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A new aromatization of ring-A of steroids. Synthesis of estrone
0040-4039/88 $3.00 + .OO Pergamon Journals Ltd.
Tetrahedron Letters, Vo1.29, No.1, pp 79-80, 1988 Printed in Great Britain
A NEW AROMATIZATION OF RING-A OF STEROIDS.
SYNTHESIS OF ESTRONE'
Hiroshi Suginome*, Hisanori Senboku and Shinji Yamada Organic synthesis Division, Department of Chemical Process Engineering, Faculty of Engineering, Hokkaido University, Sapporo 060, Japan Summary-The
transformation of cholesterol and 38-hydroxyandrost-5-en-17-one
into 19-norcholesta-1,3,5(10)-trien-3-01
and estrone by a new method for the
aromatization of their ring-A is described. A series of our previous
papers described a variety of applications of 2
the $-scission of alkoxyl radicals to the synthetic problems.
In this paper we wish to report an application of the 8-scission of alkoxyl radicals to a new transformation of steroids into 19-norsteroids and the ring-A aromatized steroids such as estrone. A cyclic hemiacetal 2 derived via 5 steps from cholesterol (1) according 3 to the procedure of Akhtar and Barton was subjected to our regioselective 8scission through the photolysis of the corresponding hypoiodite2 to give a 5:l mixture of 5-bromo-19-nor-5u-cholest-9-ene-38,68-diol and 5-bromo-l9-nor-5a-cholest-lO-ene-38,68-diol 75% yield.
3-acetate 6-formate (3)
3-acetate 6-formate (4) in a
The mixture of 3 and 4 was then subjected to a reductive elimina-
tion by treatment with zinc in acetic acid at 100 "-120°C for 0.5 h to give 19norcholesta -5,10-dien-38-01 potassium hydroxide at
acetate (5) in 89% yield.
Its hydrolysis with
room temperature for 4 h gave the corresponding crys-
talline 38-01 64 in 67% yield.
Oxidation of 6 in dichloromethane with dimethyl
sulphoxide-trifluoroacetic anhydride at -78OC according to the procedure of Swern' gave 19-norcholesta-1,3,5(10)-trien-3-01
(7)6in a 35% yield.
We then undertook the transformation of 38-hydroxyandrost-5-en-17-one
(8)
into estrone
(14) Q_ by applying a series of the above reactions. Thus, commercially available 38-hydroxyandrost-5-en-17-one 8 was transformed into a cyclic - 3 The cyclic hemiacetal 9 hemiacetal 9 according to the procedure of Barton. gave a 7:l mixture of 5-bromo-19-nor-5a-androst-9-ene-38,68-diol
3-acetate 6-
formate (10) and 5-bromo-19-nor-5a-androst-lO-ene-38,68-diol 3-acetate C-for-5 (11) in a 74% yield according to our procedure for the 8-scission. 2 1.-. Reductive elimination of 11 __ in acetic acid with zinc under the conditions applied for cholestane series gave 19-norandrosta-5,10-dien-38-01 acetate (12) __
mate
in a 89% yield. Hydrolysis of 13 in a mixture of methanol and ethanol containing potas_* sium hydroxide at room temperature gave the corresponding crystalline 38-01 (13)8 in a 78% yield. Swern Oxidation of __ 13 gave estrone and 19-norandrosta__ 5,10-dien-38-01 trifluoroacetate in 53% and 20% yields. 9 79
80
Scope of this new aromatization of ring-A of steroids as well as the synthesis of 19-norsteroids from the compounds such as 3, 4, 10 and 11 are being I I I_ II actively investigated.
R = /‘aHi *... ‘H R q0
5 steps
1
a
R
=
Ii , ii
,=aH,, *a --.
