Patent GB-839746-A (GB)
Title: Hydrophenanthrene compounds and process for their manufacture
IPC: C07D307/00
Filed: 1956-05-23
Abstract: The invention comprises hydrophenanthrene compounds of the formula <FORM:0839746/IV (b)/1> saturated or unsaturated in the ring system and in which R1 represents a free or functionally converted oxo group, R2 represents a hydrogen atom, a methyl group or a free or functionally converted hydroxymethyl group, and X is an oxo group or a free or functionally converted hydroxyl group together with a hydrogen atom; together with a process for their preparation from a compound saturated or unsaturated in the ring system of the formula <FORM:0839746/IV (b)/2> wherein R1, R2 and X are as above and R3 i a hydrocarbon radical (a) by additive combination of ozone with the double bond of the allyl or methallyl residue and reductive cleavage of the ozonide or (b) by hydroxylation of the double bond with osmium tetroxide, H2O2 in the presence of osmium tetroxide or tungsten trioxide, potassium permanganate, or silver benzoate or acetate and iodine and either cleavage of the glycol with periodic acid, lead tetra-acetate, aryl iodosoacylates, chromic acid or oxidation of the secondary hydroxyl group of a primary-secondary glycol to the oxo group while first protecting the primary hydroxyl group; and subsequently reducing the ethinyl residue of the resulting 2-acetonyl or 2-formylmethyl compounds or the intermediate glycols to the corresponding ethenyl residue by catalytic hydrogenation or alkali aluminium or boron hydrides, and converting the 1-hydroxy-1-ethenyl compounds to 1-formyl methylene compounds by the action of a halide of phosphorus or of sulphurous acid in the presence of a tertiary base.  In examples: (1) the (2 --> 4b )-lactone of D 8a-1-ethoxyethinyl-2a -methallyl - 2b  - carboxy - 4bb  - methyl - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 1,4b  - diol, (I), in pyridine-ether is treated with osmium tetroxide giving an epimeric mixture of the corresponding 2a -(21,31-dioxy-isobutyl) compounds (II) which are hydrogenated over palladium-calcium carbonate to the D 8a-1-ethoxyethenyl analogue, treated in methanol - pyridine with aqueous HIO4 and the resulting D 8a-1-ethoxyethenyl-2a -acetonyl compound reacted with PBr3 in pyridine giving the corresponding 1 : 1-formyl - methylene - 4b  - ol; (2) I is ozonized and the ozonide decomposed with zinc and acetic acid giving the 2a -acetonyl derivative (mixture of epimers separated by crystallization) also prepared by periodate oxidation of II, and subsequent hydrogenation over PdCaCO3 gives the D 8a1-ethoxyethenyl-2a -acetonyl derivative, which is then treated as in (1); (3) the (2 --> 4b ) - lactone of D 8a - 1 - ethoxyethinyl - 2a  - allyl - 2b  - carboxy - 4bb  - methyl-7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 1,4b  - diol (III) as in (1) gives the 2a -(21,31-dihydroxy-propyl) derivative, then the corresponding 1-ethoxyethenyl compound (IV), which is acetylated to the (2 --> 4b ) lactone of D 8a - 1 - ethoxyethenyl - 2a  - (21 - hydroxy - 31 - acetoxypropyl) - 2b  - carboxy - 4b b - methyl - 7 - ethylenedioxy decahydrophenanthrene - 1,4b  - diol, oxidized with CrO3 in pyridine to the 2a -(21-oxo - 31 - acetoxypropyl) derivative, which with PBr3 yields the (2 --> 4b ) - lactone of D 8a - 1,1 - formylmethylene - 2a - (21 - oxo - 31 - acetoxypropyl) - 2b  - carboxy - 4bb  - methyl - 7-ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 4b  - ol (V); (4) the 1-epimer of III is treated with OsO4 and then hydrogenated giving the 1-epimer of IV; (5) the 1-epimer of III is hydrogenated and the D 8a - 1 - ethoxyethenyl - 2a  - allyl compound obtained is treated with OsO4 giving the 1-epimer of IV, and from the mother liquors another isomer differing in respect of the 21-hydroxyl configuration; these isomers are acetylated and then the 3-acetoxy compounds oxidized with CrO3 yielding the same 2a -(21-oxo-31-acetoxy propyl) compound isomeric with that from (3); subsequent reaction with PBr3 gives V.  The (2 --> 4b ) lactone of D 8a - 1b  - formylmethyl - 2a  - acetonyl - 2b - carboxy - 4bb  - methyl-7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10, 10ab  - dodecahydrophenanthrene p  - 4b  - ol is prepared by hydrogenation of the 1 : 1-formylmethylene analogue. Specifications 805,603, 805,607, 839,747 and 839,748 are referred to.