ORDER
REPRINTS
Total Synthesis of Triciribine
35
for 30 min, at which time a white precipitate had formed. The solvent was removed
under vacuum and the residue was resuspended in ethanol (200 mL), collected by
filtration, washed with ethanol (100 mL). The resulting precipitate was recrystallized
from ethanol, collected by filtration, and dried in a vacuum oven at 60°C for 12 h to
yield 3.43 g (72%) of pure 5. mp 173–175°C dec; Rf = 0.44 (1:1 ethyl acetate:hexane);
1H NMR (CDCl3) d 3.51 (3H, s), 4.19 (2H, bs), 4.70 (1H, dd), 4.79 (1H, m), 4.90 (1H,
m), 6.43 (1H, s), 6.50 (1H, m), 6.63 (1H, m), 7.40 (6H, m), 7.57 (3H, m), 7.93 (2H, m),
8.02 (4H, m), 8.28 (1H, s). Anal. Calcd for: C34H27N6O7Br 0.50 H2O: C, 56.67; H,
3.89; N, 11.67; Found: C, 56.55; H, 3.86; N, 11.66.
ꢁ
5-Cyano-4-(1-methylhydrazino)-7-[2,3,5-tri-O-benzoyl- -D-ribofuranosyl)pyr-
rolo[2,3-d]pyrimidine (6). 6-Bromo-5-cyano-4-(1-methylhydrazino)-7-[2,3,5-tri-O-
benzoyl-b-Dribofuranosyl)pyrrolo[2,3-d]pyrimidine (5) (2.82 g, 4.0 mmol), ammonium
formate (2.5 g, 40 mmol) and 10% palladium on activated charcoal (280 mg) were
suspended in ethanol (100 mL) and the suspension was heated at reflux temperature
for 1 h. The hot reaction mixture was filtered through Celite and washed with hot
ethanol (100 mL). The solvent was removed and the residue was dissolved in ethyl
acetate (100 mL) and extracted with water (100 mL). The water layer was removed and
discarded and the ethyl acetate layer was dried over magnesium sulfate. The mag-
nesium sulfate was removed by filtration and the filtrate was evaporated to dryness.
The residue was recrystallized from a hot mixture of ethanol and water to yield 2.43 g
(97%) of pure 6. mp 100°C shrank, 120–135°C melted and resolidified, 168–170°C
1
melted; Rf = 0.40 (1:1 ethyl acetate:hexane); H NMR (CDCl3) d 3.51 (3H, s), 4.19
(2H, bs), 4.80 (3H, m), 6.15 (2H, s), 6.64 (1H, d), 7.35–8.35 (17H, m). Anal. Calcd
for: C34H28N6O7: C, 64.56; H, 4.43; N, 13.29. Found: C, 64.35; H, 4.70; N, 13.30.
6-Amino-4-methyl-8-( -D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyri-
dazine(Triciribine, TCN). 5-Cyano-4-(1-methylhydrazino)-7-[2,3,5-tri-O-benzoyl-b-
D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (6) (1.09 g, 1.72 mmol) and sodium meth-
oxide (0.42 g, 7.75 mmol) were suspended in dry methanol (100 mL) and stirred for 1
h at room temperature under argon. TLC showed the disappearance of starting material
and the appearance of a new spot at Rf = 0.28 (9:1 chloroform:methanol). The reaction
mixture was heated at reflux temperature, under argon, for 18 h. TLC showed the
disappearance of starting material and the appearance of a new spot at Rf = 0.15 (9:1
chloroform:methanol). The solvent was removed under vacuum at 60°C and the yellow
residue was suspended in ethyl acetate and stirred at room temperature for 15 min. The
precipitate was collected by vacuum filtration, dissolved in hot water (20 mL), and
neutralized with Amberlite IR-120. The hot reaction mixture was filtered, cooled to
room temperature and then cooled to 5°C for 12 h to crystallize TCN. The crystals
were collected by filtration and dried in a vacuum oven at 80°C for 18 h to yield 0.44 g
(80%) of pure TCN; mp 207°C dec. (lit.[1] mp 205°C dec); Rf = 0.15 (9:1 chloro-
form:methanol); UV [lmax (e)] (pH 1) 286 (10844), 279 (10951), (pH 7) 292 (11822),
1
(pH 11) 290 (12320); H NMR (DMSO-d6) d 8.02 (1H, s, H-2), 7.06 (1H, s, H-7), 6.27
(2H, s, NH2), 5.81 (1H, d, H-1’), 5.62 (1H, t, OH), 5.42 (1H, d, OH), 5.22 (1H, m, OH),
4.48 (1H, m), 4.08 (1H, m), 3.96 (1H, m), 3.53 (2H, m), 3.38 (3H, s, NCH3); Anal.
Calcd for: C13H16N6O4 0.50 H2O: C, 47.42; H, 5.17; N, 25.53. Found: C, 47.66; H,
ꢁ
5.40; N, 25.16.