CDCl3) δ 1.25, 1.43 (2s, 2 × 3H), 2.41 (s, 3H), 3.95 (d, 1H, J )
3.3 Hz), 4.18 (dd, 1H, J ) 6.1, 9.9 Hz), 4.30 (dd, 1H, J ) 6.1, 9.9
Hz), 4.35 (dt, 1H, J ) 3.3, 6.1 Hz), 4.45 (d, 1H, J ) 11.8 Hz),
4.56 (d, 1H, J ) 3.7 Hz), 4.60 (d, 1H, J ) 11.8 Hz), 5.85 (d, 1H,
J ) 3.7 Hz), 7.23-7.25 (m, 2H), 7.28-7.35 (m, 5H), 7.76-7.78
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 21.4, 26.1, 26.6, 66.9,
71.8, 77.4, 81.0, 81.8, 105.0, 111.9, 127.5, 127.8, 127.9, 128.3,
129.7, 132.5, 136.9, 144.8. Anal. Calcd for C22H26O7S: C, 60.81;
H, 6.03. Found: C, 61.09; H, 5.97.
2,5-Anhydro-3-O-benzyl-r-D-xylose Diethyl Acetal (12). Com-
pound 11 (217 mg, 0.5 mmol) was dissolved in anhydrous ethanol
(10 mL) containing concentrated hydrochloric acid (0.5 mL). The
mixture was stirred under reflux for 3 h and then neutralized with
saturated aqueous sodium carbonate. The aqueous layer was
extracted with EtOAc (3 × 20 mL), and the combined organic phase
was washed with brine, dried over Na2SO4, and concentrated under
vacuum. Purification of the residue by silica gel column chroma-
tography (1:1 petroleum ether-EtOAc) gave 12 as a syrup (131
mg, 89%): [R]25D + 77 (c 0.7, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 1.18 (t, 3H, J ) 7.0 Hz), 1.24 (t, 3H, J ) 7.0 Hz), 1.67 (br s,
1H), 3.50-3.55 (m, 1H), 3.67-3.80 (m, 4H), 3.94 (d, 1H, J ) 3.6
Hz), 4.12 (dd, 1H, J ) 3.7, 7.7 Hz), 4.20 (dd, 1H, J ) 4.0, 9.9
Hz), 4.33 (br d, 1H, J ) 3.9 Hz), 4.60, 4.62 (2d, 2H, J ) 11.8 Hz),
4.76 (d, 1H, J ) 7.7 Hz), 7.26-7.37 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ 15.2, 15.3, 61.5, 63.0, 72.2, 74.2, 74.4, 79.7, 84.2, 100.5,
127.4, 127.6, 128.3, 137.9. Anal. Calcd for C16H24O5: C, 64.84;
H, 8.16. Found: C, 65.09; H, 8.11.
2,5-Anhydro-3-O-benzyl-4-O-methanesulfonyl-r-D-xylose Di-
ethyl Acetal (13). To a solution of 12 (70 mg, 0.24 mmol) in
pyridine (2 mL) was added methanesulfonyl chloride (37 µL, 0.48
mmol). The mixture was stirred at room temperature for 4 h and
then coevaporated with toluene. The crude mesylate 13 was directly
used in the next step without further purification. A small sample
was purified on a silica gel column to get the physical data of 13:
[R]25D + 80 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.16 (t,
3H, J ) 7.0 Hz), 1.25 (t, 3H, J ) 7.0 Hz), 2.97 (s, 3H), 3.46-3.52
(m, 1H), 3.67-3.79 (m, 3H), 3.98 (d, 1H, J ) 11.0 Hz), 4.05 (dd,
1H, J ) 3.7, 7.6 Hz), 4.25 (d, 1H, J ) 3.6 Hz), 4.30 (dd, 1H, J )
4.4, 11.0 Hz), 4.62, 4.68 (d, 2H, J ) 11.8 Hz), 4.75 (d, 1H, J )
7.6 Hz), 5.12 (d, 1H, J ) 4.3 Hz), 7.31-7.38 (m, 5H); 13C NMR
(100 MHz, CDCl3) δ 15.1, 15.2, 38.3, 61.5, 63.0, 71.4, 72.5, 79.9,
81.1, 81.8, 100.0, 127.7, 127.9, 128.3, 137.1. Anal. Calcd for
C17H26O7S: C, 54.53; H, 7.00. Found: C, 54.76; H, 6.91.
