Novel, short, stereospecific synthesis of lyxo-(2R,3R,4R)-phytosphingosine and erythro-(2R,3S)-sphingosine

Article abstract of DOI:10.1021/jo034157w

lyxo-Phytosphingosine and erythro-sphingosine have been elaborated from a common intermediate. The key step in the reaction sequence involves stereo- and regiospecific functionalization of an olefin by intramolecular nucleophilic sulfinyl group participat

Full text of DOI:10.1021/jo034157w

Novel, Sh or t, Ster eosp ecific Syn th esis of
lyxo-(2R,3R,4R)-P h ytosp h in gosin e a n d
er yth r o-(2R,3S)-Sp h in gosin e†
Sadagopan Raghavan* and A. Rajender
Organic Division I, Indian Institute of Chemical
Technology, Hyderabad 500 007, India
purush101@yahoo.com
Received February 5, 2003
Abstr a ct: lyxo-Phytosphingosine and erythro-sphingosine
have been elaborated from a common intermediate. The key
step in the reaction sequence involves stereo- and regiospe-
cific functionalization of an olefin by intramolecular nucleo-
philic sulfinyl group participation.
F IGURE 1. Representative phytosphingosines.
The synthesis began with the â-hydroxy-γ,δ-unsatur-
ated sulfoxide (2), which was obtained by DIBAL-H
reduction11 of the ketosulfoxide (1), a compound previ-
ously reported by Solladie and co-workers.12 Treatment
of the unsaturated sulfoxide (2), with NBS in toluene in
the presence of water, afforded the bromohydrin (4) as
the sole product. The regio- and stereoselectivity of the
reaction can be explained by the intermediacy of the
sulfoxonium salt (3), (Scheme 1). The relative stereo-
chemistry at C2 and C3 in 4 was unambiguously proven
as syn by conversion to acetonide (5), the 13C spectrum
of which revealed signals at δ 27.2 and 27.5 for the
methyl groups.13 The anti disposition of the hydroxyl and
bromine at C3 and C4, respectively, is expected from an
overall trans addition of electrophile and nucleophile
across the double bond.14 It was required to introduce the
amino functionality onto bromodiol (4) with retention of
relative stereochemistry. This was achieved by a two-
step transformation.
Sphingolipids are widely distributed in eukaryotic cell
membranes1 and have been demonstrated to regulate
biological processes. The sphingolipids have long-chain
bases as the backbone, i.e., sphingosines, dihydrosphin-
gosines, and phytosphingosines, which are also bioactive.
The finding that diastereomers of sphingosines and
phytosphingosines (Figure 1) exhibit different activities
suggests subtle biostereoselectivities.2-5 A great deal of
effort has therefore been devoted toward the synthesis
of sphingolipids for use in biological studies.
Synthetic efforts have primarily focused on the prepa-
ration of arabino- and ribo-phytoshingosines starting
from compounds of the chiral pool6 or by asymmetric
induction.7 In contrast, the xylo- and lyxo-phytosphin-
gosines have attracted less attention from the synthetic
community.8 In continuation of our efforts aimed at the
utilization of the pendant sulfoxide as an intramolecular
nucleophile for regio- and stereoselective functionaliza-
tion of olefins,9,10 we disclose herein, the enantiospecific
synthesis of lyxo-(2R,3R,4R)-C18-phytosphingosine and
erythro-(2R,3S)-C18-sphingosine.
Thus, the bromohydrin (4) was converted into the
epoxide (6) by treatment with K2CO3 in methanol. The
epoxyalcohol (6) was regio- and stereoselectively trans-
formed into the azidodiol (7) using the Sharpless proto-
1
col.15 The crude H NMR spectrum of (7) did not reveal
the presence of any regiomer. The regioselectivity of the
transformation was proven once again by conversion of
the diol (7) into the acetonide (8). The 13C NMR spectrum
of 8 revealed signals at δ 26.7 and 26.9 for the methyl
groups and at δ 110.3 for the ketal carbon, proving
beyond doubt the syn disposition of the hydroxy groups
on adjacent carbons.13 The acetonide (8) was elaborated
to lyxo-phytosphingosine as depicted in Scheme 2. Having
† IICT Communication no. 030107.
