A concise total synthesis of antifungal antibiotic (+)-preussin

Article abstract of DOI:10.1002/ejoc.200500833

A short synthesis of the pharmacologically important natural product (+)-preussin is described. Two asymmetric C-C bond-formation reactions mediated by binaphthol-derived asymmetric catalysts have been applied to control the stereo-chemistry of its three stereocenters. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500833

FULL PAPER
DOI: 10.1002/ejoc.200500833
A Concise Total Synthesis of Antifungal Antibiotic (+)-Preussin
Naminita Gogoi,[a] Joshodeep Boruwa,[a] and Nabin C. Barua*[a]
Keywords: Preussin / Asymmetric synthesis / Allylation / Asymmetric nitro-aldol / Binaphthol-derived catalysts
A short synthesis of the pharmacologically important natural
product (+)-preussin is described. Two asymmetric C–C
bond-formation reactions mediated by binaphthol-derived
asymmetric catalysts have been applied to control the stereo-
chemistry of its three stereocenters.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Despite a plethora of syntheses,[6] interest in the synthesis
of (+)-preussin remains undiminished. The development of
methods with enough flexibility to allow the construction
of non-natural analogs continues to be an important topic,
particularly with a view to investigating structure–activity
relationships.
Investigations in our laboratory over the past few years
have demonstrated the utility of nitroaliphatics in the syn-
theses of pharmacologically important natural prod-
ucts.[7a–7e] In this context we report here a total synthesis of
1 by a route that has inherent flexibility enabling access to
analogs with various substituents as well as stereochemistry
at the C-2 and C-5 atoms.
Introduction
In 1988 researchers at Merck Sharp & Dohme isolated
(+)-preussin (-657, 398) (1), a pyrrolidine alkaloid, from
the fermentation broth of Aspregillius ostraceus (ATCC
29947) and subsequently from that of Preussia sp.[1] In pre-
liminary biological studies (+)-preussin was shown to in-
hibit growth of the bacteria Candida and filamentous fungi,
including Trichophyton menta and Microsporum canis.[2]
Later on, Yoshida and co-workers rediscovered (+)-preussin
as a selective inhibitor of cell growth of the fission yeast
ts mutants defective on cdc2-regulatory genes.[3] Detailed
biological studies by Muller and co-workers revealed that
(+)-preussin induces apoptosis in human tumor cells.[4] It
was also found in vitro to be a potent inhibitor of cyclin E
kinase (CDK2-cyclin E) with a 50% inhibitory concentra-
tion of around 500 n.
Results and Discussions
Recently we recorded excellent stereoselectivity during
the synthesis of (+)-boronolide[7e] by an asymmetric nitro-
aldol reaction of an α-hydroxy aldehyde catalyzed by a La-
BINOL complex. This result encouraged us to explore the
synthesis of 1. In formulating a synthetic route to 1
(Scheme 1), the displacement of an activated alcohol moiety
(tosylate, mesylate or triflate) by an amine appeared to be
the most convenient route for the construction of the 2,5-
disubstituted pyrrolidine core. We contemplated that the
stereochemistry at the C-2 and C-3 positions could be se-
cured by applying the asymmetric nitro-aldol reaction. To
install the stereochemistry at the C-5 position, we relied on
asymmetric allylation.
The present synthesis (Scheme 2) was initiated by em-
ploying the catalytic asymmetric allylstannation protocol
developed by Keck and co-workers.[8] In the presence of a
catalytic system comprising of 1 equiv. of (S)-BINOL,
1 equiv. of Ti(O-iPr)4 and 4-Å molecular sieves, which had
been premixed at reflux temperature in CH2Cl2, the reac-
tion of n-decanal and allyltributylstannane provided the
homoallylic alcohol 4[9a] in 82% yield and 94% ee[10]
{[α]2D0 = –13.2 (c = 1.1, CH2Cl2); ref.[9b]: [α]2D0 = –10.4 (c =
6.7, C6H6)}.
(+)-Preussin inhibits cell-cycle progression into the S
phase. Remarkably, the induction of apoptosis is not
blocked by a high level of B cell lymphoma-2 (Bcl-2), which
usually confers resistance to chemotherapeutic agents.
