GB1440094A - Simaroubolide - Google Patents

Abstract

1440094 Simaroubolides RESEARCH CORP 3 Aug 1973 36986/73 Heading C2C [Also in Division A5] The invention comprises a method of isolating an anti-leukemically active fraction from Brucea antidysenterica comprising the sequential steps of:(a)extracting Brucea antidysenterica with akanol; (b) partitioning the alkanolic extract between CHCl 3 and water; (c) removing the solvent from the CHCl 3 fraction and partitioning the residue of the fraction between 90% aq. CH 3 OH and petroleum ether; (d) separating said 90% aq. CH 3 OH fraction and adding thereto sufficient water to produce a 80% aq. CH 3 OH solution and extracting same with COl 4 ; (e) further diluting said 80% aq. CH 3 OH solution with sufficient water to provide a 60% aq. CH 3 OH solution and extracting the same with CHCl 3 ; (f) removing the CHCl 3 from the CHC1 3 extract, chromatographing the residue on silica gel and eluting the gel firstly with CHCl 3 containing up to 0.5% CH 3 OH ; and (g) eluting secondly with 1% CH 3 OH in CHCl 3 and collecting at least the first of the fractions which contain any compound which upon thin layer chromatography gives an immediate dark stain with FeCl 3, the fraction(s) thus isolated being the anti-leukemically active fraction(s). The invention also comprises bruceantin, its triacetate and a simaroubolide having the following physical characteristics: [α]<SP>24</SP> D -14À5‹ 7À95, 8À65, 9À47 Á; mass spectrum m/c 457, 546, 438, 430, 402, 151, 125, 110 and 091; nmr (CDCl 3 )#6.28, 7À90, 8À02, 8À19, 8À50, 8À63 (methyl singlets). These compounds may be obtained by the above process with the triacetate being obtained by acetylating bruceantin with acetic anhydride. In the above, process the solvent may be removed from the fractions obtained in step (g) to give a concentrate containing bruceantin which may be chromatographed on silica gel which is eluted with a 30% ether/70% benzene mixture from which the first and second fractions containing bruceantin and also, upon thin layer chromatography, giving an immediate dark stain with FeCI 3 are collected. The solvent may be removed from the second of said fractions to give substantially pure bruceantin. Other compounds which may be isolated from the anti-leukemically active fractions, are bruceantarin, bruceine B, isobruceine B and dihydrobruceantin.