(1) Sweeley, C. C. Biochemistry of Lipids, Lipoproteins and Mem-
branes; D. E. Vance, J . E. Vance, Eds.; Elsevier: Amsterdam, 1991.
(2) Motoki, K.; Kobayashi, E.; Uchida, T.; Fukushima, H.; Koezuka,
Y. Bioorg. Med. Chem. Lett. 1995, 5, 705.
(3) Puskareva, M.; Chao, R.; Bielavska, A.; Merrill, A. H.; Crane,
H. M.; Lagu, B.; Liotta, D.; Hannun, Y. A. Biochemistry 1995, 34, 1885.
(4) Inokuchi, J .; Usuhi, S.; J imbo, M. J . Biochem. (Tokyo) 1995, 117,
766.
(5) Kok, J . W.; Nikolavakarakashian, M.; Klappe, K.; Alexander, C.;
Merrill, A. H. J . Biol. Chem. 1997, 272, 21128.
(6) Martin, C.; Prunck, W.; Bortolussi, M.; Bloch, R. Tetrahedron:
Asymmetry 2000, 11, 1585 and references therein.
(7) (a) Kobayashi, S.; Hayashi, T.; Kawasuji, T. Tetrahedron Lett.
1994, 35, 9573. (b) Lin, G. Q.; Shi, Z. C. Tetrahedron 1996, 52, 2187.
(c) Murakami, M.; Ito, H.; Ito, Y. Chem Lett. 1996, 185. (d) Wee, A. G.
H.; Tang, F. Tetrahedron Lett. 1996, 37, 6677.
(8) (a) Nakamura T.; Shiozaki, M. Tetrahedron 2001, 57, 9087. (b)
Fernandes, R. A.; Kumar, P. Tetrahedron Lett. 2000, 41, 10309 and
references therein. (c) Shirota, O.; Nakanishi, K.; Berova, N. Tetrahe-
dron 1999, 55, 13643.
(11) (a) Solladie, G.; Demailly, G.; Greck, C. Tetrahedron Lett. 1985,
26, 435. (b) Solladie, G.; Demailly, G.; Greck, C. J . Org. Chem. 1985,
50, 1552. (c) Solladie, G.; Frechou, C.; Demailly, G.; Greck, C. J . Org.
Chem. 1986, 51, 1912. (d) Carreno, M. C.; Garcia Ruano, J . L.; Martin,
A.; Pedregal, C.; Rodrigues, J . H.; Rubio, A.; Sanchez, J .; Solladie, G.
J . Org. Chem. 1990, 55, 2120.
(12) (a) Solladie, G.; Hutt, J .; Frechou, C. Tetrahedron Lett. 1987,
28, 61. (b) Solladie, G.; Frechou, C.; Hutt, J .; Demailly, G. Bull. Soc.
Chim. Fr. 1987, 827.
(9) Raghavan, S.; Rasheed, M. A.; J oseph, S. C.; Rajender, A. J .
Chem. Soc., Chem. Commun. 1999, 1845.
(10) Raghavan, S.; Ramakrishna Reddy, S.; Tony, K. A.; Naveen
Kumar, Ch. Varma, A. K.; Nangia, A. J . Org. Chem. 2002, 67, 5838.
(13) Dana, G.; Danechpajouh, H. Bull. Soc. Chim. Fr. 1980, 395.
(14) Chamberlin, A. R.; Dezube, M.; Dussalt, P.; McMills, M. C. J .
Am. Chem. Soc. 1983, 105, 5819.
(15) Caron, M.; Sharpless, K. B. J . Org. Chem. 1985, 50, 1557.