More recent reports disclosed that (+)-preussin inhibits
programed-1 ribosomal frameshifting.[5]
In view of these observations, it has become clear that it
is imperative to provide synthetic access to this compound
to deconvolute its biological activity.
[a] Natural Products Chemistry Division, Regional Research Lab-
oratory,
Jorhat 785006, Assam, India
Fax: +91-376-2370011
E-mail: ncbarua2000@yahoo.co.in
1722
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1722–1725

A Concise Total Synthesis of Antifungal Antibiotic (+)-Preussin
FULL PAPER
tate in hexane) allowed the mixture to be separated and the
diastereomerically pure 6 (95% ee) was used for the rest of
the synthesis.
The catalytic hydrogenation of 6 with 10% Pd/C in
MeOH at 1 atm provided the corresponding amino alcohol
7 in 90% yield. Hydrolytic removal of the acetate group
with 5% aqueous HCl led to the amino diol 8. Boc-protec-
tion of the amino group followed by exposure to meth-
anesulfonyl chloride in the presence of Et3N in THF, di-
rectly afforded the pyrrolidine derivative 10. Finally, treat-
ment of N-Boc-pyrrolidine 10 with LAH under reported
conditions[14] furnished the target molecule. The physical
and spectral properties of our synthetic material closely
matched those published for the natural product.[1]
Thus, we have achieved a remarkably simple and very
economical synthesis of the target molecule. The note-
worthy feature of this synthesis is that it is an exception to
most other chiral-auxillary-based approaches[6] with excel-
lent stereocontrol resulting from Shibasaki’s nitro-aldol re-
action of a chiral β-hydroxy aldehyde.[13]
Scheme 1.
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded using a
Bruker DPX-300 NMR machine. IR spectra were recorded with
a Perkin–Elmer 1640 FT-IR spectrometer. Optical rotations were
measured with a Perkin–Elmer 343 polarimeter. Elemental analyses
were carried out using a Perkin–Elmer series II CSNS/O Model
2400 analyzer. Mass spectra were recorded with a Bruker Daltonic
Data Analysis 2.0 spectrometer. Column chromatography was per-
formed with Merck silica gel (60–120 mesh) and preparative TLC
was carried out using plates prepared with Merck silica gel G.
Moisture-sensitive reactions were conducted under nitrogen. Di-
ethyl ether and THF were distilled from benzophenone ketyl prior
to use. Dichloromethane was distilled from P2O5 and stored over
molecular sieves. All solvents were distilled at their boiling points
and other commercially available reagents were used as received
unless otherwise noted. PE: petroleum ether.
(4S)-Tridec-1-en-4-ol (4):
A mixture of (S)-BINOL (0.24 g,
Scheme 2. Reagents and conditions: (i) (S)-BINOL, Ti(O-iPr)4, al-
lyltributylstannane, CH2Cl2, –78 to –20 °C, 36 h; (ii) acetic anhy-
dride, iodine, room temp., 10 min; (iii) OsO4, 2,6-lutidine, NaIO4,
dioxane/H2O, room temp., 30 min; (iv) 2-phenyl-1-nitroethane, La-
(R)-BINOL complex, THF, –50 °C, 60 h; (v) 10% Pd/C, H2
(1 atm.), MeOH, room temp., 3 h; (vi) 5% aq. HCl, room temp.,
2 h; (vii) (Boc)2O, sat. NaHCO3 soln. EtOAc, room temp., 3 h;
(viii) MsCl, Et3N, CH2Cl2, 0 °C to room temp., 6 h; (ix) LiAlH4,
THF, reflux, 8 h.
0.84 mmol) and Ti(O-iPr)4 (0.24 g, 0.84 mmol) in CH2Cl2 (15 mL)
in presence of 4-Å molecular sieves (2.4 g) was stirred under reflux.