2,5-Anhydro-4-azido-3-O-benzyl-4-deoxy-r-L-arabinose Di-
ethyl Acetal (14). To a solution of crude mesylate 13 (88 mg, 0.23
mmol) in dry DMF (3 mL) were added NaN3 (91 mg, 1.41 mmol)
and anhydrous NH4Cl (23 mg, 0.44 mmol). The mixture was heated
to 120 °C and stirred at these conditions for about 20 h in a dark
room. The reaction was monitored by TLC (3:1 petroleum ether-
EtOAc) until all starting material disappeared, and then the mixture
was diluted with water and extracted with EtOAc (4 × 10 mL).
The organic phase was dried over anhydrous Na2SO4 and concen-
trated. Purification of the residue by silica gel column chromatog-
mL), and aqueous 50% trifluroacetic acid (1 mL) was added. The
reaction progress was monitored by TLC (2:1 petroleum ether-
EtOAc) until all 14 was consumed, the mixture was neutralized
with saturated aqueous sodium carbonate and further extracted with
CH2Cl2 (3 × 20 mL), and the combined organic layer was washed
with brine, dried over Na2SO4, and concentrated to dryness.
Purification of the residue by silica gel column chromatography
(2:1 petroleum ether-EtOAc) gave aldehyde 15 (215 mg, 90%) as
a syrup: [R]25D + 25 (c 0.2, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 3.99-4.08 (m, 3H), 4.30 (dd, 1H, J ) 2.5, 7.1 Hz), 4.50 (dd,
1H, J ) 4.5, 7.1 Hz), 4.66, 4.70 (2d, 2H, J ) 11.6 Hz), 7.31-7.39
(m, 5 H), 9.66 (br d, 1H, J ) 4.5 Hz); 13C NMR (100 MHz, CDCl3)
δ 60.9, 70.4, 73.6, 81.4, 82.3, 127.9, 128.2, 128.5, 136.5, 200.4;
HRFABMS calcd for C12H13N3O3 247.0957; found 248.0931 (M
+ H)+. Anal. Calcd for C12H13N3O3: C, 58.29; H, 5.30. Found:
C, 58.51; H, 5.23.
Synthesis of Olefin 16. To a precooled (- 40 °C) solution of
Wittig salt C13H27Ph3P+Br- (61 mg, 0.11 mmol) in THF (1.5 mL)
was slowly added n-BuLi (2.5 M in hexane, 50 µL, 0.12 mmol)
under N2 protection. The orange solution was stirred at these
conditions for about 20 min, at the end of which time, a solution
of 15 (25 mg, 0.1 mmol) in dry THF (3 mL) was dropwise added
under N2 protection. The mixture was stirred at this temperature
for another 30 min, then allowed to warm to room temperature
and quenched by saturated NH4Cl (0.2 mL). The mixture was
diluted with water and extracted with EtOAc (3 × 20 mL). The
combined organic phase was dried over anhydrous Na2SO4 and
concentrated to dryness. Purification of the residue by silica gel
column chromatography (9:1 petroleum ether-EtOAc) gave 16 (36
mg, 86%, Z/E > 10:1) as a syrup. Selected Z-isomer: 1H NMR
(400 MHz, CDCl3) δ 0.88 (t, 3H, J ) 7.1 Hz), 1.20 (br s, 20H),
2.07-2.09 (m, 2H), 3.88-3.97 (m, 3H), 4.11 (t, 1H, J ) 5.0 Hz),
4.62, 4.70 (2d, 2H, J ) 11.8 Hz), 4.71-4.72 (m, 1H), 5.65-5.73
(m, 2H, J ) 11.0 Hz), 7.29-7.37 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ 14.0, 22.6, 27.7, 29.2, 29.3, 29.4, 29.5, 29.6, 31.8, 61.5,
68.6, 73.3, 75.8, 80.4, 124.9, 127.7, 127.8, 128.3, 135.0, 137.4;
HRFABMS calcd for C25H39N3O2 413.3042, found 414.3068 (M
+ H)+. Anal. Calcd for C25H39N3O2: C, 72.60; H, 9.50. Found:
C, 72.35; H, 9.42.
