TOTAL SYNTHESIS OF (+ -)-ALPHA-LYCORANE AND 4,5-DEHYDROANHYDROLYCORINE/

The total syntheses of (+/-)-alpha-lycorane and dehydroanhydrolycorine are described. The key intermediate in both approaches is the hydroin dolone 5, prepared from the [1+4] cycloaddition reaction of 1-isocyana tocyclohexene and cyclohexyl isocyanide. Alkylation of 5 with arylbrom ide 6 afforded 7. Hydrolysis of enamide 7 followed by reduction of the resultant enol yielded 10 as a single diastereomer. Radical-based cyc lization of this intermediate gave 11 possessing the requisite trans-f usion between rings B and C in good yield. Radical deoxygenation follo wed by reduction of the amide carbonyl function afforded (+/-)-alpha-l ycorane. Similarly, alkylation of 5 with 6-(chloromethyl)-5-iodo-1,3-b enzodioxole gave 14. Treatment of 14 with Pd(OAc)(2) employing the Jef fery modification of the Heck reaction gave tetracycle 9. Hydrolysis o f 9 followed by oxidation with DDQ afforded 15. Reduction of the two c arbonyl functions in this material using lithium aluminum hydride affo rded 4-hydroxyanhydrolycorine (16). Mesylation of the hydroxyl group l ed to rapid, spontaneous elimination producing anhydrodehydrolycorine. Copyright (C) 1996 Elsevier Science Ltd