to dryness. The solid was dissolved with heating in EtOAc (3 mL) and left overnight at room temperature. The resulting
20
crystals were separated and washed with EtOAc to afford 1 (0.45 g), C H O Cl, mp 210–212°C, [α] +17.8 2° (c 0.7,
D
22 31
5
MeOH:CHCl ).
3
B. Strophanthidine-19-carboxylic acid (1.17 g) and N-chlorosuccinimide (1.9 g) were dissolved in CHCl :CH OH
3
3
(5:1, 20 mL), cooled, stirred continuously, and treated with lead tetraacetate (5.37 g). The solution immediately became dark
brown. Stirring was continued for 2.5 h at room temperature. Then, the mixture was treated with CHCl :i-PrOH (3:1, 50 mL)
3
and aqueous H SO (3%, 20 mL). The lower phase was separated; washed with water (10 mL × 2), saturated NaHCO
2
4
3
solution (15 mL), and water (10 mL × 2); and evaporated in vacuo. The solid was chromatographed over a column of silica gel
(50 g) with elution by CH Cl :MeOH of increasing polarity. Fractions of 3 mL were collected. Fractions 3–12 produced 1
2
2
21
(0.34 g), mp 210–212°C, [α] +17.4 2° (c 0.8, MeOH:CHCl ).
D
3
10-Chloro-19-norcymarin (2). The synthesis using cymarin-19-carboxylic acid (1.6 g) was carried out analogously
to that for 1 (part B) but in anhydrous DMF. The products were chromatographed over a column of Al O (Brockmann
2
3
activity III, 60 g) with elution by CH Cl and CH Cl :MeOH of increasing polarity. Fractions of 3–4 mL were collected.
2
2
2
2
Fractions 24–40 were evaporated. Crystallization of the solid from EtOAc:Et O afforded 2 (0.42 g), C H O Cl, mp 144–
2
29 43 8
20
147°C, [α] +24.1 2° (c 0.7, CHCl ).
D
3
10-Chloro-19-norconvallatoxin (3). Convallatoxin-19-carboxylic acid (0.5 g) was decarboxylated in the presence
of NH Cl as described above for 2. The products were chromatographed over a column of silica gel (30 g, particle size
4
0.04–0.06 mm) with elution by CHCl and CHCl :MeOH of increasing polarity. Fractions of 2 mL were collected. Fractions
3
3
7–12 were evaporated. Crystallization of the solid from MeOH:Et O afforded 3 (0.14 g), C H O Cl, mp 128–131°C,
2
28 41 9
22
[α] –7.3 3° (c 0.4, MeOH).
D
10-Chloro-19-norstrophalloside (4). Strophalloside-19-carboxylic acid (1.4 g) was decarboxylated in the presence
of NH Cl. The product was purified as described above for 2 to afford 4 (0.37 g), C H O Cl, mp 170–173°C (crystallization
4
28 41 9
20
from EtOAc:Et O), [α] –11.0 2° (c 0.7, MeOH).
D
2
10-Chloro-19-norbovoside A (5). Bovoside A-19-carboxylic acid (0.8 g) was decarboxylated in the presence of
NH Cl. The product was purified by the method described for 2 to afford 5, C H O Cl, mp 121–122°C (crystallization from
4
30 43 8
20
EtOAc), [α] –33.1 2° (c 0.9, MeOH).
D
Hydrolysis of 2. Compound 2 (10 mg) was placed in a glass ampul and treated with acetic acid (3 drops, 15%). The
ampul was sealed and heated at 80–85°C for 10 min. Analysis by TLC and PC showed that the hydrolysis products were
10-chloro-19-norstrophanthidine (1) and D-cymarose.
Hydrolysis of 3 and 4 was performed according to Mannich. Samples (10–15 mg) were dissolved in acetone:conc.
HCl (99:1), left at room temperature for 30–35 h, and analyzed using TLC. In both instances the aglycon was identified as 1
by direct comparison with an authentic sample.
REFERENCES
1.
General Organic Chemistry, Vol. 4, translated by N. K. Kochetkov and E. I. Nifant′ev, Khimiya, Moscow, 1983,
p. 55.
2.
3.
R. A. Sheldon and J. K. Kochi, Org. React., 19, 279 (1972).
I. F. Makarevich, N. V. Kovganko, I. S. Chekman, and G. V. Zagorii, Cardiotonic Steroids [in Russian], Original,
Kharkov, 2009.
4.
J. H. Beynon, Mass Spectrometry and Its Applications to Organic Chemistry, D. Van Nostrand Co., Princeton,
N. Y., 1960 [translated by A. A. Polyakova and R. A. Khmel′nitskii, Mir, Moscow, 1964].
I. F. Makarevich, Khim. Prir. Soedin., 221 (1968).
L. F. Fieser and M. Fieser, Steroids, Reinhold Publ. Corp., New York, 1959 [translated by N. N. Suvorov and
I. V. Torgov, Mir, Moscow, 1964].
5.
6.
7.
I. F. Makarevich and A. V. Ulesov, Khim. Prir. Soedin., 373 (2008).
655