Z. Liu et al. / Tetrahedron: Asymmetry 27 (2016) 872–881
879
(115 mg, 3.04 mmol) was added. The reaction mixture was stirred
at room temperature for 2 h when mass spectrometry showed the
completion of reaction ([M+Na]+ 271). The solvent was concen-
trated in vacuo to obtain a polar residue (320 mg). Purification
with a short column of DOWEXÒ 50WX8-200 or flash column chro-
matography was not successful. The crude diol 35 was used for the
following steps without further purification.
5.12.
ribitol 20
3-Acetamido-N-benzyl-2,4-imino-2,3,4-trideoxy-meso-
Sodium methoxide (3.2 mg, 0.06 mmol) was added to a solution
of 37 (200 mg, 0.57 mmol) in methanol (5 mL). The mixture was
stirred at 60 °C for 16 h until mass spectrometry indicated the for-
mation of product ([M+H]+ 265). After removal of the solvent in
vacuo, the residue was dissolved in ethanol (5 mL) and passed
through a glass microfiber filter paper and then loaded with water
(ꢂ1 mL) onto a short column of DOWEXÒ 50WX8-200 (pre-washed
with water, 1,4-dioxane and water sequentially until the eluent
was neutral). The ion exchange column was then washed with
water, 1,4-dioxane and then water; the pure product was then
eluted with aqueous ammonia (2 M). Removal of solvent in vacuo
gave the meso-diol 20 (120 mg, 79%) as a light yellow glass.
HRMS m/z (ESI+ve): found 265.1559 [M+H]+; C14H21N2O3+
5.10.
3-Azido-N-benzyl-1,5-di-O-acetyl-2,4-imino-2,3,4-
trideoxy-meso-ribitol 36
A solution of the diol 35 (320 mg) in acetic anhydride/pyr-
idine (1:1, 4 mL) was stirred at room temperature for 16 h
when TLC (cyclohexane/ethyl acetate, 1:1) indicated the forma-
tion of the only product (Rf 0.72). The mixture was concen-
trated in vacuo and the residue purified by flash column
chromatography
(cyclohexane/ethyl
acetate/triethylamine,
requires 265.1547; [
a]
20 = 0 (c 1.2, MeOH); mmax (thin film): 1633
D
6:1:0.01) to obtain the diacetate 36 (191 mg, 76% 3 steps from
18) as a light yellow oil.
(s, NHCO); dH (CD3OD, 400 MHz): 1.92 (3H, s, NHCOCH3), 3.08
0
0
(2H, br dt, H2, H4, J2(4),1 (5 ) = J2(4),1(5) 4.7, J2(4),3 6.9), 3.33 (2H, dd,
HRMS m/z (ESI+ve): found 355.1372 [M+Na]+; C16H20N4NaO4+
H1, H5, J1(5),
4.1, Jgem 11.7), 3.37 (2H, dd, H10, H50, J1 (5 ),
2(4)
0
0
2(4)
requires 355.1377; [
a]
20 = 0 (c 0.81, CHCl3); mmax (thin film):
5.0, Jgem 11.7), 3.77 (2H, s, CH2Ph), 3.89 (1H, t, H3, J3,2 = J3,4 6.9),
7.28–7.37 (5H, m, Ar); dC (CD3OD,100 MHz): 21.0 (NHCOCH3),
46.0 (C3), 61.3 (CH2Ph), 65.4 (C1, C5), 70.5 (C2, C4), 127.5, 128.4,
129.3, 137.2 (Ar), 169.7 (C@O),; m/z (ESI+ve): 265 ([M+H]+, 100%).
D
2104 (s, N3), 1742 (s, C@O); dH (CDCl3, 400 MHz): 2.03 (6H, s,
2 ꢁ CH3), 3.20 (2H, m, H2, H4), 3.67 (1H, t, H3, J3,2 = J3,4 6.1), 3.71
(2H, br s, CH2Ph), 3.82 (2H, dd, H1, H5, J1(5),2(4) 4.29, Jgem 11.4),
4.03 (2H, dd, H10, H50), J1 (5 ),2 (4 ) 4.29, Jgem 11.4), 7.25–7.34 (5H,
m, Ar); dC (CDCl3, 100 MHz): 20.8 (2 ꢁ CH3), 56.7 (C1, C5), 61.0
(CH2Ph), 64.4 (C3), 67.2 (C2, C4), 128.5, 129.2, 136.6 (Ar), 170.7
(2 ꢁ C@O); m/z (ESI+ve): 355 ([M+Na]+, 100%).
0
0
0
0
5.13. 3-Acetamido-2,4-imino-2,3,4-trideoxy-meso-ribitol 21
10% Palladium on charcoal (10% wt., 5 mg) was added to a solu-
tion of 20 (40 mg, 0.15 mmol) in 1,4-dioxane/water (1:1, 2 mL).
The reaction mixture was flushed with argon and hydrogen., stir-
red for 20 h when mass spectrometry showed the completion of
the reaction, filtered and concentrated in vacuo to give a residue
that was purified with a short column of DOWEXÒ 50WX8-200
(as illustrated above) to yield diol 21 (19 mg, 73%) as a light yellow
glass.
5.11.
