The purpose of this research was to form (2S, 3R)-2,3bis(3,4-dimethoxybenzyl) butyrolactone. A brief review of the main classes of lignans, their biosynthesis, biological activity and clinical utility is given in the first chapter. The main chemical synthesis routes to such compounds are also provided covering the six most commonly used routes including the Stobbe condensation. An overview of the use of <I>meso</I> compounds for the production of chiral synthons and use of the '<I>meso</I> <I>trick</I>' to enhance yields during chiral induction to <I>meso</I> substrates are discussed in chapter two. Construction of the basic C<SUB>18</SUB> lignan skeleton in chapter three is achieved <I>via</I> a double Stobbe condensation with preferential formation of the E-isomer at each stage. In the first step the Stobbe product is reduced to give the maleic anhydride. This resisted further reduction but reduction of the dimethyl maleate successfully gave the <I>meso</I> succinic anhydride with no <I>d/l</I> isomer formation. The formation of the target compound is described in chapter four. Reaction of the <I>meso</I> substrate with (+)-α-methylbenzylamine proceeded with chiral induction in 81% d.e. The use of chiral alcohols including 1-methol, 1-α phenyl ethylalcohol and S-(+)-methyl mandelate has also been examined showing widely varying diastereoselectivities. Conversion of (2S, 3R, αR)-N-(α-phenylethyl)- 2,3-bis(3,4-dimethoxybenzyl)butanedioic acid monoamide to the target dibenzyl butyrolactone has been readily achieved by reduction to the corresponding alcohol prior to lactonisation. Racemisation of (2S, 3R)-2,3-bis(3,4-dimethoxybenzyl) butyrolactone under basic conditions and comparison of the optical rotation values obtained with those in the literature allowed the absolute stereochemistry to be assigned. The attempted formation of picrostegane type lignans by non phenolic oxidative coupling is also described.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:636768 |
| Date | January 1995 |
| Creators | Edwards, M. I. |
| Publisher | Swansea University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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