10.1002/chem.201903732
Chemistry - A European Journal
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6.3, 11.8 Hz), 3.55 (dd, 1H, J = 11.8, 3.8 Hz), 3.78–3.83 (m, 1H), 3.95–
4.00 (m, 1H); 13C NMR (D2O with 1,4-dioxane, 150 MHz): δ 37.6, 44.9,
65.6, 66.0, 69.4. ES-MS: m/z 136 [M + H]+.
anhydrous MgSO4, and then filtered. The filtrate was concentrated in
vacuo to give
a yellow oil, which was purified by flash column
chromatography (silica gel, ethyl acetate/petroleum spirit 1:9, basified with
triethylamine) to give the corresponding 4-O-xanthate as a pale yellow oil
(30, 0.14 g, 0.22 mmol, 63 %) as a mixture of two rotamers in a ratio of 3:1.
1H NMR (CDCl3, 600 MHz): characteristic signals for major rotamer, δ 2.60
(s, 3H, SCH3), 5.94–5.97 (m, 1H, H-4), 8.16 (s, 1H, HCON); characteristic
signals for minor rotamer, δ 2.54 (s, 3H, SCH3), 6.04–6.07 (m, 1H, H-4),
8.17 (s, 1H, HCON); 13C NMR (CDCl3, 150 MHz): characteristic signals for
major rotamer, δ 19.5 (CH3, SCH3), 46.2 (CH2) and 47.8 (CH2, C-1 & C-5),
67.5 (CH2, PhCH2), 72.5 (CH2, PhCH2), 73.4 (CH2, PhCH2), 74.1 (CH2,
PhCH2) 75.9 (CH), 76.6 (CH), 80.5 (CH,), 164.0 (CH, HCON), 215.5 (C,
C=S); characteristic signals for minor rotamer, δ 19.3 (CH3, SCH3), 43.1
(CH2) and 52.4 (CH2, C-1 & C-5), 67.6 (CH2, PhCH2), 72.7 (CH2, PhCH2),
73.2 (CH2, PhCH2) and 73.8 (CH2, PhCH2), 77.8 (CH), 81.2 (CH), 163.3
(CH, HCON).
Synthesis of 4-deoxy-D-ribitylamine (1-Amino-1,4-dideoxy-D-ribitol, 32)
2,3,5-tri-O-benzyl-1-(N-benzyl-N-formyl)amino-1-deoxy-D-ribitol (29). Step
1. To a solution of 2,3,5-tri-O-benzyl-D-ribofuranoside[29] (27, 2.91 g, 6.92
mmol) in anhydrous methanol (17 mL) was added benzylamine (0.79 mL,
7.25 mmol) and 4Å molecular sieves (2.5 g, freshly activated). The mixture
was stirred overnight at room temperature, and then filtered through a
celite pad. After adding Adam’s catalyst (PtO2, 0.15 g, 5 wt%) to the filtrate,
the mixture was stirred at room temperature overnight under a hydrogen
atmosphere (1 atm). Filtration through a celite pad and then concentration
in vacuo gave 2,3,5-tri-O-benzyl-1-benzylamino-1-deoxy-D-ribitol (28) as a
yellow oil (3.06 g, 5.98 mmol, 87%), which was used in the next step
without further purification. 1H NMR (CDCl3, 600 MHz): δ 2.72 (dd, 1H, J =
3.3, 12.4 Hz). 3.00 (dd, 1H, J = 6.1, 12.4 Hz), 3.63–3.69 (m, 3H), 3.72–
3.76 (m, 2H), 3.88 (quint, J = 2.9 Hz, 1H), 3.98–4.01 (m, 1H), 4.52-4.64
(m, 8H), 7.23–7.32 (m, 20H). 13C NMR (CDCl3, 150 MHz): δ 48.4 (CH2),
53.7 (CH2), 69.0 (CH), 71.6 (CH2), 72.2 (CH2), 73.2 (CH2), 73.5 (CH2), 77.8
(CH). 81.3 (CH), 127.2 (CH), 127.6 (CH), 127.6(8) (CH), 127.7(1) (CH),
127.8(8) (CH), 127.9(2) (CH), 128.2(7) (CH), 128.2(8) (CH), 128.3(1) (CH),
128.4 (CH), 128.5 (CH), 138.2(5) (C), 138.3(2) (C), 138.4 (C), 139.0 (C).
ES-HRMS calcd for C33H38NO4+ [M+H]+ 512.2795; found 512.2795.
