A facile synthesis of phytosphingosine from diisopropylidene-D-mannofuranose

Article abstract of DOI:10.1021/jo034224m

In the present study, an efficient method with a high overall yield for preparing phytosphingosine and an analogue was developed. Starting with commercially available 2,3;5,6-di-O-isopropylidene-D-mannofuranose, a variety of lipid moieties were incorporated to obtain phytosphingosine and an analogue. Through an eight-step manipulation, phytosphingosine was obtained with an overall yield of 57%.

Full text of DOI:10.1021/jo034224m

There are many methods for synthesizing phyto-
sphingosines reported in the literature. Most of these
methods are based on a chiral pool strategy that usually
employs carbohydrate8- or amino acid9-derived starting
materials, and very few are based on asymmetric syn-
thesis.10 The chiral pool approach appears attractive
because most of the chiral centers required in the final
product are already present at the outset. There is also
a high degree of stereocontrol in subsequent synthetic
manipulations. However, this method suffers the draw-
back of being a multistep synthesis with a poor overall
yield (<20%).8-10
A F a cile Syn th esis of P h ytosp h in gosin e
fr om Diisop r op ylid en e-D-m a n n ofu r a n ose
Hsin-Yi Chiu, Der-Lii M. Tzou,*
Laxmikant Narhari Patkar, and Chun-Cheng Lin*
Institute of Chemistry, Academia Sinica, Nankang,
Taipei 115, Taiwan
cclin@chem.sinica.edu.tw
Received February 20, 2003
The key to cost-effective and efficient synthesis is the
choice of a proper starting material that requires minimal
protection-deprotection steps, a high level of stereocon-
trol, and a minimal number of steps required. We
recently disclosed such a synthesis of 1, which required
only six steps with an overall yield of 28%11 starting from
D-lyxofuranose. In the present study, we report a conve-
nient and concise route for the synthesis of D-ribo-
phytosphingosine 1 with an almost 2-fold increase in
overall yield to 57% starting with the readily available
2,3;5,6-di-O-isopropylidene-D-mannofuranose.
Our choice of starting material was dictated by the type
of reactions we planned to use in the synthesis of
phytosphingosine 1. The retrosynthetic analysis is shown
in Figure 1. Our plan involved a starting material 2 with
the proper stereochemistry at the gem-diol part, a hy-
droxyl group at position 4 that could be replaced with
azide, and an aldehyde function for introducing the lipid
chain by Wittig olefination. The Wittig olefination confers
versatility to this route by giving access to analogues of
phytosphingosine 1. With this in mind, 2,3;5,6-di-O-
Abstr a ct: In the present study, an efficient method with a
high overall yield for preparing phytosphingosine and an
analogue was developed. Starting with commercially avail-
able 2,3;5,6-di-O-isopropylidene-D-mannofuranose, a variety
of lipid moieties were incorporated to obtain phytosphin-
gosine and an analogue. Through an eight-step manipula-
tion, phytosphingosine was obtained with an overall yield
of 57%.
Sphingolipids and glycosphingolipids are important
elements of plasma membranes1and are physiologically
important for cell proliferation, differentiation, adhesion,
neuronal repair, and signal transduction.2 Phytosphin-
gosine 1, one of the major long-chain components of
glycosphingolipids, typically consists of an 18-carbon
chain (in a few cases a 20-carbon chain) that incorporates
a 2-amino-1,3,4-triol moiety at one end. Phytosphingosine
itself is a bioactive lipid,3 and its glycosylated derivatives
display promising antitumor4and antivirus5 activity.
Recently, the R-galactosylphytoceramide6 and an ana-
logue7 were shown to modulate different immune re-
sponses. Consequently, since phytosphingosine and its
derivatives are only available in a limited amount from
natural sources, there is a continuing interest in develop-
ing efficient methods for their synthesis.8-10
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10.1021/jo034224m CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/12/2003
5788
J . Org. Chem. 2003, 68, 5788-5791

SCHEME 1a
a
Reagents and conditions: (a) LHMDS, C13H27P+Ph3Br-, THF, 0 °C to room temperature, overnight, 98%; (b) H2, 5% Pd/C, EtOAc, rt,
3 h, 94%; (c) MsCl, pyridine, 0 °C to room temperature, overnight, 96%.