10.1021/jo034157w CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/14/2003
7094
J . Org. Chem. 2003, 68, 7094-7097

SCHEME 1. P r ep a r a tion of Azid oa ceton id e 8a
a
(a) DIBAL, THF, -78 °C, 92%; (b) NBS, H2O, toluene, rt, 88%; (c) 2,2-DMP, acetone, CSA (cat.), rt, 86%; (d) K2CO3, MeOH, 0 °C, 83%;
(e) NaN3, NH4Cl, MeOH/H2O, reflux, 85%; (f) 2,2-DMP, acetone, CSA (cat.), rt, 87%.
SCHEME 2. P r ep a r a tion of lyxo-P h ytosp h in gosin ea
a
(a)TFAA, CH2Cl2, 0 °C; (b) C13H26, SnCl4, 0 °C, 76% for the two steps; (c) Ra-Ni, H2, (Boc)2O, methanol, rt-reflux, 75%; (d) TFA/H2O;
(e) Ac2O, DMAP (cat.), pyridine, rt, 70% for the two steps.
introduced the functional groups on the C5 chain, the next
step called for chain elongation. The C13 hydrocarbon
chain was introduced by the Pummerer ene reaction.16
Thus, treatment of the sulfoxide (8) with TFAA in DCM
afforded the intermediate (9), which without isolation
was reacted in the same pot with 1-tridecene and SnCl4
to yield the sulfide (10) as the only product. The config-
uration at the newly created one in sulfide (10) was not
rigorously established, although it is expected to have
the structure depicted, since it was of no consequence for
the synthesis of the target molecules. Treatment of the
sulfide (10) with Raney Ni in ethanol in the presence of
di-tert-butyl dicarbonate under an atmosphere of hydro-
gen afforded the urethane (11) in a one-pot five-step
transformation. The double bond and the azide are
reduced, the resulting amine is transformed into an
urethane, and the toluene thio group and the benzyl ether
is hydrogenolysed under the reaction conditions. Depro-
tection of the acetonide afforded the triol (12), which was
subsequently converted into the tetraacetate (13), which
was found to be identical (except for sign of [R]D) to that
reported in the literature.8c
The erythro-(2R,3S)-sphingosine17 was synthesized fol-
lowing the reaction sequence depicted in Scheme 3. The
sulfide (10) was oxidized to the sulfone (14) by treatment
with oxone.18 The sulfone (14) was subsequently trans-
formed in a one-pot four-step operation into the urethane
(15) by reaction with Pd(OH)2/C in the presence of
(Boc)2O under an atmosphere of H2. Reduction of 15 with
Na-Hg19 led to the concomitant loss of acetone to afford
(17) For earlier synthesis of sphingosine, refer to: Koskinen, P. M.;
Koskinen, A. M. P. Synthesis 1998, 1075
(18) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981, 22, 1287.
(19) Trost, B. M.; Arndt, H. C.; Strege, P. E.; Verhoeven, T. R.
Tetrahedron Lett. 1976, 17, 3477.
(16) Ishibashi, H.; Komatsu, H.; Ikeda, M. J . Chem. Res., Synop.
1987, 296.
J . Org. Chem, Vol. 68, No. 18, 2003 7095

SCHEME 3. P r ep a r a tion of er yth r o-Sp h in gosin ea
a
(a)2KHSO5‚KHSO4‚K2SO4, MeOH/H2O/THF, 0 °C-rt, 82%; (b) Pd(OH)2/C, (Boc)2O, H2, EtOH, rt, 71%; (c) Na-Hg, Na2HPO4, MeOH,
20 °C, rt, 60%.