Step 2. The above 4-O-xanthate (30, 0.23 g, 0.37 mmol) was dissolved in
anhydrous toluene (3 mL) under an argon atmosphere. The radical initiator
1,1’-azobis(cyclohexanecarbonitrile) (ABCN, 6.6 mg, 0.03 mmol) was
added. The mixture was heated to 110 °C and then tributyltin hydride (0.4
mL, 1.48 mmol) was added dropwise. The mixture was refluxed for 6 h,
cooled to room temperature, diluted with petroleum spirit (12 mL), and then
extracted with acetonitrile (4 × 8 mL). The combined acetonitrile extracts
were concentrated in vacuo to give a clear oil, which was purified by flash
column chromatography (silica gel, ethyl acetate/petroleum spirit, 1:9
basified with triethylamine) to give 4-deoxyribitol 31 as a clear oil (0.13 g,
68 %) as a mixture of two rotamers in a ratio of 2:1. 1H NMR (CDCl3, 600
MHz): major rotamer, δ 1.64–1.79 (m, 2H, H-4), 3.14 (dd, 1H, J = 15.0, 2.4
Hz, H-1), 3.37 (dd, 1H, J = 15.0, 9.1 Hz, H-1), 3.46–3.52 (m, 3H, H-2 & H-
5), 3.74 (ddd, 1H, J = 7.5, 4.2, 2.8 Hz, H-3), 4.07–4.74 (m, 8H, 4 PhCH2),
7.08–7.37 (m, 20H, 4 Ph), 8.19 (s, 1H, HCON); minor rotamer, δ 1.77–
1.91 (m, 2H, H-4), 3.18 (dd, 1H, J = 14.2, 8.8 Hz, H-1), 3.46–3.52 (m, 1H,
H-1), 3.53–3.60 (m, 2H, H-5), 3.82 (ddd, 1H, J = 8.9, 3.7, 2.1 Hz, H-3),
3.96 (ddd, 1H, J = 8.8, 3.3, 2.3 Hz, H-2), 4.07–4.74 (m, 8H, 4 PhCH2,
overlapped with major rotamer), 7.08–7.37 (m, 20H, 4 Ph, overlapped
with major rotamer), 8.20 (s, 1H); 13C NMR (CDCl3, 150 MHz):
characteristic signals for major rotamer, δ 31.4 (CH2, C-4), 46.0 (CH2,
PhCH2), 47.6 (CH2, C-1), 66.4 (CH2, C-5), 72.4 (CH2), 72.8 (CH2) and 73.1
(CH2, 3 PhCH2), 75.8 (CH, C-3), 77.8 (CH, C-2), 163.8 (CH, HCON);
characteristic signals for minor rotamer, δ 31.1 (CH2, C-4), 43.2 (CH2, C-
1), 52.7 (CH2, PhCH2), 72.5 (CH2), 72.6 (CH2) and 72.9 (CH2, 3 PhCH2),
76.3 (CH, C-3), 79.3 (CH, C-2); and unassigned aromatic signals for both
rotamers (4 Ph): 127.56 (CH), 127.59 (CH), 127.66 (CH), 127.70 (CH),
127.73 (CH), 127.75 (CH), 127.83 (CH), 127.85 (CH), 127.89 (CH), 127.91
(CH), 128.10 (CH), 128.27 (CH), 128.33 (CH), 128.37 (CH), 128.39 (CH),
128.41 (CH), 128.48 (CH), 128.66 (CH), 128.77 (CH), 136.26 (C), 136.57
(C), 137.70 (C), 138.14 (C), 138.20 (C), 138.41 (C), 138.43 (C), 138.50
Step 2. A solution of the above N-benzyl D-ribitylamine (28, 0.37 g, 0.73
mmol) in ethyl formate (1.4 mL, 1.73 mmol) was refluxed at 58 °C overnight.
The mixture was concentrated in vacuo to give a yellow oil, and then
purified by flash chromatography to give formamide 29 as a pale yellow oil
(0.29 g, 0.53 mmol, 73 %) as a mixture of two rotamers in a ratio of 5:3.