SCHEME 2 a
a
Reagents and conditions: (e) NaIO4/H2O, THF, 0-4 °C, 1 day, 90%; (f) NaBH4, MeOH, 0 °C, 1.5 h, quantitative; (g) TMGA, DMF, 50
°C, 2 day, 84%; (h) H2, 10% Pd/C, MeOH, rt, 2 day, 94%.
TABLE 1.
procedure
yield (%)
(a) 60% AcOH, rt, 1 day
15
61
63
85
20
91
F IGURE 1. Retrosynthesis of phytosphingosine from a D-
mannofuranose derivative.
(b) acetone/H2O (9/1), DDQ, rt, 1 day
(c) 5% CBr4 in MeOH, hv 30 mins, rt, 1 h
(d) MeOH/H2O, 2 equiv of oxone, rt, 1 day
(e) 1 N HCl, MeOH/H2O, rt, 1 day
(f) concd HCl, MeOH, 0 °C, 1 day
isopropylidene-D-mannofuranose 3 appeared to be a very
attractive starting material due to its commercial avail-
ability, and after truncation of the hydroxymethylene
group at position 6, it met all of the requirements
described aboved. The synthesis of 1 is illustrated in
Scheme 1. Olefination of 3 with the Wittig reagent
derived from C13H27P+Ph3Br- in the presence of lithium
hexamethyldisilazide (LHMDS) afforded an unseparable
mixture of alkenes 4a E and Z (ratio of 1:2) in 98% yield.12
Hydrogenation of the double bond of 4a followed by
mesylation13 gave compound 6a in high yield (90% for
two steps). It should be noted that attempts to replace
the C-3 hydroxy group in 4a or 5a by using tetrameth-
ylguanidium azide (TMGA)8c as the soluble azide ion
donor and Tf2O in pyridine resulted in a low yield of the
desired product.
riodate15 gave 8a as an anomeric mixture in a ratio of
1:2 (R:â) in 90% yield, as shown in Scheme 2. The mixture
was reduced with sodium borohydride16 to furnish triol
9a in a quantitative yield. Finally, the O-mesyl group in
triol 9a was replaced by azide in an SN2 reaction by
treatment with TMGA to afford azido triol 10a in 84%
yield and with inversion at the azide bearing carbon.8c
The multiplet of H-2 of 10a in the 1H NMR spectrum was
strongly shifted upfield (4.93 to 3.92 ppm), and the signal
of C-2 in the 13C NMR was also shifted from 84.1 to 76.1
ppm, indicating the replacement of the mesylate group
by an azide group. The change of optical rotation was
also in agreement with literature data showing the
inversion of C-2 configuration.8c Azido triol 10a is a very
versatile intermediate with the possibility of transform-
ing its azido function into amino, isothiocyanate,17 and
After meticulous investigation of the deprotection of
the acetal groups in 6a , as shown in Table 1, we found
that hydrochloric acid in methanol14 was the condition
of choice to lead to the tetraol derivative 7a (91%).
Cleaving the hydroxylmethylene arm with sodium pe-
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Lett. 1992, 33, 3637-3640.
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2456.
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Mellet, C.; Defaye, J .; Garc´ıa Ferna´ndez, J . M. Carbohydr. Res. 2002,
337, 2329-2334. (b) Barluenga, J .; Palacios, F. Org. Prep. Proced. Int.
1991, 23, 1-65.
(12) Harcken, C.; Martin, S. F. Org. Lett. 2001, 3, 3591-3593.
(13) Ohlsson, J .; Magnusson, G. Carbohydr. Res. 2001, 331, 91-
94.
(14) Yoshino, T.; Nagata, Y.; Itoh, E.; Hashimoto, M.; Katoh, T.;
Terashima, S. Tetrahedron 1997, 53, 10239-10252.
