HETEROCYCLES, Vol. 76, No. 2, 2008
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Et2O (75 mL), and combined organic solutions were dried over MgSO4. After concentration, the crude oil
was subjected to column chromatography on silica gel during which it was eluted with mixtures of
1
hexane and EtOAc (4:1 and 2:1), and 2 (17.1 g, 89%) was obtained as colorless oil. H NMR (CDCl3):
δ/ppm = 1.28 (d, 3H, J = 6.8 Hz), 3.37 (s, 3H), 4.16 (d.d, 2H, J = 1.6, 5.2 Hz), 4.22 (d.q, 1H, J = 6.8 Hz),
4.58 (d, 1H, J = 6.8 Hz), 4.68 (d, 1H, J = 6.8 Hz), 5.64 (d.d.t, 1H, J = 1.6, 6.8, 15.6 Hz), 5.83 (d.t, 1H, J =
5.2, 15.6 Hz). ν/cm-1 = 3250 (O-H), 2930 (C-H) 1375, 1216, 1159, 1097, 1032, 917; Anal. Calcd for
C7H14O3: C, 57.51; H, 9.65. Found: C, 57.01; H, 9.39.
(2R,3R,4S)-2,3-epoxy-4-methoxymethoxypentan-1-ol (3). To a mixture of (+)-diisopropyl tartrate (2.98 g,
12.7 mmol), tetraisopropoxy titanium (3.01 g, 10.6 mmol), and molecular sieves 4A (7.75 g) in CH2Cl2
(155 mL) were added 80% cumene hydroperoxide (60.5 g, 0.318 mol) and 2 (15.5 g, 0.106 mol) at 0 °C.
The mixture was stirred for 18 h, and then water (16 mL) was added and the mixture was filtrated and
dried over Na2SO4. Column chromatography on silica gel eluting with mixtures of hexane and EtOAc
(10:1 and 3:1) gave 3 (16.7 g, 97%). 1H NMR (CDCl3): δ/ppm = 1.94 (d, 3H, J = 6.8 Hz), 2.93 (d.d, 1H, J
= 2.5, 5.6 Hz), 3.13 – 3.16 (m, 1H), 3.38 (s, 3H), 3.59 (d.q, 1H, J = 5.6, 6.8 Hz), 3.70 (d.d, 1H, J = 4.0,
12.4 Hz), 4.67 (d, 1H, J = 7.2 Hz), 4.69 (d, 1H, J = 7.2 Hz). IR (film): ν/cm-1 = 2930 (C-H), 1102, 1034,
914. Anal. Calcd for C7H14O4: C, 51.84; H, 8.70; Found: C, 52.07; H, 8.58.
(2R,3R,4S)-2,3-epoxy-4-methoxymethoxypentanal (4). To a solution of DMSO (5.85 g, 74.9 mmol) in
CH2Cl2 (150 mL) was added oxaryl chloride (4.70 g, 37.0 mmol) at - 60 °C, and after 30 min a solution
of 3 (1.50 g, 9.25 mmol) in CH2Cl2 (30 mL). The mixture was stirred for 30 min, and triethylamine (15.0
g, 148 mmol) was added. The reaction was quenched by the addition of water (30 mL). The organic
solution was separated, and the aqueous solution was extracted with CH2Cl2 (50 mL x 3). Combined
organic solution was dried over Na2SO4 and concentrated. Column chromatography on silica gel eluting
with a mixture of hexane and EtOAc (3:1) gave 4 (1.15 g, 78%). IR (film): ν/cm-1 = 2710 (C-H), 1690
(C=O), 1280, 1175, 1080, 1020, 920; 1H NMR (CDCl3): δ/ppm = 1.31 (d, 3H, J =6.4 Hz), 3.24 (d.d, 1H,
J = 2.0, 4.4 Hz), 3.35 (s, 3H), 3.40 (d.d, 1H, J = 2.0, 6.4 Hz), 3.77 (d.q, J = 4.4, 6.4 Hz), 4.63 (d, 1H, J =
7.2 Hz), 4.65 (d, 1H, J = 7.2 Hz), 9.07 (d, 1H, J = 6.4 Hz).
2,6-Diamino-4-cyclohexyloxy-5-nitrosopyrimidine (5). To boiling cyclohexanol (340 mL) was added 60%
NaH (12.2 g, 0.39 mol) slowly, and, then, 2,4-diamino-6-chloropyrimidine (22.0 g, 0.15 mol) was added.
After refluxing for 2 h, the mixture was concentrated by a rotary evaporator. To this were added water (75
mL) and NaNO2 (10.9 g, 0.16 mol), and the mixture was acidified to pH 5 by acetic acid. Filtration of the
resulting reddish purple precipitates followed by washing with water and Et2O gave 5 (27.9 g, 89%). Mp
260 °C (decomp); 1H NMR (DMSO-d6): δ/ppm = 1.34 (m, 3H), 1.58 (m, 3H), 1.75 (m, 2H), 2.00 (m, 2H),
5.31 (m, 1H), 7.72 (d, 2H, J = 3.6 Hz), 7.94 (d, 1H, J = 4.4 Hz), 10.09 (d, 1H, J = 4.4 Hz).
Protected biopterin: compound 8. A suspension of 5 (88.9 mg, 0.38 mmol) and 5% Pd-C (8.9 mg) in