Patent GB-1218282-A (GB)
Title: New pregnane derivatives
IPC: C07J/
Filed: 1968-03-12
Abstract: 1,218,282. 14α,17α - (Substituted methylenedioxy) - pregnenes. KONINKLIJKE NEDERLANDSCHE GIST-& SPIRITUSFABRIEK N.V. 12 March, 1968 [13 March, 1967], No. 11983/68. Heading C2U. The invention comprises compounds of the general formulµ shown in Figs. 1 and 2 in which the broken lines at the 1-2, 6-7 and 15-16 positions indicate optional second bonds, R is a C 1-9  aliphatic hydrocarbon group (optionally substituted by a halogen atom or a carboxyl or methoxycarbonyl group), an aryl group (optionally substituted by a halogen atom, a C 1-4  alkyl, nitro or amino group, or one or more C 1-4  alkoxy groups), a C 3-8  cycloalkyl group, a C 1-4  alkoxy group, or a furyl group; R 1  is C 1-4  alkyl; R 2  is hydrogen, halogen or hydroxyl; R 3  is hydrogen, halogen or C 1-4  alkyl; R 4  is hydrogen, hydroxyl, acyloxy or oxo; and R 5  and R 6  each represent hydrogen, halogen, #-hydroxyl, or methyl. A compound of Formula I is prepared from a compound of Formula III by reaction with a compound of formula RCHO or RCH- (OR 7 ) 2  wherein R 7  is C 1-4  alkyl. A compound of Formula II, wherein R and OR 1  represent identical C 1-4  alkoxy groups, is prepared from a compound of Formula III, in which the 1,2 and 6,7- positions are saturated, by reaction with a compound of formula (R 1 O) 3 CH. Compounds of Formula II (in general), are prepared from compounds of Formula I by reaction with a compound of formula R 1 OH, (R 1 O) 2 CH or CH 3 C(OR 1 ) 2 CH 3 . A compound of Formula II can be converted to a compound of Formula I in which the 1,2 and 6,7-positions are saturated by acid hydrolysis. The following additional product interconversions are described: (i) #<SP>1</SP>-dehydrogenation (chemical or microbiological) of compounds of Fig. 1, (ii) #<SP>6</SP>dehydrogenation (chemical) of compounds of Fig. 1, (iii) #<SP>15</SP>-introduction by elimination of 15#-Br (iv) 4-chlorination of compounds of Fig. 1 directly of via the 4,5- epoxide (v) 4-hydroxylation of compounds of Fig. 1 via the 4,5-epoxide (vi) conversion of a compound of Fig. 2 or corresponding 3-aoyloxy compound via the 6-formyl derivative thereof into a 6-methyl compound of Fig. 1 (vii) conversion of a compound of Fig. 2 into a 6-Cl, F or Br-compound or Fig. 1, (viii) conversion of a 3-enol ester of a compound of Fig. 1 via 3-OH-#<SP>5</SP> and 3-OH-5-Br-6-F intermediates into a 6- fluoro compound of Fig. 1, (ix) ##α isomerization of 6-substituted compounds, (x) 11a or # microbiological hydroxylation, (xi) oxidation of 11#-hydroxyl to 11-oxo (Example XIV), (xii) acetylation of 11#.hydroxyl (Example XVI), (xiii) reduction of 14α,17α - (p - nitrobenzylidenedioxy)progesterone to the corresponding amino compound (Example IIIt), (xiv) hydrolysis of 14α,17α - (3<SP>1</SP> - methoxycarbonylpropylidenedioxy)progesterone to the corresponding carboxyl compound (Example XIII). 14α,17α - Diols of Fig. 3 are preparable by microbiological 14-hydroxylation of the corresponding 14 - unsubstituted - 17α - ols, 14α,17α- Dihydroxy - pregn - 4 - ene - 3,20 - dione is alternatively prepared from 17α,21 - hydroxypregn - 4 - ene - 3,20 - dione via, 14α,17α,21- trihydroxy - pregn - 4 - ene - 3,20 - dione. Pharmaceutical compositions suitable for oral ) or parenteral administration comprises a compound of Fig. 1 or Fig. 2 2 and a pharmaceutical carrier. The active ingredients possess progestational and contraceptive activity.