NMR (75 MHz, CDCl3) δ 21.4, 51.0, 61.1, 67.9, 71.4, 73.3, 74.7,
124.1, 127.7, 127.8, 128.4, 130.1, 137.4, 139.7, 142.0. HRMS-
FAB (m/z) [M + H]+ calcd for C19H22BrO4S 427.0578, found
427.0573.
the sphingosine derivative (16) as the sole product. The
1H NMR spectrum of 16 revealed the absence of the
isomeric cis olefin. The sphingosine (16) was found to
possess identical physical characteristics (except for the
sign of rotation of plane polarized light) to those reported
in the literature.8a In conclusion, we have reported a
efficient, flexible, atom-economical, and stereospecific
synthesis of lyxo-phytosphingosine and erythro-sphin-
gosine. The key steps include stereoselective bromohydrin
formation using the sulfinyl moiety as an intramolecular
nucleophile, chain extension by Pummerer ene reaction,
and one-pot atom-economical five-/four-step transforma-
tions. It is worthwhile to note that starting from the C2
diastereomer of the alcohol (2), the lyxo-(2S,3S,4S)-
phytosphingosine and erythro-(2S,3R)-sphingosine can be
synthesized following an identical reaction sequence as
detailed above. Also the strategy is flexible and would
permit the synthesis of sphingolipids with different chain
lengths by using olefins of different chain lengths.
1-[3-Ben zyloxym et h yl-3(S)-oxir a n -2-yl]-2-(m et h ylp h e-
n ylsu lfin yl)-1-(S)-eth a n -1-ol (6). To the solution of 4 (1.8 g,
4.05 mmol) in methanol (16 mL) was added K2CO3 (615 mg, 4.45
mmol) at 0° C, and the mixture was allowed to attain room
temperture in 45 min. After the reaction mixture stirred at room
temperature for 1 h, TLC revealed the complete conversion of
starting material. Ether (15 mL) was added to the reaction
mixture, and after 10 min the mixture was filtered and evapo-
rated to afford the epoxide 6 (1.16 g, 3.35 mmol) in 83% yield as
a white solid. This was taken ahead to the next step without
further purification. Mp 104-106 °C. [R]25 -104.3 (c 0.75,
D
1
CHCl3). H NMR (200 MHz, CDCl3) δ 7.51 (d, J ) 8.2 Hz, 2H),
7.36-7.22 (m, 7H), 4.52 (s, 2H), 4.25 (m, 1H), 3.72 (dd, J ) 11.2,
3.0 Hz, 1H), 3.48 (dd, J ) 11.2, 5.2 Hz, 1H), 3.3 (d, J ) 4.5 Hz,
1H), 3.21 (m, 1H), 3.08 (dd, J ) 3.7, 2.2 Hz, 1H), 2.98 (m, 1H),
2.86 (dd, J ) 13.4, 4.5 Hz, 1H), 2.43 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 21.4, 54.4, 57.3, 59.7, 66.7, 69.1, 73.3, 124.1, 127.1,
127.7, 128.4, 130.2, 137.7, 140.1, 142.1. HRMS-FAB (m/z) [M
+ H]+ calcd for C19H27O4S 347.1317, found 347.1312.
4-Az i d o -5-b e n z y lo x y -1-(4-m e t h y lp h e n y ls u lfi n y l)-
(2S,3R,4R)-p en ta n e-2,3-d iol (7). To the epoxide 6 (1.04 g, 3.1
mmol) in a solvent mixture of MeOH/H2O (8:1, 18 mL) was added
NH4Cl (498 mg, 9.3 mmol) followed by NaN3 (1.21 g, 18.6 mmol),
and the mixture refluxed for 6 h. The reaction mixture allowed
to attain room temperature, and the solvent was evaporated.
