THE FIRST ASYMMETRIC TOTAL SYNTHESES OF (-LYCORINE AND (+)-1-DEOXYLYCORINE())

The first asymmetric total syntheses of (+)-1-deoxylycorine (2a) and ( +)-lycorine (2b), the unnatural enantiomer of lycorine (1), are descri bed. Construction of lactam 12, a key intermediate in the synthesis of both 2a and 2b, began by Birch reduction-alkylation of the chiral ben zamide 3 with 2-bromoethyl acetate followed by ester saponification to give the 6-(2-hydroxyethyl)-1-methoxy-1,4-cyclohexadiene 6a in 96% yi eld as a single diastereomer. This material was converted to the radic al cyclization substrates 11a and 11b. Both 11a and 11b gave 12 and th e reduced enamide 11c on treatment with AIBN and Bu(3)SnH in refluxing benzene solution. Lactam 12 also was obtained by photocyclization of enamide 11c. The allylic alcohol unit characteristic of the C ring of the lycorine alkaloids was fashioned by a radical induced decarboxylat ion-epoxide fragmentation of the N-hyproxy-2-thiazoline ester 21b. The resulting (+)-2-epi-deoxylycorine (22) was subjected to Mitsunobu inv ersion followed by LiAlH4 reduction to give (+)-1-deoxylycorine (2a). The synthesis of (+)-lycorine (2b) involved the conversion of 12 to al lylic alcohol 32 followed by a Torssell rearrangement of 32 to give th e rearranged allylic acetate 35. Epoxidation of 35 with dimethyldioxir ane gave 36a, which set the stage for a decarboxylation-epoxide fragme ntation of carboxylic acid 36b to give 37 by photolysis of 36b in the presence of acridine and tert-BuSH. Reduction of 37 with LiAlH4 gave ( +)-lycorine (2b).