H
R=O
R =
lo
AcOv iii
iv
AcO
6
R = &C8Hl '?-I 13 R=O
V
5
R =
12
R=O
R=O
OCHO
4
HO
HCaHi7 “..w
R
eCaHi 7 “H
q
HCaHi7 ‘XH
R=O
2 7
R
14 i) iv)
HgO-12-benzene
KOH-MeOH-EtOH,
q
0CaH17 “..H
R=O ii)
CF,COO
hv
20’ C
R q0
+
iii) v)
Zn-CH3C02H,
llO"C-120°C
TFAA-DMSO-Et3N-CH2C12,
-78’
C
References and Notes 1) 2)
3) 4) 5) 6) 7) 8) 9)
Photoinduced Molecular Transformations. Part 93. Part 92. H. Suginome and S. Yamada, Tetrahedron s., 2, 3963 (1987) e. g., H. Suginome and S. Yamada, 2. 9. w., 49, 3753 (1984); ibid so, 2489 (1985); H. Suginome, C. F. Liu and A. Furusaki; Chem. EC" 1984, 911; H. Suginome, K. Kobayashi, M. Itoh and A. Furua, Chem. s., 1985, 727; H. Suginome and S. Yamada, Tetrahedron e., 2, 37151985); Tetrahedron, in press; H. Suginome and S. Yamada, press; H. Suginome, C. F. Liu and M. Tokuda, J. C 1985, 327,; H. Suginome, M. Itoh and K. Kobay%h‘li;j_. Chem. Sot. Perkin -.' Trans I., in press.; K. Kobayashi, M. Itoh and H. Suginome, Tetrahedron Lett 28, 3369 (1987). --t M. Akhtar and D. H. R. Barton, 2. Am. m. g., %, 1528 (1964). M.P. 69.5-71.5'C S. L. Huang, K. Omura and D. Swern -. , 4_l, 3329 (1976). M.P. 114.0-116.O'C ( Lit.7 M.P. II&~; R. C. Cambie, V. F. Carlisle and T. D. R. Manning, 2. m. s., (c), 1969, 1240. M.P. 134.5-135.5oc Satisfactory spectral and analytical results were obtained for all the compounds described in this paper. (Received in Japan 17 September 1987)
Tetrahedron Letters, Vo1.29, No.1, pp 79-80, 1988 Printed in Great Britain
A NEW AROMATIZATION OF RING-A OF STEROIDS.
SYNTHESIS OF ESTRONE'
Hiroshi Suginome*, Hisanori Senboku and Shinji Yamada Organic synthesis Division, Department of Chemical Process Engineering, Faculty of Engineering, Hokkaido University, Sapporo 060, Japan Summary-The
transformation of cholesterol and 38-hydroxyandrost-5-en-17-one
into 19-norcholesta-1,3,5(10)-trien-3-01
and estrone by a new method for the
aromatization of their ring-A is described. A series of our previous
papers described a variety of applications of 2
the $-scission of alkoxyl radicals to the synthetic problems.
In this paper we wish to report an application of the 8-scission of alkoxyl radicals to a new transformation of steroids into 19-norsteroids and the ring-A aromatized steroids such as estrone. A cyclic hemiacetal 2 derived via 5 steps from cholesterol (1) according 3 to the procedure of Akhtar and Barton was subjected to our regioselective 8scission through the photolysis of the corresponding hypoiodite2 to give a 5:l mixture of 5-bromo-19-nor-5u-cholest-9-ene-38,68-diol and 5-bromo-l9-nor-5a-cholest-lO-ene-38,68-diol 75% yield.
3-acetate 6-formate (3)
3-acetate 6-formate (4) in a
The mixture of 3 and 4 was then subjected to a reductive elimina-
tion by treatment with zinc in acetic acid at 100 "-120°C for 0.5 h to give 19norcholesta -5,10-dien-38-01 potassium hydroxide at
acetate (5) in 89% yield.
Its hydrolysis with
room temperature for 4 h gave the corresponding crys-
talline 38-01 64 in 67% yield.