The residue was extracted with ethyl acetate (2 × 30 mL). The
crude reaction mixture was purified by column chromatography
using AcOEt/hexane (2:3) to afford the azidodiol 7 (1.03 g, 2.64
mmol) in 85% yield as a white solid. Mp 95-96 °C. [R]25D -103.4
(c 0.8, CHCl3). 1H NMR (200 MHz, CDCl3) δ 7.51 (d, J ) 8.2 Hz,
2H), 7.38-7.24 (m, 7H), 4.57 (s, 2H), 4.44 (m, 1H), 3.9 (m, 1H),
3.76-3.64 (m, 2H), 3.5 (d, J ) 8.2 Hz, 1H), 3.22 (bs, 2-OH), 3.1
(dd, J ) 13.4, 6.7 Hz), 2.9 (dd, J ) 13.4, 4.5 Hz,1H), 2.41 (s,
3H). 13C NMR (75 MHz, CDCl3) δ 21.4, 60.1, 62.0, 65.2, 70.5,
73.5, 124.4, 127.5, 127.7, 128.4, 130.1, 137.7, 139.2, 141.9.
HRMS-FAB (m/z) [M + H]+ calcd for C19H23N3O4S 390.1487,
found 390.1478.
Exp er im en ta l Section
All air- or moisture-sensitive reactions were carried out under
nitrogen atmosphere. Solvents were distilled freshly over Na/
benzophenone ketyl for THF, over P2O5 followed by CaH2 for
DCM, and over P2O5 for toluene. Commercially available re-
agents were used without further purification except for NBS,
which was freshly recrystallized from hot water before use. Thin-
layer chromatography was performed with precoated silica gel
plates. Column chromatography was carried out using silica gel
(60-120 mesh). NMR spectra were recorded on a 200-, 300-, or
400-MHz spectrometer. 1H NMR and 13C NMR samples were
internally referenced to TMS (0.00 ppm).
5-B e n z y lo x y -4-b r o m o -1-(4-m e t h y lp h e n y ls u lfi n y l)-
(2S,3S,4R)-p en ta n e-2,3-d iol (4). To the solution of the sulfox-
ide 2 (1.56 g, 4.75 mmol) in dry toluene (19 mL) was added water
(171 mg, 9.5 mmol) followed by N-bromosuccinimide (1.01 g, 5.7
mmol), and the reaction mixture was stirred at room tempera-
ture for 15 min. The reaction was quenched by the addition of
saturated NaHCO3 solution. The layers were separated, and the
aqueous layer was extracted with ethyl acetate. The combined
organic layers were successively washed with water and brine
and dried over Na2SO4. Evaporation of the solvent afforded crude
product, which was purified by column chromatography using
AcOEt/hexane (2:3) as the eluent to yield bromohydrin 4 (1.95
4-[1-Azid o-2-ben zyloxy-(1R)-eth yl]-2,2-d im eth yl-5-(4-m e-
th ylp h en ylsu lfin ylm eth yl)-(4R,5S)-1,3-d ioxola n e (8). To the
solution of the azidodiol 7 (973 mg, 2.5 mmol) in a mixture of
2,2-dimethoxypropane and acetone (1:3, 10 mL) was added CSA
(24 mg, 0.1 mmol), and the reaction mixture was stirred at
ambient temperature for 1 h. The organic layer was evaporated
under reduced pressure to afford the crude product, which was
purified by column chromatography using AcOEt/hexane (1:4)
as the eluent to yield acetonide 8 (925 mg, 2.15 mmol) as a visous
g, 4.18 mmol) in 88% yield as white solid. Mp 137-139 °C. [R]25
D
-120.0 (c 1.0, CHCl3). 1H NMR (200 MHz, CDCl3) δ 7.52 (d, J )
8.2 Hz, 2H), 7.4-7.25 (m, 7H), 4.68 (m, 1H), 4.59 (s, 2H), 4.2
(m, 1H), 4.01-3.81 (m, 3H), 3.1 (dd, J ) 13.4, 8.2 Hz, 1H), 2.84
(dd, J ) 13.4, 3.7 Hz, 1H), 2.8-2.5 (bs, 2-OH), 2.44 (s, 3H). 13C
liquid in 87% yield. [R]25 -47.5 (c 0.6, CHCl3). LSIMS m/z 430
D
[M + H]+. 1H NMR (200 MHz, CDCl3) δ 7.55 (d, J ) 8.2 Hz,
2H), 7.38-7.25 (m, 7H), 4.52 (s, 2H), 4.02-3.9 (m, 2H), 3.7 (dd,
7096 J . Org. Chem., Vol. 68, No. 18, 2003

J ) 9.4, 3.1 Hz, 1H), 3.62 (m, 1H), 3.54 (dd, J ) 9.4, 7.3 Hz,
1H), 3.22 (dd, J ) 13.4, 7.3 Hz, 1H), 3.07 (dd, J ) 13.4, 3.1 Hz,
1H), 2.42 (s, 3H), 1.43 (s, 3H), 1.37 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 21.4, 26.7, 26.9, 60.7, 62.7, 70.2, 73.4, 74.4, 78.2, 110.3,
124.4, 127.6, 127.8, 128.4, 129.9, 137.3, 140.0, 141.9. Anal. Calcd
for C22H27N3O4S: C, 61.52; H, 6.34; N, 9.78; S, 7.46. Found: C,
61.39; H, 6.52; N, 9.97; S, 7.49.