1H NMR (CDCl3, 600 MHz): major rotamer, 2.47 (d, 1H, J = 4.6 Hz, 4-OH),
3.24 (dd, J = 15.2, 2.6 Hz, 1H, H-1), 3.44–3.49 (m, 2H, H-1 & H-5), 3.56–
3.59 (m, 1H, H-5), 3.63–3.69 (m, 2H, H-3 & H-4), 3.86 (dt, 1H, J = 9.2, 2.1
Hz, H-2), 4.04 (d, 1H, J = 14.7 Hz) and 4.33–4.73 (m, 7H, 4PhCH2), 7.09–
7.37 (m, 20H, 4Ph), δ 8.20 (s, 1H, HCON); minor rotamer, δ 3.27 (dd, J
= 14.5, 8.5 Hz, 1H, H-1), 3.56–3.59 (m, 1H, 1H of H-5), 3.63–3.69 (m, 2H,
1H of H-1 & 1H of H-5), 3.75 (dd, J = 8.1, 1.7 Hz, H-3), 3.87–3.91 (m,
1H, H-4), 4.15 (dt, 1H, J = 8.5, 2.0 Hz, H-2), 4.33–4.73 (m, 8H, 4PhCH2),
7.09–7.37 (m, 20H, 4Ph), 8.16 (s, 1H, HCON); 13C NMR (CDCl3, 150
MHz): characteristic signals for major rotamer, δ 46.00 (CH2, PhCH2),
47.57 (CH2, C-1), 70.07 (CH, C-4), 71.19 (CH2, C-5), 72.47 (CH2, PhCH2),
73.57 (CH2, PhCH2), 73.98 (CH2, PhCH2), 76.27 (CH, C-2), 78.36 (CH, C-
3), 163.99 (CH, HCON). characteristic signals for minor rotamer, δ 52.93
(CH2, PhCH2), 70.55 (CH, C-4), 71.39 (CH2, C-5), 72.32 (CH2, PhCH2),
73.51 (CH2, PhCH2), 73.80 (CH2, PhCH2), 78.53 (CH, C-3), 78.94 (CH, C-
2), 163.46 (CH, HCON), and unassigned aromatic signals for both
rotamers (4 Ph): 127.68 (CH), 127.73 (CH), 127.78 (CH), 127.84 (CH),
127.91 (CH), 127.98 (CH), 128.00 (CH), 128.06 (CH), 128.07 (CH), 128.09
(CH), 128.11 (CH), 128.12 (CH), 128.35 (CH), 128.42 (CH), 128.53 (CH),
128.54 (CH), 128.63 (CH), 128.65 (CH), 128.67 (CH), 128.75 (CH), 128.94
(CH), 136.27 (C), 136.85 (C), 137.74 (C), 137.78 (C), 138.00 (C), 138.18
(C), 138.31 (C), 138.35 (C), [α]21d –16.2 (c 2.0, MeOH).
+
(C), 163.1 (C), 163.8 (C). ES-HRMS calcd for C34H38NO4 [M+H]+
524.2795; found 524.2794. [α]21d –7.2 (c 0.15, MeCN).
1-Amino-1,4-dideoxy-D-ribitol (32). To a solution of the above per-benzyl
protected formamide 31 (0.056 g, 0.11 mmol in 4 mL of methanol was
added PdCl2 (19 mg). The mixture was stirred at 60 °C for 2 h under a
hydrogen atmosphere (1 atm). After adding 2 drops of 5 % HCl in methanol,
the mixture was stirred for an additional 24 h. The mixture was
concentrated to give the desired amine 32 as a yellow oil, which was used
without further purification. 1H NMR (D2O, 600 MHz): δ 1.53–1.61 (m, 1H),
1.79–1.87 (m, 1H), 2.94 (dd, 1H, J = 9.3, 13.0 Hz), 3.24 (dd, 1H, J = 2.8,
13.0 Hz), 3.64–3.74 (m, 4H); 13C NMR (10 % MeOD in D2O, 150 MHz): δ
22.9, 29.7, 46.6, 58.4, 59.1.
2,3,5-Tri-O-benzyl-1-(N-benzyl-N-formyl)amino-1,4-dideoxy-D-ribitol (33).
Step 1. To a solution of the alcohol 29 (0.18 g, 0.35 mmol) in anhydrous
THF (3 mL) at 0 °C was added sodium hydride (33 mg, 0.82 mmol). The
mixture was stirred under house vacuum for 20 min. Carbon disulfide (27
μL, 0.45 mmol) was added and the mixture stirred for 10 mins at 0 °C.
Methyl iodide (28 μL, 0.45 mmol) was added and the mixture allowed to
warm up to room temperature. After stirring for an additional 20 mins, the
mixture was treated with water (8 mL) and extracted with ethyl acetate (3
× 5 mL). The combined extracts were washed with brine (7 mL), dried with
Synthesis of 5-deoxy-D-ribitylamine (1-Amino-1,5-dideoxy-D-ribitol, 40)
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