Biomimetic oxidative syntheses of spirodienone and dibenzocyclooctadiene lignans

• Main Author: Abd El Ghani, A. F. M.
• Published: Swansea University 1995
• Subjects: 547.7
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.635823

The work described in my thesis outlines the achiral and chiral synthesis of lignans by cyclisation reactions <I>via</I> oxidation of phenols. The synthesis of achiral lignans <I>via</I> oxidation of the phenolic tandem conjugate addition products to but-2-en-4-olide utilizing diphenyl thioacetals as acyl anion equivalents, followed by <I>in situ</I> trapping with aromatic aldehyde or benzyl halide afforded the adducts in good yields. Desulphurisation yielded dibenzylbutyrolactones among which were arctigenin and prestegane A. These were successfully cyclised to spirodienone and dibenzocyclooctadiene lignans stereoselectively by the oxidation of the phenolic dibenzylbutyrolactones with bis(trifluoroacetoxy)iodobenzene. The stereochemistry was defined by detailed <SUP>1</SUP>H and <SUP>13</SUP>C nmr studies and confirmed by X-ray analysis. These reactions provide the first synthesis of spirodienones which have been proposed as intermediates in both the synthesis and biosynthesis of the dibenzocyclooctadiene series. The reactions also provide an alternative biomimetic route to compounds of the steganacin and schizandrin type. The asymmetric synthesis of lignans demonstrates the formation and use of (-)-(4R)-4-menthoxybutenolide and benzyl bromide also in tandem conjugate addition reactions. Desulphurisation led to the homochiral menthoxy substituted phenolic dibenzylbutyrolactone which was cyclised successfully <I>via</I> oxidation of the phenol with bis(trifluoroacetoxy)iodobenzene to give a menthoxy substituted dibenzocyclooctadiene which was dementhylated to give the chiral dibenzocyclooctadiene plus a dibenzocyclooctadienediol as a side product. Also dementhylation of the menthoxy substituted dibenzylbutyrolactone gave a dibenzylbutanediol as a side product plus the target dibenzylbutyrolactone. The latter was cyclised <I>via</I> oxidation of the phenol with bis(trifluoroacetoxy)iodobenzene and then gave the chiral dibenzocyclooctadiene lignan.