J . Org. Chem, Vol. 68, No. 14, 2003 5789

76.5, 76.0, 73.4, 70.7, 67.0, 29.9, 26.8, 26.6, 25.3, 24.4, 22.7, 13.7;
HRMS (FAB, M - H +) calcd for C16H27O5 299.1859, found
299.1860.
other functional groups. Finally, hydrogenation of 10a
completed the synthesis of D-ribo-phytosphingosine in
94% yield. The 1H NMR data of 1 were identical with
those published in the literature.8e Thus starting with
2,3;5,6-di-O-isopropylidene-D-mannofuranose 3, phyto-
sphingosine 1 was synthesized in eight steps with an
overall yield of 57%. To our knowledge this is the highest
overall yield obtained for phytosphingosine from com-
mercially available starting material. The versatility of
this method was established by the synthesis of 10b, a
C5H11 lipid chain analogue of 10a , with an overall yield
of 50%.
In conclusion, we have developed a short and highly
efficient synthesis of D-ribo-phytosphingosine by using
simple reactions and starting with commercially avail-
able 2,3;5,6-di-O-isopropylidene-D-mannofuranose. The
generality of this high-yield method was proven by the
synthesis of the short-chain phytosphingosine analogue
10b. This method provides easy access to the synthesis
of chain-modified phytosphingosines.
(2R,3R,4R,5R)-3-H yd r oxy-1,2;4,5-d i-O-isop r op ylid en e-
n on a d eca n e (5a ). A mixture of 4a E and 4a Z (976 mg, 2.34
mmol) and 5% Pd/C (100 mg) in EtOAc (20 mL) was stirred
under a H2 atmosphere at room temperature for 3 h. The mixture
was filtered and concentrated, and the residue was purified by
column chromatography with EtOAc/hexane (1:8) to give com-
pound 5a (927 mg, 2.16 mmol, 94%). Rf 0.30 (1:6 EtOAc/hexane);
[R]26 -12.5 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.28-
D
4.21 (m, 2 H), 4.13-4.09 (m, 1 H), 4.05-4.00 (m, 2 H), 3.50 (t, 1
H, J ) 7.6 Hz), 2.20 (d, OH, J ) 7.6 Hz), 1.84-1.27 (m, 38 H),
0.89 (t, 3 H, J ) 6.8 Hz); 13C NMR (125 MHz, CDCl3) δ 109.4,
107.9, 77.7, 77.4, 77.1, 76.8, 76.3, 70.9, 67.3, 32.1, 30.0-22.9,
14.3; HRMS (FAB, M + H+) calcd for C25H49O5 429.3580, found
429.3575.
(2R,3R,4R,5R)-3-H yd r oxy-1,2;4,5-d i-O-isop r op ylid en e-
d eca n e (5b ). The synthetic procedure was the same as that
described in the synthesis of 5a . Rf 0.30 (1:6 EtOAc/hexane);
[R]27 -18.9 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3) δ 4.29-
D
4.21 (m, 2 H), 4.14-4.09 (m, 1 H), 4.05-4.01 (m, 2 H), 3.50 (td,
1 H, J ) 7.2, 0.8 Hz), 2.20 (dd, 1 H, J ) 7.6 Hz), 1.84-1.79 (m,
1 H), 1.68-1.60 (m, 1 H), 1.50 (s, 3 H), 1.41-1.31 (m, 15 H),
0.92-0.89 (m, 3 H); 13C NMR (125 MHz, CDCl3) δ 109.4, 108.0,
77.8, 76.4, 76.3, 71.0, 67.3, 32.0, 30.0, 27.1, 27.0, 26.9, 25.5, 24.9,
22.8, 14.2; HRMS (FAB, M + H+) calcd for C16H31O5 303.2172,
found 303.2178.