After 1 h the reaction mixture was cooled to room temperature, n-
decanal (1.3 g, 8.3 mmol) was added and the resulting mixture was
stirred for 10 min. The reaction mixture was then cooled to –78 °C
and allyltributylstannane (3.02 g, 9.1 mmol) was then added and
the stirring was continued at –20 °C for 36 h. Saturated NaHCO3
solution (1.5 mL) was added to quench the reaction and then the
mixture was stirred for an additional 30 min and extracted with
Acetylation of the hydroxy function with acetic anhy- CH2Cl2 (30 mL). The extract was washed with water (10 mL), dried
dride catalyzed by iodine[11] followed by oxidative cleavage
(Na2SO4), the solvent evaporated and the residue purified by
chromatography on SiO2 (EtOAc/PE, 1:10) to give 1.35 g
of the olefinic bond using OsO4 and NaIO4 in the presence
(6.8 mmol, 82%, 94% ee) of 4 as a clear liquid. [α]2D0 = –12.3 (c =
of 2,6-lutidine in dioxane/water[12] furnished the corre-
0.9, CH Cl ). IR (neat): ν = 3410 cm–1. 1H NMR (300 MHz,
˜
2
2
sponding aldehyde 3. This aldehyde without further purifi-
cation was subjected to Shibasaki’s asymmetric nitro-aldol
reaction[13] with 2-phenyl-1-nitroethane in the presence of
the La-(R)-BINOL complex in THF at –50 °C to deliver
the nitro alcohol 6 in 73% yield with a satisfactory dia-
stereoselectivity (diastereomeric ratio = 20:1, as determined
CDCl3): δ = 0.93 (t, J = 6.7 Hz, 3 H), 1.30–1.62 (m, 16 H), 2.06–
2.13 (m, 2 H), 2.35 (br. s, 1 H), 3.54–3.61 (m, 1 H), 5.05 (dd, J =
16.1, 11.3 Hz, 1 H), 5.13 (dd, J = 16.1, 1.5 Hz, 1 H), 5.74–5.77 (m,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.07, 22.81, 25.07,
28.94, 29.5, 32.0, 36.8, 40.6, 71.0, 116.7, 135.2 ppm. MS (ESI):
m/z = 221.0 [M + Na]+. C13H26O (198.4): calcd. C, 78.72, H 13.20;
by 1H NMR spectroscopy). Preparative TLC (9% ethyl ace- found C 78.80, H 13.14.
Eur. J. Org. Chem. 2006, 1722–1725
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1723

N. Gogoi, J. Boruwa, N. C. Barua
FULL PAPER
(1S)-1-Allyldecyl Acetate (5): Iodine (75 mg, 0.59 mmol) was added
to a stirred solution of homoallylic alcohol 4 (1.3 g, 6.6 mmol) and
acetic anhydride (1.35 g, 13.2 mmol) and the reaction mixture was
then stirred at room temperature for 10 min. 10% Na2S2O3 solu-
tion (10 mL) was added and the mixture was extracted with diethyl
ether (60 mL) and then washed successively with 10% NaHCO3
solution (3×10 mL) and H2O (20 mL). The organic phase was
dried (Na2SO4), the solvent evaporated and the residue was puri-
fied by chromatography on SiO2 (EtOAc/PE, 1:20) to give 1.46 g
(2 mL) at room temperature for 2 h. The reaction mixture was then
extracted with Et2O (20 mL), washed with 20% NaHCO3 solution
and then with water. The organic phase was then dried (Na2SO4).
The solvent was evaporated and the residue purified by chromatog-
raphy on SiO2 (EtOAc/PE, 1:3) to give 0.636 g (1.98 mmol, 80%)
of the amino diol 8 as a clear liquid. [α]2D0 = –11.7 (c = 0.6, CH2Cl2).
1
IR (CHCl ): ν = 3410, 3300 cm–1. H NMR (300 MHz, CDCl ): δ
˜
3
3
= 0.93 (t, J = 6.7 Hz, 3 H), 1.20–1.33 (br. s, 14 H), 1.48–1.50 (br.
s, 2 H), 2.07–2.15 (m, 2 H), 2.68 (br. s, 2 H), 2.81 (d, J = 7.3 Hz,
2 H), 2.95–3.07 (m, 1 H), 3.22–3.28 (m, 1 H), 3.73–3.80 (m, 1 H),
7.10–7.24 (m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.0,
21.9, 25.8, 28.7, 29.5, 29.6, 36.9, 38.1, 40.8, 54.5, 72.1, 126.8, 128.1,
128.9, 141.1 ppm. MS (ESI): m/z = 344.1 [M + Na]+. C20H35NO2
(321.5): calcd. C 74.72, H 10.97, N 4.36; found C 74.80, H 10.88,
N 4.30.
