A process for the manufacture of cardio-active materials from the glucosides of digitalis and scilla

摘要

The glucosides of Digitalis and Scilla or mixtures thereof are treated with enzymes present in Digitalis and Scilla, whereby they are hydrolysed, and cardioactive glucosides not containing a glucose residue are obtained. The glucosides may be treated before, during or after their extraction from the fresh or dried drug, and the treatment may be effected in water or in an aqueous solution of an organic solvent, or--when starting from the fresh drug--in the presence of a compound capable of killing the cells and arresting putrefaction, e.g. ethyl acetate, chloroform, toluene, methanol or ethanol. Glucoside A of Digitalis lanata (cf. Specification 370,344) is converted by the process into a new glucoside which yields on acid hydrolysis an aglucone (digitoxigenin), digitoxose, and acetic acid; if the new glucoside is disacetylated with dilute alkali solution, digitoxin is obtained. Glucoside B of Digitalis lanata is converted into a new glucoside which yields on acid hydrolysis an aglucone (gitoxigenin), digitoxose, and acetic acid; if the new glucoside is disacetylated, gitoxin is obtained. Glucoside C of Digitalis lanata is converted into a new glucoside which yields on acid hydrolysis an aglucone (digoxigenin), digitoxose, and acetic acid; if the new glucoside is disacetylated, digoxin is obtained. The disacetylated glucosides A, B, and C of Digitalis lanata (cf. Specification 406,197) are similarly converted into nonglucosic glucosides. The Scilla glucoside scillaren A is converted into a new glucoside, called proscillaridin A, which yields on acid hydrolysis an aglucone (scillaridin A) and rhamnose. In the examples: (1) comminuted fresh bulbs of Scilla maritima are allowed to stand in ethyl acetate for five days, during which time the enzyme present (scillarenase) converts the scillaren A into proscillaridin A, which is then isolated by a series of operations described in detail; (2) an enzyme preparation is obtained from comminuted bulbs of Scilla maritima by immersing them in water saturated with thymol, allowing the mixture to stand for 14 days, and filtering the product successively through cloth and a talc filter; the portion retained by the talc filter contains the enzyme; scillaren A is treated with this preparation in a mixture of water, toluene and acetic acid, and after 20 hours the mixture is filtered and proscillaridin A isolated from the filter residue by an extraction process; (3) comminuted leaves of Digitalis purpurea are allowed to stand in ethyl acetate for 3--4 days, whereby the glucosides are coverted into digitoxin, the isolation of which from the product is described; (4) dried leaves of Digitalis lanata are treated as in example 3 to produce a mixture of nonglucosic glucosides; (5) the disacetylated glucoside A of Digitalis lanata is treated for 2--3 days in ethanol solution with comminuted leaves of Digitalis purpurea; a nonglucosic glucoside resembling digitoxin is obtained. Specification 357,926 also is referred to.