11 (169 mg, 0.37 mmol) as a white solid in 74% yield. Mp 47-
49 °C. [R]25 +12.8 (c 2.5, CHCl3). LSIMS m/z 458 [M + H]+. 1H
D
NMR (200 MHz, CDCl3) δ 5.05 (bs, NH, 1H), 3.88-3.72 (m, 2H),
3.62-3.47 (m, 3H), 1.92 (bs, OH, 1H), 1.51-1.01 (m, 42H), 0.8
(t, J ) 6.7 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ 14.0, 22.6, 26.2,
27.0, 27.2, 28.3, 29.3, 29.6, 31.9, 33.8, 52.9, 62.6, 79.3, 81.8, 108.7,
156.0. Anal. Calcd for C26H51NO5: C, 68.23; H, 11.23; N, 3.06.
Found: C, 68.62; H, 11.41; N, 3.09.
2-Azid o-2-[2,2-d im et h yl-5-[1-(4-m et h ylp h en ylsu lfin yl)-
(E )-3-t e t r a d e c e n y l]-(4R ,5S )-1,3-d io x o la n -4-y l]-e t h y l-
ben zyl eth er (10). To the mixture of the acetonide 8 (885 mg,
2.05 mmol) and 1-tridecene (560 mg, 3.08 mmol) in dichlo-
romethane (10 mL) cooled at 0 °C was added trifluoroacetic
anhydride (1.3 g, 6.15 mmol) dropwise over 5 min, and the
mixture was stirred for 1 h at the same temperature. SnCl4 (550
mg, 2.05 mmol) was added, and after 10 min at 0 °C the reaction
mixture was quenched by the addition of saturated Na2CO3
solution. Extraction into diethyl ether and usual workup followed
by purification by column chromatography using AcOEt/hexane
(1:49) afforded 10 (930 mg, 1.57 mmol) in 76% yield as pale
2-(N-ter t-Bu toxycar bon yl)am in o-(2R,3S,4E)-4-octadecen e-
1,3-d iol (16). Na-Hg (6%, 250 mg) was added to the solution
of 15 (100 mg, 0.16 mmol) and Na2HPO4 (58 mg, 0.32 mmol) in
methanol (3.2 mL) at -20 °C, and the mixture was allowed to
attain room temperature in 30 min. After further stirring for 1
h, the reaction mixture was cooled to 0 °C, diluted with water
(3.2 mL), and evaporated under pressure. The residue was
extracted with ethyl acetate to afford the crude product. After
evaporation of the solvent, purification by column chromatog-
raphy using AcOEt/hexane (1:4) afforded the sphingosine 16 (38
mg, 0.097 mmol) in 60% yield as a low melting oily solid. [R]25
D
yellow liquid. [R]25 +15.8 (c 1.0, CHCl3). LSIMS m/z 593 (M+).
