMR (75 MHz, CDCl3):
d
159.3, 130.4, 129.4, 129.2, 113.9, 79.4, 71.2, 64.1, 55.2, 31.9, 30.4,
29.7, 29.5, 29.3, 27.2, 25.4, 22.7, 14.1; MS (ESI, positive ion): m/z
(%)¼390.0 (100) [Mþ].
4.2.14. Compound 2a. To a stirred solution of alcohol 13a (0.100 g,
0.256 mmol) in DCM (5 mL) were added NaHCO3 (0.215 g,
2.56 mmol) and 15% DesseMartin periodinane solution in DCM
(1.1 mL, 0.384 mmol) at room temperature and continued to stir for
2 h. Then the reaction was quenched with saturated Na2S2O5 and
saturated NaHCO3 aqueous solution and extracted with DCM. The
combined organic extracts were dried and evaporated to give the
aldehyde, which was used for the next step without further puri-
CDCl3)
d
7.42 (2H, d, J¼8.7 Hz, aromatic), 6.91 (2H, d, J¼8.7 Hz, ar-
omatic), 5.86 (0.5H, s, benzylidene acetal proton), 5.75 (0.5H, s,
benzylidene acetal proton), 5.39e5.33 (2H, m, CH]CH), 4.25 (2H,
m, CH2), 4.07 (1H, m, CH), 3.81 (3H, s, CH3O), 2.12e1.98 (4H, m, CH2),
1.65e1.54 (8H, m, CH2), 1.26 (12H, br s, (CH2)6), 0.90 (3H, t, J¼6.3 Hz,
CH3); 13C NMR (75 MHz, CDCl3):
d 160.4, 160.2, 130.6, 130.0, 129.0,
128.0, 127.8, 113.7, 103.9, 102.9, 70.7, 70.0, 33.0, 32.9, 32.6, 31.9, 29.7,
29.5, 29.3, 27.2, 27.0, 25.8, 22.6, 14.0; MS (ESI, positive ion): m/z
(%)¼388.1 (100) [Mþ].
t
fication. The above crude aldehyde was dissolved in BuOH (5 mL)
and to it H2O2 (0.83 mL) was added at 0 ꢁC. Then a solution of
NaClO2 (0.031 g, 0.768 mmol) and NaH2PO4 (0.092 g, 0.768 mmol)
in H2O (5 mL) was added dropwise and continued to stir for 1 h.
After completing the reaction it was quenched with saturated
aqueous NH4Cl solution and extracted with ethyl acetate. Then the
combined organic extracts were washed with brine and dried with
Na2SO4. Evaporation of the solvent gave a residue, which was pu-
rified by column chromatography to furnish compound 2a (0.090 g,
0.222 mmol, 87%) as white waxy solid; mp: 49e51 ꢁC; Elemental
4.2.11. Compound 12b. Compound 12b was synthesized following
the procedure described for the synthesis of compound 12a. Col-
ourless oil (0.200 g, 0.516 mmol, 87%); Elemental analysis calcd.
Found: C, 77.22; H, 10.33. C25H40O3 requires C, 77.27; H, 10.38; O,
12.35; Rf (EtOAc/Hexane 1:9) 0.56; IR nmax (film) 3003, 2926, 2854,
1615, 1518, 1249, 826; 1H NMR (300 MHz CDCl3)
d 7.42 (2H, d,
J¼8.7 Hz, aromatic), 6.90 (2H, d, J¼8.7 Hz, aromatic), 5.85 (0.5H, s,
benzylidene acetal proton), 5.74 (0.5H, s, benzylidene acetal pro-
ton), 5.40e5.36 (2H, m, CH]CH), 4.23 (2H, m, CH2), 4.02 (1H, m, CH),
3.81 (3H, s, CH3O), 2.12e1.98 (4H, m, CH2), 1.64e1.55 (8H, m, CH2),
1.26 (12H, br s, (CH2)6), 0.90 (3H, t, J¼6.3 Hz, CH3); 13C NMR (75 MHz,
analysis calcd. Found: C, 74.21; H, 9.95. C25H40O4 requires C, 74.22;
H, 9.97; O, 15.82; Rf (CHCl3/MEOH 19:1) 0.23; [
CHCl3); IR nmax (film) 3420, 2925, 2854, 1708, 1465, 1294, 1016, 741;
20
a
]
ꢀ6.9 (c 1.06,
D
1H NMR (300 MHz CDCl3)
d
7.20 (2H, d, J¼7.5 Hz, aromatic), 6.90
CDCl3):
d
160.3, 160.1, 130.5, 130.0, 129.1, 128.0, 127.6, 113.4, 103.7,
(2H, d, J¼8.4 Hz, aromatic), 5.36e5.16 (2H, m, CH]CH), 4.67 (1H, d,
J¼9.6 Hz, benzylic proton), 4.47 (1H, d, J¼11.1 Hz, benzylic proton),
3.99 (1H, m, CH), 3.80 (3H, s, CH3O), 2.05e1.97 (4H, m, CH2), 1.82
(2H, m, CH2), 1.50 (4H, m, CH2), 1.25 (14H, br s, (CH2)7), 0.87 (3H, t,
102.8, 70.8, 70.2, 33.1, 33.0, 32.4, 31.5, 29.6, 29.4, 29.1, 27.0, 26.9, 25.7,
22.5, 14.2; MS (ESI, positive ion): m/z (%)¼388.0 (100) [Mþ].