(6.08 mmol, 92%) of 5 as a clear liquid. [α]2D0 = –13.2 (c = 1.1,
1
CH Cl ). IR (neat): ν = 1734 cm–1. H NMR (300 MHz, CDCl ):
˜
2
2
3
δ = 0.93 (t, J = 6.7 Hz, 3 H), 1.30–1.61 (m, 16 H), 2.02–2.10 (m, 2
H), 2.13 (s, 3 H), 4.88–4.92 (m, 1 H), 5.05 (dd, J = 16.1, 11.3 Hz,
1 H), 5.14 (dd, J = 16.1, 1.5 Hz, 1 H), 5.74–5.79 (m, 1 H) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 14.07, 20.08, 22.8, 25.0, 28.6, 29.6,
32.1, 36.7, 74.0, 116.7, 135.2 ppm. MS (ESI): m/z = 240.3 [M]+.
C15H28O2 (240.4): calcd. C 74.95, H 11.74; found C 75.01, H 11.69.
tert-Butyl
(1S,2S,4S)-(1-Benzyl-2,4-dihydroxytridecyl)carbamate
(9): A saturated NaHCO3 solution (10 mL) followed by (Boc)2O
(0.37 g, 1.72 mmol) were added to a well stirred solution of amino
diol 8 (0.59 g, 1.72 mmol) in AcOEt (10 mL) and the resulting mix-
ture was continued to be stirred at room temperature. After com-
pletion, the layers were separated and the organic phase dried
(Na2SO4), the solvent evaporated and the residue purified by
chromatography on SiO2 (EtOAc/PE, 1:15) to give 0.66 g
(1.57 mmol, 91%) of 9 as a clear liquid. [α]2D0 = –13.2 (c = 1.1,
(3S)-3-Acetoxydodecanal (3): 2,6-Lutidine (1.28 g, 11.9 mmol),
OsO4 (4% solution in i-PrOH, 0.012 mL) and NaIO4 (5.1 g,
23.9 mmol) were added to a solution of the acetate 5 (1.46 g,
6.08 mmol) in dioxane/H2O (60 mL, 3:1). The mixture was stirred
at room temperature and upon completion H2O (30 mL) was added
and the solution extracted with CH2Cl2 (3×20 mL). The organic
layer was dried (Na2SO4) and the solvent evaporated to give 1.27 g
(5.25 mmol, 86%) of 3 as a pale yellow liquid which, without fur-
ther purification, was applied in the next step.
CH Cl ). IR (CHCl ): ν = 3410, 3300, 1734 cm–1. 1H NMR
˜
2
2
3
(300 MHz, CDCl3): δ = 0.90 (t, J = 6.7 Hz, 3 H), 1.18–1.30 (br. s,
14 H), 1.39 (s, 9 H), 1.46–1.48 (s, 2 H), 2.07–2.13 (m, 2 H), 2.81
(d, J = 7.3 Hz, 2 H), 3.23 (dt, J = 3.1, 4.6 Hz, 1 H), 3.73–3.78 (m,
1 H), 3.98 (dt, J = 3.2, 4.8 Hz, 1 H), 6.27 (br. s, 1 H), 7.19–7.28
(m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 22.9, 25.8,
28.2, 28.6, 29.5, 29.6, 36.7, 38.2, 41.1, 54.3, 70.6, 72.0, 79.7, 126.8,
128.1, 128.9, 140.9, 155.8 ppm. MS (ESI): m/z = 421.1 [M]+.
C25H43NO4 (421.6): calcd. C 71.22, H 10.28, N 3.32; found C
71.28, H 10.34, N 3.27.
(1S,2S,3S)-1-(2-Hydroxy-3-nitro-4-phenylbutyl)decyl Acetate (6):
The La-(R)-BINOL catalyst (3.7 mL) was gradually added using a
syringe to a mixture of aldehyde 3 (1.25 g, 5.2 mmol) and 2-phenyl-
1-nitroethane (1.6 g, 10.6 mmol) in THF (15 mL) cooled to –50 °C.