Exp er im en ta l Section
(2R,3R,4R,5R)-3-Hyd r oxy-1,2;4,5-d i-O-isop r op ylid en e-6-
n on a d ecen e (4a ). To a mixture of C13H27 P+Ph3Br- (4.04 g,
7.68 mmol) in dried THF (40 mL) under Ar at 0 °C was added
7.8 mL of LHMDS (1.0 M THF solution). The reaction was
stirred at 0 °C for 90 min. The anion solution was then added
to a solution of 2,3;5,6-di-O-isopropylidene-D-mannofuranose in
dried THF (20 mL) with LHMDS (3.9 mL, 1.0 M THF solution)
under Ar at 0 °C and stirred at 0 °C for 90 min. The mixture
was further stirred at 0 °C for 2 h and then at room temperature
for 1 day. The mixture was quenched with MeOH, extracted with
EtOAc, dried with MgSO4, and concentrated. The residue was
purified by column chromatography with EtOAc/hexane (1:8) to
give 4a E and 4a Z as a mixture (1.61 g, 3.77 mmol, 98%), E/Z
(2R,3R,4R,5R)-3-O-Meth a n esu lfon yl-1,2;4,5-d i-O-isop r o-
p ylid en e-3-n on a d eca n ol (6a ). To a solution of compound 5a
(600 mg, 1.4 mmol) in anhydrous pyridine (13 mL) was added
MsCl (0.325 mL, 4.2 mmol) at 0 °C, and the solution was stirred
at 0 °C to room temperature overnight. The reaction mixture
was quenched with MeOH and extracted with EtOAc. After
drying with MgSO4, the solvent was concentrated and the
resulting residue was purified by column chromatography with
EtOAc/hexane (1:6) to give compound 6a (683 mg, 1.35 mmol,
96%). Rf 0.25 (1:6 EtOAc/hexane); [R]26 +9.6 (c 2.4, CHCl3); 1H
D
NMR (400 MHz, CDCl3) δ 4.80 (t, 1 H, J ) 6 Hz), 4.22-4.15 (m,
4 H), 4.09-4.03 (m, 1 H), 3.13 (s, 3 H), 1.68-1.27 (m, 36 H),
0.90 (t, 3 H, J ) 3.6 Hz); 13C NMR (125 MHz, CDCl3) δ 110.2,
108.8, 79.6, 77.6, 77.1, 75.0, 66.7, 39.8, 32.1, 29.9-22.9, 14.4;
HRMS (FAB, M + H+) calcd for C26H51O7S 507.3356, found
507.3365.
1/2. Rf 0.15 (1:8 EtOAc/hexane). For 4a E: [R]26 -19.7 (c 0.5,
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 5.89-5.82 (m, 1 H), 5.75-
5.70 (m, 1 H), 4.69 (t, 1 H, J ) 7.6 Hz), 4.33 (dd, 1 H, J ) 7.6,
0.8 Hz), 4.10 (m, 1 H), 4.02 (m, 2 H), 3.47 (m, 1 H), 2.22 (d, OH,
J ) 8 Hz), 2.06 (m, 2 H), 1.53 (s, 3 H), 1.41-1.27 (m, 29 H), 0.89
(t, 1 H, J ) 7.2 Hz); 13C NMR (125 MHz, CDCl3) δ 138.4, 125.3,
109.5, 108.5, 79.3, 76.8, 76.3, 70.9, 67.2, 32.6, 32.1, 29.9-22.9,
14.3; HRMS (FAB, M - H +) calcd for C25H45O5 425.3267, found
(2R,3R,4R,5R)-3-O-Meth a n esu lfon yl-1,2;4,5-d i-O-isop r o-
p ylid en e-3-d eca n ol (6b). The synthetic procedure was the
same as that described in the synthesis of 6a . Rf 0.13 (1:8 EtOAc/
hexane); [R]27D +20.8 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 4.79 (t, 1 H, J ) 6 Hz), 4.21-4.14 (m, 4 H), 4.07-4.05 (m, 1
H), 3.12 (s, 3 H), 1.70-1.50 (m, 4 H), 1.47 (s, 3 H), 1.43 (s, 3 H),
1.36-1.26 (m, 10 H), 0.90 (t, 3 H, J ) 6.8 Hz); 13C NMR (125
MHz, CDCl3) δ 110.2, 108.8, 79.6, 77.6, 77.1, 75.1, 66.8, 39.8,
31.8, 29.5, 27.7, 26.3, 26.2, 25.9, 25.4, 22.7, 14.2; HRMS (FAB,
M - H+) calcd for C17H31O7S 379.1790, found 379.1796.
