Total synthesis of (±)-α-lycorane and 4,5-dehydroanhydrolycorine

Article abstract of DOI:10.1016/0040-4020(96)00605-9

The total syntheses of (±)-α-lycorane and dehydroanhydrolycorine are described. The key intermediate in both approaches is the hydroindolone 5, prepared from the [1 + 4] cycloaddition reaction of 1-isocyanatocyclohexene and cyclohexyl isocyanide. Alkylation of 5 with arylbromide 6 afforded 7. Hydrolysis of enamide 7 followed by reduction of the resultant enol yielded 10 as a single diastereomer. Radical-based cyclization of this intermediate gave 11 possessing the requisite trans-fusion between rings B and C in good yield. Radical deoxygenation followed by reduction of the amide carbonyl function afforded (±)-α-lycorane. Similarly, alkylation of 5 with 6-(chloromethyl)-5-iodo-1,3-benzodioxole gave 14. Treatment of 14 with Pd(OAc)₂ employing the Jeffery modification of the Heck reaction gave tetracycle 9. Hydrolysis of 9 followed by oxidation with DDQ afforded 15. Reduction of the two carbonyl functions in this material using lithium aluminum hydride afforded 4-hydroxyanhydrolycorine (16). Mesylation of the hydroxyl group led to rapid, spontaneous elimination producing anhydrodehydrolycorine.