8
36
A. R. McKinney, D. D. Ridley and P. Turner
◦
[7]
◦
3
.50–3.60 (1 H, m, H3), 4.25 (1 H, dd, J 3.2, 10.0, H16). δC (100 MHz,
CD3OD) 10.3, 15.8, 24.3, 26.9, 29.8, 32.3, 34.4, 35.1, 35.4, 36.8, 42.9,
3.4, 44.5, 48.1, 71.4, 82.2, 86.2 (three signals obscured or overlap-
ping). The most polar product was recrystallized from acetone to give
63%) as a white crystalline solid, mp 220–223 C (lit. 222–223 C).
δH (200 MHz, CDCl3) 0.87 (3 H, s, H18), 2.57 (1 H, s, H21).
4
1
9-Nor-5α,17α-pregn-20-yne-3β,17β-diol (26)
5
α-estrane-3β,16α,17β-triol (19) (46 mg, 27%) as a white crystalline
◦
solid, mp 231–233 C (Found: C 73.7, H 10.6%. C18H30O3 requires C
7
J 5.8, H17), 3.49–3.59 (1 H, m, H3), 4.03 (1 H, ddd, J 1.9, 5.8, and 8.5,
H16). δC (100 MHz, CD3OD) 13.1, 26.7, 29.8, 32.0, 35.0, 35.3, 36.8,
Sodium borohydride (756 mg) was added to a solution of (25) (1.20 g) in
1,4-dioxan (95 mL) and water (5 mL) in small portions with stirring and
cooling so as to maintain the solution at around 20–25 C. After stirring
3.4, H 10.3%). δH (400 MHz, CD3OD) 0.79 (3 H, s, H18), 3.42 (1 H, d,
◦
for 1 h at room temperature the solvent was removed by evaporation at
reduced pressure. Water (250 mL) was added to the residue and the mix-
ture was extracted with ethyl acetate (250 mL). The organic fraction was
washed with water (2 × 250 mL) and brine (250 mL), dried (Na SO ),
3
8.3, 42.5, 42.9, 44.5, 45.2, 48.1, 49.6, 49.9, 71.4, 79.0, 91.0.
1
7-Oxo-5α-estran-3β,16β-diyl diacetate (20)
2
4
and evaporated at reduced pressure. The extracted residue was purified
by chromatography on silica using ethyl acetate/dichloromethane (20%
v/v) and recrystallized from acetone/light petroleum to give (26) (1.09 g,
A solution of (10) (420 mg) and lead(iv) acetate (568 mg) in acetic acid
glacial, 20 mL) and acetic anhydride (500 µL) was stirred for 18 h at
(
room temperature. The solvent was then removed by evaporation at
reduced pressure. The residue was reconstituted in dry ether (25 mL),
and water-saturated ether (25 mL) was added to decompose the lead
complex. After stirring for about 5 min the mixture was filtered and
the filtrate was washed with sodium carbonate solution (0.5 M, 50 mL),
water (50 mL), and brine (50 mL), dried (Na2SO4), and evaporated at
reduced pressure. The residue was purified by chromatography on silica
using ethyl acetate/dichloromethane (5% v/v) and recrystallized from
ether/light petroleum to give (20) (320 mg, 73%) as a white crystalline
◦ [7] ◦
9
(
0%) as a white crystalline solid, mp 191–193 C (lit. 192–193 C). δH
200 MHz, CD3OD) 0.87 (3 H, s, H18), 2.89 (1 H, s, H21), 3.45–3.65
(
1 H, m, H3).
1
9-Nor-5α,17α-pregn-20-yne-3β,17β-diyl Diformate (27)
Diol (26) (930 mg) was added to ice-cold formic acid (130 mL) and
stirred in an ice bath until dissolution was complete. Toluenesulfonic
acid monohydrate (50 mg) was added and the stirring continued until
this also dissolved. The solution was then allowed to stand for 2 days at
C. After diluting with cold ether (500 mL), the acid was neutralized
by stirring in an ice bath with successive portions of ice-cold sodium
carbonate solution (1 M, 1 L) until the aqueous fraction remained basic.
