SYNTHESIS OF 14
β
ꢀCYANOMETHYL DERIVATIVES OF ESTRADIOL
89
19,
J
2 9, H16), 2.33 (1H, td,
1 19,
2.5, H4), 6.99 (1H, dd,
2 2.5, H2), 7.34 (1H, d, 8.5, H1), 7.51 (2H, t,
mꢀPh), 7.64 (1H, t, 7.5, pꢀPh), 8.20 (2H, d, 8, oꢀPh);
J
1 11, J2 4, H9), 2.44 (1H, arated by chromatography, which made it possible to
2 8.5, H16), 2.95 (2H, detect ketone ( ) as a minor component (3–8%) of
1 8.5, the products.
8,
m, H11 ), 2.52 (1H, dd,
m, H6), 6.95 (1H, d,
J
J
J
X
α
J
J
J
J
3ꢀBenzoyloxyestraꢀ1,3,5(10),14ꢀtetraenꢀ17ꢀone
J
J
1
(VIII). mp 164–165°C (MeOH); H NMR (CDCl3):
13C NMR (CDCl3): 13.98 (C18), 21.74 (C15), 25.93
(C7), 26.51 (C11), 29.57 (C6), 31.72 (C12), 35.99
(C16), 38.19 (C8), 44.34 (C9), 48.09 (C13), 50.61
(C14), 119.01 (C2), 121.84 (C4), 126.60 (C1), 128.67
(C3'), 129.71 (C1'), 130.28 (C2'), 133.64 (C4'), 137.58
and 138.22 (C5 and C10), 149.00 (C3), 165.56
(COPh), 220.83 (C17).
1.18 (3H, s, H18), 2.92 (1H, m, Н16 ), 3.00 (2H, m,
α
H6), 3.07 (1H, m, Н16 ) 5.64 (1H, br s, H15), 6.98
(1H, d,
7.35 (1H, d,
(1H, t, 7.5, pꢀPh), 8.20 (2H, d,
CDCl3, , ppm): 20.18 (C18), 24.82 and 26.55 (C11
J
2.5, H4), 7.00β(1H, dd,
J
1 8.5, J2 2.5, H2),
8.5, H1), 7.51 (2H, t, , mꢀPh), 7.64
8, oꢀPh); 13C NMR
J
J 8
J
J
(
δ
and C7), 29.64 (C6), 33.37 (C12), 38.74 (C8), 41.71
(C16), 45.01 (C9), 51.09 (C13), 113.59 (C15), 119.16
(C2), 122.03 (C4), 126.93 (C1), 128.69 (C3'), 129.75
(C1'), 130.29 (C2'), 133.69 (C4'), 137.07 and 138.21
(C5 and C10), 149.11 (C3), 152.34 (C14), 165.57
3ꢀBenzoyloxyꢀ16 ꢀbromoestraꢀ1,3,5(10)ꢀtrienꢀ
α
17ꢀone (VII). CuBr2 (5.58 g, 25 mmol) was added to a
solution of steroid (VI) (3.75 g, 10 mmol) in a methaꢀ
nol—benzene mixture 1 : 1 (80 mL). The reaction
mixture was refluxed for 1.5 h and cooled. The precipꢀ
itate was filtered and washed with chloroform. The filꢀ
trates were combined, evaporated, and dissolved again
in chloroform (150 mL). The solution was washed
with water and a saturated NaCl solution, filtered, and
dried over Na2SO4. After the evaporation of the solꢀ
vent, the residue was crystallized from MeOH to yield
(COPh), 222.33 (C17); MS:
m/z (I, %): 373 ([M ,
H]+
100%), 355 ([
M
HꢀH2O]+, 80%).
3ꢀBenzoyloxyꢀ14βꢀestraꢀ1,3,5(10),15ꢀtetraenꢀ
17ꢀone (IX). 1H NMR (CDCl3): 1.18 (3H, s, H18),
1.50 (1H, m, H11 ), 1.73 (1H, qd, J1 12, J2 5.5, H7 ),
α
2.23 (1H, m, H11β), 2.35 (1H, m, H9 ), 2.90 (1H, m,
β
α
H14 ), 2.93 (2H,αm, H6), 6.24 (1H, dd, J1 6, J2 2,
3.2 g (71%) of bromide (VII); mp 146–147
(MeOH); IR (KBr,
, cm–1): 2930, 2865, 1745 (CO),
1730 (Bz), 1495, 1450, 1260, 1060; 1H NMR (CDCl3):
0.96 (3H, s, H18), 2.95 (2H, m, H6), 4.60 (1H, d, 7,
H16 ), 6.96 (1H, d, 2.5, H4), 7.00 (1H, dd, 1 8.5, J2
8.5, H1), 7.51 (2H, t, 8, mꢀPh),
7.5, pꢀPh), 8.20 (2H, d,
8, oꢀPh); 13C
°
C
H16), 6.92 (1H, d,
2.5, H2), 7.21 (1H, d,
Ph), 7.62 (2H, m, pꢀPh and H15), 8.19 (2H, d,
J
2.5, H4), 6.97 (1H, dd,
J
1 8.5, J2
8, mꢀ
8, oꢀ
, ppm): 22.45 (C18), 27.39
ν
J
8.5, H1), 7.51 (2H, t,
J
J
J
13
Ph); C NMR (CDCl3,
δ
J
J
β
and 27.62 (C7 and C11), 30.54 (C6), 31.35 (C12),
35.87 and 37.91 (C8 and C9), 47.88 (C13), 54.74
(C14), 119.44 (C2), 121.66 (C4), 128.19 (C1), 128.68
(C3'), 129.74 (C1'), 130.28 (C2'), 133.14 (C16),
133.68 (C4'), 137.78 and 138.23 (C5 and C10), 148.80
(C3), 162.07 (C15), 165.56 (COPh), 214.65 (C17).
