Enantiospecific synthesis of (S)-(−)-8-oxoxylopinine

The enantiospecific synthesis of (S)-(−)-8-oxoxylopinine 1 was performed using a lateral metallation strategy, in which (S)-alaninol or (S)-phenylalaninol was applied as chiral auxiliary and building block. (4S)-3-(4,5-Dimethoxy-2-methylbenzoyl)-2,2,4-trimethyl-1,3-oxazolidine 12 was synthesized starting from veratraldehyde 13. The addition reaction of benzylic anion generated in situ from chiral amide 12 into 6,7,-dimethoxy-3,4-dihydroisoquinoline 7a proceeded with simultaneous cyclization leading to the protoberberine alkaloid with high enantioselectivity.

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(2S)-2-(4,5-Dimethoxy-2-methylbenzamide)-1-propanolC13H19NO4[α]D20 = −5.9 (c 0.97, CHCl3)[α]D20 = +6.4 (c 1.2, MeOH)Source of chirality: (S)-(+)-alaninolAbsolute configuration (2S)

(4S)-3-(4,5-Dimethoxy-2-methylbenzoyl)-2,2,4-trimethyl-1,3-oxazolidineC16H23NO4[α]D20 = +46.8 (c 0.55, CHCl3)Source of chirality: (S)-(+)-alaninolAbsolute configuration (4S)

(S)-8-Oxoxylopinine ((S)-2,3,10,11-tetramethoxy-5,6,13,13a-tetrahydroisoquino[3,2-a]isoquinolin-8-one)C21H23NO5[α]D20 = −301.8 (c 0.115, CHCl3)Source of chirality: (S)-(+)-alaninolAbsolute configuration (13aS)