The reaction mixture was stirred at –50 °C for 60 h and then
quenched by the addition of 1  HCl (1 mL). The reaction mixture
was then extracted with diethyl ether (30 mL), washed with a 10%
NaHCO3 solution (3×10 mL) and then with H2O (15 mL). The
organic phase was dried (Na2SO4), the solvent evaporated and the
residue purified by preparative TLC (9% EtOAc in PE) to give
tert-Butyl (2S,3S,5R)-2-Benzyl-3-methylsulfonyloxy-5-nonylpyrroli-
dine-1-carboxylate (10): Triethylamine (0.21 g, 2.12 mmol) and
methanesulfonyl chloride (0.244 g, 2.13 mmol) were added to a
well-stirred solution of N-Boc-protected diol 9 (0.6 g, 1.42 mmol)
in dry CH2Cl2 (14 mL) cooled to 0 °C under N2. The reaction mix-
ture was then stirred for 4 h at room temperature. After comple-
tion, the reaction mixture was extracted with Et2O and washed
with water and brine. The organic phase was dried (Na2SO4), the
solvent evaporated and the residue purified by chromatography on
SiO2 (EtOAc/PE, 1:10) to give 0.52 g (1.07 mmol, 75%) of 10 as a
1.5 g (3.8 mmol, 73%, 95% ee) of 6 as a pale yellow oil. [α]2D0
–11.7 (c = 0.6, CH Cl ). IR (CHCl ): ν = 3410, 1734, 1557 cm–1.
=
˜
2
2
3
1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 6.7 Hz, 3 H), 1.22–
1.34 (m, 14 H), 1.42–1.46 (br. s, 2 H), 2.06 (m, 2 H), 2.16 (s, 3 H),
2.45 (br. s, 1 H), 2.81 (d, J = 7.3 Hz, 2 H), 3.28 (dt, J = 3.2, 4.6 Hz,
1 H), 4.77 (m, 1 H), 4.84 (dt, J = 3.4, 4.6 Hz, 1 H), 7.11–7.24 (m,
5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.07, 20.8, 22.7, 25.0,
28.8, 29.5, 29.6, 32.0, 33.7, 39.5, 41.0, 54.2, 72.7, 74.2, 126.8, 128.1,
128.8, 138.7 ppm. MS (ESI): m/z = 393.1 [M]+. C22H35NO5 (393.5):
calcd. C 67.15, H 8.96, N 3.56; found C 67.23, H 9.05, N 3.64.
clear liquid. [α]2D0 = +11.2 (c = 1.1, CH Cl ). IR (CHCl ): ν = 3410,
˜
2
2
3
3300, 1734 cm–1. 1H NMR (300 MHz, CDCl3): δ = 0.89 (t, J =
6.7 Hz, 3 H), 1.19–1.28 (m, 14 H), 1.42 (s, 9 H), 1.46–1.53 (m, 2
H), 1.78–1.81 (m, 1 H), 1.96–2.00 (m, 1 H), 2.20–2.29 (m, 2 H),
2.66 (dd, J = 14.0, 6.7 Hz, 1 H), 2.98 (dd, J = 14.0, 6.1 Hz, 1 H),
3.15 (s, 3 H), 3.38 (ddd, J = 9.2, 5.5, 3.7 Hz, 1 H), 7.18–7.25 (m, 5
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1, 24.2, 25.0, 28.8,
29.5, 29.7, 33.1, 37.6, 54.2, 58.2, 71.1, 82.0, 126.9, 128.1, 137.9,
153.6 ppm. MS (ESI): m/z = 481.3 [M]+. C26H43NO5S (481.2):
calcd. C 64.83, H 9.00, N 2.91; found C 64.89, H 9.15, N 2.84.