Oxidation of 6 in dichloromethane with dimethyl
sulphoxide-trifluoroacetic anhydride at -78OC according to the procedure of Swern' gave 19-norcholesta-1,3,5(10)-trien-3-01
(7)6in a 35% yield.
We then undertook the transformation of 38-hydroxyandrost-5-en-17-one
(8)
into estrone
(14) Q_ by applying a series of the above reactions. Thus, commercially available 38-hydroxyandrost-5-en-17-one 8 was transformed into a cyclic - 3 The cyclic hemiacetal 9 hemiacetal 9 according to the procedure of Barton. gave a 7:l mixture of 5-bromo-19-nor-5a-androst-9-ene-38,68-diol
3-acetate 6-
formate (10) and 5-bromo-19-nor-5a-androst-lO-ene-38,68-diol 3-acetate C-for-5 (11) in a 74% yield according to our procedure for the 8-scission. 2 1.-. Reductive elimination of 11 __ in acetic acid with zinc under the conditions applied for cholestane series gave 19-norandrosta-5,10-dien-38-01 acetate (12) __
mate
in a 89% yield. Hydrolysis of 13 in a mixture of methanol and ethanol containing potas_* sium hydroxide at room temperature gave the corresponding crystalline 38-01 (13)8 in a 78% yield. Swern Oxidation of __ 13 gave estrone and 19-norandrosta__ 5,10-dien-38-01 trifluoroacetate in 53% and 20% yields. 9 79
80
Scope of this new aromatization of ring-A of steroids as well as the synthesis of 19-norsteroids from the compounds such as 3, 4, 10 and 11 are being I I I_ II actively investigated.
R = /‘aHi *... ‘H R q0
5 steps
1
a
R
=
Ii , ii
,=aH,, *a --.
H
R=O
R =
lo
AcOv iii
iv
AcO
6
R = &C8Hl '?-I 13 R=O
V
5
R =
12
R=O
R=O
OCHO
4
HO
HCaHi7 “..w
R
eCaHi 7 “H
q
HCaHi7 ‘XH
R=O
2 7
R
14 i) iv)
HgO-12-benzene
KOH-MeOH-EtOH,
q
0CaH17 “..H
R=O ii)
CF,COO
hv
20’ C
R q0
+
iii) v)
Zn-CH3C02H,
llO"C-120°C
TFAA-DMSO-Et3N-CH2C12,
-78’
C
References and Notes 1) 2)
3) 4) 5) 6) 7) 8) 9)
Photoinduced Molecular Transformations. Part 93. Part 92. H. Suginome and S. Yamada, Tetrahedron s., 2, 3963 (1987) e. g., H. Suginome and S. Yamada, 2. 9. w., 49, 3753 (1984); ibid so, 2489 (1985); H. Suginome, C. F. Liu and A. Furusaki; Chem. EC" 1984, 911; H. Suginome, K. Kobayashi, M. Itoh and A. Furua, Chem. s., 1985, 727; H. Suginome and S. Yamada, Tetrahedron e., 2, 37151985); Tetrahedron, in press; H. Suginome and S. Yamada, press; H. Suginome, C. F. Liu and M. Tokuda, J. C 1985, 327,; H. Suginome, M. Itoh and K. Kobay%h‘li;j_. Chem. Sot. Perkin -.' Trans I., in press.; K. Kobayashi, M. Itoh and H. Suginome, Tetrahedron Lett 28, 3369 (1987). --t M. Akhtar and D. H. R. Barton, 2. Am. m. g., %, 1528 (1964). M.P. 69.5-71.5'C S. L. Huang, K. Omura and D. Swern -. , 4_l, 3329 (1976). M.P. 114.0-116.O'C ( Lit.7 M.P. II&~; R. C. Cambie, V. F. Carlisle and T. D. R. Manning, 2. m. s., (c), 1969, 1240. M.P. 134.5-135.5oc Satisfactory spectral and analytical results were obtained for all the compounds described in this paper. (Received in Japan 17 September 1987)