Patent GB-1171306-A (GB)
Title: Gonapolyenes
Inventor: KUO CHAN-HWA
IPC: C07D309/12
Filed: 1967-02-21
Abstract: 1,171,306. Gonapolyenes. MEKCK & CO. Inc. 21 Feb., 1967 [24 Feb., 1966; 14 July, 1966], No. 8240/67. Headings C2C and C2U. Compounds of the Formula (VIII) are prepared from compounds of the Formulµ (I) and (III) by the process illustrated below. In the reaction scheme R is H, C 3-6  cycloaliphatic, C 1-5  alkyl, aryl or heterocyclic; R 2  is C 1-5  alkyl or phenyl; R 3  is H or C 1-6  acyl ; and R 1  is the same as R if R is not H and is the same as R 3  if R is H. The compounds may be of the optical configuration shown or the enantiomeric compounds or the d,l-forms; and the optically active and racemic forms of compounds of the Formulµ (V) and (VI) in which R 3  is not acyl if R 1  is H are novel, as are the optically active and racemic forms of the 17-acylates of compounds of the Formula (VII) in which R 1  is not H. Compounds I and III on reduction give racemic compounds II and IV respectively; these, or their optically active forms obtained by resolution, may be acylated to give the 17α- acylates or 3,17α-diacylates if R 1  is H. The racemic acylates may also be resolved. Compounds IV, racemic or optically active, may also be obtained by hydrogenation of compounds II. Oxidation of the 17α-ols II and IV gives the starting materials I and III; this process may be used to convert undesired optical isomers to starting materials which may then be re-used. Compounds IV (racemic or optically active) may be cyclized to compounds V by acid treatment. Reduction of compounds V (racemic or optically active) to compounds VI may be effected by chemical or catalytic hydrogenation. Compounds VI (racemic or optically active) are reduced to compounds VII by the action of an alkali metal in liquid ammonia, a 17α-acyloxy group being hydrolysed to a 17α-OH group in this process. Racemic compounds V, VI and VII may be resolved. Compounds VII (racemic or optically active) on oxidation give compounds VIII, a 3-hydroxy group being protected by substitution. 17α-ols V, VI and VII may be 17-acylated if the 3-OH group is protected; and the 17α- acylates may be hydrolysed. A number of methods of resolution are described including, for compounds II and IV, formation of a d- or l-menthhydrazone by reaction with d- or l-3-carbazoyloxymenthane or of a 4-(4-carboxyphenyl)-semicarbazone by reaction with 4-carbazoylaminobenzoic acid and forming a salt of the semicarbazone with an optically active alkaloid base, e.g. brucine, quinine, followed by separating the optically active diastereoisomers and regenerating the required optically active isomers of compounds II and IV. Another method of resolution involves formation of a diastereoisomeric ester with an optically active acid, by reaction with, e.g. an acid chloride such as 3#-acetoxy-#<SP>5</SP>- etiocholenic acid chloride. Starting materials of the formula (I) are prepared by reaction of a 2-R 2 -4-(C 1-5  acyloxy)- cyclopentane 1,3 - dione with a 1 - vinyl - 1 - hydroxy - 6 - OR - 1,2,3,4 - tetrahydronaphthalene, as described for similar compounds in British Specification 1,153,489. 3-Tetrahydropyranyloxy - 8(14) - seco - 13 - ethylgona- 1,3,5(10),9(11),15 - pentaene - 14,17 - dione is prepared by the methods disclosed in the aforementioned British Specification and Specification 1,153,488.