The organic fraction was then washed with water (500 mL) and brine
500 mL), dried (Na2SO4), and evaporated at reduced pressure. The
extracted residue was purified by chromatography on silica using ethyl
acetate/dichloromethane (10% v/v) and recrystallized from ether/light
◦
solid, mp 191–193 C (Found: C 70.0, H 8.3%. C22H32O5 requires C
−
1
7
(
0.2, H 8.6%). νmax (CHCl3)/cm 1737. δH (400 MHz, CDCl3) 0.95
3 H, s, H18), 2.00 (3 H, s, OCOCH3 at C3), 2.09 (3 H, s, OCOCH3 at
C16), 4.62–4.72 (1 H, m, H3), 4.97 (1 H, dd, J8.6 and 8.6, H16). δC
100 MHz, CDCl3) 15.2, 21.4, 22.1, 25.6, 28.8, 29.8, 30.5, 32.4, 32.4,
◦
5
(
3
2
3.7, 39.8, 40.4, 41.6, 45.7, 46.8, 47.9, 48.8, 73.5, 75.4, 170.9, 171.3,
15.4.
(
1
9-Nor-5α,17α-pregnane-3β,16β,17β-triol (9)
petroleum to give (27) (1.00 g, 91%) as a white crystalline solid, mp 84–
6 C (Found: C 73.8, H, 8.3%. C22H30O4 requires C 73.7, H, 8.4%).
Magnesium turnings (142 mg) were stirred with ethyl iodide (914 mg)
and anhydrous ether (478 mg) in anhydrous benzene (20 mL) with gen-
tle heating until all the metal was dissolved. The solution was then
cooled, and a solution of (20) (220 mg) in anhydrous benzene (5 mL)
was added and stirred for 18 h at room temperature. The reaction was
quenched by the careful addition of cold ethyl acetate (50 mL) and the
resulting mixture was washed with hydrochloric acid (0.5 M, 50 mL),
water (50 mL), and brine (50 mL), dried (Na2SO4), and evaporated at
reduced pressure. The extracted residue was resolved into two products
by chromatography on silica using ethyl acetate/dichloromethane (40%
◦
8
−1
νmax (CHCl3)/cm 3304, 2118, 1724. δH (400 MHz, CDCl3) 0.88 (3 H,
s, H18), 2.69 (1 H, s, H21), 4.77–4.87 (1 H, m, H3), 8.02 (1 H, s, OCOH
at C3), 8.16 (1 H, s, OCOH at C17). δC (100 MHz, CDCl3) 14.1, 24.0,
6.1, 28.8, 31.1, 32.5, 33.7, 33.9, 38.3, 39.8, 41.6, 42.1, 46.7, 48.0, 48.5,
8.9, 73.6, 77.2, 83.4, 86.0, 160.9, 161.4.
2
4
20-Oxo-19-nor-5α,17α-pregnan-3β,17β-diyl Diformate (28)
A solution of (27) (850 mg), N-bromoacetamide (1.31 g), and sodium
acetate (4.00 g) in acetic acid (200 mL) and water (20 mL) was stirred
for 45 min at room temperature. Zinc powder (1.24 g) was added and the
mixture was heated at reflux until colourless (20 min). The mixture was
then cooled and filtered, and the solvent was removed by evaporation
at reduced pressure. Sodium carbonate solution (0.5 M, 100 mL) was
added to the residue and the mixture was extracted with ethyl acetate
v/v). The less-polar product was recrystallized from acetone to give (9)
◦
(
92 mg, 49%) as a white crystalline solid, mp 239–240 C (Found: C
7
4.9, H 10.9%. C20H34O3 requires C 74.5, H 10.6%). δH (400 MHz,
CD3OD) 0.88 (3 H, s, H18), 0.95 (3 H, t, J 7.2, H21), 1.63 (2 H, q,
J 7.2, H20), 3.49–3.59 (1 H, m, H3), 3.83 (1 H, dd, J 6.2 and 8.1,
H16). δC (100 MHz, CD3OD) 7.8, 15.3, 27.0, 28.5, 29.9, 32.5, 34.0,
3
6.4, 36.8, 42.9, 43.2, 44.5, 47.4, 47.5, 48.3, 49.8, 71.4, 73.7, 81.6. The
(
100 mL). The organic fraction was washed with water (100 mL) and
more-polar product was recrystallized from acetone to give 5α-estrane-
brine (100 mL), dried (Na2SO4), and evaporated at reduced pressure.