2.5, H2), 7.34 (1H, d,
7.64 (1H, t,
J
J
J
J
NMR (CDCl3): 14.37 (C18), 25.75 (C11), 26.44 (C7),
29.40 (C6), 32.43 (C12), 34.08 (C15), 37.41 (C8),
44.14 (C9), 46.36 (C16), 47.20 (C14), 48.13 (C13),
119.13 (C2), 121.91 (C4), 126.55 (C1), 128.56 (C3'),
129.74 (C1'), 130.29 (C2'), 133.70 (C4'), 137.20
(C10), 138.05 (C5), 149.08 (C3), 165.59 (COPh),
3ꢀBenzoyloxyestraꢀ1,3,5(10),15ꢀtetraenꢀ17ꢀone (X).
IR (KBr,
, cm–1): 2955, 2920, 2865, 1730 (Bz), 1700
ν
1
m/z (I, %): 455 and 453 ([M ,
H]+
(CO), 1265, 1065; H NMR (CDCl3): 1.13 s (3H, s,
213.22 (C17); MS:
100%).
H18), 3.00 (2H, m, H6), 6.10 (1H, dd, J1 6, J2 3,
H16), 6.97 (1H, d,
2.5, H2), 7.34 (1H, d,
7.64 m (2H, m, pꢀPh and H15), 8.20 (2H, d,
J
2.5, H4), 7.00 (1H, dd,
8.5, H1), 7.51 (2H, t, 8, mꢀPh),
8, oꢀPh);
J1 8.5, J2
Dehydrobromination of compound (VII). A mixture
of steroid (VII) (1.0 g, 2.2 mmol) and anhydrous LiBr
(1.36 g, 15.64 mmol) and Li2CO3 (1.17 g, 15.83 mmol)
in absolute dimethylformamide (8 mL) was degassed
and then refluxed in an atmosphere of argon for 2.5 h.
After the termination of the reaction, the mixture was
cooled, a 50% acetic acid solution (40 mL) was added,
and the organic phase was extracted by EtOAc. The
extract was washed with water, a sodium bicarbonate
solution, and a saturated NaCl solution and dried over
Na2SO4. The solvent was evaporated, and the residue
was dissolved in pyridine (10 mL) after which benzoyl
J
J
J
13C NMR (CDCl3): 21.05 (C18), 25.46 and 26.65 (C7
and C11), 29.20 and 29.34 (C6 and C12), 35.39 (C8),
45.41 (C9), 51.54 (C13), 56.26 (C14), 119.11 (C2),
121.90 (C4), 126.33 (C1), 128.69 (C3'), 129.74 (C1'),
130.29 (C2'), 132.16 (C16), 133.70 (C4'), 137.45 and
137.94 (C5 and C10), 149.09 (C3), 158.18 (C15),
165.59 (COPh), 213.01 (C17); MS:
([M
m/z (I, %): 373
H]+, 100%).
3ꢀBenzoyloxyestraꢀ1,3,5(10),14,16ꢀpentaenꢀ17ꢀyl
chloride (0.11 mL, 1 mmol) was added under stirring. acetate (XI). TsOH (0.115 g, 0.67 mmol) was added to
After 2 h, the reaction mixture was poured into a satuꢀ a solution of a mixture of ketones (VIII)–( ) (0.478 g)
X
rated sodium hydrocarbonate solution, and the preꢀ in isopropenyl acetate (8 mL) and acetic anhydride
cipitate was filtered, washed with water, dried, and (1.5 mL). The mixture was degassed and then refluxed
purified on a short column of silica gel (eluent in an atmosphere of argon for 4.5 h. After the terminaꢀ
EtOAc–toluene 1 : 5) to remove polar contaminaꢀ tion of the reaction, the solution was cooled to 0 C,
°
tions. A mixture of ketones (VIII) and (IX) (ca. 1 : 1; and EtOAc (20 mL) was added under vigorous stirring
0.66 g) was obtained, which was used at the next stage. after which sodium bicarbonate (4 g) and water
For analytical purposes, a part of the mixture was sepꢀ (10 mL) were added portionwise. After the cessation
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 42
No. 1
2016