4.2.12. Compound 13a. To a stirred solution of acetal 12a (0.150 g,
0.386 mmol) in DCM (5 mL) was added 20% DIBAL in toluene so-
lution (0.78 mL, 1.54 mmol) at ꢀ78 ꢁC and continued to stir for
30 min under N2 atmosphere. The reaction mixture was allowed to
warm at 0 ꢁC and stirred for 1 h and another 1 h at room temper-
ature. After completing the reaction (monitored by TLC), it was
quenched at 0 ꢁC by adding acetone (1 mL), methanol (1 mL) and
saturated aqueous NH4Cl solution (1 mL). The whole mixture was
diluted with diethyl ether and extracted with diethyl ether and
dried. Evaporation of the solvent gave a residue, which was purified
by column chromatography to furnish 13a (0.144 g, 0.370 mmol,
96%) as clear oil; Elemental analysis calcd. Found: C, 76.80; H, 10.87.
C25H42O3 requires C, 76.87; H, 10.84; O, 12.29; Rf (EtOAc/Hexane
J¼6.9 Hz, CH3); 13C NMR (75 MHz, CDCl3):
d 177.5, 159.5, 132.0,
130.7, 129.8, 129.1,128.7, 128.0, 113.9, 94.7, 72.1, 55.2, 32.2, 31.9, 29.7,
29.5, 29.3, 27.2, 26.7, 25.2, 25.0, 22.7,14.1; MS (ESI, positive ion): m/z
(%)¼404.0 (100) [Mþ].
4.2.15. Compound 2b. Compound 2b was synthesized following
the procedure described for the synthesis of compound 2a. White
waxy solid; (0.088 g, 0.217 mmol, 85%); mp: 49e51 ꢁC; Elemental
analysis calcd. Found: C, 74.20; H, 9.95. C25H40O4 requires C, 74.22;
H, 9.97; O, 15.82; Rf (CHCl3/MEOH 19:1) 0.23; [
20
a]
þ7.1 (c 1.04,
D
CHCl3); IR nmax (film) 3421, 2925, 2854, 1709, 1467, 1294, 1016, 742;
1H NMR (300 MHz CDCl3)
d
7.22 (2H, d, J¼7.5 Hz, aromatic), 6.91
(2H, d, J¼8.4 Hz, aromatic), 5.36e5.16 (2H, m, CH]CH), 4.67 (1H, d,
J¼9.6 Hz, benzylic proton), 4.47 (1H, d, J¼11.1 Hz, benzylic proton),
3.99 (1H, m, CH), 3.80 (3H, s, CH3O), 2.06e1.99 (4H, m, CH2), 1.82
(2H, m, CH2), 1.50 (4H, m, CH2), 1.22 (14H, br s, (CH2)7), 0.86 (3H, t,
1:4) 0.4; [
a]
20 þ8.9 (c 0.88, CHCl3). IR nmax (film) 3420, 3003, 2925,
D
2854, 1613, 1514, 1464, 1248, 1038, 771; 1H NMR (300 MHz CDCl3)
d
7.29 (2H, d, J¼8.1 Hz, aromatic), 6.91 (2H, d, J¼8.7 Hz, aromatic),
5.39e5.32 (2H, m, CH]CH), 4.58 (1H, d, J¼11.1 Hz, benzyl proton),
4.48 (1H, d, J¼11.4 Hz, benzyl proton), 3.80 (3H, s, CH3O), 3.68 (1H,
m, CH), 3.51e3.48 (2H, m, CH2), 2.05e1.97 (6H, m, CH2), 1.60 (4H, m,
CH2), 1.26 (14H, br s, (CH2)7), 0.90 (3H, t, J¼6.3 Hz, CH3); 13C NMR
J¼6.9 Hz, CH3); 13C NMR (75 MHz, CDCl3):
d 177.6,159.8,132.1,130.7,
129.8, 129.1, 128.7, 128.0, 113.9, 94.7, 72.1, 55.2, 32.2, 31.9, 29.7, 29.5,
29.3, 27.2, 26.7, 25.2, 22.9, 14.1; MS (ESI, positive ion): m/z (%)¼
404.0 (100) [Mþ].