(2R,3R,4R,5R)-3-O-Meth an esu lfon yl-1,2,3,4,5-n on adecan e-
p en tol (7a ). To a solution of compound 6a (390 mg, 0.77 mmol)
in MeOH (2.7 mL) was added HCl (0.39 mL, 4.12 mmol)
dropwise at 0 °C and the mixture was stirred at room temper-
ature overnight. The solvent was evaporated and the residue
was purified by column chromatography with MeOH/EtOAc/
hexane (1:10:10) to give compound 7a (300 mg, 0.70 mmol, 91%).
Rf 0.25 (1:10:10 MeOH/EtOAc/hexane); [R]28D +16.3 (c 0.5, CH3-
OH); 1H NMR (400 MHz, CD3OD) δ 5.00 (dd, 1 H, J ) 6, 1.2
Hz), 4.01-3.97 (m, 1 H), 3.82-3.78 (m, 1 H), 3.68-3.61 (m, 2
H), 3.57-3.52 (m, 1 H), 3.21-3.20 (m, 3 H), 1.86-1.81 (m, 1 H),
1.58-1.56 (m, 1 H), 1.39-1.29 (m, 24 H), 0.92-0.88 (m, 3 H);
13C NMR (125 MHz, CD3OD) δ 82.5, 74.4, 73.1, 71.3, 64.0, 38.8,
34.9, 33.2, 31.1-23.9, 14.6; HRMS (FAB, M + H+) calcd for
C20H43O7S 427.2730, found 427.2729.
425.3263. For 4a Z: [R]26 -56.4 (c 0.5, CHCl3); 1H NMR (400
D
MHz, CDCl3) δ 5.76-5.65 (m, 2 H), 5.09 (t, 1 H, J ) 7.6 Hz),
4.37 (d, 1 H, J ) 7.6 Hz), 4.12-3.99 (m, 3 H), 3.44 (t, 1 H, J )
8 Hz), 2.17 (d, OH, J ) 8 Hz), 2.13-2.02 (m, 2 H), 1.69-1.27
(m, 32 H), 0.90 (t, 1 H, J ) 6.8 Hz); 13C NMR (125 MHz, CDCl3)
δ 135.8, 125.5, 109.5, 108.5, 76.7, 76.2, 73.6, 70.9, 67.2, 32.1,
29.9-22.9, 14.3; HRMS (FAB, M - H+) calcd for C25H45O5
425.3267, found 425.3263.
(2R,3R,4R,5R)-3-Hyd r oxy-1,2;4,5-d i-O-isop r op ylid en e-6-
d ecen e (4b). The synthetic procedure was the same as that
described in the synthesis of 4a . Rf 0.38 (1:3 EtOAc/hexane). For
1
4bE: [R]27 -9.5 (c 2.5, CHCl3); H NMR (400 MHz, CDCl3) δ
D
5.88-5.81 (m, 1 H), 5.76-5.70 (m, 1 H), 4.69 (t, 1 H, J ) 7.6
Hz), 4.33 (dd, 1 H, J ) 7.6, 1.6 Hz), 4.12-4.05 (m, 1 H), 4.03-
3.99 (m, 2 H), 3.49-3.45 (m, 1 H), 3.22 (d, OH, J ) 8 Hz), 2.12-
2.05 (m, 2 H), 1.52 (s, 3 H), 1.48-1.42 (m, 2 H), 1.40-1.38 (m,
6 H), 1.37-1.35 (m, 3 H), 0.92 (t, 3 H, J ) 7.6 Hz); 13C NMR
(125 MHz, CDCl3) δ 137.8, 125.4, 109.2, 108.2, 79.1, 76.6, 76.1,
70.7, 67.0, 34.4, 26.8, 26.6, 25.3, 24.4, 22.1, 13.6; HRMS (FAB,
M - H +) calcd for C16H27O5 299.1859, found 299.1859. For
1
4bZ: [R]27 -137.1 (c 0.5, CHCl3); H NMR (400 MHz, CDCl3)
D
δ 5.77-5.67 (m, 2 H), 5.10 (t, 3 H, J ) 7.6 Hz), 4.38 (dd, 1 H, J
) 7.6,0.8 Hz), 4.12-4.07 (m, 1 H), 4.03-3.98 (m, 2 H), 3.44 (t, 1
H, J ) 8 Hz), 2.17 (dd, OH, J ) 8.4 Hz), 2.13-2.01 (m, 2 H),
