Patent GB-808903-A (GB)
Title: Polyhydrochrysene compounds and process of making same
IPC: C07J63/00
Filed: 1955-02-16
Abstract: The invention comprises polyhydrochrysene compounds of the general formula: <FORM:0808903/IV (b)/1> wherein R1 represents a free or functionally converted oxo group, R2 is a hydroxyl group, R3 is an oxygenated functionally converted methyl group or R2 and R3 form a lactol or lactone grouping and functional derivatives of these groupings, R4 is a free or functionally converted oxygenated methyl group, which compounds may further contain a double bond in the 4:5 or 5:6 position, together with a process for their preparation by reacting a compound of formula: <FORM:0808903/IV (b)/2> (which may contain an 8-:8a double bond) with an activated acetylene or ethylene, e.g. acrolein, if necessary converting the substituent in the 2-position into the formylethyl group, treating the resulting 2-substituted compound with a lower aliphatic alcohol R5OH in the presence of an inorganic acid, oxidizing the product, which has the partial formula: <FORM:0808903/IV (b)/3> to yield a (2\sY4) lactone, introducing an alkoxyacetylene by additive combination with the carbonyl group at the 1-position, converting the substituent in the 1-position of the obtained product into a formylmethyl group by reduction, dehydration and reduction or by dehydration, rearrangement, reduction and oxidation, converting the substituent in position 2 into a formyl group by partial hydrolysis, and subjecting the resulting compound to ring closure, if desired reducing and esterifying the obtained 17-formyl group and/or setting free the functionally converted hydroxyl and/or oxo groups.  In examples: (1) 4bb -methyl-2-hydroxymethylene - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab  - dodecahydrophenanthrene - 4b  - ol - 1-one in t-butanol is treated with acrolein, the product reacted with pyridine-acetic anhydride and then with ethanolic HCl giving the crude acetate of the cyclosemiacetal of 4bb -methyl-2b  - formyl - 2a - (31,31 - diethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 4b  - ol - 1 - one; (2) 4bb  - methyl - 2 - hydroxymethylene - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10, 10ab -dodecahydrophenanthrene-4b -ol-1-one is treated in dioxane with acrolein containing hydroquinone, aqueous methanolic HCl added and resulting 2b -formyl-2a -(31-oxopropyl) derivative either acetylated to a compound of formula: <FORM:0808903/IV (b)/4> or with methanolic HCl gives the 2a -(31,31-dimethoxypropyl) derivative (I) which with HCl in aqueous acetone regenerates the dialdehyde; (3) as in (2) isolating from the mother liquor 4bb  - methyl - 2a  - (31:31 - dimethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab  - dodecahydrophenanthrene-4b -ol-1-one, (II); I treated with pyridineacetic anhydride and with pyridine-benzoyl chloride gives the acetate and benzoate of the cyclosemiacetal of 4bb -methyl-2b -formyl-2a -(31,31 - dimethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab  - dodecahydrophenanthrene - 4b  - ol - 1 - one respectively; (4) I is treated with methanolic HCl yielding the monomethyl ether of acetalized 4bb -methyl-2b  - formyl - 2a  - (31 - oxopropyl) - 1,2,3,4,4aa ,4b,5,6,7,9,10,10ab  - dodecahydrophenanthrene-4b  - ol - 1,7 - dione (III); (5) I is boiled with aqueous methanolic NaOH to give II, which with potassium carbonate and formalin gives a mixture of epimeric 2-(hydroxymethyl)-2-(31,31-dimethoxypropyl) derivatives oxidizable with chromium-trioxide/pyridine to I; (6) the acetate or benzoate of the cyclosemiacetal of 4bb  - methyl - 2b  - formyl - 2a  - (31,31 - dimethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab  - dodecahydrophenanthrene - 4b  - ol - 1 - one is treated with ethoxy acetylene lithium compound giving the corresponding 1 - ethoxyethin - 1 - ethoxyethinyl - 1 - ol/yl - 1 - ol derivative, and from the mother liquor after chromatography there obtained II and its 2b -epimer, which is epimerized by boiling with methanolic NaOH; (7) I is oxidized to the lactone of 4bb -methyl-2b - carboxy - 2a  - (3,31 - dimethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 4b  - ol - 1 - one, which can be converted to the free 31-oxopropyl derivative as in (2); subsequent reaction with the lithium ethoxy acetylene compound yields the lactone of 4bb -methyl-2b -carboxy-1-ethoxyethinyl - 2a  - (31,31 - dimethoxypropyl)-7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab  - dodecahydrophenanthrene - 1,4b  - diol; (8) I is treated with methanolic HCl to give a compound of formula: <FORM:0808903/IV (b)/5> which on treatment with HCl in aqueous acetone yields III; (9) hydrogenation of the product of (7), using palladium on calcium carbonate gives the corresponding 1-ethoxyvinyl derivative, which is dehydrated with thionyl chloride to the 1,1-formylmethylene compound and hydrogenated over palladized barium sulphate to the lactone of 4bb -methyl-2b -carboxy-1b -formylmethyl - 2a  - (31,31 - dimethoxypropyl) - 7 - ethylenedioxy - 1,2,3,4,4aa ,4b,5,6,7,8,10,10ab -dodecahydrophenanthrene - 4b  - ol, which is treated with HCl in aqueous acetone and the 31-oxopropyl compound obtained then cyclized in piperidine/acetic acid to the lactone of d,l - D 5,16 - 11b  - hydroxy - 3 - ethylenedioxy - 17 - formyl - D - homo - androstadiene - 18 - carboxylic acid, which (10) is reduced with sodium borohydride and benzoylated giving the benzoate of (18\sY11b ) lactone of d,l- D 5,16-11b -hydroxy - 3 - ethylenedioxy - 17 - hydroxymethyl - D - homo - androstadiene - 18 - acid, and similarly the corresponding acetate; (11) subsequent reduction of these esters with lithium aluminium hydride in tetrahydrofuran, followed by further acylation gives the dibenzoate or diacetate of the cyclosemiacetal of d,l - D 5,16 - 11b  - hydroxy - 17 - hydroxymethyl - 18 - oxo - 3 - ethylenedioxy - D - homoandrostadiene.