(75 MHz, CDCl3):
d 159.2, 130.5, 129.4, 129.1, 113.9, 79.3, 71.2, 64.2,
55.2, 31.9, 30.4, 29.7, 29.5, 29.3, 27.2, 25.4, 22.7, 14.1; MS (ESI, pos-
4.2.16. Compound 1a.7 Compound 2a (0.024 g, 0.058 mmol) dis-
solved in SOCl2 (0.2 mL, 1.62 mmol) was refluxed for 90 min. After
completing the reaction the excess SOCl2 was removed under re-
duced pressure to give the crude acid chloride. Then the crude acid
chloride was dissolved in dry THF (0.5 mL) and added with vigorous
stirring to a solution of amine 3 (0.025 g, 0.058 mmol) in THF/
NaOAc (aq) 8 M (1:1, 1.5 mL). After vigorous stirring for 2 h, the
itive ion): m/z (%)¼390.0 (100) [Mþ].
4.2.13. Compound 13b. Compound 13b was synthesized following
the procedure described for the synthesis of compound 13a.
Clear oil; (0.143 g, 0.366 mmol, 95%); Elemental analysis calcd.
Found: C, 76.79; H, 10.81. C25H42O3 requires C, 76.87; H, 10.84; O,

9462
T.J. Devi et al. / Tetrahedron 69 (2013) 9457e9462
reaction mixture was allowed to stand and the phases were sepa-
rated. The aqueous phase was extracted with THF and the com-
bined organic extract was dried with sodium sulfate and
evaporated under reduced pressure to give a residue. Again the
residue was dissolved in CH2Cl2eMeOH (10:1, 1 mL) and to it DDQ
(0.015 g, 0.069 mmol) was added. Then the mixture was stirred for
1.5 h at room temperature. After completing the reaction the
mixture was diluted with CH2Cl2 and washed with minimum
amount of saturated aqueous NaHCO3 solution and again extracted
the aqueous phase with DCM (3ꢂ5 mL). Evaporation of the com-
bined organic solvent gave a residue, which was purified by column
chromatography (CH2Cl2/MeOH 1:19) to furnish the compound 1a
(0.028 g, 0.040 mmol, 70%) as white solid; mp 130e132 ꢁC; Ele-
mental analysis calcd. Found: C, 74.21; H, 12.29; N, 2.03. C43H85NO5
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.08.068.
References and notes
1. Pruett, S. T.; Bushnev, A.; Hagedorn, K.; Adiga, M.; Haynes, C. A.; Sullards, M. C.;
Liotta, D. C.; Merrill, A. H. J. Lipid Res. 2008, 49, 1621e1639.
2. Dickson, R. C. Annu. Rev. Biochem. 1998, 67, 27e48.
3. Schurer, N. Y.; Plewig, G.; Elias, P. M. Dermatologica 1991, 183, 77e94.
4. (a) Veerman, E. C. I.; Valentijn-Benz, M.; van’t Hof, W.; Nazmi, K.; van Marle, J.;
Amerongen, A. V. N. Biol. Chem. 2010, 391, 65e71; (b) Dickson, R. C.; Nagiec, E.
E.; Skrzypek, M.; Tillman, P.; Wells, G. B.; Lester, R. L. J. Biol. Chem. 1997, 272,
30196e30200; (c) Kawano, T.; Cui, J.; Koezuka, Y.; Toura, Y.; Kaneko, Y.; Motoki,
K.; Ueno, H.; Nakagawa, R.; Sato, H.; Kondo, E.; Koseki, H.; Taniguchi, M. Science
1997, 278, 1626e1629.
requires C, 74.19; H, 12.31; N, 2.01; O, 11.49; Rf (10% MeOH/CH2Cl2)
5. Feingold, K. R. J. Lipid Res. 2009, 50, 417e422.
20
0.31; [
a
]
D
ꢀ6.1 (c 0.108, C5H5N); IR nmax (film) (KBr) 3400, 3201,
6. Holleran, W. M.; Takagi, Y.; Uchida, Y. FEBS Lett. 2006, 580, 5456e5466.
7. Sandjo, L. P.; Hannewald, P.; Yemloul, M.; Kirsch, G.; Ngadjui, B. T. Helv. Chim.
Acta 2008, 91, 1326e1335.