1.53 (s, 3 H), 1.48-1.35 (m, 8 H), 1.35 (s, 3 H), 0.92 (t, 3 H, J )
7.2 Hz);13C NMR (125 MHz, CDCl3) δ 135.2, 125.6, 109.2, 108.3,
(2R,3R,4R,5R)-3-O-Meth a n esu lfon yl-1,2,3,4,5-d eca n ep en -
tol (7b). The synthetic procedure was the same as that described
in the synthesis of 7a . Rf 0.12 (1:10:10 MeOH/EtOAc/hexane);
[R]28D +25.3 (c 0.5, CH3OH); 1H NMR (400 MHz, CD3OD) δ 5.00
(dd, 1 H, J ) 6, 1.6 Hz), 4.01-3.97 (m, 1 H), 3.82-3.78 (m, 1 H),
5790 J . Org. Chem., Vol. 68, No. 14, 2003

3.68-3.61 (m, 2 H), 3.57-3.52 (m, 1 H), 3.20 (s, 3 H), 1.86-1.81
(m, 1 H), 1.60-1.56 (br, 1 H), 1.43-1.34 (br, 6 H), 0.92 (t, 3 H,
J ) 6.8 Hz); 13C NMR (125 MHz, CD3OD) δ 82.6, 74.4, 73.1,
71.3, 64.1, 38.9, 34.9, 33.3, 26.2, 23.9, 14.6; HRMS (FAB, M +
H+) calcd for C11H25O7S 301.1321, found 301.1316.
synthesis of 9a . Rf 0.15 (1:1 EtOAc/CH2Cl2); [R]24 +11.8 (c 1.0,
D
CHCl3); 1H NMR (400 MHz, CD3OD) δ 4.93 (td, 1 H, J ) 5.6, 2
Hz), 3.89-3.79 (m, 2 H), 3.58-3.48 (m, 2 H), 3.17 (s, 3 H), 1.83-
1.78 (m, 1 H), 1.59-1.55 (br, 1 H), 1.44-1.28 (br, 6 H), 0.94-
0.91 (m, 3 H); 13C NMR (125 MHz, CD3OD) δ 84.0, 74.1, 71.4,
62.7, 38.8, 34.7, 33.2, 26.2, 23.8, 14.5; HRMS (FAB, M + H+)
calcd for C10H23O6S 271.1215, found 271.1216.
2-O-Met h a n esu lfon yl-5-C-t r id ecyl-5-d eoxy-D-r ib ofu r a -
n ose (8a ). To a solution of compound 7a (100 mg, 0.23 mmol)
in THF (2.3 mL) was added a solution of NaIO4 (50 mg, 0.23
mmol) in H2O (2.3 mL) at 0 °C and the mixture was stirred at
0 °C for 1 day. The solvent was evaporated and the resulting
residue was purified by column chromatography with EtOAc/
CH2Cl2 (1:3) to give compound 8a as anomeric mixture (83 mg,
0.21 mmol, 90%), R/â ) 1/2. Rf 0.25 (1:3 EtOAc/CH2Cl2); For the
R isomer: 1H NMR (400 MHz, CD3OD) δ 5.49 (s, 1 H), 4.70-
4.68 (m, 1 H), 4.11-4.08 (m, 1 H), 3.66-3.60 (m, 1 H), 1.72-
1.22 (m, 26 H), 0.90 (t, 3 H, J ) 6.8 Hz); 13C NMR (125 MHz,
CD3OD) δ 95.1, 85.7, 81.8, 77.6, 38.8, 36.5, 34.3-23.9, 14.6;
HRMS (FAB, M+ - OH) calcd for C19H37O5S 377.2362, found
377.2354. For the â isomer: 1H NMR (400 MHz, CD3OD) δ 5.30
(m, 1 H), 4.72 (dd, 1 H, J ) 4.4, 2 Hz), 3.97 (td, 1 H, J ) 7.6, 4.4
Hz), 3.86-3.83 (m, 1 H), 1.72-1.22 (m, 26 H), 0.90 (t, 3 H, J )
6.8 Hz); 13C NMR (125 MHz, CD3OD) δ 100.5, 92.6, 82.8, 80.7,
38.6, 34.3-23.9, 14.6; HRMS (FAB, M+ - OH) calcd for
C19H37O5S 377.2362, found 377.2354.
