The Preparation of Intermediates in the Synthesis of (1R,7'R)-Decumbensine and (13R,14R)-Ophiocarpine

Abstract

<p> The synthesis of 2-ethoxycarbonyl-1-hydroxymethyl-1,2,3,4-tetrahydro-6,7-methylenedioxyisoquinoline 117 and 2-acetyl-1,2,3,4-tetrahydro-6,7-methylenedioxyisoquinoline-1-carboxaldehyde 126 are described. These compounds are potentially useful intermediates for the asymmetric synthesis of two tetrahydroisoquinoline alkaloids, (1R,7'R)-decumbensine and (13R,14R)-ophiocarpine. Decumbensine is a simple 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloid having a hydroxyl group at the carbon atom adjacent to C-1 of the isoquinoline ring. Ophiocarpine belongs to the tetrahydroprotoberberine group of isoquinoline alkaloids and has a hydroxyl group in the same relative position in its ring system as that found in decumbensine.</p> <p> The first synthesis led to a racemic intermediate which would require resolution before proceeding with the asymmetric synthesis. The second synthesis led directly to an optically active aldehyde and would appear to be the more satisfactory route.</p> <p> A procedure for the preparation of 3-benzyloxy-4-methoxy bromobenzene is also described. This compound, after halogen-metal exchange, would be used to introduce the second aromatic ring in the ophiocarpine synthesis.</p> <p> The literature on asymmetric synthesis of tetrahydroisoquinoline alkaloids has been reviewed in the introduction. (Diagrams included in thesis)</p>