The First Asymmetric Total Syntheses of (+)-Lycorine and (+)-1-Deoxylycorine

Autor:	Arthur G. Schultz, Mark A. Holoboski, Mark S. Smyth
Rok vydání:	1996
Předmět:	Chemistry Diastereomer General Chemistry Lycorine Biochemistry Medicinal chemistry Radical cyclization Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Yield (chemistry) Lactam Enantiomer Benzamide Saponification
Zdroj:	Journal of the American Chemical Society. 118:6210-6219
ISSN:	1520-5126 0002-7863
DOI:	10.1021/ja9606440
Popis:	The first asymmetric total syntheses of (+)-1-deoxylycorine (2a) and (+)-lycorine (2b), the unnatural enantiomer of lycorine (1), are described. Construction of lactam 12, a key intermediate in the synthesis of both 2a and 2b, began by Birch reduction-alkylation of the chiral benzamide 3 with 2-bromoethyl acetate followed by ester saponification to give the 6-(2-hydroxyethyl)-1-methoxy-1,4-cyclohexadiene 6a in 96% yield as a single diastereomer. This material was converted to the radical cyclization substrates 11a and 11b. Both 11a and 11b gave 12 and the reduced enamide 11c on treatment with AIBN and Bu3SnH 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 decarboxylation-epoxide fragmentation of the N-hydroxy-2-thiazoline ester 21b. The resulting (+)-2-epi-deoxylycorine (22) was subjected to Mitsunobu inversion followed by LiAlH4 reduction to giv...
Databáze:	OpenAIRE
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