(2S,3S,4R)-2-Azid o-1,3,4-oct a d eca n et r iol (10a ).8c Com-
pound 9a (60 mg, 0.15 mmol) was stirred with tetrameth-
ylguanidinium azide (120 mg, 0.76 mmol) in dried DMF (0.5 mL)
at 50 °C for 2 days. The solution was concentrated and the
residue was purified by column chromatography with EtOAc/
hexane (1:1) to give compound 10a (43 mg, 0.13 mmol, 84%). Rf
0.38 (1:10:10 MeOH/EtOAc/hexane); [R]26D +3.0° (c 1.0, CHCl3);
1H NMR (400 MHz, CD3OD) δ 3.92 (dd, 1 H, J ) 11.6, 3.2 Hz),
3.78-3.73 (m, 1 H), 3.62-3.52 (m, 3 H), 1.68-1.65 (br, 1 H),
1.54-1.41 (br, 1 H), 1.38-1.24 (m, 24 H), 0.90 (t, 3 H, J ) 7.2);
13C NMR (125 MHz, CD3OD) δ 76.1, 73.0, 66.9, 62.6, 34.0, 33.2,
30.9-23.9, 14.6; HRMS (FAB, M + H+) calcd for C18H38O3N3
344.2913, found 344.2910.
(2S,3S,4R)-2-Azid o-1,3,4-n on a n etr iol (10b). The synthetic
procedure was the same as that described in the synthesis of
10a . Rf 0.35 (1:10:10 MeOH/EtOAc/hexane); [R]27 +3.7 (c 1.0,
D
1
CHCl3); H NMR (400 MHz, CD3OD) δ 3.92 (dd, 1 H, J ) 11.6,
3-O-Me t h a n e su lfon yl-5-C-b u t yl-5-d e oxy-D-r ib ofu r a -
n ose (8b). The synthetic procedure was the same as that
described in the synthesis of 8a . Rf 0.20 (1:3 EtOAc/CH2Cl2). For
the R isomer: 1H NMR (400 MHz, CD3OD) δ 5.30 (m, 1 H), 4.70-
4.68 (m, 1 H), 4.10 (t, 1 H, J ) 7.2 Hz), 3.66-3.61 (m, 1 H), 3.16
(s, 3 H), 1.72-1.28 (br, 8 H), 0.92 (m, 3 H); 13C NMR (125 MHz,
CD3OD) δ 95.1, 85.7, 81.7, 77.6, 38.8, 36.4, 33.0, 26.5, 23.7, 14.5;
HRMS (FAB, M + Na+) calcd for C10H20O6SNa 291.0878, found
291.0885. For the â isomer: 1H NMR (400 MHz, CD3OD) δ 5.30
(s, 1 H), 4.73-4.71 (m, 1 H), 4.00-3.95 (td, 1 H, J ) 7.6, 4.4
Hz), 3.85 (dd, 1 H, J ) 7.2, 4 Hz), 3.16 (s, 3 H), 1.72-1.28 (br,
8 H), 0.92 (m, 3 H); 13C NMR (125 MHz, CDCl3) δ 100.5, 92.5,
82.8, 80.6, 38.6, 34.2, 33.0, 26.6, 23.7, 14.5; HRMS (FAB, M +
Na+) calcd for C10H20O6SNa 291.0878, found 291.0885.
