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FORMANOVSKY et al.
washed with 5% NaHCO3 (5 × 300 ml), 10% NaCl/3% (I). A suspension of (XVII) (41.74 g, 28.09 mmol),
10% Pd/C (8.6 g), and trifluoroacetic acid (25 ml) in
methanol (1100 ml) was stirred for 24 h in a hydrogen
flow. The catalyst was separated, the filtrate was evapo-
rated in a vacuum, and the residue was lyophilized from
a water solution. Compound (I) (30.7 g) was obtained
in the form of a salt with trifluoroacetic acid; the yield
was practically quantitative; H NMR: 6.96 (1 H, d, J
8.4, ç5Ar), 6.35 (1 H, d, J 2.4, H3Ar), 6.30 (1 H, dd, J 2.4
and 8.4, H6Ar), 4.62 (1 H, t, J 6.0, H2Asn), 3.89 (1 H, t, J
ammonia (5 × 300 ml), and water (3 × 300 ml). The solution
was dried with Na2SO4 and evaporated to give (XV); slightly
yellow oil; yield 59.18 g (95%); Rf 0.65 (C); it was used with-
out any additional purification.
A solution of (XV) (59.18 g, 55.1 mmol) in dry
dichloromethane (280 ml) was treated under ice cool-
ing with CF3COOH (110 ml). The solution was stirred
for 2 h at room temperature, evaporated in a vacuum,
1
and the residue was dried in a vacuum for 4 h at 40°ë. 6.5, H2Arg), 3.45–2.80 (16 H, m, H2, H4, H6, H8, H10,
H14, H5Arg, CH2Ar), 2.70 (2 H, d, J 6.0, H3Asn), 2.07 (2
H, m, H7), 1.97–1.85 (4 H, m, H3, H3Arg), 1.70–1.51 (6
H, m, H10, H13, H4Arg), 1.48–1.29 (2 H, m, H12); MS,
m/z 637 (M + 1+).
Dry THF (300 ml) was added and then, successively,
triethylamine (38 ml) and (XIV) (19.77 g, 56 mmol)
during cooling with ice. The reaction mixture was kept
overnight at room temperature when monitoring the
disappearance of (XIV) by TLC, Rf 0.38 (D); then two-
fold concentrated in a vacuum and treated with dry
DMF (200 ml), Et3N (30 ml); and, dropwise at cooling
with ice, with BnOCOCl (29.0 g, 170 mmol). The reaction
mixture was stirred overnight at room temperature, poured
into 2 M ammonia (3 l), and stirred for 3 h. The precipi-
tated solid was separated and washed on a filter with 2 M
ammonia and water up to colorless washings. The precip-
itate was dissolved in dichloromethane (600 ml) and addi-
tionally washed with ammonia to the complete discolora-
tion of the organic layer. The solvent was evaporated in a
vacuum to give (XVI); yield 63.67 g (92%); Rf 0.45 (D).
ACKNOWLEDGMENTS
This work was supported by the grant CRDF RBO-
11023.
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15-(N-(2,4-Dihydroxyphenylacetyl)-L-asparaginyl)-1-
L-arginyl-1,5,9,15-tetraazapenadecane
(argiopine)
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 35 No. 6 2009