DE720829C - Process for the preparation of sugar derivatives of polyphenylaethane and polyphenylaethylene compounds with steroid hormone action - Google Patents

Description

Process for the preparation of sugar derivatives of polyphenylethane and Polyphenylene compounds with steroid hormone action It has been found that one to new sugar derivatives of polyphenylethane and polyphenylethylene compounds with steroid hormone effects can be achieved if one of the compounds mentioned working methods known per se converted into their saccharide derivatives.

Any polyphenylethane and polyphenylethylene compounds with steroid hormone action can be used as starting materials, which are characterized by the content of one or more reactive hydroxyl groups. In particular, the following compounds may be mentioned as examples: alkyl or alkenyl mono- and poly- phenols, such as q., 4'-Dioxy-a, ß-diethyldiphenyl- ethane, 4th, q .'- a, P-tetraoxy-a, i3-diethyldiphenyl- ethane, anol and dianols, oxy compounds of the stilbene series, like 4th, q! -dioxystilbene, a, ä - Dialkyl-, a, ä -dialkenyl-, a, ä -dialkinyl-, a, ä - Alkylaryl- or a, a'-diaryl-4,4'-diO. '[Ystil- bene, such as a, a'-dimethyl-4,4'-dioxystilbene, a, ä -Diethyl-4,, -dioxystilbene, a-methyl-ä - ethyl-q., 4-diokystilbene, a, ä -diisopropyl-4, 4 .'- dioxystilbene, a, ä- diethinyl-4, 4'-dioxystilbene or a, d-diphenyl-4, 4-dioxystilbene, furthermore a-monoalkyl-, -alkenyl-, -alkynyl- or -aryl- q., 4 .'- dioxystilbenes, such as methyl, ethyl, ether nyl-, ethynyl-, allyl- or phenyl-4, q .'- dioxy- stiibene. Furthermore also oxy compounds of Polyphenyläthanreilie, which are substituted in a- and or or a'-position by alkeny 1, alkynyl or alkylidene, such as. B. 3, 4- (4 ', @ "- Dioxydiphenyl) -2, 4-hexadiene, 2, 3 - (.1.', 4" -Dioxydiphenyl) -i, 3-butadiene, a, -Diethinyl -, 4 ', 4 "-dioxydiphenylethane, a, ä -Diallvl-2', 2" -dioxydiphenylätliane. α-Ethynyl-4 '4 "- dioxydiphenylethane, α-ethenyl-2'-oxydiphenylethane, ethylidene-4', 4", 4 "'- trioxytriplienylethane.

The saccharides used are 7.B. Mono-, dis- and trisaccharides, such as glucoses, Galactoses or galactose glucose.

The present process is carried out according to working methods known per se, such as those described, for. B. in Richter-Anschütz, Chemistry of Carbon Compounds, 12th Edition, Vol. 2, i. Half, 1935, p. 359, and reports dd chem. Ges. Vol. 62, 1929, pp. 99o ff. And B d. 66, 1933, p. 378 ff. Are carried out.

The new compounds can contain one or more saccharide residues in their molecule, next to it. but also free, esterified or etherified hydroxyl groups contain. The saccharide residues can for their part also be in the form of derivatives, such as B. in the form of their acyl compounds.

The new compounds have steroid hormone effects and are said to be therapeutic Find use. Example i i part .1,. -Dioxy-a, ß-diethylstilbene, 3 parts pentaacetylglucose and o, i part of p-toluenesulphonic acid are dissolved in io parts of benzene for 5 hours Boiling heated. The solution is then washed with dilute sodium hydroxide solution and water and dry them over sodium sulfate. After the benzene has evaporated, last in the Vacuum, one wins the octaacetyl-bis-glucoside of the Dioxydiethylstilben in colorless Crystals from F.227 to 23o °. It can be redissolved from methanol or ethanol.

The saponification takes place by heating the methyl alcoholic solution of the acetyl derivative with 1 part of a solution of 1 part sodium in 100 parts of methanol for a short time. Water is added, the 4, 4! -Bis - (ß-glucosido) -a, ß-Diethylstilbene precipitates as a white powder. It can be recrystallized from butanol and shows the decomposition point of about 245o.

In the same way, the representation of polysaccharides succeeds, such as z. B. that of 4, 4'-bis- (P-lactosido) - or 4, q .'- bis- (ß-gentiobiosido) -d-glucoside of the same starting material.

The representation of the saccharides mentioned can just as easily be done using the corresponding Acetohalogenous sugars take place or by reacting acetyl sugars in the presence of zinc chloride.