(2R ,3R ,4R )-2-O-Me t h a n e su lfon yl-1,2,3,4-oct a d e ca n e -
tetr ol (9a ).8c To a solution of compound 8a (85 mg, 0.22 mmol)
in dried MeOH (3 mL) was added NaBH4 (4 mg, 0.11 mmol) at
0 °C and the mixture was stirred at room temperature for 1.5
h. The reaction mixture was quenched with 10% aqueous
hydrochloric acid, and the resulting solution was extracted with
EtOAc. The organic layer was dried over MgSO4 and evaporated
in vacuo to give compound 9a (88 mg, 0.22 mmol, quantitative).
Rf 0.15 (1:1 EtOAc/CH2Cl2); [R]24D +13.0 (c 1.0, CHCl3); 1H NMR
(400 MHz, CD3OD) δ 4.93 (td, 1 H, J ) 6.4, 2 Hz), 3.89-3.79
(m, 2 H), 3.58-3.48 (m, 2 H), 3.18-3.17 (m, 3 H), 1.83-1.78 (br,
1 H), 1.57-1.55 (br, 1 H), 1.44-1.22 (m, 24 H), 0.90 (t, 3 H, J )
7.2 Hz); 13C NMR (125 MHz, CD3OD) δ 83.9, 74.2, 71.4, 62.7,
38.7, 34.8, 33.2, 31.1-23.9, 14.5; HRMS (FAB, M + H+) calcd
for C19H41O6S 397.2624, found 397.2624.
3.6 Hz), 3.79-3.74 (m, 1 H), 3.61-3.53 (m, 3 H), 1.72-1.48 (br,
2 H), 1.46-1.20 (br, 6 H), 0.93 (t, 3 H, J ) 6.8 Hz); 13C NMR
(125 MHz, CD3OD) δ 76.2, 73.1, 66.8, 62.7, 34.0, 33.2, 26.5, 23.8,
14.5; HRMS (FAB, M + H+) calcd for C9H20N3O3 218.1505, found
218.1508.
(2S,3S,4R)-2-Am in o-1,3,4-octa d eca n etr iol (D-r ibo-P h yto-
sp h in gosin e) (1).8e Compound 10a (20 mg, 0.058 mmol) and
10% Pd/C (20 mg) in dried MeOH (1 mL) was stirred under a
H2 atmosphere at room temperature for 2 days. The mixture
was filtered and concentrated and the resulting residue was
evaporated in vacuo to give compound 1 (17 mg, 0.054 mmol,
94%). Rf 0.30 (1:10:10 MeOH/EtOAc/hexane); [R]24 +7.9 (c 1.0,
D
C5H5N); 1H NMR (400 MHz, pridine-d5/D2O) δ 4.32 (br, 1 H),
4.22 (dd, 1 H, J ) 9.3, 6.1 Hz), 4.19 (m, 1 H), 3.97 (t, 1 H, J )
7.1 Hz), 3.52 (br, 1 H), 2.16-2.30 (m, 1 H), 1.78-1.95 (m, 2 H),
1.66 (m, 1 H), 1.37 (m, 1 H), 1.21 (br, 21 H), 0.83 (t, 3 H, J ) 6.7
Hz).
Ack n ow led gm en t. We thank the Academia Sinica
and National Science Council in Taiwan (NSC 91-2113-
M-001-013 and 90-2133-M-001-029) for their financial
supports.
Su p p or tin g In for m a tion Ava ila ble: General consider-
1
ations of the Experimental Section and H and 13C spectra of
compounds 4∼10. This material is available free of charge via
the Internet at http://pubs.acs.org.
(2R,3R,4R)-2-O-Meth an esu lfon yl-1,2,3,4-n on an etetr ol (9b).
The synthetic procedure was the same as that described in the
J O034224M
J . Org. Chem, Vol. 68, No. 14, 2003 5791