3-Acetamido-N-benzyl-1,5-di-O-acetyl-2,4-imino-2,3,4-
trideoxy-meso-ribitol 37
5.11.1. Method 1 (reductive acetylation of 35)
Zinc powder (494 mg, 7.6 mmol) and copper sulfate (sat, aq,
0.95 mL) were added to a solution of crude diol 35 (from 18
(100 mg, 0.38 mmol)) in THF/acetic acid/acetic anhydride
(3:2:1, 6 mL). The mixture was stirred at room temperature
for 1 h until mass spectrometry showed the formation of
desired product ([M+Na]+ 371). Then the mixture was filtered
with Celite and the solvent was removed in vacuo to give a
residue that was purified by flash column chromatography
(ethyl acetate/methanol/triethylamine, 10:1:0.01) to give the
protected amide compound 37 (31 mg, 24%, 3 steps from 18)
as a light yellow solid.
HRMS m/z (ESI+ve): found 175.1074 [M+H]+; C7H15N2O3+
requires 175.1075; [a]
20 = 0 (c 1.0, H2O); mmax (thin film): 3283
D
(br, OH, NH); dH (D2O, 400 MHz): 1.98 (3H, s, NHCOCH3), 3.61
(2H, dd, H1 and H5, J1(5), 2(4) 6.4, Jgem 11.7), 3.65 (2H, dd, H10 and
H50, J1 (5 ), 2(4) 4.9, Jgem 11.7), 3.74 (2H, m, H2 and H4), 4.00 (1H, t,
H3, J3,2 = J3,4 7.3); dC (D2O,100 MHz): 22.3 (NHCOCH3), 48.3 (C3),
62.2 (C1, C5), 64.1 (C2, C4), 174.2 (C@O); m/z (ESI+ve): 175 ([M
+H]+, 100%).
0
0
5.14. Methyl 3-azido-N-benzyl-5-O-(tert-butyldimethylsilyl)-
5.11.2. Method 2 (reductive acetylation of 36)
2,4-imino-2,3,4-trideoxy-L-ribonate 38
Zinc powder (743 mg, 11.4 mmol) and copper sulfate (sat, aq,
1.42 mL) were added to a solution of the diacetate 36 (190 mg,
0.57 mmol) in THF/acetic acid/acetic anhydride (3:2:1, 6 mL).
The reaction mixture was stirred at room temperature for 1 hour
until mass spectrometry showed the formation of desired product
([M+Na]+ 371). Then the mixture was filtered with celite and sol-
vent was removed in vacuo to give the title compound 37
tert-Butyldimethylsilyl chloride (90 mg, 0.60 mmol) and imida-
zole (56 mg, 0.72 mmol) was added to a solution of methyl ester 19
(138 mg, 0.50 mmol) in DMF (3 mL) and the reaction mixture was
stirred at room temperature for 2 h when TLC analysis (cyclohex-
ane/ethyl acetate, 1:1) indicated the disappearance of starting
material (Rf 0.50) and the formation of a major product (Rf 0.80).
The reaction mixture was diluted with ethyl acetate (10 mL) and
washed with 1:1 water/brine (satd, aq, 2 ꢁ 10 mL). The organic
layer was dried (MgSO4), filtered and the solvent removed in vacuo
to yield the silyl ether 38 as a brown oil (188 mg, 96%).
(202 mg, 100%) as
purification.
a
light yellow solid without further
HRMS m/z (ESI+ve): found 371.1576 [M+Na]+; C18H24N2NaO5+
requires 371.1577; [a]
20 = 0 (c 1.0, CHCl3); mmax (thin film): 1741
D
(s, COCH3), 1658 (s, NHCO); dH (CDCl3, 400 MHz): 1.94 (3H, s,
NHCOCH3), 1.98 (6H, s, 2 ꢁ OCOCH3), 3.15 (2H, ddd, H2 and H4,
HRMS (ESI+ve): found 413.1978 [M+Na+]; C19H30N4NaO3Si+
requires 413.1979; [a]
20 = +55 (c 0.36, CHCl3); mmax 2105 (s, N3),
D
0
0
J2(4),1 (5 ) 4.29, J2(4),1(5) 5.6, J2(4),3 7.1), 3.73 (2H, s, CH2Ph), 3.90 (2H,
1747 (s, C@O); dH (CDCl3, 400 MHz): 0.00 (6H, s, 2 ꢁ CH3), 0.86
dd, H1 and H5, J1(5), 2(4) 5.6, Jgem 11.9), 4.12 (2H, dd, H10 and H50,
(9H, s, C(CH3)3), 3.13 (2H, ddd, H4, J4,5 5.1, J4,3 6.6, J4,5 6.9), 3.36
0
J1 (5 ),
4.3, Jgem 11.9), 5.89 (1H, br s, NH), 7.25–7.33 (5H, m,
(1H, dd, H5, J5,4 5.1, Jgem 10.5), 3.41 (1H, dd, H50, J5 ,4 6.9, Jgem
0
0
0
2(4)
Ar); dC (CDCl3,100 MHz): 20.8 (2 ꢁ OCOCH3), 23.1 (NHCOCH3),
45.9 (C3), 60.8 (CH2Ph), 65.4 (C1, C5), 67.6 (C2, C4), 127.5, 128.4,
129.3, 137.2 (Ar), 169.7 (NHCO), 170.9 (2 ꢁ OCO); m/z (ESI+ve):
349 ([M+H]+, 100%).
10.5), 3.47 (1H, d, H2, J2,3 6.6), 3.7 (3H, s, OCH3), 3.71 (1H, d, CH2-
Ph, Jgem 12.5), 3.90 (1H, t, H3, J3,2 = J3,4 6.6), 3.92 (1H, d, CH2Ph, Jgem
12.5); dC (CDCl3, 100 MHz): ꢀ5.46 (2 ꢁ CH3), 18.3 (3 ꢁ CH3), 25.8
(OCH3), 52.1 (C3), 56.9 (CH2Ph), 61.0 (C5), 64.5 (C2), 69.0 (C4),