+1.4 (c 1, CHCl3) [lit.8a [R]24 -1.4 (c 1.0 CHCl3) for the
D
D
1H NMR (200 MHz, CDCl3) δ 7.34-7.25 (m, 7H), 7.02 (d, J )
7.2 Hz, 2H), 5.47 (dt, J ) 15.3, 6.6 Hz, 1H), 5.32 (dt, J ) 15.3,
6.8 Hz, 1H), 4.54 (s, 2H), 4.19-4.1 (m, 2H), 3.77 (dd, J ) 9.7,
3.1 Hz, 1H), 3.66 (td, J ) 7.5, 3.1 Hz, 1H), 3.54 (dd, J ) 9.7, 7.5
Hz, 1H), 3.14 (m, 1H), 2.46-2.41 (m, 2H), 2.32 (s, 3H), 1.97-
1.92 (m, 2H), 1.45 (s, 3H), 1.44-1.40 (m, 2H), 1.35 (s, 3H), 1.32-
1.2 (m, 17H), 0.88 (t, J ) 6.7 Hz, 3H). 13C (75 MHz, CDCl3) δ
14.1, 21.0, 22.6, 26.9, 27.0, 29.1, 29.3, 29.5, 29.6, 31.9, 32.5, 37.6,
52.1, 63.8, 70.8, 73.4, 76.6, 80.0, 109.8, 126.6, 127.5, 127.7, 128.4,
129.6, 132.0, 132.3, 134.0, 137.0, 137.6. Anal. Calcd for
C35H51N3O3S: C, 70.79; H, 8.66; N, 7.08; S, 5.40. Found: C,
70.56; H, 8.91; N, 7.12; S, 5.44.
2-(N-ter t-Bu tyloxyca r bon yl)a m in o-2-[2,2-d im eth yl-5-tet-
r a d ecyl-(4R,5S)-1,3-d ioxa la n -4yl]-1-eth a n ol (11). To the mix-
ture of 10 (297 mg, 0.5 mmol), (Boc)2O (218 mg, 1.0 mmol) in
methanol (5 mL) was added Raney Ni (2.5 g). The reaction
mixture was stirred under H2 pressure for 2 h at room temper-
ature and then refluxed for 6 h, when TLC examination revealed
completion of the reaction. The reaction mixture was allowed
to attain room temperature and was filtered through a small
pad of Celite, which was repeatedly washed with methanol (25
mL × 5). Evaporation of the solvent under reduced pressure
followed by purificaion of the crude product by column chroma-
tography using AcOEt/hexane (1:4) afforded the amino alcohol
enantiomer]. LSIMS m/z 400 [M + H]+. 1H NMR (200 MHz,
CDCl3) δ 5.77 (dt, J ) 15.1, 6.7 Hz, 1H), 5.52 (dd, J ) 15.1, 6.7
Hz, 1H), 4.31 (m, 1H), 3.88 (m, 1H), 3.64 (m, 1H), 3.53 (m, 1H),
2.6-2.24 (bs, OH), 2.05 (m, 2H), 1.44-1.11 (m, 31H), 0.88 (t, J
) 6.7 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 14.1, 22.7, 28.4,
29.1, 29.2, 29.3, 29.5, 29.6, 29.7, 31.9, 32.3, 55.5, 62.7, 74.8, 79.9,
128.9, 134.2, 156.2. Anal. Calcd for C23H45NO4: C, 69.13; H,
11.35; N, 3.51. Found: C, 69.45, H, 11.62, N, 3.59.
Ack n ow led gm en t. S.R. is thankful to Dr. J . S.
Yadav, Head, Organic Div. I for constant support and
encouragement and to Dr. A. C. Kunwar for NMR
spectra. A.R, is thankful to CSIR (New Delhi) for the
senior research fellowship. Financial assistance from
DST is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for the preparation of compounds 2, 5, 14, and 15 and
copies of 1H and 13C NMR data of all reported compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O034157W
J . Org. Chem, Vol. 68, No. 18, 2003 7097