Synthesis of isoquinoline and yohimbinoid alkaloids

Abstract

A systematic survey of the different synthetic methodologies available for the syntheses of isoquinoline and yohimbinoid alkaloids revealed that the general approaches to these compounds involved either an A/B → C → D/ → E approach or a D/E → C/B/A approach% We have now devised a novel method for the syntheses of both the isoquinoline and indole alkaloids belonging to the tetra-hydroprotoberberine and yohimbinoid skeleton. In the method developed by us a suitable 'D' ring is first chosen on which the 'C' ring is built. This bicyclic C/D ring system is then cleaved by condensing with a suitable A/B unit bearing an amine so that an overall A/B → seco C/D ring system is generated. By appropriate reactions the total synthesis of the alkaloids has been achieved in which the seco 'C' ring undergoes cyclisation. The total syntheses of two tetrahydroprotoherberine alkaloids, (±) 2,3-dimethoxyberbine and (+)-norcoralydine and three pentacyclic indole compounds, (±) decarbcethoxy dihydrogambirtannine, (±)alloyohimbine aid (±)rauwolscine will be discussed. Our method for the synthesis of these alkaloids was based on the choice of 3-isochromanone derivative as a suitable synthon for the construction of the nonnitrogenous moiety. The nitrogenous portion was derived from tryptamine. Since 3-isochromanones belong to σ-lactcnes they can readily be prepared from 2-indanones by Bayer-Villiger oxidation. However, the conventional method for the synthesis of 2-indanone is not a simple procedure. An improved method for 2-indenone and its derivatives has been developed by us using a diazoketone intermediate. A unique acid catalysed diazoketone cyclisation procedure yielded the desired 2-indanones in good yields.