1642, 1612, 1541, 1073; 1H NMR (300 MHz CD3OD)
d 8.21 (1H, d,
J¼8.1 Hz, NH), 5.39e5.30 (2H, m, CH]CH), 4.77e4.63 (1H, m, CH),
4.43e4.39 (1H, m, CH), 4.13 (1H, dd, J¼10.6, 5.1 Hz, CHa), 4.07 (1H,
dd, J¼10.3, 5.0 Hz, CHb), 3.88e3.75 (1H, m, CH), 3.68e3.67 (1H, m,
CH), 1.99e1.95 (4H, m, CH2), 1.75e1.70 (2H, m, CH2), 1.48e1.43 (4H,
m, CH2), 1.31 (56H, br s, (CH2)28), 0.86 (6H, t, J¼7.0 Hz, CH3); 13C
8. (a) Saikia, P. P.; Baishya, G.; Goswami, A.; Barua, N. C. Tetrahedron Lett. 2008, 49,
6508e6511; (b) Saikia, P. P.; Goswami, A.; Baishya, G.; Barua, N. C. Tetrahedron
Lett. 2009, 50, 1328e1330; (c) Devi, T. J.; Saikia, P. P.; Barua, N. C. Lett. Org. Chem.
2009, 6, 616e618; (d) Saikia, B.; Saikia, P. P.; Goswami, A.; Barua, N. C.; Saxena,
A. K.; Suri, N. Synthesis 2011, 19, 3173e3179; (e) Goswami, A.; Saikia, P. P.; Saikia,
B.; Chaturvedi, D.; Barua, N. C. Tetrahedron Lett. 2011, 52, 5133e5135; (f) Saikia,
B.; Devi, T. J.; Barua, N. C. Org. Biomol. Chem. 2013, 11, 905e913; (g) Saikia, B.;
Devi, T. J.; Barua, N. C. Tetrahedron 2013, 69, 2157e2166.
9. Devi, T. J.; Saikia, B.; Barua, N. C. Tetrahedron 2013, 69, 3817e3822.
10. (a) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.;
Jeong, K. S.; Kwong, H. L.; Morikawa, K.; Wang, Z. M. J. Org. Chem. 1992, 57,
2768e2771; (b) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483e2547; (c) Franc¸ ais, A.; Bedel, O.; Haudrechy, A. Tetrahedron
2008, 64, 2495e2524.
11. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974e5976; (b)
Martin, V. S.; Woodward, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B.
J. Am. Chem. Soc. 1981, 103, 6237e6240.
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7355e7358.
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J. S.; Johnson, C. J. Org. Chem. 1991, 56, 4196e4204.
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rahedron 2007, 63, 4310e4318.
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75, 2820e2835.
NMR (75 MHz, CD3OD):
d 174.6, 130.6, 130.3, 76.5, 72.5, 72.1, 61.6,
53.0, 36.5, 34.0, 33.8, 33.5, 32.0, 29.9, 27.1, 24.0, 23.1, 21.1, 13.8; MS
(ESI, positive ion): m/z (%)¼695.1 (100) [Mþ].
4.2.17. Compound 1b. Compound 1b was synthesized following the
procedure described for the synthesis of compound 1a. White solid;
(0.027 g, 0.039 mmol, 68%); mp 127 ꢁC; Elemental analysis calcd.
Found: C, 74.20; H, 12.27; N, 2.01. C43H85NO5 requires C, 74.19; H,
20
12.31; N, 2.01; O, 11.49; Rf (10% MeOH/CH2Cl2) 0.31; [
a
]
D
þ1.7 (c
0.112, C5H5N); IR nmax (film) (KBr) 3402, 3201,1642,1621,1541,1071;
1H NMR (300 MHz CD3OD)
d
8.1 (1H, d, J¼8.1 Hz, NH), 5.33e5.40 (2H,
m, CH]CH), 4.58e4.76 (1H, m, CH), 4.21e4.30 (1H, m, CH), 4.20 (1H,
dd, J¼10.6, 5.1 Hz, CHa), 4.15 (1H, dd, J¼10.3, 5.0 Hz, CHb), 3.90 (1H,
m, CH), 3.86 (1H, m, CH),1.88e1.90 (3H, m, CH & CH2),1.65e1.76 (5H,
m, CH & CH2), 1.49 (1H, m, CH2), 1.32 (56H, br s, (CH2)28), 0.85 (6H, t,
J¼7.0 Hz, CH3); 13C NMR (75 MHz, CD3OD):
d 175.1, 131.3, 76.8, 72.5,
72.0, 61.8, 54.0, 36.6, 34.0, 33.8, 33.1, 32.0, 29.8, 27.5, 24.0, 23.1, 21.1,
~
13.7; MS (ESI, positive ion): m/z (%)¼695.0 (100) [Mþ].
Acknowledgements
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We would like to thank the Director, CSIR-NEIST, Jorhat-785006
for providing necessary facilities to carry out this work. T.J.D. and
B.S. thanks to CSIR-New Delhi for the award of fellowship.