Synthesis of Pachastrissamine (Jaspine B) 1. A mixture of
olefin 16 (42 mg, 0.1 mmol) and Pd(OH)2/C (10% content, 10 mg)
in MeOH/EtOAc (1:1 v/v, 6 mL) was bubbled into H2 at a flow
rate of 100 mL/min at room temperature and 1 atm pressure. The
hydrogenation was kept at these conditions for about 5 h, at the
end of which time TLC (4:1 EtOAc/methanol) showed only one
product generated. The Pd(OH)2/C was filtered, and the filtrate was
concentrated. The residue was purified on a short silica gel column,
which was pre-eluted with methanol containing 2% Et3N (v/v) using
4:1 EtOAc/methanol as eluent to furnish target compound 1 (28
1
mg, 92%) as a white solid: [R]25 +7 (c 0.2, CHCl3); H NMR
D
(400 MHz, CD3OD) δ 0.89 (t, 3H, J ) 7.0 Hz), 1.26-1.45 (m,
24H), 1.60-1.65 (m, 2H), 3.70 (dt, 1H, J ) 3.5, 6.8 Hz), 3.79 (dd,
1H, J ) 4.8, 7.9 Hz), 3.82-3.93 (m, 2H), 4.23 (dd, 1H, J ) 3.5,
4.8 Hz); 13C NMR (100 MHz, CD3OD) δ 14.5, 23.7, 27.2, 29.7,
30.5, 30.7, 30.8, 30.9, 33.1, 54.3, 68.9, 70.9, 84.4. HRFABMS calcd
for C18H37NO2 299.2824, found 300.2856 (M + H)+.
raphy (3:1 petroleum ether-EtOAc) gave 14 (54 mg, 71% for two
1
steps) as a syrup: [R]25 + 106 (c 1.3, CHCl3); H NMR (400
D
MHz, CDCl3) δ 1.18 (t, 3H, J ) 7.0 Hz), 1.24 (t, 3H, J ) 7.0 Hz),
3.41-3.45 (m, 1H), 3.66-3.77 (m, 3H), 3.83 (dd, 1H, J ) 4.5, 7.8
Hz), 3.90 (dd, 1H, J ) 4.0, 7.7 Hz), 3.98 (dd, 1H, J ) 7.7, 8.5
Hz), 4.04 (dd, 1H, J ) 4.3, 8.5 Hz), 4.19 (t, 1H, J ) 4.3 Hz), 4.66
(d, 1H, J ) 11.2 Hz), 4.76 (d, 1H, J ) 7.7 Hz), 4.82 (d, 1H, J )
11.2 Hz), 7.31-7.41 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 15.2,
15.3, 61.4, 62.0, 62.8, 68.4, 74.2, 79.7, 80.7, 100.4, 127.6, 127.7,
128.2, 137.6. HRFABMS calcd for C16H23N3O4 321.1689, found
322.1660 (M + H)+. Anal. Calcd for C16H23N3O4: C, 59.80; H,
7.21. Found: C, 59.57; H, 7.29.
Acknowledgment. This work was supported by National
Basic Research Program of China (2003CB415001), NNSF of
China (30330690), and NIH of the US (HL62244).
Supporting Information Available: Detailed experimental
procedures and spectral data for compounds 1, 7-9, and 11-16.
This material is available free of charge via the Internet at
2,5-Anhydro-4-azido-3-O-benzyl-4-deoxy-r-L-arabinose (15).
The acetal 14 (310 mg, 0.96 mmol) was dissolved in CH2Cl2 (3
JO051644Y
J. Org. Chem, Vol. 71, No. 3, 2006 1253