Patent GB-1413630-A (GB)
Title: Process for the manufacture of 14, 18-epoxyethano-iminosteroids
IPC: A23K1/165
Filed: 1973-05-30
Abstract: 1413630 14,18-Epoxyethanoimino steroids CIBA-GEIGY AG 30 May 1973 [30 May 1972 25 Jan 1973] 25831/73 Heading C2U Steroids of the formula and their salts, wherein P is -CH(R)CH 3  in which R is a free, esterified or etherified OH group in the α- or #-configuration (alternatively known as 20S- and 20R-configuration); R 1  is a free or ketalized oxo group or a free, esterified or etherified OH group together with a H atom; R 2  is H 2  or H when a #<SP>7</SP>-double bond is present, or a free or ketalized oxo group or a free, esterified or etherified OH group together with a H atom; R 3  is H, C 1-6  alkyl or C 7-13  aralkyl ; R 4  is H 2 , or H when a #<SP>9(11)</SP>-double bond is present, or a free or ketalized oxo group, or a free, esterified OH group together with a H atom; R 5  is a H atom, or a free, esterified or etherified OH group, or together with R 1 , a 3α,9α-epoxy group, in which case R 1  is a free, esterified oretherified #-OH group and a 5#-H atom is present; R 6  is H 2  or O; and the #<SP>4</SP>-, #<SP>5</SP>-, #<SP>7</SP>- and #<SP>9(11)</SP>-double bonds are optional, are prepared by reacting corresponding 14#- (etherified hydroxy)-18-als with amines R 3 NH 2  to give 13-CH=NR 3  steroids, reducing these with metal hydride reducing agents to give 13-CH 2 NHR 3  steroids, reacting these with haloacetyl halides to give 13-CH 2 N(R 3 )COCH 2 X steroids (X is a halogen), treating these with a strong acid to release the free 14#-OH group and cyclizing the resulting compounds with a basic agent. Optionally and in any desired order the lactan group may then be reduced to the corresponding amino group using a complex metal hydride, functionally modified hydroxy and keto groups liberated, free OH groups esterified or etherified, a 7-OH group split off with the formation of a #<SP>7</SP>- double bond (if appropriate after prior protection of further free OH groups) and an 11-OH group oxidized to an 11-keto group. Specified products include batrachotoxinin A 7,8-dihydrobatrachotoxinin A; 20-epi-batrachotoxinin A; and 7,8-dihydro-20-epi-batrachotoxinin A; and esters and ethers of these compounds. (20S) - 3# - methoxy - 3α,9α - oxido - 7α,11α,20- triacetoxy - 14# - methylthio - methoxy - 18 - oxo- #<SP>16</SP> - 5# - pregnene is obtained from 3# - methoxy - 3α,9α : 14#,15#- dioxido - 7α,11α,18- triacetoxy - 20 - oxo - #<SP>16</SP> - 5# - pregnene via 3# - methoxy - 3α,9α - oxido - 7α,11α,18 - triacetoxy - 14# - hydroxy - 20 - oxo - #<SP>16</SP> - 5#- pregnene, the corresponding 14,18-diol, its 14,18- acetonide, the corresponding 20-ol (20R-form also isolated and (20S) - 3# - methoxy - 3α,9α - oxido - 7α,11α,- 20 - triacetoxy - 14#,18 - dihydroxy - #<SP>16</SP> - 5#- pregnene. The steroids produced by the novel process have therapeutic actions which resemble those of cardiac-active digitalis substances, and they may be made up into pharmaceutical compositions with suitable carriers. Specification 1,413,629 is referred to. Reference has been directed by the Comptroller to Specifications 1,318,932 and 1,336,434.