GB762706A - Colchicine derivatives - Google Patents

Abstract

The invention comprises colchicine derivatives of the formula <FORM:0762706/IV(b)/1> where R is hydrogen, alkyl, a sugar residue or an acylated sugar residue and R1 is alkyl which may be substituted. These are made by treating colchicine or its derivatives of the formula <FORM:0762706/IV(b)/2> (or corresponding compounds of the isocolchicine series) with alkyl (or substituted alkyl) mercaptans or their alkali metal salts, R1 and R2 being as above or may also be acyl. The reaction may be carried out in a solvent at room temperature or above or slightly below, preferably at 10-50 DEG C. When the mercaptan itself is used it is desirable to use an acidic substance as catalyst, e.g. hydrochloric acid, boron trifluoride, benzenesulphonic acid or toluene-p-sulphonic acid. Suitable solvents are chloroform and tetrahydrofuran. The reaction with alkali mercaptides may be carried out in water or an organic solvent or a mixture of the two, suitable solvents being C1-C5 alcohols (e.g. methanol, ethanol), tetrahydrofuran and dioxan. The mercaptide (e.g. lithium, sodium or potassium) may be used in the solid form or formed in situ in solution. The product is extracted with a water-immiscible solvent and the residue after evaporation purified by fractional crystallization or chromatography. The radical R may be exchanged for a different radical before or after reaction with the mercaptan or mercaptide, e.g. a hydroxyl group may be reacted with diazomethane or a haloacyl-sugar and in the latter case the acyl groups may be subsequently split off. Examples show the production of the following compounds: (1) R=R1=methyl, from colchicine, isocolchicine, O-acetyl-colchiceine and demethyl-thiocolchicine (R=H); (2) R=H, R1=methyl, from demethyl-colchicine, O-acetyl-demethyl-colchicine, thiocolchicoside and O-tetracetyl-thiocolchicoside; (3) R=methyl, R1=ethyl, from colchicine; (4) R=methyl, R1=hydroxyethyl, from colchicine; (5) R=glucose residue, R1= methyl, from colchicoside, O-tetracetyl-thiocolchicoside and demethyl-thiocolchicine; (6) R=tetracetyl-glucose residue, R1-methyl, from demethyl-thiocolchicine and O-tetracetylcolchicoside. The last-named compound is made as in Specification 738,612. Specification 732,265 also is referred to.ALSO:Compounds of the formula: <FORM:0762706/I/1> where R is hydrogen, alkyl or an acylated or unacylated sugar residue and R1 is alkyl or substituted alkyl, are used for the modification of karyokinesis and the production of polyploids either by spreading aqueous solutions or suspensions on the soil or by pretreating seeds with the compounds alone or in a solvent or on a carrier. Suitable compounds are mentioned. Specifications 732,265 and 738,612 [both in Group IV (b)] are referred to.