The extracted residue was resolved into two products by chromato-
graphy on silica using ethyl acetate/light petroleum (20% v/v). The less
polar product was recrystallized from ether/light petroleum to give (28)
509 mg, 57%) as a white crystalline solid, mp 138–140 C (Found: C
0.2, H 8.7%. C22H32O5 requires C 70.2, H, 8.6%). νmax (CHCl3)/cm
720. δH (400 MHz, CDCl3) 1.01 (3 H, s, H18), 2.07 (3 H, s, H21),
.74–4.84 (1 H, m, H3), 8.00 (1 H, s, OCOH at C3), 8.09 (1 H, s, OCOH
at C17). δC (100 MHz, CDCl3) 15.6, 25.1, 26.1, 27.9, 28.8, 31.1, 32.5,
33.6, 33.9, 34.5, 39.8, 41.6, 41.9, 46.6, 47.3, 47.8, 48.2, 73.6, 97.6, 161.4,
161.7, 208.1.The more polar product was recrystallized from ether/light
petroleum to give 3β-hydroxy-20-oxo-19-nor-5α,17α-pregnan-17β-yl
formate (29) (125 mg, 15%) as a white crystalline solid, mp 200–201 C
(Found: C 72.4, H 9.0%. C21H32O4 requires C 72.4, H, 9.3%). νmax
(CHCl3)/cm 3460 (broad), 1721. δH (400 MHz, CDCl3) 1.01 (3 H, s,
H18), 2.07 (3 H, s, H21), 3.51–3.61 (1 H, m, H3), 8.09 (1 H, s, OCOH
at C17). δC (100 MHz, CDCl3) 15.6, 25.1, 26.2, 27.9, 29.0, 31.2, 33.6,
34.1, 34.6, 36.4, 41.7, 42.0, 44.0, 46.7, 47.3, 47.9, 48.3, 71.1, 97.7,
161.7, 208.2.
3
2
1
β,16β,17β-triol (21) (46 mg, 27%) as a white crystalline solid, mp
◦
53–255 C (Found: C 73.1, H 10.3%. C18H30O3 requires C 73.4, H
0.3%). δH (400 MHz, CD3OD) 0.85 (3 H, s, H18), 3.33 (1 H, d, J 7.7,
H17), 3.49–3.59 (1 H, m, H3), 4.11 (1 H, ddd, J 5.0, 7.7, and 7.7, H16).
δC (100 MHz, CD3OD) 12.9, 26.8, 29.9, 32.2, 35.1, 36.1, 36.8, 39.0,
◦
(
−1
7
1
4
4
2.4, 42.9, 44.1, 44.5, 48.2, 48.3, 49.9, 71.1, 71.4, 82.5.
1
7β-Hydroxy-19-nor-5α,17α-pregn-20-yn-3-one (25)
A solution of (24) (2.00 g) in anhydrous 1,4-dioxan (40 mL) was added
to a vigorously stirred solution of lithium (1.00 g) in anhydrous liquid
ammonia (200 mL). The reaction was immediately quenched by the
addition of ammonium chloride (10 g), after which the ammonia was
allowed to evaporate. Water (250 mL) was added to the residue and the
mixture was extracted with ethyl acetate (250 mL). The organic fraction
was washed with water (250 mL) and brine (250 mL), dried (Na2SO4),
and evaporated at reduced pressure. The extracted residue was purified
by chromatography on silica using ethyl acetate/dichloromethane (10%
v/v) and recrystallized from acetone/light petroleum to give (25) (1.27 g,
◦
−
1