(1S,2S,3S)-1-(3-Amino-2-hydroxy-4-phenylbutyl)decyl Acetate (7):
A mixture of the nitro alcohol 6 (1.45 g, 3.7 mmol) and 10% Pd/C
(0.3 g) in anhydrous MeOH (40 mL) was stirred vigorously under
hydrogen for 3 h. The reaction mixture was then filtered, the sol-
vent removed and the residue purified by chromatography on SiO2
(EtOAc/PE, 1:5) to give 1.2 g (3.33 mmol, 90%) of 7 as a clear
liquid. [α]2D0 = –11.7 (c = 0.6, CH Cl ). IR (CHCl ): ν = 3410,
˜
2
2
3
1734 cm–1. H NMR (300 MHz, CDCl3): δ = 0.91 (t, J = 6.7 Hz,
3 H), 1.19–1.34 (br. s, 14 H), 1.42–1.50 (br. s, 2 H), 2.06–2.13 (m,
2 H), 2.16 (s, 3 H), 2.70 (br. s, 2 H), 2.84 (d, J = 7.3 Hz, 2 H),
2.96–3.03 (m, 1 H), 3.22 (m, 1 H), 4.77–4.81 (m, 1 H), 7.10–7.24
(m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.0, 20.9, 22.8,
25.1, 28.8, 29.5, 29.6, 32.0, 33.7, 38.5, 41.4, 55.0, 71.7, 126.9, 127.9,
128.8, 141.0 ppm. MS (ESI): m/z = 363.0 [M]+. C22H37NO3 (363.5):
calcd. C 72.69, H 10.26, N 3.85; found C 72.76, H 10.33, N 3.91.
1
(2S,3S,5R)-2-Benzyl-3-hydroxy-1-methyl-5-nonylpyrrolidine (1): Li-
AlH4 (0.36 g, 9.3 mmol) was added to a solution of N-Boc-pyrrol-
idine 9 (0.45 g, 0.93 mmol) in THF (10 mL) and the mixture was
refluxed. Upon completion the mixture was cooled to 0 °C and a
saturated NH4Cl solution (15 mL) was added slowly followed by
water (30 mL). The resulting solution was then extracted with di-
ethyl ether (3×50 mL), the combined extracts were washed with
brine and dried (Na2SO4). The solvent was then evaporated and
(2S,3S,5S)-2-Amino-1-phenyltetradecane-3,5-diol (8): The amino
alcohol 7 (0.9 g, 2.47 mmol) was stirred with 5% aqueous HCl
1724
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1722–1725

A Concise Total Synthesis of Antifungal Antibiotic (+)-Preussin
FULL PAPER
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the residue purified by chromatography on SiO2 (EtOAc/PE, 1:3)
to give 0.176 g (0.55 mmol, 60%) of preussin as a colored wax.
[α]2D0 = +13.2 (c = 1.1, CH2Cl2); ref.[2b] [α]2D5 = +22.0 (c = 1.0
CHCl ). IR (CHCl ): ν = 3410, 2910, 1490 cm–1. 1H NMR
˜
3
3
(300 MHz, CDCl3): δ = 0.87 (t, J = 6.9 Hz, 3 H), 1.20–1.28 (m, 14
H), 1.33 (dd, J = 14.0, 5.9 Hz, 1 H), 1.56–1.64 (m, 2 H), 1.76–1.81
(m, 1 H), 1.99–2.05 (m, 1 H), 2.19 (dt, J = 14.0, 6.1 Hz, 1 H), 2.25
(ddd, J = 10.8, 7.6, 5.1 Hz, 1 H), 3.19 (s, 3 H), 3.32 (ddd, J = 9.0,
5.2, 3.9 Hz, 1 H), 3.42 (dd, J = 13.1, 7.9 Hz, 1 H), 3.87 (m, 1 H),
7.17–7.25 (m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.0,
23.0, 25.6, 28.9, 29.4, 29.7, 30.2, 32.0, 33.1, 34.6, 40.2, 47.8, 66.1,
71.1, 72.8, 126.9, 128.1, 132.9, 138.9 ppm. MS (ESI): m/z = 317.5
[M]+. C21H35NO (317.5): calcd. C 79.44, H 11.11, N 4.41; found C
79.52, H 11.17, N 4.37.
Acknowledgments
The authors are thankful to the Director, RRL Jorhat, for provid-
ing facilities. J.B. also thanks CSIR (New Delhi) for a Research
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Received: October 24, 2005
Published Online: February 3, 2006
Eur. J. Org. Chem. 2006, 1722–1725
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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