In a very similar way, sugar derivatives of polyanols, like Dianol. Example e To a solution of 2.4 parts of .1-Oxy - @ '- benzoxy-a, ß-diethyldiphenylethane and 7.2 parts of acetobromoglucose in 5o parts of dry quinoline become fresh with vigorous stirring at room temperature in small portions 5 parts given precipitated and sharply dried silver oxide. After prolonged stirring it becomes the reaction product was added to zoo parts of chloroform. To remove the silver oxide and silver bromide, the chloroform solution is sucked off through an aluminum oxide filter, then washed with dilute sulfuric acid, with sodium hydroxide solution and with water .and finally evaporated in vacuo after drying over sodium sulfate. The thus obtained Monotetracetyl-ßglucosid this is 4-oxy-4 '-: benzoxy-a, ß-diethyldiphenylethans purified by chromatography and melts after recrystallization from methanol at i56 °.

The saponification is carried out by adding a suspension of 1.9 parts of this product in 60 parts of methanol with a solution of 0.3 part of sodium in 30 parts of methanol and by constant stirring at Zirnner temperature. After a few hours a complete solution is obtained, which is precisely neutralized with dilute acetic acid and then evaporated to a small volume. After adding water, the monoglucoside des .1, 4'-Dioxy-a, ß-diethyldiphenylethans, which melts after recrystallization from aqueous methanol at 203 to 2o4 °.

To obtain the starting material used in this example can be worked as follows: A solution of 4.4 parts .1, γ-Dioxya, ß-diethyldiphenylethane and 3.6 parts of benzoic anhydride in so parts of dry pyridine is 2 hours refluxed. The pyridine is then distilled off in vacuo and the Residue taken up in ether. In the process, that which is difficult to dissolve in ether is separated Di: benzoate des 4,4'-dioxy-a, /> - diethyldiphenylethans almost quantitatively from. It will Aspirated and washed several times with ether. The ether solution is diluted with Sulfuric acid, then washed with dilute soda solution and finally with water, dried and evaporated. The oily ether residue is taken up in methanol and the ethanol solution with water up to slightly cloudy. The monobenzoate crystallized overnight and was recrystallized in methanol pure state melts at z23 to r26 °.

In an analogous manner, for. B. the monoacetate or monopropionate des 4, 4'-Dioxy-a, ßdiäthyldiphenyläthans are obtained and from these the corresponding Monotetracyl-ß-glucoside are produced, which in turn are produced by saponification into the mono-ß-glucoside described above: des 4,4'-dioxy-a, ß-diethyldiphenylethane let transfer from the F. 2o3 to 2o4 °. Example 3 7.2 parts of acetobromoglucose become with 2 parts of 4-oxy-4'-propionyloxy-a, ß-diethylstilbene in that given in Example 2 Wise implemented. The monotetracetyl - f is obtained; - glucoside des 4 - oxy - 4'- propionyloxy-a, ß-diethyl stilbene.

To obtain the starting material used in this example can be worked as follows: i Part 4., 4'-Dioxy-a, ß-diethylstilbene is in io Dissolved parts of pyridine, and 0.65 parts of propionic anhydride are added to this solution and let it stand at room temperature for about 16 hours. This is followed in the Evaporated in vacuo and the residue obtained taken up in ether. The ethereal solution is washed with dilute hydrochloric acid, with dilute soda solution and water, then dried and evaporated. The residue is with a benzene-pentane mixture (i: i) added and chromatographed over aluminum oxide. When developing the Chromatogram with Benzolpen.tan (i: i) the dipropionate of the 4, 4'- Dioxy - a, ß - diethylstilbene from the red temperature to 14 °, then with benzene alone the monopropionate of the 4th, 4'-dioxy-a, ß-diethyl stilbene obtained. Recrystallized from ether pentane the latter melts at 92 to 94 °.

In an analogous manner, for. B. the monobenzoate of the 4th, 4'-dioxy-a, ß-diethyldiphenylstilbene from F. 14o to 141 'can be won. The monotetracetyl-ß-glucoside can be derived from this of 4-oxy-4'-benzoxy-a, ß-diethylstil'ben of F. 16o, 5 Abis 161 °. Analogue one also obtains the monotetrapropionyl-ß-gluCoside des 4 - oxy-4'-propionyloxy-a, ß-diethylstilbene from 119 °.

The acylated glucosides result in the example given Saponification of the mono-ß-glucoside of 4, 4'-dioxy-a, ß-diethylstilbene from F. 177 to iSil.

Furthermore, equimolecular amounts of 4,4'-Dioxy-a, a-diethylstilbene and acetobromoglucose or the like, the monotetracetyl-ß-glucoside of Dioxydiäthylstilben from the F. 173 to 175 ° or similar derivatives in addition to the im Example i described octaacetyl-bis-glucoside from F.227 to 23o ° or others. bis-glocuside derivatives.

Claims (1)

PATENT CLAIM: Process for the production of sugar derivatives from Polyphenylethane and polyphenylethylene compounds with steroid hormone effects, thereby characterized in that the compounds mentioned by working methods known per se converted into their saccharide derivatives.