DE1274571C2 - Process for the preparation of water-soluble thiocarbamic acid-O- [p-thioglucosido-phenyl] esters - Google Patents

Description

A611

GERMAN JVnt PATENT OFFICE German class: 12 ο -17/01

12o-6
30i-3

PATENT LETTERN »I _{274 571}

File number: P 12 74 571.0-42 (D 38484) \ 274 571 Filing date: March 26, 1962

Open date: August 8, 1968
Issue date: March 27, 1969
The patent specification corresponds to the patent specification

It is known for the production of bactericidal, fungicidal and virustatic thiocarbamic acid -O- aryl esters thiocarbonic acid -O- aryl ester chlorides with primary or secondary amines in React the presence of a hydrochloric acid binding agent. However, these compounds are insoluble in water and therefore have only a limited pharmaceutical application area.

It has now been found that thiocarbamic acid 0- [thioglucosidophenyl] ester the general formula

R - NH - C - 0 - f V - S - glucose

II \ = /

s

in which R denotes an alkyl, cycloalkyl, aryl or aralkyl radical, the bactericid, fungicid and are effective against viruses and have significantly improved solubility properties, especially a higher one Have water solubility, obtained when the thiocarbonic acid - 0 - [p - tetraacetylthio - glucosidophenyl] ester chloride the formula

Cl - C - O

S - tetraacetyl glucose

with a primary aliphatic, cycloaliphatic, aromatic or araliphatic amine in excess or reacted in the presence of a hydrochloric acid binding agent and the thiocarbamic acid thus obtained - 0 - [p - tetraacetylthio - glucosido - phenyl] - ester by heating with methanolic hydrochloric acid to Deacetylated boiling.

The hydrochloric acid binding agent can be, for. B. a tertiary amine or an inorganic base such as Use NaHCCb.

It is already the conversion of acetobromoglucose with phenolate to an alkaline resistant one acetylated phenyl glucoside with subsequent alkaline deacetylation described (P. K a r r e r, Textbook of Organic Chemistry, 1959, p. 368). But since it is known that N-monosubstituted Thiocarbamic acid esters especially under the action of alkalis easily in Senjol and the corresponding hydroxy components disintegrate (M. H. R ί ν i e r, Bull. Soc. chim. France, 3, 35,837 [1906]), was the process of alkaline deacetylation in the present case, in which an alkali-labile acetylated glucoside is present, not transferable. So there was no possibility so far. N-mono method for the production of water-soluble

Thiocarbamic acid-0- [p-thioglucosido-phenyl] -

ester

Patented for:

German Academy of Sciences in Berlin, Berlin-Adlershof, Rudower Chaussee 126

Named as inventor:
Dr. Dieter Martin,
Dr. Anna Elisabeth Martini,
Dr. Alfred Rieche, Berlin

to convert substituted thiocarbamic acid O-aryl esters into hydrophilic compounds.

The process of the invention can be carried out in such a way that thiocarbonic acid 0- [4-S-tetraacetyl- /? - D -glucosido] phenyl ester chloride with 2 mol / S -phenylethylamine is converted into the N - /? - phenylethylthiocarbamic acid -0- [4-S-tetraacetyl - / S -i »-glucosido] -phenyl ester and then deacetylated with methanolic hydrochloric acid to give N- β- phenylethyl-thiocarbamic acid 0- [4-S - / SD -glucosido] phenyl ester .

example

Preparation of the starting compound

Vio mole of 4-hydroxybenzene-thiol-l-S-tetraacetyl / SD-glucoside and Vio mole of thiophosgene dissolved in 300 ml of chloroform, are added under stirring at room temperature with Vio mol of NaOH as a 10 ° / o solution. After stirring for 1 hour, the chloroform layer is separated off, washed with water and dried with CaCb. The carbonic acid O- [4-S-tetraacetyl-O- D -glucosido] phenyl ester chloride remains as a solid, slightly yellow residue after the chloroform has been distilled off in vacuo; Yield: 92.5% of theory.

Method of the invention

² / io moles / i-phenylethylamine, dissolved in 200 ml of acetone, are added dropwise, while stirring at room temperature, with one- half moles of the crude acid chloride mentioned above, dissolved in the appropriate amount of acetone *. After 1 hour of stirring, it is poured onto ice and the product, which soon solidifies, is suctioned off: should it remain oily, it is

909 613/2405

Claims (1)

ether isolated. After drying, the N - β - phenylethyl - thiocarbamic acid - O - [4 - S - tetraacetyl-0-p-glucosido] -phenyl ester is recrystallized from acetone-ether; Yield: 73% of theory. Mp. 73 to 75 ⁰ C. Vio moles of the N - /? - Phenyläthylthiocarbamidsäure-O- [4-S-tetraacetyl- / JD-glucosido] -phenylesters are dissolved in 360 ml of methanol, heated to boiling on a water bath, with 75 ml of conc. Hydrochloric acid is added and the mixture is heated to boiling for a further 50 minutes. It is then cooled, mixed with cold water and the precipitated product is filtered off with suction. After recrystallization from methanol-water, 90% of the theory of N - β - phenylethylthiocarbamic acid 0- [4-S - /? - D-glucosido] phenyl ester with a melting point of 138 ° to 140 ° C. are obtained. The thiocarbamic acid - O - aryl esters consistently arise in good yield and are colorless, crystalline, stable and water - soluble, injectable compounds. They are characterized by a bactericidal and strong fungicidal effect against yeasts and fungi of all kinds, especially against pathogenic skin fungi. The compounds also show a strong virustatic action and, in a concentration of a few y / cm ³ , are able to suppress virus growth in living cells without damaging them themselves. They are also applicable in veterinary medicine. In the table below is the limit concentration for the bactericide and fungicide Effect of N- / J-phenylethyl-thiocarbamic acid-O- [4-S-0-D-glucosido] phenyl ester indicated. formula bacteria Eschert chia coli Baz. Mesenter. Yeasts Endomyces ! actis Rhodotorula mushrooms Epidermo phyton interdigitale Microsporum gypseum N-0-phenylethyl-thiocarbamic acid 0- [4-S - /? - D-glucosido-phenyl] ester CH ₂ - CH, - NH II
s 1: 50000 CH ₂ OH 1: 50000 1: 100000 1: 100000 1: 500000 1: 500000 Claim: Process for the preparation of water-soluble thiocarbamic acid O - [p-thioglucosido - phenyl] esters of the general formula R - NH - C - O - / V - S - glucose 50 in which R denotes an alkyl, cycloalkyl, aryl or aralkyl radical, characterized in that the thiocarbonic acid-O - [p - tetraacetylthio - glucosido - phenyl] - ester chloride of the formula Cl - C-O II ' 55 6o S - tetraacetylglucose with a primary aliphatic, cycloaliphatic, aromatic or araliphatic amine reacted in excess or in the presence of a hydrochloric acid binding agent and the thiocarbamic acid thus obtained - O - [p - tetraacetylthio-glucosido-phenyl] -ester by heating with methanolic hydrochloric acid deacetylated to boiling. Considered publications: R. W a g η e r and Η. Z ο ο k, Synthetic Organic Chemistry, 1953, No. 95 ;. Houben - Weyl, Methods of Organic Chemistry, Vol. 9, 1955, pp. 833, 890 and 891; P. K a r r e r, Textbook of Organic Chemistry, 13th Edition, 1959, p. 368. Ht Mt / 471 7. M · BundHdrueIurel Berlin